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The Effects of Pesticide Exposure Among the Population

“Injustice anywhere is a threat to justice everywhere.” - Dr. Martin Luther King Jr.

When people think of pesticides, they think of toxic chemicals used by companies to control pests. Many people picture planes flying overhead, or trucks driving by, or tractors in agricultural fields spraying a concoction of chemicals, misting the land in a suffocating fog. Others may picture the products they or others apply to their lawns and gardens for aesthetic purposes. However, pesticides also include chemicals used around your home every day. Household cleaners, including disinfectants, antimicrobial products (i.e., personal care products, cosmetics, household bug killers like Raid, bug repellents like OFF!, rat or mouse pellets, and pet shampoos and collars all contain toxic chemicals compounds.

Although pesticide exposure is widespread, these toxic chemicals can cause severe health effects among certain communities. Pesticide exposure itself does not discriminate, as these toxic chemicals impact the health of all men, women, and children alike. Ninety percent of US citizens have at least one pesticide compound detectable in their bodies. However, pesticide exposure patterns tend to cause elevated rates of racial and socioeconomic health disparities and disorders (i.e., brain and nervous system disorders, birth abnormalities, cancer, developmental and learning disorders, immune and endocrine disruption, reproductive dysfunction, among others). 

Vulnerable Communities

• Those fighting for environmental justice understand that the harms inflicted by toxic chemical production and use cause disproportionate adverse effects on people of color—from communities near chemical production plants, to the hazardous and inhumane working conditions in agricultural fields, to the elevated risk factors for black and brown people from toxic pesticide exposure patterns. 

Imperiled Species

• By protecting vulnerable communities, we also protect endangered species at greatest risk of pesticide poisoning as impacts on wildlife— including mammals, bees and other pollinators, fish and other aquatic organisms, birds, and the biota within soil —include reproductive, neurological, renal, hepatic, endocrine disruptive, and developmental anomalies, as well as cancers, in a wide range of species.
• Additionally, pesticide impacts are ubiquitous, with some of the most common used pesticides adversely affect 97% of species listed as endangered or candidates for endangerment.

Biodiversity for All

• Pesticide impacts are ubiquitous, and excessive pesticide use can hamper biodiversity, decreasing species richness of all organisms as a reduction in biodiversity can have grave effects on the environment, economy, and society as a whole. Reducing biodiversity is not simply about reducing numbers; it is also about reducing the strength of the structure supporting the whole.

Environmental justice advocates understand harms imposed by toxic chemical production and use, such as pesticides, can have unequal adverse effects on people of color due to elevated risk factors for black and brown people from toxic pesticide exposure patterns as communities can be adjacent chemical plants, and work conditions (especially in agriculture) can be hazardous and inhumane. By protecting vulnerable communities, we also protect endangered species at greatest risk of toxic chemical poisoning as impacts on wildlife— including mammals, bees and other pollinators, fish and other aquatic organisms, birds, and the biota within soil —include reproductive, neurological, renal, hepatic, endocrine disruptive, and developmental anomalies, as well as cancers. Additionally, toxic chemicals impacts are ubiquitous, and excessive use can reduce biodiversity, decreasing species richness of all organisms as a reduction in biodiversity can have grave effects on the environment, economy, and society, as a whole.

Relevant Articles/News

• Environmental Justice (Including People of Color)
• Farmworkers
• Gender-Specific Effects (Women)
• Infants and Children (1), (2)

Scientific Studies

Farmworkers and Farmworkers' Children • Gender-Specific Effects • Infants/Children • People of Color • Comorbidities/Immunocompromised and the Elderly

Farmworkers and Farmworkers' Children

According to Farmworker Justice, 76% of all farmworkers identify as Latinx/Hispanic. Unfortunately, persistent exposure to pesticides decreases the average lifespan of a farmer to just 49 years, a 29-year difference from the average lifespan of the general population (78 years). Considering the average life expectancy for those in the Latinx communities is above the national average, this is a glaring revelation.

Read More on Beyond Pesticides' Agricultural Justice Page.

• A Comprehensive Review on Pesticide Residues in Human Urine
  Numerous studies worldwide have evaluated pesticide residues detected in urine. This review serves as a contribution to this field by presenting an overview of scientific research studies published from 2001 to 2023, including details of study characteristics and research scope. Encompassing 72 papers, the review further delves into addressing key challenges in study design and method used such as sampling and analytical approaches, results adjustments, risk assessment, estimations, and results evaluation. The review explores urinary concentrations and detection frequency of metabolites of organophosphates and pyrethroids, as well as herbicides such as 2,4-D and glyphosate and their metabolites, across various studies. The association of the results with demographic and lifestyle variables were explored. While farmers generally have higher pesticide exposure, adopting organic farming practices can reduce the levels of pesticides detected in their urine. Residence close to agricultural areas has shown high exposure in some cases. Dietary exposure is especially high among people adopting a conventionally grown plant-rich dietary pattern. A higher detection level and frequency of detection are generally found in females and children compared to males. The implications of transitioning to organic and sustainable plant-rich diets for reducing pesticide exposure and potential health benefits for both adults and children require further investigation.
  [Hakme, E., Poulsen, M. and Lassen, A. (2024) A Comprehensive Review on Pesticide Residues in Human Urine, Journal of Agricultural and Food Chemistry. Available at: https://pubs.acs.org/doi/abs/10.1021/acs.jafc.4c02705.]
• Ecological Crisis Due to Chemical Toxicity: Addressing Soil Health for Better Human Health
  When environmental changes undermine a species' or population's ability to survive, it is said to be in an ecological crisis. Pesticides, particularly persistent organic pollutants (POPs), are among the top ten chemicals and hazardous compounds that the WHO has recognized as being a concern for global health. The overuse and improper handling of agrochemicals is the primary driver of the ecological disaster. According to the GBD 2019, pollution of any type, including air pollution, lead, and other chemicals, causes one in six deaths globally. Industrialization, urbanization, population growth, the burning of fossil fuels, and a lack of adequate national or international chemical policies account for the 66% increase in deaths. Because of lack of awareness, training, and proper expertise regarding agrochemicals, it is particularly challenging to determine the influence on human health or the environment in developing nations. Studies in Northern India have shown evidence of the presence of heavy metals and pesticides in samples of fodder, vegetables, milk, urine, and blood. In addition to signs of genotoxic effect, there were significantly more spontaneous abortions, premature births, stillbirths that were five times as frequent, delay in milestone development, language delays, blue lines in the gums, mottled teeth, and gastrointestinal diseases, which may have been brought on by water contamination with pesticides and heavy metals. The greater rates of cancer including breast, uterus/cervix, ovary cancers of the blood and lymphatic system, oesophagus, and bones, are associated with farming, pesticides exposure, alcohol and smoking. Hence the soil and water have cocktail of pesticides and heavy metals. Pesticides have been widely used, and it is possible to find their remnants in the air, water, and soil. The three most important environmental problems affecting the globe now are pollution, climate change, and biodiversity loss. Various new concepts, including sustainable agriculture reforms and food production that uses sustainable practices, have been inspired by the pressing need for a more sustainable and ecological approach. This review elaborates the extent of pollution due to heavy metals and pesticides with their health impacts and the regulatory measures to overcome this by various methods such as concept of soil security, food security, Natueco farming and multisectoral approach.
  [Thakur, J.S. and Paika, R. (2024) Ecological crisis due to chemical toxicity: Addressing soil health for better human health, Journal of Environmental Science and Public Health. Available at: https://www.fortunejournals.com/articles/ecological-crisis-due-to-chemical-toxicity-addressing-soil-health-for-better-human-health.html.]
• Improving consumer understanding of pesticide toxicity labels: experimental evidence
  Consumers often inadvertently misperceive the health hazards associated with over-the-counter pesticides under the current textual labeling policy, potentially leading to improper use. We conducted an incentivized framed field experiment with eye tracking to evaluate the effectiveness of the current pesticide labels that convey risk using signal words (Caution, Warning, Danger) compared to two visually focused label alternatives: traffic light colors and skull intensity symbols. A total of 166 participants were randomly assigned to one of three label formats and asked to rank toxicity levels and make purchasing decisions within multiple price lists. Results show that signal words fail to adequately communicate toxicity levels. Specifically, participants’ correct assessment of toxicity level dramatically improves from 54% under the existing signal word label to 95% under the traffic light and 83% under the skull intensity symbol labels. We also find that participants are more likely to choose the less toxic alternatives under the new labels, suggesting the current labeling system may affect choice and have unintended adverse effects on human health.
  [Hosni, H. et al. (2024) Improving consumer understanding of pesticide toxicity labels: Experimental evidence, Scientific Reports. Available at: https://www.nature.com/articles/s41598-024-68288-9. ]
• Pesticide exposure in greenspaces: Comparing field measurement of dermal contamination with values predicted by registration models
  Since 2014, the Agricultural Operator Exposure Model (AOEM) has been the harmonised European model used for estimating non-dietary operator exposure to pesticide. It is based on studies conducted by the pesticide companies and it features 13 different crops including non-agricultural areas such as amenity grasslands. The objective of this study was to compare the dermal exposure measured during a field study conducted in a non-agricultural area with the corresponding values estimated by the model AOEM. The non-controlled field study was conducted in France in 2011 and included 24 private and public gardeners who apply glyphosate with knapsack sprayers. Dermal exposure was measured using the whole-body method and cotton gloves. Each measured value had an estimated value given by AOEM and we tested their correlation using linear regression.

  The model overestimated body exposure for all observations and there was no correlation between values. However, it underestimated hand exposure by 42 times and it systematically underestimated the exposure when the operators were wearing gloves, especially during the application. The model failed at being conservative regarding hand exposure and highly overestimated the protection afforded by the gloves. At a time of glyphosate renewed approval in Europe, non-controlled field studies conducted by academics are needed to improve AOEM model, especially in the non-agricultural sector. Indeed, among the 34 studies included in the model, none were conducted on a non-agricultural area and only four assessed the exposure when using a knapsack sprayer. Moreover, knapsack sprayers being the main equipment used worldwide in both agricultural and non-agricultural settings, it is also crucial to integrate new data specific to this equipment in the model. Operator exposure should be estimated with accuracy in the registration process of pesticides to ensure proper safety as well as in epidemiological studies to improve exposure assessment.
  [de Graaf, L. et al. (2024) Pesticide exposure in greenspaces: Comparing field measurement of dermal contamination with values predicted by registration models, Science of The Total Environment. Available at: https://www.sciencedirect.com/science/article/pii/S0048969724009550.]

• Pesticide Exposure or Pesticide Poisoning and the Risk of Depression in Agricultural Populations: A Systematic Review and Meta-Analysis
  Evidence suggests that farm workers represent a high-risk population for the development of depression. The aim of the study was to clarify the association between pesticide exposure/poisoning and depression. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis were conducted in this systematic review and meta-analysis. Relevant studies were included through searching in PubMed, Scopus, Web of Science, ProQuest, CINAHL and pre-print services databases. A total of eight studies were included. A positive but non-significant association was observed between pesticide use and depression (OR = 1.123; 95% CI, 0.932–1.354, p-value = .221) while a significant positive association was observed between pesticide poisoning and depression (OR = 2.942; 95% CI, 1.791–4.831, p-value < .001). The present meta-analysis suggested clearly a significant positive association between pesticide poisoning and depression, confirming the hypothesis that pesticide poisoning is a risk factor of depression. It also revealed positive, yet non-significant association, between pesticide exposure and depression, a finding that enhances recent research but requires to be further supported by future cohort studies, including socioeconomic factors and biomarkers of depression.
  [Frengidou, E., Galanis, P. and Malesios, C. (2024) Pesticide Exposure or Pesticide Poisoning and the Risk of Depression in Agricultural Populations: A Systematic Review and Meta-Analysis, Journal of Agromedicine. Available at: https://www.tandfonline.com/doi/full/10.1080/1059924X.2023.2278801. ]
• Pre-Conception And First Trimester Exposure To Pesticides And Associations With Stillbirth
  Associations of pesticide exposures during pre-conception with stillbirth have not been well explored. We linked Arizona pesticide use records with birth certificates from 2006-2020 and estimated associations of living within 500meters of any pyrethroid, organophosphate (OP), or carbamate pesticide applications during a 90 day pre-conception window or the first trimester, with stillbirth. We considered a binary measure of exposure (any exposure), as well as log-pounds and log-acres applied within 500m, in a negative control exposure framework with log-binomial regression. We included 1,237,750 births, 2,290 stillbirths, and 27 pesticides.

  During pre-conception, any exposure to pesticides were associated with stillbirth, including cyfluthrin (RR=1.97, 95% CI 1.17,3.32), zeta-cypermethrin (RR=1.81, 95%CI 1.20, 2.74), organophosphates as a class (RR=1.60, 95%CI 1.16, 2.19), malathion (RR=2.02, 95%CI 1.26, 3.24), carbaryl (RR=6.39, 95%CI 2.07, 19.74), and propamocarb hydrochloride (RR=7.72, 95%CI 1.10, 54.20) . During the first trimester, fenpropathrin (RR=4.36, 95%CI 1.09, 17.50), permethrin (RR=1.57, 95%CI 1.02, 2.42), organophosphates as a class (RR=1.50, 95%CI 1.11, 2.01), acephate (RR=2.31, 95%CI 1.22, 4.40), and formetanate hydrochloride (RR=7.22, 95%CI 1.03, 50.58) were associated with stillbirth. Interpretations were consistent when using continuous measures of pounds or acres of exposure. Pesticide exposures during pre-conception and first trimester may be associated with stillbirth.
  [Furlong, M. et al. (2024) Pre-conception and first trimester exposure to pesticides and associations with stillbirth, American Journal of Epidemiology. Available at: https://academic.oup.com/aje/advance-article-abstract/doi/10.1093/aje/kwae198/7714541.]

• Redox imbalance and inflammation: A link to depression risk in Brazilian pesticide-exposed farmers
  

  Abstract

  This study aims to elucidate the mechanisms linking occupational pesticide exposure to depression among rural workers from Maravilha, Brazil. We assessed the mental health, oxidative, and inflammatory profiles of farmers exposed to pesticides (N = 28) and compared them to an urban control group without occupational exposure to pesticides (N = 25). Data on sociodemographic, occupational history, and clinical records were collected. Emotional states were evaluated using the State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI). Biochemical, hematological, inflammatory, and redox parameters were examined in blood samples from both groups. Results showed educational disparities between groups and unveiled a concerning underutilization of personal protective equipment (PPEs) among farmers. Glyphosate was the predominant pesticide used by farmers. Farmers exhibited higher BDI scores, including more severe cases of depression. Additionally, elevated levels of creatinine, ALT, AST, and LDH were observed in farmers, suggesting potential renal and hepatic issues due to pesticide exposure. Oxidative stress markers, such as increased lipid peroxidation and superoxide dismutase (SOD) activity, along with decreased catalase (CAT) activity and ascorbic acid levels, were noted in the pesticide-exposed group compared to controls. Elevated levels of inflammatory cytokines, particularly IL-1β, IL-6 and TNF-α, were also observed in pesticide-exposed group. Our findings suggest that inflammation, oxidative distress and lower educational levels may be associated with depression in pesticide-exposed farmers. This study highlights the impact of occupational pesticide exposure on the mental health of rural workers. The underuse of PPEs and the link between depressive symptoms, inflammation, and oxidative stress underscore the urgent need for improved safety measures in agricultural practices. Addressing these issues will contribute to a deeper understanding of the intricate relationship between environmental exposures and mental health outcomes.

  
  [Zanchi, M.M. et al. (2024) ‘Redox imbalance and inflammation: A link to depression risk in Brazilian pesticide-exposed farmers’, Toxicology, 501, p. 153706. doi:10.1016/j.tox.2023.153706. ]
• Use of Antibiotics in Animal Agriculture: Implications for Pediatrics: Technical Report
  Antimicrobial resistance is a global public health threat. Antimicrobial-resistant infections are on the rise and are associated with increased morbidity, mortality, and health care costs. Infants and children are affected by transmission of antimicrobial-resistant zoonotic pathogens through the food supply, direct contact with animals, environmental pathways, and contact with infected or colonized humans. Although the judicious use of antimicrobial agents is necessary for maintaining the health and welfare of humans and animals, it must be recognized that all use of antimicrobial agents exerts selective pressure that increases the risk of development of resistance. This report describes historical and recent use of antibiotics in animal agriculture, reviews the mechanisms of how such use contributes to development of resistance and can adversely affect child health, and discusses US initiatives to curb unnecessary use of antimicrobial agents in agriculture.
  [Katz, S.E. and Banerjee, R. (2024) Use of Antibiotics in Animal Agriculture: Implications for Pediatrics: Technical Report, Pediatrics. Available at: https://publications.aap.org/pediatrics/article/doi/10.1542/peds.2024-068467/199441/Use-of-Antibiotics-in-Animal-Agriculture. ]
• Follicular DNA Damage and Pesticide Exposure Among Latinx Children in Rural and Urban Communities
  The intersectional risks of children in United States immigrant communities include environmental exposures. Pesticide exposures and their biological outcomes are not well characterized in this population group. We assessed pesticide exposure and related these exposures to DNA double-strand breaks (DSBs) in Latinx children from rural, farmworker families (FW; N = 30) and from urban, non-farmworker families (NFW; N = 15) living in North Carolina. DSBs were quantified in hair follicular cells by immunostaining of 53BP1, and exposure to 72 pesticides and pesticide degradation products were determined using silicone wristbands. Cholinesterase activity was measured in blood samples. DSB frequencies were higher in FW compared to NFW children. Seasonal effects were detected in the FW group, with highest DNA damage levels in April–June and lowest levels in October–November. Acetylcholinesterase depression had the same seasonality and correlated with follicular DNA damage. Organophosphate pesticides were more frequently detected in FW than in NFW children. Participants with organophosphate detections had increased follicular DNA damage compared to participants without organophosphate detection. Follicular DNA damage did not correlate with organochlorine or pyrethroid detections and was not associated with the total number of pesticides detected in the wristbands. These results point to rural disparities in pesticide exposures and their outcomes in children from vulnerable immigrant communities. They suggest that among the different classes of pesticides, organophosphates have the strongest genotoxic effects. Assessing pesticide exposures and their consequences at the individual level is key to environmental surveillance programs. To this end, the minimally invasive combined approach used here is particularly well suited for children.
  [Lepetit, C. et al. (2023) Follicular DNA Damage and Pesticide Exposure Among Latinx Children in Rural and Urban Communities, Exposure and Health. Available at: https://link.springer.com/article/10.1007/s12403-023-00609-1.]
• Influence of pesticide exposure on farmers’ cognition: A systematic review
  

  Abstract

  Objectives:

  Pesticide application has become necessary to increase crop productivity and reduce losses. However, the use of these products can produce toxic effects. Farmers are individuals occupationally exposed to pesticides, thus subject to associated diseases as well as cognitive impairment. However, this relation is not well established in the literature, requiring further investigation. To assess the potential association between farmers’ pesticide exposure and cognitive impairment, we followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, considering participants, interventions, comparators, outcomes, and study strategies.

  Materials and Methods:

  This study included articles published between 2000 and 2021 on the Scopus, Web of Science, ScienceDirect, and PubMed databases, retrieved by the terms “pesticides and cognition” and “pesticides and memory.”

  Results:

  In total, ten studies fit the established criteria and were included in the sample. All had farmers occupationally exposed to pesticides in their sample and only one study dispensed with a control group. Of the neurobehavioral tests, four studies used mini-mental state examination, six neurobehavioral core test batteries (tests recognized in the area), and the remaining, other tests. We observed that 90% of articles found an association between cognitive impairment and pesticide exposure. Overall, five studies measured the activity of cholinesterases in their sample, of which three found significant differences between groups, confirming intoxication in those exposed.

  Conclusion:

  Despite the limited number of trials, we found scientific evidence to support the existence of adverse effects of pesticides on farmers’ cognition. We recommend that future studies research similar projects, expanding knowledge on the subject.

  
  [Finhler, S. et al. (2023) ‘Influence of pesticide exposure on farmers’ cognition: A systematic review’, Journal of Neurosciences in Rural Practice, 14, pp. 574–581. doi:10.25259/jnrp_58_2023. ]
• Occupational exposure to pesticides and symptoms of depression in agricultural workers. A systematic review.
  The use of pesticides can result in harm to both the environment and human health. There is a growing concern in the field of occupational health about the impact on the mental health of agricultural workers. The objective of this review was to systematize scientific evidence from the last ten years on the impact of occupational exposure to pesticides on the development of depression symptoms in agricultural workers. We conducted a comprehensive search in the PubMed and Scopus databases from 2011 to September 2022. Our search included studies in English, Spanish, and Portuguese that examined the association between occupational exposure to pesticides and symptoms of depression in agricultural workers, following the guidelines recommended by the PRISMA statement and the PECO strategy (Population, Exposure, Comparison, and Outcomes). Among the 27 articles reviewed, 78% of them indicated a link between exposure to pesticides and the incidence of depression symptoms. The pesticides most frequently reported in the studies were organophosphates (17 studies), herbicides (12 studies), and pyrethroids (11 studies). The majority of the studies were rated as having intermediate to intermediate-high quality, with the use of standardized measures to assess both exposure and effect. The updated evidence presented in our review indicates a clear association between pesticide exposure and the development of depressive symptoms. However, more high-quality longitudinal studies are necessary to control for sociocultural variables and utilize pesticide-specific biomarkers and biomarkers of depression. Given the increased use of these chemicals and the health risks associated with depression, it is crucial to implement more stringent measures to monitor the mental health of agricultural workers regularly exposed to pesticides and to enhance surveillance of companies that apply these chemicals.
  [Cancino, J., Soto, K., Tapia, J., Muñoz-Quezada, M.T., Lucero, B., Contreras, C. and Moreno, J., 2023. Environmental Research, p.116190.]
• Occupational Exposures and Risks of Non-Hodgkin Lymphoma: A Meta-Analysis
  Non-Hodgkin lymphoma (NHL) is a heterogeneous group with different types of diseases. It remains unclear as to what has led to an increase in incidences of NHL, however, chemical substance exposure is known to be one of the risk factors for the disease. Therefore, we performed a systematic review and meta-analysis including case-control, cohort, and cross-sectional observational epidemiological studies to verify the association between occupational exposure to carcinogens and NHL risk. Articles between the years 2000 and 2020 were collected. Two different reviewers performed a blind selection of the studies using the Rayyan QCRI web app. Post-completion, the selected articles were extracted and analyzed via the RedCap platform. Our review resulted in 2719 articles, of which 51 were included in the meta-analysis, resulting in an overall OR of 1.27 (95% CI 1.04-1.55). Furthermore, it was observed that the main occupation associated with the increased risk of NHL was that in which workers are exposed to pesticides. We therefore conclude that the evidence synthesis of the epidemiological literature supports an increased risk for NHL, regardless of subtype, considering occupational exposure to certain chemical compounds, mainly pesticides, benzene, and trichlorethylene, and certain classes of work, primarily in the field of agriculture.
  [Francisco, L.F.V., da Silva, R.N., Oliveira, M.A., dos Santos Neto, M.F., Gonçalves, I.Z., Marques, M.M. and Silveira, H.C., 2023. Cancers, 15(9), p.2600.]
• Occurrence of pesticide residues in indoor dust of farmworker households across Europe and Argentina.
  Pesticides are widely used as plant protection products (PPPs) in farming systems to preserve crops against pests, weeds, and fungal diseases. Indoor dust can act as a chemical repository revealing occurrence of pesticides in the indoor environment at the time of sampling and the (recent) past. This in turn provides information on the exposure of humans to pesticides in their homes. In the present study, part of the Horizon 2020 funded SPRINT project, the presence of 198 pesticide residues was assessed in 128 indoor dust samples from both conventional and organic farmworker households across Europe, and in Argentina. Mixtures of pesticide residues were found in all dust samples (25-121, min-max; 75, median). Concentrations varied in a wide range (<0.01 ng/g-206 μg/g), with glyphosate and its degradation product AMPA, permethrin, cypermethrin and piperonyl butoxide found in highest levels. Regarding the type of pesticides, insecticides showed significantly higher levels than herbicides and fungicides. Indoor dust samples related to organic farms showed a significantly lower number of residues, total and individual concentrations than those related to conventional farms. Some pesticides found in indoor dust were no longer approved ones (29 %), with acute/chronic hazards to human health (32 %) and with environmental toxicity (21 %).
  [Navarro, I., de la Torre, A., Sanz, P., Baldi, I., Harkes, P., Huerta-Lwanga, E., Nørgaard, T., Glavan, M., Pasković, I., Pasković, M.P. and Abrantes, N., 2023. Science of The Total Environment, p.167797.]
• Prevalence of neonicotinoid insecticides in paired private-well tap water and human urine samples in a region of intense agriculture overlying vulnerable aquifers in eastern Iowa
  A pilot study among farming households in eastern Iowa was conducted to assess human exposure to neonicotinoids (NEOs). The study was in a region with intense crop and livestock production and where groundwater is vulnerable to surface-applied contaminants. In addition to paired outdoor (hydrant) water and indoor (tap) water samples from private wells, urine samples were collected from 47 adult male pesticide applicators along with the completions of dietary and occupational surveys. Estimated Daily Intake (EDI) were then calculated to examine exposures for different aged family members. NEOs were detected in 53% of outdoor and 55% of indoor samples, with two or more NEOs in 13% of samples. Clothianidin was the most frequently detected NEO in water samples. Human exposure was ubiquitous in urine samples. A median of 10 different NEOs and/or metabolites were detected in urine, with clothianidin, nitenpyram, thiamethoxam, 6-chloronicotinic acid, and thiacloprid amide detected in every urine samples analyzed. Dinotefuran, imidaclothiz, acetamiprid-N-desmethyl, and N-desmethyl thiamethoxam were found in ≥70% of urine samples. Observed water intake for study participants and EDIs were below the chronic reference doses (CRfD) and acceptable daily intake (ADI) standards for all NEOs indicating minimal risk from ingestion of tap water. The study results indicate that while the consumption of private well tap water provides a human exposure pathway, the companion urine results provide evidence that diet and/or other exposure pathways (e.g., occupational, house dust) may contribute to exposure more than water contamination. Further biomonitoring research is needed to better understand the scale of human exposure from different sources.
  [Thompson, D.A., Kolpin, D.W., Hladik, M.L., Lehmler, H.J., Meppelink, S.M., Poch, M.C., Vargo, J.D., Soupene, V.A., Irfan, N.M., Robinson, M. and Kannan, K., 2023. Chemosphere, 319, p.137904.]
• Risk of breast cancer in daughters of agricultural workers in Denmark.
  Agricultural workers face unique occupational hazards such as pesticide exposure, which has been associated with breast cancer. However, research considering the association between parental agricultural work and breast cancer in female offspring is lacking. Therefore, the aim of the present nested case-control study was to explore this association. The Danish Cancer Registry was utilized to identify women diagnosed with primary breast cancer. A total of 5587 cases were included in the study, and for each case, 20 cancer-free female controls were selected, matched on year of birth. It was a requisition that both cases and controls were born in Denmark and that either maternal or paternal employment history was available. Adverse associations were consistently noted for different time windows of maternal employment in "Horticulture" and breast cancer. Inverse associations were observed for paternal employment in most of the examined agricultural industries, although a small increased risk was indicated for perinatal employment in "Horticulture". Furthermore, maternal preconceptional employment in "Horticulture" was observed to increase the risk of ER + tumors (odds ratio [OR] = 1.79, 95% confidence interval [CI]: 1.13-2.85, whereas parental perinatal employment was linked to an elevated risk of ER-tumors (maternal employment: OR = 2.48, 95% CI: 1.18-5.21; paternal employment: OR = 1.62, 95% CI: 0.70-3.77). The present study indicates that maternal horticultural employment in different potential susceptible time windows may elevate the risk of breast cancer subtypes. These findings need to be reproduced in future prospective cohort studies, including information on e.g., pesticide exposure withing job categories and lifestyle factors.
  [Pedersen, J.E. and Hansen, J., 2023. Environmental Research, p.117374.]
• Association between pesticide exposure and obesity: A cross-sectional study of 20,295 farmers in Thailand
  Background: Obesity is a serious condition because it is associated with other chronic diseases which affect the quality of life. In addition to problems associated with diet and exercise, recent research has found that pesticide exposure might be another important risk factor. The objective of this study was to determine the association between pesticide exposure and obesity among farmers in Nakhon Sawan and Phitsanulok province, Thailand.
  Methods: This study was a population-based cross-sectional study. Data on pesticide use and obesity prevalence from 20,295 farmers aged 20 years and older were collected using an in-person interview questionnaire. The association was analysed using multivariable logistic regression, adjusted for its potential confounding factors.
  Results: Obesity was found to be associated with pesticide use in the past. The risk of obesity was significantly predicted by types of pesticides, including insecticides (OR = 2.10, 95% CI 1.00-4.38), herbicides (OR = 4.56, 95% CI 1.11-18.62), fungicides (OR = 2.12, 95% CI 1.34-3.36), rodenticides (OR = 2.55, 95% CI 1.61-4.05), and molluscicides (OR = 3.40, 95% CI 2.15-5.40). Among 35 surveyed individual pesticides, 22 were significantly associated with higher obesity prevalence (OR = 1.78, 95% CI 1.10-2.88 to OR = 8.30, 95% CI 2.54-27.19), including herbicide butachlor, 15 insecticides (two carbamate insecticides, five organochlorine insecticides, and eight organophosphate insecticides), and six fungicides.
  Conclusion: This study found obesity in farmers in Nakhon Sawan and Phitsanulok province, Thailand, to be associated with the long-term use of several types of pesticides. The issue should receive more public attention, and pesticide use should be strictly controlled.
  [Noppakun, K. and Juntarawijit, C. (2022) Association between pesticide exposure and obesity: A cross-sectional study of 20,295 farmers in Thailand, F1000Research. Available at: https://f1000research.com/articles/10-445/v3. ]
• Pesticide toxicity assessment and geographic information system (GIS) application in small-scale rice farming operations, Thailand
  The objectives of the study were to evaluate the impact of pesticide exposure on farmer health during non-active rice farming and active rice farming periods and present the change in the individual cholinesterase activities (%reduction) on the geographic information system (GIS) mapping in Nakhon Ratchasima Province, Thailand. Acetyl- and butyryl-cholinesterase (AChE and BuChE) activities were monitored during both study periods using Test-mate ChE (Model 400). The location of paddy fields was specified using Garmin geographic positioning system MAP 62s. Fifty-eight farmers who participated in this study had an average age of 49.2 ± 6.9 years. Higher prevalence of all health symptoms was observed among farmer participants during the active rice farming period comparing to the non-active rice farming period (p < 0.01). Furthermore, farmers had significantly lower activities of AChE and BuChE during the active rice farming period comparing to the non-active rice farming period (p < 0.01). Our findings indicate that the GIS mapping indicate that the cases with a significant enzyme inhibition have dispersed across the agricultural and the nearby residential areas. This, investigation can be used to promote safer use of pesticides among farmers and mitigate pesticide exposure among residents living in close proximity to a rice field.
  [Sombatsawat, E., Barr, D.B., Panuwet, P., Robson, M.G. and Siriwong, W. Scientific Reports, 12(1), pp.1-9.]
• Cancer and occupational exposure to pesticides: a bibliometric study of the past 10 years
  Occupational exposure to pesticides has been identified as a major trigger of the development of cancer. Pesticides can cause intoxication in the individuals who manipulate them through either inhalation, ingestion, or dermal contact. Given this, we investigated the association between the incidence of cancer and occupational exposure to pesticides through a bibliometric analysis of the studies published between 2011 and 2020, based on 62 papers selected from the Scopus database. The results indicated an exponential increase in the number of studies published over the past decade, with most of the research being conducted in the USA, France, India, and Brazil, although a further 17 nations were also involved in the research on the association between cancer and pesticides. The principal classes of pesticides investigated in relation to their role in intoxication and cancer were insecticides, herbicides, and fungicides. The types of cancer reported most frequently were multiple myeloma, bladder cancer, non-Hodgkin’s lymphoma, prostate cancer, leukemia, and breast cancer. Despite the known association between pesticides and cancer, studies are still relatively scarce in comparison with the global scale of the use of these xenobiotic substances, which is related to the increasing demand for agricultural products throughout the world
  [Pedroso, T.M.A., Benvindo-Souza, M., de Araújo Nascimento, F., Woch, J., Dos Reis, F.G. and de Melo e Silva, D. Environmental Science and Pollution Research, pp.1-12.]
• Farming, Pesticides, and Brain Cancer: A 20-Year Updated Systematic Literature Review and Meta-Analysis
  Twenty additional years of epidemiologic literature have become available since the publication of two meta-analyses on farming and brain cancer in 1998. The current systematic literature review and meta-analysis extends previous research and harmonizes findings. A random effects model was used to calculate meta-effect estimates from 52 studies (51 articles or reports), including 11 additional studies since 1998. Forty of the 52 studies reported positive associations between farming and brain cancer with effect estimates ranging from 1.03 to 6.53. The overall meta-risk estimate was 1.13 (95% CI = 1.06, 1.21), suggesting that farming is associated with a 13% increase in risk of brain cancer morbidity or mortality. Farming among white populations was associated with a higher risk of brain cancer than among non-white populations. Livestock farming (meta-RR = 1.34; 95% CI = 1.18, 1.53) was associated with a greater risk compared with crop farming (meta-RR = 1.13; 95% CI = 0.97, 1.30). Farmers with documented exposure to pesticides had greater than a 20% elevated risk of brain cancer. Despite heterogeneity among studies, we conclude that the synthesis of evidence from 40 years of epidemiologic literature supports an association between brain cancer and farming with its potential for exposure to chemical pesticides.
  [Gatto, N.M., Ogata, P. and Lytle, B. Cancers, 13(17), p.4477.]
• Genetic Polymorphisms of Pesticide-Metabolizing Enzymes and Transporters in Agricultural Workers and Thyroid Hormone Levels
  Chronic exposure to pesticides has been associated with thyroid dysfunction owing to their endocrine disruption ability. Genetic variations in genes encoding phase I and II enzymes and phase III transporters are partly responsible for individual responses to chemical pesticides. This study investigated the association between variations in genes involved in pesticide metabolism and altered thyroid hormone concentrations. The study assessed thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) in organic agriculture workers (n = 216) and workers who used chemical pesticides (n = 229). A questionnaire was used to collect sociodemographic, pesticide exposure, and health status data. Blood samples were analyzed for TSH, FT3, and FT4. Genomic DNA was extracted and genotyped using the TaqMan real-time PCR genotyping assay and restriction fragment length polymorphism method for 15 metabolically related genes. Results: Significant differences in the TSH (1.58 vs 1.12 µIU/mL) and FT3 (0.34 vs 0.31 ng/dL) concentrations between the chemical and organic worker groups were observed. The frequencies of all single nucleotide polymorphisms were in Hardy–Weinberg equilibrium and were mostly consistent with Asian populations. The findings showed the association between SNPs of enzymes and transporters and TSH, FT3, and FT4. The odd ratio and adjusted odd ratio (with sex, age, smoking status, alcohol consumption and exposure parameters) for subclinical thyroid disease by the variant alleles CYP1A1 rs1048943, CYP2B6 rs2279343, CYP2C19 rs4244285, NAT2 rs1799931, and PON1 rs662 in the chemical workers compared with the organic workers were found (P values < 0.05). This is the first study to assess gene–environment interactions in Thai agricultural workers by investigating disruptions of the hypothalamic–pituitary–thyroid axis. The investigated SNP profiles revealed several gene–thyroid hormone associations in which even low levels of pesticide exposure could disturb thyroid homeostasis. These findings provide a foundation for planning future studies investigating associations between complex diseases and occupational pesticide exposure
  [Sirivarasai, J., Chanprasertyothin, S., Kongtip, P. and Woskie, S. Risk Management and Healthcare Policy, 14, p.3435.]
• Assessment of Risk Factors for Health Disparities among Latina Farm Workers
  

  Latina farm workers may experience a unique intersection of social and environmental factors that are known to affect health and well-being. The disadvantages inherent in their gender, race and social class may be compounded by their immigration status, rural location and the hazards of farm work. We propose to identify the most critical risk factors for poor health facing this underserved and understudied population. Our study uses a mixed-methods approach that combines qualitative data from focus groups (n=3 groups of 10 participants each) and semi-structured interviews (n=15) with quantitative and qualitative survey data (n=100) and biological monitoring (n=45). The study includes six domains of inquiry: sociodemographics, food security and food access, housing conditions, social isolation, access to medical care and occupational hazards. Urinary biomonitoring is used to assess exposure to common agricultural pesticides. All study participants identify as Latina or Hispanic and, among those recruited to date (n=25), range in ages from 25 to 71 and report an average of 12 years working in agriculture. While sample and data collection is in progress, preliminary analysis indicate that these participants spend an average of 7.5 months per year employed in agricultural work.Participants report working with a range of crops common in Southern Idaho, including onions, sugarbeets, peas, corn, grapes, and hops. More than 25% of the study participants report that their employers do not provide water, cups and hand washing facilities on a daily basis. Participants report use of backpack and air blast sprayers, and approximately one-third report receiving training from their employers on the use of pesticides. This research will assess the prevalence of social and environmental risk factors among Latina farm workers using an interdisciplinary approach that combines surveys, in-depth interviews and focus groups, biological monitoring and field observations.

  
  [Curl, C., Meierotto, L. and Som, R., 2019. Research & Practice, 12(5).]
• Hearing Loss in Agricultural Workers Exposed to Pesticides and Noise
  Agricultural workers who have concurrent exposure to pesticides and noise are at increased risk of hearing loss. We recruited 163 Thai conventional and 172 organic farmers to answer our questionnaires about personal demographics, agricultural activities, and pesticide and agricultural machinery use. This information was used to calculate the years of conventional (pesticide use) farming and the years of agricultural noise exposure, and to estimate semiquantitative metrics for pesticide exposure (cumulative intensity score-years) and cumulative noise exposure (dB(A)-years) for each conventional farmer. All participants underwent pure tone audiometric testing. The mean hearing threshold in the low-frequency band (0.5–2 kHz) and high-frequency band (3–6 kHz) were used for analysis. Years involved in conventional farming and years using agricultural machinery were associated with an increase in the average hearing threshold for the high-frequency band after controlling for age, ever exposed to industrial noise and cigarette smoking. The highest category of cumulative insecticide exposure (score-years), cumulative organophosphates exposure (score-years) and cumulative noise exposure (dB(A)-years) were also associated with an increased high-frequency band hearing threshold among conventional farmers. Results from the full cohort and the subcohort of conventional farmers support each other and the hypothesis that pesticide and noise have an additive effect on hearing, since no model interactions were significant.
  [Choochouy, N., Kongtip, P., Chantanakul, S., Nankongnab, N., Sujirarat, D. and Woskie, S.R., 2019. Annals of work exposures and health, 63(7), pp.707-718.]
• Literature review: dermal monitoring data for pesticide exposure assessment of farm workers.
  A systematic literature search was performed on eight online databases. Two screening phases with predetermined criteria identified the qualifying literature. Standard information and dermal pesticide monitoring data were recorded and summarized from each qualifying study to assess its usefulness for future pesticide exposure assessment. A total of 31 farm studies qualified for review; task information was used to standardize all farm job(s) evaluated into 5 job groups: operators, applicators, mixer-loaders, field workers, and flaggers. When attempting to compare dermal exposure levels between studies, two types of variation were identified: (1) variation in study focus and reporting and 2) variation in exposure levels. The former variation type prevented exposure level comparisons between studies. Within studies, exposure levels were compared across body parts to identify that which had the highest measured exposure and to determine if results were similar in other studies that evaluated the same farm job. Using studies that measured exposure for multiple farm jobs, within study comparisons of total body exposure were performed to evaluate work factors. Future dermal pesticide exposure monitoring studies should standardize reporting procedures, as suggested in this review, to allow for more extensive dermal data comparisons. Body parts with highest measured levels of dermal exposure were identified by farm job, along with work factors to be further investigated as potential dermal pesticide exposure determinants for farm workers.
  [Garzia NA, Spinelli JJ, Gotay CC, Teschke K. 2018. J Agromedicine. 23(3):187-214.]
• A longitudinal study of atrazine and 2,4-D exposure and oxidative stress markers among iowa corn farmers.
  Reactive oxygen species, potentially formed through environmental exposures, can overwhelm an organism's antioxidant capabilities resulting in oxidative stress. Long-term oxidative stress is linked with chronic diseases. Pesticide exposures have been shown to cause oxidative stress in vivo. Study utilized a longitudinal study of corn farmers and non-farming controls in Iowa to examine the impact of exposure to the widely used herbicides atrazine and 2,4-dichlorophenoxyacetic acid (2,4-D) on markers of oxidative stress. 225 urine samples were collected during five agricultural time periods (pre-planting, planting, growing, harvest, off-season) for 30 farmers who applied pesticides occupationally and 10 controls who did not; all were non-smoking men ages 40-60. Atrazine mercapturate (atrazine metabolite), 2,4-D, and oxidative stress markers (malondialdehyde [MDA], 8-hydroxy-2'-deoxyguanosine [8-OHdG], and 8-isoprostaglandin-F2α [8-isoPGF]) were measured in urine. Farmers had higher urinary atrazine mercapturate and 2,4-D levels compared with controls. In regression models, after natural log transformation, 2,4-D was associated with elevated levels of 8-OHdG (β = 0.066, 95%CI = 0.008-0.124) and 8-isoPGF (β = 0.088, 95%CI = 0.004-0.172). 2,4-D may be associated with oxidative stress because of modest increases in 8-OHdG, a marker of oxidative DNA damage, and 8-isoPGF, a product of lipoprotein peroxidation, with recent 2,4-D exposure. Future studies should investigate the role of 2,4-D-induced oxidative stress in the pathogenesis of human diseases.
  [Lerro CC, Beane Freeman LE, Portengen L, Kang D, et al. 2017. Environ Mol Mutagen. 58(1):30-38.]
• Central nervous system tumors and agricultural exposures in the prospective cohort AGRICAN.
  Studies in farmers suggest a possible role of pesticides in the occurrence of Central Nervous System (CNS) tumors but scientific evidence is still insufficient. Using data from the French prospective agricultural cohort AGRICAN (Agriculture & Cancer), authors investigated the associations between exposure of farmers and pesticide users to various kinds of crops and animal farming and the incidence of CNS tumors, overall and by subtypes. Over the 2005-2007, 181,842 participants completed the enrollment questionnaire that collected a complete job calendar with lifetime history of farming types. Associations were estimated using proportional hazards models with age as underlying timescale. During a 5.2 years average follow-up, 273 incident cases of CNS tumors occurred, including 126 gliomas and 87 meningiomas. Analyses showed several increased risks of CNS tumors in farmers, especially in pesticide users (hazard ratio = 1.96; 95% confidence interval: 1.11-3.47). Associations varied with tumor subtypes and kinds of crop and animal farming. The main increases in risk were observed for meningiomas in pig farmers and in farmers growing sunflowers, beets and potatoes and for gliomas in farmers growing grasslands. In most cases, more pronounced risk excesses were observed among pesticide applicators. 
  [Piel C, Pouchieu C, Tual S, Migault L., et al. 2017. Int J Cancer. doi: 10.1002/ijc.30879. ]
• Longitudinal assessment of occupational determinants of chlorpyrifos exposure in adolescent pesticide workers in Egypt.
  Chlorpyrifos (CPF) is an organophosphourus insecticide applied to cotton fields by adolescents employed by the Egyptian Ministry of Agriculture. Urinary 3,5,6-trichloro-2-pyridinol (TCPy) is a biomarker of CPF exposure that has substantial variability among these applicators. In order to identify predictors of CPF exposure, we conducted a longitudinal study of 43 adolescent pesticide applicators in Egypt from April 2010 to January 2011 in Egypt. Urinary TCPy was quantified at 25 time-points, prior to, during, and following application. We used log-linear regression and a best subset selection approach to identify the exposure determinants that were most predictive of cumulative TCPy and participants' highest TCPy values (peak exposure). Applicators had cumulative urinary TCPy levels ranging from 167 to 49,8208μg/g creatinine. Total hours applying CPF (semi-partial r2=0.32), and total hours in the field applying other pesticides (semi-partial r2=0.08) were the strongest predictors of cumulative TCPy. Applicators had peak urinary TCPy levels ranging from 4 to 5715μg/g creatinine. The amount of time applying pesticides prior to blood draw was the strongest predictor of peak TCPy (semi-partial r2=0.30). We also observed evidence that wearing clean clothes to work was associated with lower longitudinal TCPy. Our results suggest there is an opportunity for targeted interventions, particularly related to hygiene or implementation of personal protective equipment usage to reduce CPF exposure among adolescent pesticide workers
  [Callahan CL, Hamad LA, Olson JR, Ismail AA, et al. 2017. Int J Hyg Environ Health. 220(8):1356-1362]
• Occurrence of commonly used pesticides in personal air samples and their associated health risk among paddy farmers.
  This study aims to determine the concentrations of commonly used pesticides (azoxystrobin, buprofezin, chlorantraniliprole, difenoconazole, fipronil, imidacloprid, isoprothiolane, pretilachlor, propiconazole, pymetrozine, tebuconazole, tricyclazole, and trifloxystrobin) in personal air samples and their associated health risks among paddy farmers. Eighty-three farmers from Tangjung Karang, Selangor were involved in this study. A solid sorbent tube was attached to the farmer's breathing zone with a clip, and an air pump was fastened to the belt to collect personal air samples. Pesticides collected in the XAD-2 resin were extracted with acetone, centrifuged, concentrated via nitrogen blowdown and reconstituted with 1mL of 3:1 ultrapure water/HPLC-grade methanol solution. The target compounds were detected with a maximum concentration reaching up to 462.5ngm-3 (fipronil). The hazard quotient (HQ) was less than 1 and the hazard index (HI) value was 3.86×10-3, indicating that the risk of pesticides related diseases was not significant. The lifetime cancer risk (LCR) for pymetrozine was at an acceptable level (LCR<10-6) with 4.10×10-8. The results reported in this study can be beneficial in terms of risk management within the agricultural community.
  [Hamsan , Ho YB, Zaidon SZ, et al. 2017. Sci Total Environ. 603-604:381-389. ]
• Pesticides: Perceived Threat and Protective Behaviors Among Latino Farmworkers.
  The purpose of this study was to assess the knowledge and beliefs of 72 Latino farmworkers in North Carolina about the threat of health effects of pesticides, including cancer. It sought to explore relationships between threat perceptions and pesticide protective behaviors observed in the field. Utilizing stepwise multiple regression, the authors found that years worked in agriculture in the United States was associated with decreased use of protective clothing. Pesticide protective behaviors in the field may be improved by utilizing moderately experienced farmworkers (less 10 years) as lay advisors to reinforce training.
  [Walton AL, LePrevost C, Wong B, et al. 2017. J Agromedicine. 22(2):140-147.]
• Association between Parkinson's Disease and Cigarette Smoking, Rural Living, Well-Water Consumption, Farming and Pesticide Use: Systematic Review and Meta-Analysis.
  Bradford Hill's viewpoints were used to conduct a weight-of-the-evidence assessment of the association between Parkinson's disease (PD) and rural living, farming and pesticide use. The results were compared with an assessment based upon meta-analysis. For comparison, we also evaluated the association between PD and cigarette smoking as a "positive control" because a strong inverse association has been described consistently in the literature. PubMed was searched systematically to identify all published epidemiological studies that evaluated associations between Parkinson's disease (PD) and cigarette smoking, rural living, well-water consumption, farming and the use of pesticides, herbicides, insecticides, fungicides, or paraquat. There was a consistent inverse (negative) association between current cigarette smoking and PD risk. In contrast, associations between PD and rural living, well-water consumption, farming and the use of pesticides, herbicides, insecticides, fungicides or paraquat were less consistent when assessed quantitatively or qualitatively. The weight of the evidence and meta-analysis support the conclusion that there is a causal relationship between PD risk and cigarette smoking, or some unknown factor correlated with cigarette smoking. There may be risk factors associated with rural living, farming, pesticide use or well-water consumption that are causally related to PD, but the studies to date have not identified such factors. To overcome the limitations of research in this area, future studies will have to better characterize the onset of PD and its relationship to rural living, farming and exposure to pesticides.
  [Breckenridge CB, Berry C, Chang ET, et al. 2016. PLoS One.11(4):e0151841]
• Prostate cancer risk among French farmers in the AGRICAN cohort.
  Prostate cancer is one of the most frequent cancers among men worldwide. Its etiology is largely unknown, but an increased risk has been repeatedly observed among farmers. Our aim was to identify occupational risk factors for prostate cancer among farmers in the prospective cohort study AGRICAN.Data on lifetime agricultural exposures (type of crops, livestock and tasks including pesticide use, re-entry and harvesting) were collected from the enrolment questionnaire. During the period from enrolment (2005-2007) to 31 December 2009, 1672 incident prostate cancers were identified. We found an increased risk for cattle breeders using insecticides [HR 1.20, 95% confidence interval (95% CI) 1.01-1.42] with a significant dose-response relationship with number of cattle treated (P for trend 0.01). A dose-response relationship was also observed with the number of hogs (P for trend 0.06). We found an excess of prostate cancer risk among people involved in grassland activities, mainly in haymaking (HR 1.18, 95% CI 1.02-1.36). Pesticide use and harvesting among fruit growers were associated with an elevated prostate cancer risk, with a two-fold increased risk for the largest area. For potato and tobacco producers, an elevated prostate cancer risk was observed for almost all tasks, suggesting a link with pesticide exposure since all of them potentially involved pesticide exposure.Our analysis suggests that the risk of prostate cancer is increased in several farming activities (cattle and hog breeding, grassland and fruit-growing) and for some tasks including pesticide use.
  [Lemarchand C, Tual S, Boulanger M, Levêque-Morlais N, et al. 2016. Scand J Work Environ Health. 42(2):144-52.]
• "Where they (live, work and) spray": pesticide exposure, childhood asthma and environmental justice among Mexican-American farmworkers
  Asthma prevalence is reportedly low for children of Mexican descent compared with other ethnic groups and Latino subgroups. The results of this exploratory ethnographic research among children of farmworkers in California dramatically suggest otherwise. Little work has been reported employing photovoice, a community-based participatory research method, to study childhood exposure to pesticides. A rich narrative about perceptions of pesticide exposure emerged from the ethnographic interviews. Thematic analysis yielded beliefs about the relationship between air quality and childhood asthma. The findings suggest that childhood asthma should be reviewed within the context of local levels of environmental exposure and the principles of environmental justice.
  [Schwartz NA, von Glascoe CA, Torres V, et al. 2015. Health Place. 32:83-92.]
• EPA's proposed Worker Protection Standard and the burdens of the past.
  This review considers the proposed revisions' likelihood of addressing historical gaps in farmworker protection. The proposal was compared to the existing Worker Protection Standard, and key aspects were analyzed in relation to existing science on farm labor hazards, as well as historic occupational health, labor and immigration policy. US law historically has left farm workers largely unprotected. These exclusions and delays have been tolerated in part thanks to the myth of the independent family farmer, but more significant is the stingy nativism that presumes to benefit from immigrant labor without assuming any responsibility to protect the humans who provide it. Key aspects of the proposed revision include stronger protections against drift and re-entry exposures, better information provision and training, and increased protections for workers under 16 years. The proposed changes represent an improvement over existing legislation, but do not go far enough. The revision should be strengthened along lines suggested by farm workers themselves, and other labor laws must also be amended to give the men, women, and children who work in the fields of this country full rights and protections.
  [Bohme SR. 2015. Int J Occup Environ Health. 37(1):161-5]
• Farmworker Housing in the United States and Its Impact on Health.
  Farmworkers in the United States occupy a range of housing, including both on- and off-farm family and communal dwellings. As the farmworker population is becoming more settled, housing needs are changing. Existing regulations designed originally for grower-supplied migrant housing may need to be expanded. Much of farmworker housing is in poor condition, and likely linked to negative mental and physical health outcomes of residents because of exposures to crowding; mold, mildew, and other allergens; pesticides; and structural deficiencies. The existing research literature, both on housing conditions and their associations with farmworker health, is sparse, and large areas of the country and significant domains of health are omitted. This paper reviews this literature and formulates research and policy recommendations for addressing these deficiencies.
  [Quandt SA, Brooke C, Fagan K, Howe A, et al. 2015. New Solut. 25(3):263-86.]
• Home-based community health worker intervention to reduce pesticide exposures to farmworkers' children: A randomized-controlled trial.
  Authors conducted a randomized-controlled trial of a home-based intervention to reduce pesticide exposures to farmworkers' children in Monterey County, California (n=116 families). Measurements of organophosphate (OP) insecticide metabolites in child urine (n=106) and pesticides in home floor wipes (n=103) were collected before and after the intervention. Median child urinary dialkyl phosphate (DAP) metabolite levels were slightly lower among the intervention group children at follow-up compared with baseline, albeit nonsignificantly. DAP metabolite levels in the control group children were markedly higher at follow-up compared with baseline. In adjusted models, intervention participation was associated with a 51% decrease in total DAP metabolite levels. Carbaryl, chlorpyrifos, cypermethrin, dacthal, diazinon, malathion, and trans-permethrin were commonly detected in the floor wipes. In adjusted models, intervention participation was significantly associated with a 37% decrease in trans-permethrin floor wipe levels in homes, but not OP or other agricultural pesticides. In summary, intervention group children had slightly reduced pesticide exposures, whereas child exposures were higher among the control group. Additional intervention studies evaluating methods to reduce pesticide exposures to farmworker families and children are needed.
  [Salvatore AL, Castorina R, Camacho J, et al. 2015. J Expo Sci Environ Epidemiol. 25(6):608-15]
• Perceptions of housing conditions among migrant farmworkers and their families: implications for health, safety and social policy.
  This study used qualitative descriptive data and directed content analysis to analyse semi-structured interviews and photographs that were data elements of a larger community-based participatory research study designed to document housing quality and health among North Carolina farmworkers.Specific problems described by the participants include exposure to pesticides, safety issues, pests, water supply and air quality, temperature and moisture.This study describes migrant farmworkers' perceptions of housing quality and numerous potential impacts on health and safety. Research, social policy and practice-based implications derived from this research could serve to improve the health status of these individuals and their families. This study suggests there is much room for sustained advocacy and action, given that many of the farmworkers' descriptions and photographs depicted housing conditions below accepted standards of living. Access to adequate and safe employer-provided housing for migrant farmworkers should be considered a basic human right.
  [Keim-Malpass J, Spears Johnson CR, Quandt SA, Arcury TA. 2015. Rural Remote Health. 15:3076]
• Amyotrophic Lateral Sclerosis and Agricultural Environments: A Systematic Review
  The aim of this study was to examine the relationship between the risk of amyotrophic lateral sclerosis (ALS) and exposure to rural environments. Studies were identified through OVID MEDLINE and EMBASE search up to September 2013 using as keywords rural residence, farmers, and pesticide exposure. Twenty-two studies were included for this meta-analysis. Summary odds ratios (ORs) were calculated using random effect model by type of exposure index, and subgroup analyses were conducted according to study design, gender, region, case ascertainment, and exposure assessment. The risk of ALS was significantly increased with pesticide exposure (OR, 1.44; 95% CI, 1.22-1.70) and with farmers (OR, 1.42; 95% CI, 1.17-1.73), but was not significant with rural residence (OR, 1.25; 95% CI, 0.84-1.87). The risk estimates for subgroup analysis between pesticide exposure and ALS indicated a significant positive association with men (OR, 1.96), and in studies using El Escorial criteria for ALS definition (OR, 1.63) and expert judgment for pesticide exposure (OR, 2.04) as well. No significant publication bias was observed. Our findings support the association of pesticide exposure and an increased risk for ALS, stressing that the use of more specific exposure information resulted in more significant associations.
  [Kang, H., Cha, E.S., Choi, G.J. and Lee, W.J., 2014. Journal of Korean medical science, 29(12), pp.1610-1617.]
• Assessing the effectiveness of the Pesticides and Farmworker Health Toolkit: a curriculum for enhancing farmworkers' understanding of pesticide safety concepts
  The crop-specific Pesticides and Farmworker Health Toolkit (Toolkit) is a pesticide safety and health curriculum designed to communicate to farmworkers pesticide hazards commonly found in their working environments and to address Worker Protection Standard (WPS) pesticide training criteria for agricultural workers. The goal of this preliminary study was to test evaluation items for measuring knowledge increases among farmworkers and to assess the effectiveness of the Toolkit in improving farmworkers' knowledge of key WPS and risk communication concepts when the Toolkit lesson was delivered by trained trainers in the field. After receiving training on the curriculum, four participating trainers provided lessons using the Toolkit as part of their regular training responsibilities and orally administered a pre- and post-lesson evaluation instrument to 20 farmworker volunteers who were generally representative of the national farmworker population. Farmworker knowledge of pesticide safety messages significantly increased after participation in the lesson. Further, items with visual alternatives were found to be most useful in discriminating between more and less knowledgeable farmworkers. The pilot study suggests that the Pesticides and Farmworker Health Toolkit is an effective, research-based pesticide safety and health intervention for the at-risk farmworker population and identifies a testing format appropriate for evaluating the Toolkit and other similar interventions for farmworkers in the field.
  [LePrevost CE, Storm JF, Asuaje CR, Arellano C, Cope WG. 2014. J Agromedicine. 19(2):96-102.]
• Health Status of Children of Migrant Farm Workers: Farm Worker Family Health Program, Moultrie, Georgia
  Objectives. We evaluated the health status of migrant farmworkers’ children served by the Farm Worker Family Health Program (FWFHP) in Moultrie, Georgia.

  Methods. We analyzed data from children aged 0 to 16 years examined through the FWFHP from 2003 to 2011 (n across years = 179–415). We compared their prevalence of overweight, obesity, elevated blood pressure, anemia, and stunting with that of children in the United States and Mexico.

  Results. Across study years, prevalence of overweight, obesity, elevated blood pressure, anemia, and stunting ranged from 13.5% to 21.8%, 24.0% to 37.4%, 4.1% to 20.2%, 10.1% to 23.9%, and 1% to 6.4%, respectively. Children in the FWFHP had a higher prevalence of obesity than children in all comparison groups, and FWFHP children aged 6 to 12 years had a higher prevalence of elevated blood pressure than all comparison groups. Older FWFHP children had a higher prevalence of anemia than US children and Mexican children. Children in FWFHP had a higher prevalence of stunting than US and Mexican American children.

  Conclusions. We observed an elevated prevalence of obesity, anemia among older age groups, and stunting in this sample of children of migrant workers.
  [Nichols, M., Stein, A.D. and Wold, J.L. (2014) ‘Health status of children of migrant farm workers: Farm Worker Family Health Program, Moultrie, Georgia’, American Journal of Public Health, 104(2), pp. 365–370. Available at: https://ajph.aphapublications.org/doi/full/10.2105/AJPH.2013.301511. ]

• Lifetime and current pesticide exposure among Latino farmworkers in comparison to other Latino immigrants.
  This analysis documents lifetime and current pesticide exposure of North Carolina Latino migrant farmworkers, with comparison to non-farmworker Latino immigrants.During May to October 2012, 235 Latino farmworkers and 212 Latino non-farmworkers completed interviews with items to construct measures of lifetime, current residential and occupational pesticide exposure.Farmworkers experience levels of lifetime and residential pesticide exposure that are consistently greater than among non-farmworkers. Farmworkers report a large number of occupational pesticide exposures. Lifetime exposure and current residential pesticide exposure are related to social determinants. Education is inversely related to lifetime pesticide exposure for farmworkers and non-farmworkers; farmworkers with H-2A visas report greater residential pesticide exposure than those without H-2A visas. Occupational safety policy needs to consider these patterns of lifetime exposure when setting standards. Health care providers should be aware of the lifetime and current exposure of this vulnerable population.
  [Arcury TA, Nguyen HT, Summers P, Talton JW, et al. 2014. Am J Ind Med. 57(7):776-87]
• Macro-activity patterns of farmworker and non-farmworker children living in an agricultural community.
  Children of farmworkers have significantly higher exposure to pesticides than do other children living in the same agricultural communities, but there is limited information about how and where older farmworker children (>6) spend their time and how their activities might influence the risk of pesticide exposure. Using data from the Community Based Participatory Research Study for Healthy Kids, study compared activity patterns recorded over 7 days during two agricultural seasons (pre thinning and thinning) between farmworker and non-farmworker children aged 6-12 years old living in Eastern Washington State. Study observed substantial differences in child activity patterns between the two seasons. The children in this sample spent more time outdoors and were more likely to engage in behaviors, such as playing in the fields and accompanying their parents to work in the fields during the high-spray thinning season. There were some differences in activities and behaviors between farmworker and non-farmworker children during the thinning season.
  [Shepherd-Banigan M, Ulrich A, Thompson B. 2014. Environ Res. 132:176-81]
• Pesticide exposures to migrant farmworkers in Eastern NC: detection of metabolites in farmworker urine associated with housing violations and camp characteristics.
  The purpose of this paper is to present and evaluate descriptively bivariate associations between urinary metabolites of pesticides and herbicides and migrant camp conditions, violations, and personal worker behaviors at home for farmworkers who do not apply pesticides.Authors studied 183 migrant farmworker camps in eastern North Carolina in 2010. Cockroaches and bathroom violations were predictive of increased exposure to pyrethroids and cyfluthrin/chlorpyrifos, respectively. Changing and storing clothing and shoes in sleeping rooms increased the number of detects for the diazinon metabolite.Farmworkers had exposures to multiple chemicals. No single housing domain was identified as critical to mitigating housing-related exposure; specific attention should be paid to changing and storing soiled clothing in sleeping rooms, and insect infestations.
  [Raymer JH, Studabaker WB, Gardner M, Talton J, et al. 2014. Am J Ind Med. 57(3):323-37.]
• Pesticides present in migrant farmworker housing in North Carolina
  This analysis (1) describes the presence of organophosphorous (OP) and pyrethroid pesticides in North Carolina migrant farmworker houses, and (2) delineates associations of farmworker camp characteristics with pesticide detection and concentration.In 2010, 186 migrant farmworkers camps in NC were recruited and pesticide wipe samples for 176 houses were analyzed. OPs were found in 166 of 176 houses (average of 2.4/house); pyrethroids were found in 171 houses (average of 4.3/house). The number of different OPs detected in each camp and concentrations of these OPs were not associated with camp and housing characteristics. The number of different pyrethroids detected in each camp and concentrations of these pyrethroids were associated with camps having residents with H2-A visas, a posted North Carolina Department of Labor Certificate of Inspection, no barracks, fewer residents, no bedroom weather protection or floor violations, and no roaches.Farmworkers are exposed to pesticides where they live. Policy on removing pesticides from farmworker houses is needed. Reducing pesticides in farmworker houses will reduce one health risk confronted by this vulnerable population.
  [Arcury TA, Lu C, Chen H, Quandt SA. 2014. Am J Ind Med. 57(3):312-22.]
• Safety and injury characteristics of youth farmworkers in North Carolina: a pilot study.
  The primary aim for this analysis is to describe the personal characteristics, work characteristics, occupational safety behaviors, and occupational injuries of North Carolina youth farmworkers. Participants included males (62.1%) and females (37.9%), with 26.4% aged 10-13 years, 39.1% 14-15 years, and 34.5% 16-17 years. The majority (78.2%) were born in the United States. Most worked in tobacco (46.0%), sweet potatoes (28.7%), and berries (28.7%). Three quarters wore a hat, and 63.2% wore gloves while working. Five (5.7%) had received pesticide use training in the past year. Over half reported a musculoskeletal injury (54.0%), a traumatic injury (60.9%), or a dermatological injury (72.4%) in the last year. Six of the injuries led to medical treatment, and 10 resulted in missed school or work. Farmworker youth in North Carolina are at times not treated fairly when they work, occupational safety behaviors are limited (increasing exposure to pesticides and other environmental hazards), and they commonly experience injuries. Research on the occupational exposures and health experienced by youth farmworkers is needed to inform policy. Changes in policy are warranted to improve the safety of youth farmworkers.
  [Arcury TA, Rodriguez G, Kearney GD, et al. 2014. J Agromedicine. 19(4):354-63.]
• Female farmworkers' health during pregnancy: health care providers' perspectives.
  Pregnant farmworkers and their fetuses are at increased risk of negative health outcomes due to environmental and occupational factors at their workplaces. Health care providers who serve farm communities can positively affect workers' health through the informed care they deliver. Yet, interviews with rural health care providers reveal limited knowledge about agricultural work or occupational and environmental health risks during pregnancy. Professional associations, government organizations, academic institutions, and practice settings must renew their efforts to ensure that environmental and occupational health education, especially as it relates to women and their children, is incorporated into academic and practice environments.
  [Kelley MA, Flocks JD, Economos J, McCauley LA. 2013. Workplace Health Saf. 61(7):308-13]
• Pesticide risk perception and biomarkers of exposure in Florida female farmworkers.
  Study compared workplace characteristics, workplace behaviors, and the health beliefs of female farmworkers of childbearing age with actual biomarkers of exposure to organophosphate pesticides and to the fungicide mancozeb.Hispanic and Haitian farmworkers between the ages of 18 and 40 years working in nursery or fernery operations were recruited to participate in a cross-sectional survey, examining demographics, work practices, work-related hygiene, and pesticide exposure beliefs.Women in nurseries worried less frequently about the effects of pesticides on their health than those in fernery operations. In summary, organophosphate and ethylenethiourea levels in nursery workers were significantly higher than levels in fernery workers and the control group.Results showed that perceived pesticide exposure did not correspond to actual metabolite levels within differing agricultural subpopulations.
  [Runkle JD, Tovar-Aguilar JA, Economos E, et al.2013. J Occup Environ Med. 55(11):1286-92.]
• Relative pesticide and exposure route contribution to aggregate and cumulative dose in young farmworker children.
  The Child-Specific Aggregate Cumulative Human Exposure and Dose (CACHED) framework integrates micro-level activity time series with mechanistic exposure equations, environmental concentration distributions, and physiologically-based pharmacokinetic components to estimate exposure for multiple routes and chemicals. CACHED was utilized to quantify cumulative and aggregate exposure and dose estimates for a population of young farmworker children and to evaluate the model for chlorpyrifos and diazinon. Micro-activities of farmworker children collected concurrently with residential measurements of pesticides were used in the CACHED framework to simulate 115,000 exposure scenarios and quantify cumulative and aggregate exposure and dose estimates. Modeled metabolite urine concentrations were not statistically different than concentrations measured in the urine of children, indicating that CACHED can provide realistic biomarker estimates. Analysis of the relative contribution of exposure route and pesticide indicates that in general, chlorpyrifos non-dietary ingestion exposure accounts for the largest dose, confirming the importance of the micro-activity approach. The risk metrics computed from the 115,000 simulations, indicate that greater than 95% of these scenarios might pose a risk to children's health from aggregate chlorpyrifos exposure. The variability observed in the route and pesticide contributions to urine biomarker levels demonstrate the importance of accounting for aggregate and cumulative exposure in establishing pesticide residue tolerances in food.
  [Beamer PI, Canales RA, Ferguson AC, et al. 2012. Int J Environ Res Public Health. 9(1):73-96.]
• Acute Pesticide Illnesses Associated with Off-Target Pesticide Drift from Agricultural Applications — 11 States, 1998–2006
  A study by the Centers for Disease Control and Prevention's (CDC) National Institute for Occupational Safety and Health (NIOSH) and state agency partners finds that pesticide drift from conventional, chemical-intensive farming has poisoned thousands of farmworkers and rural residents in recent years. According to the authors, agricultural workers and residents in agricultural regions were found to have the highest rate of pesticide poisoning from drift exposure, and soil fumigations were a major hazard causing large drift incidents. Daily News
  [Lee, SJ. et al. 2011. Environ Health Perspect. 119:1162–1169]
• Esophageal cancer among Brazilian agricultural workers: case-control study based on death certificates.
  In the present study, the magnitude of the association between agricultural working and esophageal cancer mortality was evaluated in a high pesticide use area in Brazil, through a death certificate-based case-control study. Results showed that, in general, agricultural workers were at significantly higher risk to die by esophageal cancer, when compared to non-agricultural workers. Stratified analysis also revealed that the magnitude of such risk was slightly higher among illiterate agricultural workers, and simultaneous adjustment for several covariates showed that the risk was quantitatively higher among younger southern agricultural workers. These results suggest the esophageal cancer may be included among those types of cancer etiologically associated to agricultural working.
  [Meyer A, Alexandre PC, Chrisman Jde R, et al. 2011. Int J Hyg Environ Health. 214(2):151-5.]
• Organophosphate pesticide exposure and residential proximity to nearby fields: evidence for the drift pathway.
  Residential proximity to pesticide-treated farmland is an important pesticide exposure pathway. In-person interviews and biological samples were collected from 100 farmworker and 100 non-farmworker adults and children living in Eastern Washington State. Study examined the relationship of residential proximity to farmland to urinary metabolite concentrations of dimethylphosphate (DMTP) and levels of pesticide residues in house dust. DMTP concentrations were higher in farmworkers than non-farmworkers and in farmworker children than non-farmworker children. Compared to non-farmworker households, farmworker households had higher levels of azinphos-methyl and phosmet. Overall, a 20% reduction in DMTP concentration was observed per mile increase in distance from farmland.
  [Coronado GD, Holte S, Vigoren E, Griffith WC, et al. 2011. J Occup Environ Med. 53(8):884-91.]
• Pesticides in house dust from urban and farmworker households in California: an observational measurement study.
  Authors conducted a study in low-income homes from urban and agricultural communities to: characterize and compare house dust levels of agricultural and residential-use pesticides; evaluate the correlation of pesticide concentrations in samples collected several days apart; examine whether concentrations of pesticides phased-out for residential uses, but still used in agriculture (i.e., chlorpyrifos and diazinon) have declined in homes in the agricultural community; and estimate resident children's pesticide exposures via inadvertent dust ingestion.In 2006, reserchers collected up to two dust samples 5-8 days apart from each of 13 urban homes in Oakland, California and 15 farmworker homes in Salinas, California, an agricultural community (54 samples total). More than half of the households reported applying pesticides indoors. Analytes frequently detected in both locations included chlorpyrifos, diazinon, permethrin, allethrin, cypermethrin, and piperonyl butoxide. Chlorthal-dimethyl was detected solely in farmworker homes, suggesting contamination due to regional agricultural use. Additionally, diazinon and chlorpyrifos concentrations in Salinas farmworker homes were 40-80% lower than concentrations reported in samples from Salinas farmworker homes studied between 2000-2002, suggesting a temporal reduction after their residential phase-out. Finally, estimated non-dietary pesticide intake for resident children did not exceed current U.S. Environmental Protection Agency's (U.S. EPA) recommended chronic reference doses (RfDs).Study concludes low-income children are potentially exposed to a mixture of pesticides as a result of poorer housing quality. Historical or current pesticide use indoors is likely to contribute to ongoing exposures. Agricultural pesticide use may also contribute to additional exposures to some pesticides in rural areas. The frequent pesticide use reported and high detection of several home-use pesticides in house dust suggests that families would benefit from integrated pest management strategies to control pests and minimize current and future exposures.
  [Quirós-Alcalá L, Bradman A, Nishioka M, et al. 2011. Environ Health. 10:19.]
• Repeated pesticide exposure among North Carolina migrant and seasonal farmworkers
  Data were collected from 196 farmworkers four times at monthly intervals in 2007. Urine samples were tested for 12 pesticide urinary metabolites. Farmworkers had at least one detection for many pesticide urinary metabolites; for example, 84.2% had at least one detection for acephate, 88.8% for 3,5,6-trichloro-2-pyridinol. Most farmworkers had multiple detections for specific metabolites.
  [Arcury, T. et al. 2010. Am. J. Ind. Med. 53:802–813]
• A case-control study of farming and prostate cancer in African-American and Caucasian men
  A population-based case-control study in South Carolina finds farming is associated with increase risk of prostate cancer in Caucasians (OR 1.8) but not African-Americans. The study also finds that farmers who mixed or applied pesticides have a greater risk (OR 1.6); and, the increased risk is found only for those farming less than 5 years. The authors conclude that the racial difference in the association between farming and prostate cancer may be explained by different farming activities or different gene–environment interactions by race.
  [Meyer, T.E., et al. 2007. Occup Environ Med 64(3):155-160.]
• Agreement of pesticide biomarkers between morning void and 24-h urine samples from farmers and their children
  In pesticide biomonitoring studies, researchers typically collect either single voids or daily (24-h) urine samples. Collection of 24-h urine samples is considered the "gold-standard", but this method places a high burden on study volunteers, requires greater resources, and may result in misclassification of exposure or underestimation of dose due to noncompliance with urine collection protocols. To evaluate the potential measurement error introduced by single void samples, we present an analysis of exposure and dose for two commonly used pesticides based on single morning void (MV) and 24-h urine collections in farmers and farm children. The agreement between the MV concentration and its corresponding 24-h concentration was analyzed using simple graphical and statistical techniques and risk assessment methodology. A consistent bias towards overprediction of pesticide concentration was found among the MVs, likely in large part due to the pharmacokinetic time course of the analytes in urine. These results suggest that the use of single voids can either over- or under-estimate daily exposure if recent pesticide applications have occurred. This held true for both farmers as well as farm children, who were not directly exposed to the applications. As a result, single void samples influenced the number of children exposed to chlorpyrifos whose daily dose estimates were above levels of toxicologic significance. In populations where fluctuations in pesticide exposure are expected (e.g., farm families), the pharmacokinetics of the pesticide and the timing of exposure events and urine collection must be understood when relying on single voids as a surrogate for longer time-frames of exposure.
  [Scher, D. et al. 2007, J. Exposure Science and Environmental Epidemiology; 17, 350–357]
• Agricultural exposures and gastric cancer risk in Hispanic farm workers in California
  Occupation in the citrus industry (OR 2.88) and in areas with high 2,4-D use (OR 1.85) and use of acaricide propargite (OR 2.86) or trifluralin (OR 1.69) are associated with gastric cancer.
  [Mills, P.K., and Yang, R.C. 2007. Environ Res 104(2):282-289.]
• Pesticides and their metabolites in the homes and urine of farmworker children living in the Salinas Valley, CA.
  In support of planning efforts for the National Children's Study, authors conducted a study to test field methods for characterizing pesticide exposures to 20 farmworker children aged 5-27 months old living in the Salinas Valley of Monterey County, California. Study tested methods for collecting house dust, indoor and outdoor air, dislodgeable residues from surfaces and toys, residues on clothing (sock and union suits), food, as well as spot and overnight diaper urine samples. Authors measured 29 common agricultural and home use pesticides in multiple exposure media samples. A subset of organophosphorus (OP), organochlorine (OC) and pyrethroid pesticides were measured in food. Urine samples were also analyzed. Pesticides were detected more frequently in house dust, surface wipes, and clothing than other media, with chlorpyrifos, diazinon, chlorthal-dimethyl, and cis- and trans-permethrin detected in 90% to 100% of samples. Levels of four of these five pesticides were positively correlated among the house dust, sock, and union suit samples. Pesticide loading on socks and union suits was higher for the group of 10 toddlers compared to the 10 younger crawling children. Several OP pesticides, as well as 4,4'-DDE, atrazine, and dieldrin were detected in the food samples. Future uses of these data include the development of pesticide exposure models and risk assessment.
  [Bradman A, Whitaker D, Quirós L, Castorina R, et al. 2007. J Expo Sci Environ Epidemiol;17(4):331-49]
• Association of in utero organochlorine pesticide exposure and fetal growth and length of gestation in an agricultural population.
  Although substantial evidence exists for the fetal toxicity of organochlorines in animals, information on human reproductive effects is conflicting. Study investigated whether infants' length of gestation, birth weight, and crown-heel length were associated with maternal serum levels of 11 different organochlorine pesticides: p,p -dichlorodiphenyltrichloroethane (p,p -DDT), p,p -dichlorodiphenyldichloroethylene (p,p -DDE), o,p -dichlorodiphenyltrichloroethane (o,p -DDT), hexachlorobenzene (HCB), gamma-hexachlorocyclohexane (gamma-HCCH), gamma-hexachlorocyclohexane (gamma-HCCH), dieldrin, heptachlor epoxide, oxychlordane, trans-nonachlor, and mirex. Our subjects were a birth cohort of 385 low-income Latinas living in the Salinas Valley, an agricultural community in California. Results found no adverse associations between maternal serum organochlorine levels and birth weight or crown-heel length. Decreased length of gestation with increasing levels of lipid-adjusted HCB was found. Study did not find reductions in gestational duration associated with any of the other organochlorine pesticides. Study's finding of decreased length of gestation related to HCB does not seem to have had clinical implications for this population, given its relatively low rate of preterm delivery (6.5%).
  [Fenster L, Eskenazi B, Anderson M, Bradman A. 2006. Environ Health Perspect. 114(4):597-602]
• Biomonitoring of exposure in farmworker studies
  Although biomonitoring has been used in many occupational and environmental health and exposure studies, we are only beginning to understand the complexities and uncertainties involved with the biomonitoring process--from study design, to sample collection, to chemical analysis--and with interpreting the resulting data. Author presents an overview of concepts that should be considered when using biomonitoring or biomonitoring data, assess the current status of biomonitoring, and detail potential advancements in the field that may improve our ability to both collect and interpret biomonitoring data. Author also discusses issues such as the appropriateness of biomonitoring for a given study, the sampling time frame, temporal variability in biological measurements to nonpersistent chemicals, and the complex issues surrounding data interpretation. In addition, we provide recommendations to improve the utility of biomonitoring in farmworker studies.
  [Barr DB, et al. 2006. Environ Health Perspect.;114(6):936-42]
• Cancer incidence among farmers exposed to lindane while sheep dipping
  The objective of this study was to determine whether site-specific cancer incidence among farmers exposed to the insecticide lindane (g-hexachlorocyclohexane) while dipping sheep differs from that of the general population in Iceland.Cohorts of 7882 men and 429 women, who, according to records on sheep dipping, were sheep owners, were followed from 1962 to 2003 in the Cancer Registry for cancer incidence.For men the standardized incidence ratio (SIR) for all cancer sites was 0.79, with a 95% confidence interval (95% CI) of 0.76-0.83. For both the men and the women a significantly increased risk for lip cancer was found, with SIR of 1.50 (95% CI 1.08-2.04) and 9.09 (95% CI 1.02-32.82), respectively. Cancer of the lip was the only cancer type in significant excess among both genders, and the stomach cancer rates were near unity, but, in previous studies on Icelandic farmers, an increase had been found for stomach cancer. The site-specific cancer incidence for sheep-dipping farmers did not differ substantially from that of the general population.
  [Rafnsson V. 2006. Scand J Work Environ Health. 32(3):185-9.]
• Paraoxonase polymorphisms, haplotypes, and enzyme activity in Latino mothers and newborns.
  Recent studies have demonstrated widespread pesticide exposures in pregnant women and in children. Plasma paraoxonase 1 (PON1) plays an important role in detoxification of various organophosphates. The goals of this study were to examine in the Center for Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort of Latina mothers and their newborns living in the Salinas Valley, California, the frequencies of five PON1 polymorphisms in the coding region (192QR and 55LM) and the promoter region (-162AG, -909CG, and -108CT) and to determine their associations with PON1 plasma levels [phenylacetate arylesterase (AREase) ] and enzyme activities of paraoxonase (POase) and chlorpyrifos oxonase (CPOase) . Authors found that PON1-909, PON1-108, and PON1(192) had an equal frequency (0.5) of both alleles, whereas PON1-162 and PON1(55) had lower variant allele frequencies (0.2) . Nearly complete linkage disequilibrium was observed among coding and promoter polymorphisms (p < 0.001) , except PON1(192) and PON1-162 (p > 0.4) . Children's PON1 plasma levels (AREase ranged from 4.3 to 110.7 U/mL) were 4-fold lower than their mothers' (19.8 to 281.4 U/mL) . POase and CPOase activities were approximately 3-fold lower in newborns than in mothers. The genetic contribution to PON1 enzyme variability was higher in newborns (R2 = 25.1% by genotype and 26.3% by haplotype) than in mothers (R2 = 8.1 and 8.8%, respectively) . However, haplotypes and genotypes were comparable in predicting PON1 plasma levels in mothers and newborns. Most of the newborn children and some pregnant women in this Latino cohort may have elevated susceptibility to organophosphate toxicity because of their PON1192 genotype and low PON1 plasma levels.
  [Holland N, Furlong C, Bastaki M, et al. 2006. Environ Health Perspect. 114(7):985-91]
• Biologic monitoring to characterize organophosphorus pesticide exposure among children and workers: an analysis of recent studies in Washington State.
  Study examined findings from five organophosphorus pesticide biomonitoring studies conducted in Washington State between 1994 and 1999 and compared urinary dimethylthiophosphate (DMTP) concentrations for all study groups and composite dimethyl alkylphosphate (DMAP) concentrations for selected groups. Children of pesticide applicators had substantially higher metabolite levels than did Seattle children and farmworker children. Metabolite levels of children living in agricultural communities were elevated during periods of crop spraying. Median DMTP concentrations for Seattle children and farmworker children did not differ significantly; however, the DMAP concentrations were higher for Seattle children than for farmworker children. DMTP concentrations of U.S. children 6-11 years of age (1999-2000 National Health and Nutrition Examination Survey population) were higher than those of Seattle children and farmworker children. DMTP concentrations for workers actively engaged in apple thinning were 50 times higher than DMTP concentrations for farmworkers sampled outside of peak exposure periods. Study concludes that workers who have direct contact with pesticides should continue to be the focus of public health interventions and that elevated child exposures in agricultural communities may occur during active crop-spraying periods and from living with a pesticide applicator. Timing of sample collection is critical for the proper interpretation of pesticide biomarkers excreted relatively soon after exposure. Authors surmise that differences in dietary exposure can explain the similar exposures observed among farmworker children, children living in the Seattle metropolitan area, and children sampled nationally.
  [Fenske RA, Lu C, Curl CL, Shirai JH, Kissel JC. 2005. Environ Health Perspect.;113(11):1651-7]
• Urinary and hand wipe pesticide levels among farmers and nonfarmers in Iowa
  In the spring and summer of 2001, as part of a larger study investigating farm family pesticide exposure and home contamination in Iowa, urine and hand wipe samples were collected from 24 male farmers and 23 male nonfarmer controls. The samples were analyzed for the parent compound or metabolites of six commonly used agricultural pesticides: alachlor, atrazine, acetochlor, metolachlor, 2,4-dichlorophenoxyacetic acid (2,4-D) and chlorpyrifos. For atrazine, acetochlor, metolachlor and 2,4-D, farmers who reported applying the pesticide had significantly higher urinary metabolite levels than nonfarmers, farmers who did not apply the pesticide, and farmers who had the pesticide commercially applied. Generally, there were no differences in urinary pesticide metabolite levels between nonfarmers, farmers who did not apply the pesticide, and farmers who had the pesticide commercially applied. Among farmers who reported applying 2,4-D themselves, time since application, amount of pesticide applied, and the number of acres to which the pesticide was applied were marginally associated with 2,4-D urine levels. Among farmers who reported applying atrazine themselves, time since application and farm size were marginally associated with atrazine mercapturate urine levels. Farmers who reported using a closed cab to apply these pesticides had higher urinary pesticide metabolite levels, although the difference was not statistically significant. Farmers who reported using closed cabs tended to use more pesticides. The majority of the hand wipe samples were nondetectable. However, detection of atrazine in the hand wipes was significantly associated with urinary levels of atrazine above the median.
  [Curwin, B. et al. 2005. J of Exposure Analysis and Environmental Epidemiology 15, 500–508]
• Cancer risk and parental pesticide application in children of Agricultural Health Study participants.
  Parental exposure to pesticides may contribute to childhood cancer risk. Through the Agricultural Health Study, a prospective study of pesticide applicators in Iowa and North Carolina, we examined childhood cancer risk and associations with parental pesticide application. Identifying information for 17,357 children of Iowa pesticide applicators was provided by parents via questionnaires (1993-1997) and matched against the Iowa Cancer Registry. Fifty incident childhood cancers were identified (1975-1998). Risk of all childhood cancers combined was increased [standardized incidence ratio (SIR) = 1.36; 95% confidence interval (CI), 1.03-1.79]. Risk of all lymphomas combined was also increased (SIR = 2.18; 95% CI, 1.13-4.19), as was risk of Hodgkin's lymphoma (SIR = 2.56; 95% CI, 1.06-6.14). We used logistic regression to explore associations between self-reported parental pesticide application practices and childhood cancer risk. No association was detected between frequency of parental pesticide application and childhood cancer risk. An increased risk of cancer was detected among children whose fathers did not use chemically resistant gloves [odds ratio (OR) = 1.98; 95% CI, 1.05-3.76] compared with children whose fathers used gloves. Of 16 specific pesticides used by fathers prenatally, ORs were increased for aldrin (OR = 2.66), dichlorvos (OR = 2.06), and ethyl dipropylthiocarbamate (OR = 1.91). However, these results were based on small numbers and not supported by prior biologic evidence. Identification of excess lymphoma risk suggests that farm exposures including pesticides may play a role in the etiology of childhood lymphoma.
  [Flower, K., et al. 2004. Environmental Health Perspectives 112:631-635]
• Glyphosate biomonitoring for farmers and their families: results from the Farm Family Exposure Study.
  Glyphosate is the active ingredient in Roundup agricultural herbicides and other herbicide formulations that are widely used for agricultural, forestry, and residential weed control. As part of the Farm Family Exposure Study, we evaluated urinary glyphosate concentrations for 48 farmers, their spouses, and their 79 children (4-18 years of age). We evaluated 24-hr composite urine samples for each family member the day before, the day of, and for 3 days after a glyphosate application. Sixty percent of farmers had detectable levels of glyphosate in their urine on the day of application. The geometric mean (GM) concentration was 3 ppb, the maximum value was 233 ppb, and the highest estimated systemic dose was 0.004 mg/kg. Farmers who did not use rubber gloves had higher GM urinary concentrations than did other farmers (10 ppb vs. 2.0 ppb). For spouses, 4% had detectable levels in their urine on the day of application. Their maximum value was 3 ppb. For children, 12% had detectable glyphosate in their urine on the day of application, with a maximum concentration of 29 ppb. All but one of the children with detectable concentrations had helped with the application or were present during herbicide mixing, loading, or application. None of the systemic doses estimated in this study approached the U.S. Environmental Protection Agency reference dose for glyphosate of 2 mg/kg/day. Nonetheless, it is advisable to minimize exposure to pesticides, and this study did identify specific practices that could be modified to reduce the potential for exposure.
  [Acquavella, J, F. et al. 2004. Environ Health Perspect; 112(3): 321–326]
• Arrested Development: A study on the Human Health Impacts of Pesticides
  A study found a strong link between pesticide exposure and cognitive abilities among farmers' children in India. The study revealed serious mental development disorders that ranged from severely impaired analytical abilities, motor skills, concentration and memory among the children in the chemical-intensive cotton belts of India (A 2004 study reveals serious mental development disorders that range from severely impaired analytical abilities, motor skills, concentration and memory among the children in the chemical-intensive cotton belts of India.
  [Kuruganti, K. 2003. Greenpeace. Bangalore India.]
• Children's Exposure to Chlorpyrifos and Parathion in an Agricultural Community in Central Washington State
  Authors measured two diethyl organophosphorus (OP) pesticides--chlorpyrifos and parathion--in residences, and their metabolic by-products, in the urine of children 6 years old or younger in a central Washington State agricultural community. Median chlorpyrifos house dust concentrations were highest for the 49 applicator homes (0.4 microg/g), followed by the 12 farm-worker homes (0.3 microg/g) and the 14 nonagricultural reference homes (0.1 microg/g); authors observed a similar pattern for parathion in house dust. Chlorpyrifos was measurable in the house dust of all homes, whereas parathion in only 41% of the homes was found. Child urinary metabolite concentrations did not differ across parental occupational classifications. Homes in close proximity (200 ft/60 m) to pesticide-treated farmland had higher chlorpyrifos (p = 0.01) and parathion (p = 0.014) house dust concentrations than did homes farther away, but this effect was not reflected in the urinary metabolite data. Use of OP pesticides in the garden was associated with an increase in TCPy concentrations in children's urine. Parathion concentrations in house dust decreased 10-fold from 1992 to 1995, consistent with the discontinued use of this product in the region in the early 1990s.
  [Fenske, R.A., Lu, C, Barr, D, and Needham, L. 2002. Environ Health Perspect. 11(5):: 549–553]
• Evaluation of take-home organophosphorus pesticide exposure among agricultural workers and their children.
  Researchers analyzed organophosphorus pesticide exposure in 218 farm worker households in agricultural communities in Washington State to investigate the take-home pathway of pesticide exposure and to establish baseline exposure levels for a community intervention project. House dust samples were collected from within the homes, and vehicle dust samples were collected from the vehicles used by the farm workers to commute to and from work. Urine samples were obtained from a farm worker and a young child in each household. Dust samples were analyzed for six pesticides, and urine samples were analyzed for five dialkylphosphate (DAP) metabolites. Azinphosmethyl was detected in higher concentrations than the other pesticides. Dimethyl DAP metabolite concentrations were higher than diethyl DAP metabolite concentrations in both child and adult urine. Azinphosmethyl concentrations in house dust and vehicle dust from the same household were significantly associated. Dimethyl DAP levels in child and adult urine from the same household were also significantly associated, and this association remained when the values were creatinine adjusted. The results of this work support the hypothesis that the take-home exposure pathway contributes to residential pesticide contamination in agricultural homes where young children are present.
  [Curl CL, Fenske RA, Kissel JC, et al. 2002. Environ Health Perspect;110(12):A787-92]
• An exploratory analysis of the effect of pesticide exposure on the risk of spontaneous abortion in an Ontario farm population.
  The Ontario Farm Family Health Study collected data by questionnaire on the identity and timing of pesticide use on the farm, lifestyle factors, and a complete reproductive history from the farm operator and eligible couples living on the farm. A total of 2,110 women provided information on 3,936 pregnancies, including 395 spontaneous abortions. To explore critical windows of exposure and target sites for toxicity, authors examined exposures separately for preconception (3 months before and up to month of conception) and postconception (first trimester) windows and for early (< 12 weeks) and late (12-19 weeks) spontaneous abortions. They observed moderate increases in risk of early abortions for preconception exposures to phenoxy acetic acid herbicides, triazines, and any herbicide. For late abortions, preconception exposure to glyphosate, thiocarbamates, and the miscellaneous class of pesticides was associated with elevated risks. This study shows that timing of exposure and restricting analyses to more homogeneous endpoints are important in characterizing the reproductive toxicity of pesticides.
  [Arbuckle,TE, Lin, Z and Mery, LS. 2001. Environ Health Perspect. 109(8): 851–857.]
• Biological monitoring survey of organophosphorus pesticide exposure among pre-school children in the Seattle metropolitan area
  In this study we assessed organophosphorus (OP) pesticide exposure among children living in two Seattle metropolitan area communities by measuring urinary metabolites, and identified possible exposure risk factors through a parental interview. We recruited children in clinic and outpatient waiting rooms. We obtained spot urine samples in the spring and fall of 1998 from 110 children ages 2-5 years, from 96 households. We analyzed urine samples for six dialkylphosphate (DAP) compounds, the common metabolites of the OP pesticides. Through parental interviews we gathered demographic and residential pesticide use data. At least one of the DAP metabolites was measured in 99% of the children, and the two predominant metabolites (DMTP and DETP) were measured in 70-75% of the children. We found no significant differences in DAP concentrations related to season, community, sex, age, family income, or housing type. Median concentrations of dimethyl and diethyl DAPs were 0.11 and 0.04 micromol/L, respectively (all children). Concentrations were significantly higher in children whose parents reported pesticide use in the garden (0.19 vs. 0.09 micromol/L for dimethyl metabolites, p = 0.05; 0.04 vs. 0.03 micromol/L for diethyl metabolites, p = 0.02), but were not different based on reported pet treatment or indoor residential use. Nearly all children in this study had measurable levels of OP pesticide metabolites. Some of this exposure was likely due to diet. Garden pesticide use was associated with elevated metabolite levels. It is unlikely that these exposure levels would cause acute intoxication, but the long-term health effects of such exposures are unknown. We recommend that OP pesticide use be avoided in areas where children are likely to play.
  [Lu C, Knutson DE, Fisker-Andersen J, Fenske RA. 2001. Environ Health Perspect;109(3):299-303]
• Agricultural work and the risk of Parkinson's disease in Denmark, 1981-1993
  This study examined the possible association between agricultural and horticultural work and the subsequent morbidity of Parkinson's disease. A high risk of Parkinson's disease was found for the men and women in agriculture and horticulture (134 cases, SHR 132, 95% CI 111-156). Statistically significantly high risks were found for farmers (79 cases, SHR 130, 95% CI 103-163) and for all men in agriculture and horticulture (109 cases, SHR 134, 95% CI 109-162).
  [Tuchsen, F., et al. 2000. Scand J Work Environ Health 26(4):359-362]
• Biological monitoring of organophosphorus pesticide exposure among children of agricultural workers in central Washington State.
  Children up to 6 years of age who lived with pesticide applicators were monitored for increased risk of pesticide exposure: 48 pesticide applicator and 14 reference families were recruited from an agricultural region of Washington State in June 1995. A total of 160 spot urine samples were collected from 88 children, including repeated measures 3-7 days apart. Dimethylthiophosphate (DMTP) was the dominant metabolite and levels were significantly higher in applicator children than in reference children, with median concentrations of 0.021 and 0.005 microg/ml, respectively; maximum concentrations were 0.44 and 0.10 microg/ml, respectively. Percentages of detectable samples were 47% for applicator children and 27% for reference children. A marginally significant trend of increasing concentration was observed with decreasing age among applicator children, and younger children within these families had significantly higher concentrations when compared to their older siblings. Applicator children living less than 200 feet from an orchard were associated with higher frequency of detectable DMTP levels than nonproximal applicator children. These results indicate that applicator children experienced higher organophosphorus pesticide exposures than did reference children in the same community and that proximity to spraying is an important contributor to such exposures. Trends related to age suggest that child activity is an important variable for exposure. It is unlikely that any of the observed exposures posed a hazard of acute intoxication. This study points to the need for a more detailed understanding of pesticide exposure pathways for children of agricultural workers.
  [Loewenherz C, Fenske RA, Simcox NJ, Bellamy G, Kalman D. 1997. Environ Health Perspect.;105(12):1344-53]
• Cancer in offspring of parents engaged in agricultural activities in Norway: incidence and risk factors in the farm environment.
  In this study of cancer in offspring we demonstrate that factors linked to horticulture and use of pesticides are associated with cancer at an early age, whereas factors in animal husbandry, in particular poultry farming, are associated with cancers in later childhood and young adulthood. Incident cancer was investigated in offspring born in 1952-1991 to parents identified as farm holders in agricultural censuses in Norway in 1969-1989. In the follow-up of 323,292 offspring for 5.7 million person-years, 1,275 incident cancers were identified in the Cancer Registry for 1965-1991. The standardized incidence for all cancers was equal to the total rural population of Norway, but cohort subjects had an excess incidence of nervous-system tumours and testicular cancers in certain regions and strata of time that could imply that specific risk factors were of importance. Classification of exposure indicators was based on information given at the agricultural censuses. Risk factors were found for brain tumours, in particular non-astrocytic neuroepithelial tumours: for all ages, pig farming tripled the risk [rate ratio (RR), 3.11; 95% confidence interval (CI), 1.89-5.13]; indicators of pesticide use had an independent effect of the same magnitude in a dose-response fashion, strongest in children aged 0 to 14 years (RR, 3.37; 95% CI, 1.63-6.94). Horticulture and pesticide indicators were associated with all cancers at ages 0 to 4 years, Wilms' tumour, non-Hodgkin's lymphoma, eye cancer and neuroblastoma. Chicken farming was associated with some common cancers of adolescence, and was strongest for osteosarcoma and mixed cellular type of Hodgkin's disease. The main problem in this large cohort study is the crude exposure indicators available; the resulting misclassification is likely to bias any true association towards unity.
  [Kristensen, P., et al. 1996. Int J Cancer 65(1):39-50]
• Pesticides in household dust and soil: exposure pathways for children of agricultural families.
  Child of agriculture families are likely to be exposed to agricultural chemicals, even if they are not involved in farm activities. This study was designed to determine whether such children are exposed to higher levels of pesticides than children whose parents are not involved in agriculture and whose homes are not close to farms. Household dust and soil samples were collected in children's play areas from 59 residences in eastern Washington State (26 farming, 22 farmworker, and 11 nonfarming families). The majority of the farm families lived within 200 feet of an operating apple or pear orchard, whereas all reference homes were located at least a quarter of a mile from an orchard. Four organophosphorous (OP) insecticides commonly used on tree fruit were targeted for analysis: azinphosmethyl, chlorpyrifos, parathion, and phosmet. Pesticide concentrations in household dust were significantly higher than in soil for all groups. OP levels for farmer/farm-worker families ranged from nondetectable to 930 ng/g in soil (0.93 ppm) and from nondetectable to 17,000 ng/g in dust (17 ppm); all four OP compounds were found in 62% of household dust samples, and two-thirds of the farm homes contained at least one OP above 1000 ng/g.These results demonstrate that children of agricultural families have a higher potential for exposure to OP pesticides than children of nonfarm families in this region. Children's total and cumulative exposure to this pesticide class from household dust, soil, and other sources warrants further investigation.
  [Simcox N.J., Fenske, R.A, Wolz. S.A, Lee, I.C, and Kalman, D.A. 1995. Environ Health Perspect. 103(12):1126-34.]
• A case-control study of brain gliomas and occupational exposure to chemical carcinogens: the risk to farmers.
  A case control study shows an increased risk for brain gliomas for farmers who reported the use of pesticides and fertilizers (RR 1.6) with a significant increased risk for those that used insecticides and fungicides (RR 2.0).
  [Musicco, M., et al. 1988. American Journal of Epidemiology 128(4):778-785]

Infants/Children

Infants and children take in more chemicals relative to body size than adults and are especially vulnerable to toxic exposure because their organ systems are still developing. Those children living in poverty are the hardest hit from pesticide exposure in residential areas, coupled with poor nutrition and, inadequate health care, lack of information on pesticide hazards and nontoxic alternatives to pesticides, and contaminated air and water from chemical manufacturing plants and waste sites located in their communities. 

• Assessing Chemical Intolerance in Parents Predicts the Risk of Autism and ADHD in Their Children
  Background: We sought to replicate our 2015 findings linking chemical intolerance in parents with the risk of their children developing autism and/or ADHD. Drawing upon our 2021 discovery of a strong association between chemical intolerance and mast cells, we propose an explanation for this link. Methods: In a population-based survey of U.S. adults, we used the internationally validated Quick Environmental Exposure and Sensitivity Inventory (QEESI) to assess symptom severity and chemical intolerance. Parents were asked how many of their biological children had been diagnosed with autism and/or ADHD. Results: Parents with chemical intolerance scores in the top versus bottom tenth percentile had 5.7 times the risk of reporting a child with autism and 2.1 times for ADHD. Conclusions: High chemical intolerance scores among parents of children with autism, coupled with our 2021 discovery of mast cell activation as a plausible biomechanism for chemical intolerance, suggest that (1) the QEESI can identify individuals at increased risk, (2) environmental counseling may reduce personal exposures and risk, and (3) the global rise in autism and ADHD may be due to fossil-fuel-derived and biogenic toxicants epigenetically “turning on” or “turning off” critical mast cell genes that can be transmitted transgenerationally. It is important to note that this study was observational in nature; as such, further research is needed using controlled trials to confirm causality and explore the proposed mechanism.
  [Palmer, R.F. et al. (2024) Assessing chemical intolerance in parents predicts the risk of autism and ADHD in their children, J. Xenobiot. Available at: https://www.mdpi.com/2039-4713/14/1/22. ]
• Exposure to agricultural pesticides and wheezing among 5–12-year-old children in the Imperial Valley, CA, USA
  Background:
  Exposure to pesticides has been linked to adverse respiratory health outcomes in children.

  Methods:
  We leveraged the Children’s Assessing Imperial Valley Respiratory Health and the Environment cohort located in the rural community of Imperial Valley near the US–Mexico border. We calculated the kilograms of total pesticides applied within 400 m of children’s residential addresses for the years 2016–2020. Estimated pesticide usage near homes was categorized into three groups (none vs. low vs. high [split at the median]). All health variables (i.e., asthma status and wheezing) were derived from a parent-reported questionnaire on respiratory health. We used generalized linear models, controlling for child sex, the language of survey, health insurance, respondents’ highest education, and exposure to environmental secondhand smoking, to calculate prevalence differences between none versus low and high exposure to agricultural pesticides.

  Results:
  Approximately 62% of the 708 children (aged 5–12 years) lived within 400 m of at least one pesticide application within 12 months prior to survey administration. Exposure to pesticides within 400 m of children’s residences was associated with 12-month prior wheeze. Those in the “high” exposure group had a prevalence of wheezing that was 10 (95% confidence interval: 2%, 17%) percentage points higher than among children not exposed to pesticide applications. Associations for high exposure to specific categories of pesticide applications, sulfur only, all pesticides except sulfur, chlorpyrifos, and glyphosate, also were observed with a higher prevalence of wheezing than among children not exposed to pesticide applications.

  Conclusions:
  We observed associations between living near pesticide applications and more wheeze symptoms among children.
  [Ornelas Van Horne, Y. et al. (2024) Exposure to agricultural pesticides and wheezing among 5–12-year-old children in the Imperial Valley, CA, USA, Environmental Epidemiology. Available at: https://journals.lww.com/environepidem/fulltext/2024/10000/exposure_to_agricultural_pesticides_and_wheezing.2.as]

• Exposure to pesticides, persistent and non − persistent pollutants in French 3.5-year-old children: Findings from comprehensive hair analysis in the ELFE national birth cohort
  Introduction
  Exposure to endocrine disruptors during early childhood poses significant health risks. This study examines the exposure levels of French 3.5-year-old children to various persistent and non-persistent pollutants and pesticides using hair analysis as part of the ELFE national birth cohort. Differences in sex and geographical location among the children were investigated as ppossible determinants of exposure.

  Methods
  Exposure biomarkers from 32 chemical families were analyzed using LC-MS/MS and GC-MS/MS in 222 hair samples from children in the ELFE cohort. Of these, 46 mother–child pairs from the same cohort provided unique insight into prenatal and postnatal exposure. Regressions, correlations and discriminate analysis were used to assess relationships between exposure and possible confounding factors.

  Results and Discussion
  Among the biomarkers tested in children’s hair samples, 69 had a detection frequency of ≥ 50 %, with 20 showing a 100 % detection rate. The most detected biomarkers belonged to the bisphenol, organochlorine and organophosphate families. Sex-specific differences were observed for 26 biomarkers, indicating the role of the child’s sex in exposure levels. Additionally, regional differences were noted, with Hexachlorobenzene varying significantly across the different French regions. Nicotine presented both the highest concentration (16 303 pg/mg) and highest median concentration (81 pg/mg) measured in the children’s hair. Statistically significant correlations between the levels of biomarkers found in the hair samples of the mothers and their respective children were observed for fipronil (correlation coefficient = 0.32, p = 0.03), fipronil sulfone (correlation coefficient = 0.34, p = 0.02) and azoxystrobin (correlation coefficient = 0.29, p = 0.05).

  Conclusions
  The study highlights the elevated exposure levels of young children to various pollutants, highlighting the influence of sex and geography. Hair analysis emerges as a crucial tool for monitoring endocrine disruptors, offering insights into exposure risks and reinforcing the need for protective measures against these harmful substances.
  [Macheka, L. et al. (2024) Exposure to pesticides, persistent and non − persistent pollutants in French 3.5-year-old children: Findings from comprehensive hair analysis in the ELFE national birth cohort, Environment International. Available at: https://www.sciencedirect.com/science/article/pii/S0160412024004677.]

• Herbicides and pesticides synergistically interact at low concentrations in complex mixtures
  Assessing a complex mixture of pesticides at the impacted sites has been challenging for risk assessors for 50 years. The default assumption is that at low concentrations, pesticides interact additively with one another; thus, the risk posed by each component of a complex mixture could be simply added up. The EPA interaction-based hazard index (HIInteraction) modifies this assumption using a binary weight-of-evidence (BINWOE). However, data gaps often preclude HIInteraction use at most sites. This study evaluated these assumptions using the BINWOE to estimate the hazard index (HI) of select pesticide mixtures. The lack of in vivo binary interaction data led us to use a cell line, SH-SY5Y, to obtain the data necessary for the BINWOE approach. In the risk assessment, we considered the most active exposure scenario inhaling a mixture of volatile pesticides from contaminated soil and groundwater. The potential interactions between pesticides in 15 binary mixtures were investigated using the MTT assay in SH-SY5Y cells. Our findings showed that 60% of the binary mixtures elicited synergism (in at least one concentration), 27% displayed antagonism, and 13% showed additive effects in SH-SY5Y cells. Combining human safety data with in vitro interaction data indicated that adults and toddlers were at the highest risk when considering industrial and commercial land use, respectively, compared to other subpopulations. Incorporating interaction data into the risk assessment either increased the risk by up to 20% or decreased the risk by 2%, depending on the mixture. Our results demonstrate the predominant synergistic interactions, even at low concentrations, altered risk characterization at the complex operating site. Most concerning, organochlorine pesticides with the same mechanism of action did not follow dose additivity when evaluated by SH-SY5Y cell lines. Based on our observations, we caution that current HI methods based on additivity assumptions may underestimate the risk of organochlorine mixtures.
  [Alehashem, M. et al. (2024) Herbicides and pesticides synergistically interact at low concentrations in complex mixtures, Chemosphere. Available at: https://www.sciencedirect.com/science/article/pii/S0045653524003242?via%3Dihub. ]
• Maternal exposure to pyrethroid insecticides during pregnancy and respiratory allergy symptoms among children participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE)
  Background
  Pyrethroid insecticides use for indoor residual spraying (IRS) in malaria-endemic areas results in high levels of exposure to local populations. Pyrethroids may cause asthma and respiratory allergies but no prior study has investigated this question in an IRS area.
  Methods
  We measured maternal urinary concentrations of pyrethroid metabolites (cis-DBCA, cis-DCCA, trans-DCCA, 3-PBA) in samples collected at delivery from 751 mothers participating in the Venda Health Examination of Mothers, Babies, and their Environment (VHEMBE), a birth cohort study based in Limpopo, South Africa. At 3.5-year and 5-year follow-up visits, caregivers of 647 and 620 children, respectively, were queried about children's respiratory allergy symptoms based on validated instruments. We applied marginal structural models for repeated outcomes to estimate associations between biomarker concentrations and asthma diagnosis as well as respiratory allergy symptoms at ages 3.5 and 5 years.
  Results
  We found that a10-fold increase in maternal urinary cis-DCCA, trans-DCCA and 3-PBA concentrations were associated with more than a doubling in the risk of doctor-diagnosed asthma (cis-DCCA: RR = 2.1, 95% CI = 1.3, 3.3; trans-DCCA: RR = 2.1, 95% CI = 1.1, 3.9; 3-PBA: RR = 2.4, 95% CI = 1.0, 5.8) and an about 80% increase in the risk of wheezing or whistling in the chest (cis-DCCA: RR = 1.8, 95% CI = 1.1, 3.0; trans-DCCA: RR = 1.7, 95% CI = 1.1, 2.6; 3-PBA: RR = 1.8, 95% CI = 1.0, 3.3) and suspected asthma (cis-DCCA: RR = 1.8, 95% CI = 1.1, 3.1; trans-DCCA: RR = 1.8, 95% CI = 1.1, 2.8). We also observed that higher concentrations of cis-DBCA and 3-PBA were related to increases in the risks of dry cough at night (RR = 3.5, 95% CI = 1.3, 9.5) and seasonal rhinoconjunctivitis (RR = 2.0, 95% CI = 1.1, 3.9), respectively.
  Conclusion
  Maternal exposure to pyrethroids may increase the risk of asthma and other respiratory allergy symptoms among preschool children from an IRS area.
  [Elsiwi, B. et al. (2024) Maternal exposure to pyrethroid insecticides during pregnancy and respiratory allergy symptoms among children participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE), Environmental Research. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0013935123024088. ]
• Pesticide exposure and spontaneous abortion risk: A comprehensive systematic review and meta-analysis
  Backgrounds and aim
  Exposure to pesticides has been proposed as a potential contributor to adverse pregnancy outcomes, possibly through the induction of inflammation, oxidative stress, and disruption of endocrine functions. Nevertheless, the definitive link between prenatal pesticide exposure and the risk of Spontaneous Abortion (SAB) remains uncertain. The objective of this systematic review is to explore and analyze the existing evidence regarding the link between pesticide exposure and the risk of SAB.
  Methods
  A comprehensive systematic literature search was carried out on PubMed, Web of Science, and Scopus from their inception until February 2024 to identify relevant studies exploring the potential link between pesticide exposure and SAB. The frequency of SAB events and the total number of patients in each group were used to calculate the Relative Risk (RR) using the Mantel-Haenszel random-effects model. Heterogeneity among the studies was evaluated by visually inspecting the forest plot and performing the Chi-square test and I2 tests. We also used RevMan version 5.4 for Windows for the analysis. We also used the NIH tool to assess the quality of the included studies.
  Results
  The initial database search yielded 2121 results, with 1525 articles remaining after removing duplicates. After screening, 29 articles were eligible for full-text review, and 18 studies (Four case-control, eleven cohorts, three cross-sectional) were included in the meta-analysis, comprising 439,097 participants. All included studies evaluated the primary outcome, SAB. Most of the included studies were cross-sectional in design, and pesticide exposure was primarily assessed through questionnaires administered to patients. We found that most of our observational studies, precisely 12 out of the total, were deemed fair quality. Four studies were rated poor quality, while only two received a good quality rating. The analysis demonstrated a significant 41 % increase in SAB risk among pregnant women exposed to pesticides compared to pregnant women without exposure to pesticides (RR= 1.41, 95 % CI; [1.10, 1.80], P= 0.006).
  Conclusion
  Our systematic review and meta-analysis revealed a significant 41 % increase in the risk of SAB among pregnant women exposed to pesticides. However, it is essential to acknowledge the limitations of the current evidence: potential publication bias and the inability to establish causality. Moving forward, future research should focus on longitudinal studies, mechanistic insights, and risk reduction strategies. In summary, our findings underscore the urgency of public health measures to protect maternal and fetal health in pesticide-exposed areas. Rigorous research and preventive strategies are crucial to mitigate adverse outcomes.
  [Albadrani, M.S., Aljassim, M.T. and El-Tokhy, A.I. (2024) Pesticide exposure and spontaneous abortion risk: A comprehensive systematic review and meta-analysis, Ecotoxicology and Environmental Safety. Available at: https://www.sciencedirect.com/science/article/pii/S0147651324010765.]
• Pre-Conception And First Trimester Exposure To Pesticides And Associations With Stillbirth
  Associations of pesticide exposures during pre-conception with stillbirth have not been well explored. We linked Arizona pesticide use records with birth certificates from 2006-2020 and estimated associations of living within 500meters of any pyrethroid, organophosphate (OP), or carbamate pesticide applications during a 90 day pre-conception window or the first trimester, with stillbirth. We considered a binary measure of exposure (any exposure), as well as log-pounds and log-acres applied within 500m, in a negative control exposure framework with log-binomial regression. We included 1,237,750 births, 2,290 stillbirths, and 27 pesticides.

  During pre-conception, any exposure to pesticides were associated with stillbirth, including cyfluthrin (RR=1.97, 95% CI 1.17,3.32), zeta-cypermethrin (RR=1.81, 95%CI 1.20, 2.74), organophosphates as a class (RR=1.60, 95%CI 1.16, 2.19), malathion (RR=2.02, 95%CI 1.26, 3.24), carbaryl (RR=6.39, 95%CI 2.07, 19.74), and propamocarb hydrochloride (RR=7.72, 95%CI 1.10, 54.20) . During the first trimester, fenpropathrin (RR=4.36, 95%CI 1.09, 17.50), permethrin (RR=1.57, 95%CI 1.02, 2.42), organophosphates as a class (RR=1.50, 95%CI 1.11, 2.01), acephate (RR=2.31, 95%CI 1.22, 4.40), and formetanate hydrochloride (RR=7.22, 95%CI 1.03, 50.58) were associated with stillbirth. Interpretations were consistent when using continuous measures of pounds or acres of exposure. Pesticide exposures during pre-conception and first trimester may be associated with stillbirth.
  [Furlong, M. et al. (2024) Pre-conception and first trimester exposure to pesticides and associations with stillbirth, American Journal of Epidemiology. Available at: https://academic.oup.com/aje/advance-article-abstract/doi/10.1093/aje/kwae198/7714541.]

• Prenatal and childhood exposure to organophosphate pesticides and functional brain imaging in young adults
  Background
  Early life exposure to organophosphate (OP) pesticides has been linked with poorer neurodevelopment from infancy to adolescence. In our Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort, we previously reported that residential proximity to OP use during pregnancy was associated with altered cortical activation using functional near infrared spectroscopy (fNIRS) in a small subset (n = 95) of participants at age 16 years.

  Methods
  We administered fNIRS to 291 CHAMACOS young adults at the 18-year visit. Using covariate-adjusted regression models, we estimated associations of prenatal and childhood urinary dialkylphosphates (DAPs), non-specific OP metabolites, with cortical activation in the frontal, temporal, and parietal regions of the brain during tasks of executive function and semantic language.

  Results
  There were some suggestive associations for prenatal DAPs with altered activation patterns in both the inferior frontal and inferior parietal lobes of the left hemisphere during a task of cognitive flexibility (β per ten-fold increase in DAPs = 3.37; 95% CI: −0.02, 6.77 and β = 3.43; 95% CI: 0.64, 6.22, respectively) and the inferior and superior frontal pole/dorsolateral prefrontal cortex of the right hemisphere during the letter retrieval working memory task (β = −3.10; 95% CI: −6.43, 0.22 and β = −3.67; 95% CI: −7.94, 0.59, respectively). We did not observe alterations in cortical activation with prenatal DAPs during a semantic language task or with childhood DAPs during any task.

  Discussion
  We observed associations of prenatal OP concentrations with mild alterations in cortical activation during tasks of executive function. Associations with childhood exposure were null. This is reasonably consistent with studies of prenatal OPs and neuropsychological measures of attention and executive function found in CHAMACOS and other birth cohorts.
  [Sagiv, S. et al. (2024) Prenatal and childhood exposure to organophosphate pesticides and functional brain imaging in young adults, Environmental Research. Available at: https://www.sciencedirect.com/science/article/pii/S0013935123025604?via%3Dihub. ]

• Prenatal exposure to per- and polyfluoroalkyl substances, fetal thyroid function, and intelligence quotient at 7 years of age: Findings from the Sheyang Mini Birth Cohort Study
  Background
  Prenatal exposure to per- and polyfluoroalkyl substances (PFASs) influences neurodevelopment. Thyroid homeostasis disruption is thought to be a possible underlying mechanism. However, current epidemiological evidence remains inconclusive.
  Objectives
  This study aimed to explore the effects of prenatal PFAS exposure on the intelligence quotient (IQ) of school-aged children and assess the potential mediating role of fetal thyroid function.
  Methods
  The study included 327 7-year-old children from the Sheyang Mini Birth Cohort Study (SMBCS). Cord serum samples were analyzed for 12 PFAS concentrations and 5 thyroid hormone (TH) levels. IQ was assessed using the Wechsler Intelligence Scale for Children-Chinese Revised (WISC-CR). Generalized linear models (GLM) and Bayesian Kernel Machine Regression (BKMR) were used to evaluate the individual and combined effects of prenatal PFAS exposure on IQ. Additionally, the impact on fetal thyroid function was examined using a GLM, and a mediation analysis was conducted to explore the potential mediating roles of this function.
  Results
  The molar sum concentration of perfluorinated carboxylic acids (ΣPFCA) in cord serum was significantly negatively associated with the performance IQ (PIQ) of 7-year-old children (β = -6.21, 95 % confidence interval [CI]: −12.21, −0.21), with more pronounced associations observed among girls (β = -9.57, 95 % CI: −18.33, −0.81) than in boys. Negative, albeit non-significant, cumulative effects were noted when considering PFAS mixture exposure. Prenatal exposure to perfluorooctanoic acid, perfluorononanoic acid, and perfluorooctanesulfonic acid was positively associated with the total thyroxine/triiodothyronine ratio. However, no evidence supported the mediating role of thyroid function in the link between PFAS exposure and IQ.
  Conclusions
  Increased prenatal exposure to PFASs negatively affected the IQ of school-aged children, whereas fetal thyroid function did not serve as a mediator in this relationship.
  [Zhang, B. et al. (2024) Prenatal exposure to per- and polyfluoroalkyl substances, fetal thyroid function, and intelligence quotient at 7 years of age: Findings from the Sheyang Mini Birth Cohort Study, Environment International. Available at: https://www.sciencedirect.com/science/article/pii/S0160412024003064. ]
• The economic impacts of ecosystem disruptions: Costs from substituting biological pest control
  Biodiversity loss is accelerating, yet we know little about how these ecosystem disruptions affect human well-being. Ecologists have documented both the importance of bats as natural predators of insects as well as their population declines after the emergence of a wildlife disease, resulting in a potential decline in biological pest control. In this work, I study how species interactions can extend beyond an ecosystem and affect agriculture and human health. I find that farmers compensated for bat decline by increasing their insecticide use by 31.1%. The compensatory increase in insecticide use by farmers adversely affected health—human infant mortality increased by 7.9% in the counties that experienced bat die-offs. These findings provide empirical validation to previous theoretical predictions about how ecosystem disruptions can have meaningful social costs.
  [Frank, E. (2024) The economic impacts of ecosystem disruptions: Costs from substituting biological pest control, Science. Available at: https://www.science.org/doi/10.1126/science.adg0344.]
• Thyroid under Attack: The Adverse Impact of Plasticizers, Pesticides, and PFASs on Thyroid Function
  Endocrine-disrupting chemicals (EDCs) are synthetic or natural compounds that interfere with the endocrine system, inducing harmful effects on organisms depending on the dose and period of exposure. Numerous studies have identified concerning amounts of EDCs in environmental and human samples. The thyroid gland is essential for thyroid hormone production and controls several body functions. Several EDCs have been classified as thyroid disruptors, impairing thyroid hormone production, synthesis, metabolism, transport, and/or actions. Notably, thyroid disorders are the second most prevalent endocrine disease worldwide, with incidence increasing significantly in recent years. Some studies have correlated this rise in thyroid dysfunctions and cancers with increased exposure to EDCs. Although many EDCs are linked to thyroid dysfunction, this review focuses on the deleterious effects of plasticizers, organochlorine pesticides, and per- and poly-fluoroalkyl substances on thyroid function. These contaminants are commonly found in food, water, and everyday products. Although the impact of human exposure to these EDCs is controversial, numerous epidemiological, in vivo, and in vitro studies have indicated their harmful effects on thyroid function. Given the critical role of thyroid function and hormone production in growth, metabolism, and development, this review summarizes the consequences of exposure to thyroid disruptors for human health.
  [Rodrigues, V.G. et al. (2024) Thyroid under Attack: The Adverse Impact of Plasticizers, Pesticides, and PFASs on Thyroid Function, Endocrines. Available at: https://www.mdpi.com/2673-396X/5/3/32.]
• Use of Antibiotics in Animal Agriculture: Implications for Pediatrics: Technical Report
  Antimicrobial resistance is a global public health threat. Antimicrobial-resistant infections are on the rise and are associated with increased morbidity, mortality, and health care costs. Infants and children are affected by transmission of antimicrobial-resistant zoonotic pathogens through the food supply, direct contact with animals, environmental pathways, and contact with infected or colonized humans. Although the judicious use of antimicrobial agents is necessary for maintaining the health and welfare of humans and animals, it must be recognized that all use of antimicrobial agents exerts selective pressure that increases the risk of development of resistance. This report describes historical and recent use of antibiotics in animal agriculture, reviews the mechanisms of how such use contributes to development of resistance and can adversely affect child health, and discusses US initiatives to curb unnecessary use of antimicrobial agents in agriculture.
  [Katz, S.E. and Banerjee, R. (2024) Use of Antibiotics in Animal Agriculture: Implications for Pediatrics: Technical Report, Pediatrics. Available at: https://publications.aap.org/pediatrics/article/doi/10.1542/peds.2024-068467/199441/Use-of-Antibiotics-in-Animal-Agriculture. ]
• Agricultural exposures and risk of childhood neuroblastoma: a systematic review and meta-analysis.
  While neuroblastoma accounts for an estimated 8% of childhood cancers, it causes about 15% of childhood cancer deaths in the United States. The role of agricultural exposures in the development of neuroblastoma is unclear. We conducted a systematic review and meta-analysis of studies examining the relationship between agricultural exposures and neuroblastoma. MEDLINE, EMBASE, Scopus, and Google Scholar were searched in February 2022, identifying 742 publications. Seventeen articles met the inclusion criteria; all were published between 1985 and 2020 and included 14 case-control, one cross-sectional, and two cohort studies. Random and fixed effects models were used to calculate summary odds ratios (sORs) and 95% confidence intervals (CIs). An increased odds of developing neuroblastoma with parental exposure to any pesticides (sOR = 1.25, 95% CI: 1.03-1.48; 4 studies), insecticides (sOR = 1.55, 95% CI: 1.19-1.91; 3 studies), and residential exposure to crops/vegetables (sOR = 1.04, 95% CI: 1.01-1.06; 2 studies) was seen. Heterogeneity was low in all analyses, and no publication bias was evident. No significant associations were found with agricultural occupations, herbicides, and agricultural dusts. The studies were limited by exposure measurements and small sample sizes. Further studies are needed to explore mechanisms in the development of neuroblastoma in children with parental agricultural exposures, especially pesticides, and to improve methods of measuring agricultural-related exposures.
  [Hymel, E., Degarege, A., Fritch, J., Farazi, E., Napit, K., Coulter, D., Schmidt, C. and Watanabe-Galloway, S., 2023. Environmental Science and Pollution Research, pp.1-12.]
• Association between persistent organic pollutants in human milk and the infant growth and development throughout the first year postpartum in a cohort from Rio de Janeiro, Brazil.
  Persistent organic pollutants (POPs) are compounds that are recalcitrant and ubiquitous that bioaccumulate in human milk (HM) and can impact infant growth and development. We explore the association between POP concentration in HM at 2-50 days postpartum and infant growth and development trajectory throughout the first year of life. A cohort of 68 healthy adult Brazilian women and their infants were followed from 28 to 35 gestational weeks to 12 months postpartum. HM samples were collected between 2 and 50 days postpartum, and POP concentrations were analyzed using gas chromatography with mass spectrometry. Concentrations of POPs >limit of quantification (LOQ) were defined as presence, and concentrations ≤LOQ as an absence. Growth z-scores were analyzed according to WHO growth charts and infant development scores according to Age & Stages Questionnaires at 1 (n = 66), 6 (n = 50), and 12 months (n = 45). Linear mixed effects (LME) models were used to investigate the association of POPs in HM with infant growth and development. Benjamini-Hochberg (BH) correction for multiple testing was performed to reduce the false discovery ratio. P < 0.1 was considered for models with the interaction between POPs and time/sex. After BH correction, adjusted LME models with time interaction showed (1) a positive association between the presence of β hexachlorocyclohexane and an increase in head circumference-for-age z-score (β = 0.003, P = 0.095); (2) negative associations between total POPs (β = -0.000002, P = 0.10), total organochlorine pesticides (β = -0.000002, P = 0.10), and dichlorodiphenyldichloroethylene concentrations in HM (β = -0.000002, P = 0.10) and fine motor scores. No statistical difference between the sexes was observed. Postnatal exposure to organochlorine pesticides in HM shows a positive association with the trajectory of head circumference-for-age z-score and a negative association with the trajectories of fine motor skills scores. Future studies on POP variation in HM at different postpartum times and their effect on infant growth and development should be encouraged.
  [Figueiredo ACC, Padilha M, Alves-Santos NH, Kac G. 2023. Environ Sci Pollut Res Int.]
• Association of Lifetime Exposure to Glyphosate and Aminomethylphosphonic Acid (AMPA) with Liver Inflammation and Metabolic Syndrome at Young Adulthood: Findings from the CHAMACOS Study
   We aimed to assess whether lifetime exposure to glyphosate and its degradation product, aminomethylphosphonic acid (AMPA), is associated with elevated liver transaminases and metabolic syndrome among young adults. We conducted a prospective cohort study (lowercase italic n equals 480n=480 mother–child dyads) and a nested case–control study (lowercase italic n equals 60n=60 cases with elevated liver transaminases and 91 controls) using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS). We measured glyphosate and AMPA concentrations in urine samples collected during pregnancy and at child ages 5, 14, and 18 y from cases and controls. We calculated glyphosate residue concentrations: [glyphosate plus open parenthesis 1.5 times uppercase a m p a close parenthesisglyphosate + (1.5×AMPA)]. We estimated the amount of agricultural-use glyphosate applied within a 1 kilometer1−km radius of every residence from pregnancy to age 5 y for the full cohort using California Pesticide Use Reporting data. We assessed liver transaminases and metabolic syndrome at 18 y of age. Urinary AMPA at age 5 y was associated with elevated transaminases [relative risk (RR) per two-fold increase equals 1.272−fold increase=1.27, 95% confidence interval (CI): 1.06, 1.53] and metabolic syndrome (relative risk equals 2.07RR=2.07, 95% CI: 1.38, 3.11). Urinary AMPA and glyphosate residues at age 14 y were associated with metabolic syndrome [relative risk equals 1.80RR=1.80 (95% CI: 1.10, 2.93) and relative risk equals 1.88RR=1.88 (95% CI: 1.03, 3.42), respectively]. Overall, a 2-fold increase in urinary AMPA during childhood was associated with a 14% and a 55% increased risk of elevated liver transaminases and metabolic syndrome, respectively. Living near agricultural glyphosate applications during early childhood (birth to 5 y of age) was also associated with metabolic syndrome at age 18 y in the case–control group (relative risk equals 1.53RR=1.53, 95% CI: 1.16, 2.02). Childhood exposure to glyphosate and AMPA may increase risk of liver and cardiometabolic disorders in early adulthood, which could lead to more serious diseases later in life.
  [Eskenazi, B., Gunier, R.B., Rauch, S., Kogut, K., Perito, E.R., Mendez, X., Limbach, C., Holland, N., Bradman, A., Harley, K.G. and Mills, P.J., 2023. Environmental Health Perspectives, 131(3), p.037001.]
• Association of Prenatal Exposure to Organophosphate, Pyrethroid, and Neonicotinoid Insecticides with Child Neurodevelopment at 2 Years of Age: A Prospective Cohort Study.
  Widespread insecticide exposure might be a risk factor for neurodevelopment of our children, but few studies examined the mixture effect of maternal coexposure to organophosphate insecticides (OPPs), pyrethroids (PYRs), and neonicotinoid insecticides (NNIs) during pregnancy on child neurodevelopment, and critical windows of exposure are unknown. We aimed to evaluate the association of prenatal exposure to multiple insecticides with children's neurodevelopment and to identify critical windows of the exposure. Pregnant women were recruited into a prospective birth cohort study in Wuhan, China, from 2014-2017. Eight metabolites of OPPs (mOPPs), three metabolites of PYRs (mPYRs), and nine metabolites of NNIs (mNNIs) were measured in 3,123 urine samples collected at their first, second, and third trimesters. Children's neurodevelopment [mental development index (MDI) and psychomotor development index (PDI)] was assessed using the Bayley Scales of Infant Development at 2 years of age (N=1,041). Multivariate linear regression models, generalized estimating equation models, and weighted quantile sum (WQS) regression were used to estimate the association between the insecticide metabolites and Bayley scores. Potential sex-specific associations were also examined. Single chemical analysis suggested higher urinary concentrations of some insecticide metabolites at the first trimester were significantly associated with lower MDI and PDI scores, and the associations were more prominent among boys. Each 1-unit increase in ln-transformed urinary concentrations of two mOPPs, 3,5,6-trichloro-2-pyridinol and 4-nitrophenol, was associated with a decrease of 3.16 points [95% confidence interval (CI):−5.59,−0.74] and 3.06 points (95% CI:−5.45,−0.68) respectively in boys' MDI scores. Each 1-unit increase in that of trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid (trans-DCCA; an mPYR) was significantly associated with a decrease of 2.24 points (95% CI:−3.89,−0.58) in boys' MDI scores and 1.90 points (95% CI:−3.16,−0.64) in boys' PDI scores, respectively. Significantly positive associations of maternal urinary biomarker concentrations [e.g., dimethyl phosphate (a nonspecific mOPP) and desmethyl-clothianidin (a relatively specific mNNI)] with child neurodevelopment were also observed. Using repeated holdout validation, a 1-quartile increase in the WQS index of the insecticide mixture (in the negative direction) at the first trimester was significantly associated with a decrease of 3.02 points (95% CI:−5.47,−0.57) in MDI scores among the boys, and trans-DCCA contributed the most to the association (18%). Prenatal exposure to higher levels of certain insecticides and their mixture were associated with lower Bayley scores in children, particularly in boys. Early pregnancy may be a sensitive window for such an effect. Future studies are needed to confirm our findings
  [Wang, A., Wan, Y., Mahai, G., Qian, X., Li, Y., Xu, S. and Xia, W., 2023. Environmental Health Perspectives, 131(10), p.107011.]
• Developmental Exposure to DDT Disrupts Transcriptional Regulation of Postnatal Growth and Cell Renewal of Adrenal Medulla
  Dichlorodiphenyltrichloroethane (DDT) is the most widespread persistent pollutant with endocrine-disrupting properties. DDT has been shown to disrupt secretory and morphogenetic processes in the adrenal cortex. The present investigation aimed to evaluate transcriptional regulation of postnatal growth of the adrenal medulla and formation of the pools necessary for self-renewal of medullary cells in rats that developed under low-dose exposure to DDT. The study was performed using male Wistar rats exposed to low doses of o,p'-DDT during prenatal and postnatal development. Light microscopy and histomorphometry revealed diminished medulla growth in the DDT-exposed rats. Evaluation of Ki-67 expression in chromaffin cells found later activation of proliferation indicative of retarded growth of the adrenal medulla. All DDT-exposed rats exhibited a gradual decrease in tyrosine hydroxylase production by adrenal chromaffin cells. Immunohistochemical evaluation of nuclear β-catenin, transcription factor Oct4, and ligand of sonic hedgehog revealed increased expression of all factors after termination of growth in the control rats. The DDT-exposed rats demonstrated diminished increases in Oct4 and sonic hedgehog expression and lower levels of canonical Wnt signaling activation. Thus, developmental exposure to the endocrine disruptor o,p'-DDT alters the transcriptional regulation of morphogenetic processes in the adrenal medulla and evokes a slowdown in its growth and in the formation of a reserve pool of cells capable of dedifferentiation and proliferation that maintain cellular homeostasis in adult adrenals.
  [Yaglova, N.V., Nazimova, S.V., Obernikhin, S.S., Tsomartova, D.A., Yaglov, V.V., Timokhina, E.P., Tsomartova, E.S., Chereshneva, E.V., Ivanova, M.Y. and Lomanovskaya, T.A., 2023. International Journal of Molecular Sciences, 24(3), p.2774.]
• Disparities in Toxic Chemical Exposures and Associated Neurodevelopmental Outcomes: A Scoping Review and Systematic Evidence Map of the Epidemiological Literature.
  Children are routinely exposed to chemicals known or suspected of harming brain development. Targeting Environmental Neuro-Development Risks (Project TENDR), an alliance of more than 50>50 leading scientists, health professionals, and advocates, is working to protect children from these toxic chemicals and pollutants, especially the disproportionate exposures experienced by children from families with low incomes and families of color. This scoping review was initiated to map existing literature on disparities in neurodevelopmental outcomes for U.S. children from population groups who have been historically economically/socially marginalized and exposed to seven exemplar neurotoxicants: combustion-related air pollution (AP), lead (Pb), mercury (Hg), organophosphate pesticides (OPs), phthalates (Phth), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs). Systematic literature searches for the seven exemplar chemicals, informed by the Population, Exposure, Comparator, Outcome (PECO) framework, were conducted through 18 November 2022, using PubMed, CINAHL Plus (EBSCO), GreenFILE (EBSCO), and Web of Science sources. We examined these studies regarding authors’ conceptualization and operationalization of race, ethnicity, and other indicators of sociodemographic and socioeconomic disadvantage; whether studies presented data on exposure and outcome disparities and the patterns of those disparities; and the evidence of effect modification by or interaction with race and ethnicity. Two hundred twelve individual studies met the search criteria and were reviewed, resulting in 218 studies or investigations being included in this review. AP and Pb were the most commonly studied exposures. The most frequently identified neurodevelopmental outcomes were cognitive and behavioral/psychological. Approximately a third (74 studies) reported investigations of interactions or effect modification with 69% (51 of 74 studies) reporting the presence of interactions or effect modification. However, less than half of the studies presented data on disparities in the outcome or the exposure, and fewer conducted formal tests of heterogeneity. Ninety-two percent of the 165 articles that examined race and ethnicity did not provide an explanation of their constructs for these variables, creating an incomplete picture. As a whole, the studies we reviewed indicated a complex story about how racial and ethnic minority and low-income children may be disproportionately harmed by exposures to neurotoxicants, and this has implications for targeting interventions, policy change, and other necessary investments to eliminate these health disparities. We provide recommendations on improving environmental epidemiological studies on environmental health disparities. To achieve environmental justice and health equity, we recommend concomitant strategies to eradicate both neurotoxic chemical exposures and systems that perpetuate social inequities.
  [Payne-Sturges, D.C., Taiwo, T.K., Ellickson, K., Mullen, H., Tchangalova, N., Anderko, L., Chen, A. and Swanson, M., 2023. Environmental Health Perspectives, 131(9), p.096001.]
• Effects of pesticide exposure on oxidative stress and DNA methylation urinary biomarkers in Czech adults and children from the CELSPAC-specimen cohort
  Current-use pesticide (CUP) exposure occurs mainly through diet and environmental application in both agricultural and urban settings. While pesticide exposure has been associated with many adverse health outcomes, the intermediary molecular mechanisms are still not completely elucidated. Among others, their roles in epigenetics (DNA methylation) and DNA damage due to oxidative stress are presumed. Scientific evidence on urinary biomarkers of such body response in general population is limited, especially in children.

  A total of 440 urine samples (n = 110 parent-child pairs) were collected during the winter and summer seasons in order to describe levels of overall DNA methylation (5-mC, 5-mdC, 5-hmdC, 7-mG, 3-mA) and oxidative stress (8-OHdG) biomarkers and investigate their possible associations with metabolites of pyrethroids (3-PBA, t/c-DCCA), chlorpyrifos (TCPY), and tebuconazole (TEB-OH). Linear mixed-effects models accounting for intraindividual and intrahousehold correlations were utilized. We applied false discovery rate procedure to account for multiplicity and adjusted for potential confounding variables.

  Higher urinary levels of most biological response biomarkers were measured in winter samples. In adjusted repeated measures models, interquartile range (IQR) increases in pyrethroid metabolites were associated with higher oxidative stress. t/c-DCCA and TCPY were associated with higher urinary levels of cytosine methylation biomarkers (5-mC and/or 5-mdC). The most robust association was observed for tebuconazole metabolite with 3-mA (−15.1% change per IQR increase, 95% CI = −23.6, −5.69) suggesting a role of this pesticide in reduced demethylation processes through possible DNA glycosylase inhibition.

  Our results indicate an urgent need to extend the range of analyzed environmental chemicals such as azole pesticides (e.g. prothioconazole) in human biomonitoring studies. This is the first study to report urinary DNA methylation biomarkers in children and associations between CUP metabolites and a comprehensive set of biomarkers including methylated and oxidized DNA alterations. Observed associations warrant further large-scale research of these biomarkers and environmental pollutants including CUPs.
  [Janoš, T. et al. (2023) Effects of pesticide exposure on oxidative stress and DNA methylation urinary biomarkers in Czech adults and children from the CELSPAC-specimen cohort, Environmental Research. Available at: https://www.sciencedirect.com/science/article/pii/S0013935123001603?via%3Dihub. ]

• Endocrine Disruptor Chemicals and Children’s Health
  We are all exposed to endocrine-disrupting chemicals (EDCs) starting from embryonic life. The fetus and child set up crucial developmental processes allowing adaptation to the environment throughout life: they are extremely sensitive to very low doses of hormones and EDCs because they are developing organisms. Considering the developmental origin of well-being and diseases, every adult organism expresses consequences of the environment in which it developed. The molecular mechanisms through which the main EDCs manifest their effects and their potential association with endocrine disorders, such as diabetes, obesity, thyroid disease and alteration of adrenal hormones, will be reviewed here. Despite 40 years having passed since the first study on EDCs, little is yet known about them; therefore, our purpose is to take stock of the situation to establish a starting point for further studies. Since there is plenty of evidence showing that exposure to EDCs may adversely impact the health of adults and children through altered endocrine function—suggesting their link to endocrinopathies—it is essential in this context to bear in mind what is already known about endocrine disruptors and to deepen our knowledge to establish rules of conduct aimed at limiting exposure to EDCs’ negative effects. Considering that during the COVID-19 pandemic an increase in endocrine disruptor effects has been reported, it will also be useful to address this new phenomenon for better understanding its basis and limiting its consequences.
  [Di Pietro, G., Forcucci, F. and Chiarelli, F. (2023) Endocrine Disruptor Chemicals and Children’s Health, International Journal of Molecular Science. Available at: https://www.mdpi.com/1422-0067/24/3/2671. ]
• Endocrine-Disrupting Chemicals and Persistent Organic Pollutants in Infant Formulas and Baby Food: Legislation and Risk Assessments
  Human milk is the healthiest option for newborns, although, under specific circumstances, infant formula is a precious alternative for feeding the baby. Except for the nutritional content, infant formulas and baby food must be pollutant-free. Thus, their composition is controlled by continuous monitoring and regulated by establishing upper limits and guideline values for safe exposure. Legislation differs worldwide, although there are standard policies and strategies for protecting vulnerable infants. This work presents current regulations and directives for restricting endocrine-disrupting chemicals and persistent organic pollutants in infant formulas. Risk assessment studies, which are limited, are necessary to depict exposure variations and assess the health risks for infants from dietary exposure to pollutants.
  [Hatzidaki, E., Pagkalou, M., Katsikantami, I., Vakonaki, E., Kavvalakis, M., Tsatsakis, A.M. and Tzatzarakis, M.N., 2023. Foods, 12(8), p.1697.]
• Follicular DNA Damage and Pesticide Exposure Among Latinx Children in Rural and Urban Communities
  The intersectional risks of children in United States immigrant communities include environmental exposures. Pesticide exposures and their biological outcomes are not well characterized in this population group. We assessed pesticide exposure and related these exposures to DNA double-strand breaks (DSBs) in Latinx children from rural, farmworker families (FW; N = 30) and from urban, non-farmworker families (NFW; N = 15) living in North Carolina. DSBs were quantified in hair follicular cells by immunostaining of 53BP1, and exposure to 72 pesticides and pesticide degradation products were determined using silicone wristbands. Cholinesterase activity was measured in blood samples. DSB frequencies were higher in FW compared to NFW children. Seasonal effects were detected in the FW group, with highest DNA damage levels in April–June and lowest levels in October–November. Acetylcholinesterase depression had the same seasonality and correlated with follicular DNA damage. Organophosphate pesticides were more frequently detected in FW than in NFW children. Participants with organophosphate detections had increased follicular DNA damage compared to participants without organophosphate detection. Follicular DNA damage did not correlate with organochlorine or pyrethroid detections and was not associated with the total number of pesticides detected in the wristbands. These results point to rural disparities in pesticide exposures and their outcomes in children from vulnerable immigrant communities. They suggest that among the different classes of pesticides, organophosphates have the strongest genotoxic effects. Assessing pesticide exposures and their consequences at the individual level is key to environmental surveillance programs. To this end, the minimally invasive combined approach used here is particularly well suited for children.
  [Lepetit, C. et al. (2023) Follicular DNA Damage and Pesticide Exposure Among Latinx Children in Rural and Urban Communities, Exposure and Health. Available at: https://link.springer.com/article/10.1007/s12403-023-00609-1.]
• Infantile Internal and External Exposure to Neonicotinoid Insecticides: A Comparison of Levels across Various Sources
  Little is known about exposure of infants to neonicotinoid insecticides (NEOs). In this study, concentrations of six parent NEOs (p-NEOs) and N-desmethyl-acetamiprid (N-dm-ACE) were measured in urine and whole blood samples from infants, in addition to breast milk, infant formula, and tap water collected in South China. The p-NEO with the highest median concentration in urine (0.25 ng/mL) and blood (1.30) samples was dinotefuran (DIN), while imidacloprid (IMI) was abundant in breast milk (median: 0.27 ng/mL), infant formula (0.22), and tap water (0.028). The older infants (181–360 days) might face higher NEO and N-dm-ACE exposure than younger infants (0–180 days). Blood samples contained a significantly (p < 0.01) higher median concentration of ∑6p-NEOs (2.03 ng/mL) than that of urine samples (0.41), similar to acetamiprid (ACE), IMI, thiacloprid (THD), DIN, and N-dm-ACE, suggesting that NEOs readily partition into blood. Furthermore, breast-fed infants tend to have higher exposure levels than formula-fed infants. Infant formula prepared with tap water augmented the daily intake of ∑NEOs. The external sources contributed 80% of the total dose to IMI and clothianidin (CLO) exposure, while other unknown sources contributed to ACE, THD, and DIN exposure in infants. To the best of our knowledge, this is the first study to assess levels and sources of infantile exposure to NEOs through internal and external exposure assessment.
  [Zhang, H., Wang, Y., Zhu, H., Lu, S., Wang, Y., Xue, J., Zhang, T., Kannan, K. and Sun, H., 2023. Environmental Science & Technology, 57(13), pp.5358-5367.]
• Pesticide exposure and risk of Central Nervous System tumors in children: a systematic review with meta-analysis.
  Central Nervous System (CNS) tumors represent more than half of all childhood malignant neoplasms. The aim of this study was to determine the relationship between environmental exposure to pesticides and the development of CNS tumors in children. We conducted a systematic review of the literature in the PubMed/MEDILINE, Embase, Web of Science, Scopus, and CINAHL databases. The inclusion criteria were cohort and case-control studies investigating the association between exposure to pesticides and CNS tumors (all histological types included in group III of the WHO Classification of Childhood Cancer) in children aged 0-14 years. The meta-analysis was performed using a random effects model and the Mantel-Haenszel method. Strength of association was measured using odds ratios (OR). The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under identification number CRD42021209354. The search identified 1,158 studies, 14 of which were included in the review. There was evidence of an association between the development of astrocytomas and exposure to all classes of pesticides (OR 1.50; 95%CI 1.15-1.96; p=0.03). The synthesis of the evidence pointed to a relationship between exposure to pesticides and some histological types of CNS tumors in childhood.
  [Mota, A.L.C., Barbosa, I.M., Rodrigues, A.B., Chaves, E.M.C. and Almeida, P.C.D., 2023. Ciência & Saúde Coletiva, 28, pp.2583-2594.]
• Prenatal and childhood chlordecone exposure, cognitive abilities and problem behaviors in 7-year-old children: the TIMOUN mother-child cohort in Guadeloupe
  Background: Chlordecone is a highly persistent organochlorine insecticide that was intensively used in banana fields in the French West Indies, resulting in a widespread contamination. Neurotoxicity of acute exposures in adults is well recognized, and empirical data suggests that prenatal exposure affects visual and fine motor developments during infancy and childhood, with greater susceptibility in boys.

  Objective: To assess the associations between pre- and postnatal exposures to chlordecone and cognitive and behavioral functions in school-aged children from Guadeloupe.

  Methods: We examined 576 children from the TIMOUN mother-child cohort in Guadeloupe at 7 years of age. Concentrations of chlordecone and other environmental contaminants were measured in cord- and children's blood at age 7 years. Cognitive abilities of children were assessed with the Wechsler Intelligence Scale for Children-IV (WISC-IV), and externalizing and internalizing problem behaviors documented with the Strengths and Difficulties Questionnaire (SDQ) completed by the child's mother. We estimated covariate-adjusted associations between cord- and 7-years chlordecone concentrations and child outcomes using structural equations modeling, and tested effect modification by sex.

  Results: Geometric means of blood chlordecone concentrations were 0.13 µg/L in cord blood and 0.06 µg/L in children's blood at age 7 years. A twofold increase in cord blood concentrations was associated with 0.05 standard deviation (SD) (95% Confidence Interval [CI]: 0.0, 0.10) higher internalizing problem scores, whereas 7-years chlordecone concentrations were associated with lower Full-Scale IQ scores (FSIQ) and greater externalized behavioral problem scores. A twofold increase in 7-year chlordecone concentrations was associated with a decrease of 0.67 point (95% CI: -1.13, -0.22) on FSIQ and an increase of 0.04 SD (95% CI: 0.0, 0.07) on externalizing problems. These associations with Cognitive abilities were driven by decreases in perceptive reasoning, working memory and verbal comprehension. Associations between 7-year exposure and perceptive reasoning, working memory, and the FSIQ were stronger in boys, whereas cord blood and child blood associations with internalizing problems were stronger in girls.

  Conclusions: These results suggests that cognitive abilities and externalizing behavior problems at school age are impaired by childhood, but not in utero, exposure to chlordecone, and that prenatal exposure is related to greater internalizing behavioral problems.
  [Oulhote, Y., Rouget, F., Michineau, L., Monfort, C., Desrochers-Couture, M., Thomé, J.P., Kadhel, P., Multigner, L., Cordier, S. and Muckle, G., 2023. Environmental Health, 22(1), pp.1-13.]

• Prenatal exposure to pesticides and domain-specific neurodevelopment at age 12 and 18 months in Nanjing, China.
  The extensive usage of pesticides has led to a ubiquitous exposure in the Chinese general population. Previous studies have demonstrated developmental neurotoxicity associated with prenatal exposure to pesticides. We aimed to delineate the landscape of internal pesticides exposure levels from pregnant women’s blood serum samples, and to identify the specific pesticides associated with the domain-specific neuropsychological development. Participants included 710 mother-child pairs in a prospective cohort study initiated and maintained in Nanjing Maternity and Child Health Care Hospital. Maternal spot blood samples were collected at enrollment. Leveraging on an accurate, sensitive and reproducible analysis method for 88 pesticides, a total of 49 pesticides were measured simultaneously using gas chromatography-triple quadrupole tandem mass spectrometry (GC–MS/MS). After implementing a strict quality control (QC) management, 29 pesticides were reported. We assessed neuropsychological development in 12-month-old (n = 172) and 18-month-old (n = 138) children using the Ages and Stages Questionnaire (ASQ), Third Edition. Negative binomial regression models were used to investigate the associations between prenatal exposure to pesticides and ASQ domain-specific scores at age 12 and 18 months. Restricted cubic spline (RCS) analysis and generalized additive models (GAMs) were fitted to evaluate non-linear patterns. Longitudinal models with generalized estimating equations (GEE) were conducted to account for correlations among repeated observations. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were applied to examining the joint effect of the mixture of pesticides. Several sensitivity analyses were performed to assess the robustness of the results. We observed that prenatal exposure to chlorpyrifos was significantly associated with a 4 % decrease in the ASQ communication scores both at age 12 months (RR, 0.96; 95 % CI, 0.94–0.98; P < 0.001) and 18 months (RR, 0.96; 95 % CI, 0.93–0.99; P < 0.01). In the ASQ gross motor domain, higher concentrations of mirex (RR, 0.96; 95 % CI, 0.94–0.99, P < 0.01 for 12-month-old children; RR, 0.98; 95 % CI, 0.97–1.00, P = 0.01 for 18-month-old children), and atrazine (RR, 0.97; 95 % CI, 0.95–0.99, P < 0.01 for 12-month-old children; RR, 0.99; 95 % CI, 0.97–1.00, P = 0.03 for 18-month-old children) were associated with decreased scores. In the ASQ fine motor domain, higher concentrations of mirex (RR, 0.98; 95 % CI, 0.96–1.00, P = 0.04 for 12-month-old children; RR, 0.98; 95 % CI, 0.96–0.99, P < 0.01 for 18-month-old children), atrazine (RR, 0.97; 95 % CI, 0.95–0.99, P < 0.001 for 12-month-old children; RR, 0.98; 95 % CI, 0.97–1.00, P = 0.01 for 18-month-old children), and dimethipin (RR, 0.94; 95 % CI, 0.89–1.00, P = 0.04 for 12-month-old children; RR, 0.93; 95 % CI, 0.88–0.98, P < 0.01 for 18-month-old children) were associated with decreased scores. The associations were not modified by child sex. There was no evidence of statistically significant nonlinear relationships between pesticides exposure and RRs of delayed neurodevelopment (P nonlinearity > 0.05). Longitudinal analyses implicated the consistent findings. This study gave an integrated picture of pesticides exposure in Chinese pregnant women. We found significant inverse associations between prenatal exposure to chlorpyrifos, mirex, atrazine, dimethipin and the domain-specific neuropsychological development (i.e., communication, gross motor and fine motor) of children at 12 and 18 months of age. These findings identified specific pesticides with high risk of neurotoxicity, and highlighted the need for priority regulation of them.
  [Wei, H., Zhang, X., Yang, X., Yu, Q., Deng, S., Guan, Q., Chen, D., Zhang, M., Gao, B., Xu, S. and Xia, Y., 2023. Environment International, 173, p.107814.]
• Respiratory and allergic outcomes among 5-year-old children exposed to pesticides
  Background Little is known about the effects of pesticides on children’s respiratory and allergic outcomes. We evaluated associations of prenatal and current pesticide exposures with respiratory and allergic outcomes in children from the Infants’ Environmental Health Study in Costa Rica.

  Methods Among 5-year-old children (n=303), we measured prenatal and current specific gravity-corrected urinary metabolite concentrations of insecticides (chlorpyrifos, pyrethroids), fungicides (mancozeb, pyrimethanil, thiabendazole) and 2,4-D. We collected information from caregivers on respiratory (ever doctor-diagnosed asthma and lower respiratory tract infections (LRTI), wheeze and cough during last 12 months) and allergic (nasal allergies, itchy rash, ever eczema) outcomes. We fitted separate multivariable logistic regression models for high (≥75th percentile (P75)) vs low (<P75) metabolite concentrations with respiratory and allergic outcomes. We also ran models including metabolite concentrations as continuous exposure variables.

  Results Children’s respiratory outcomes were common (39% cough, 20% wheeze, 12% asthma, 5% LRTI). High current pyrethroid metabolite concentrations (∑pyrethroids) were associated with wheeze (OR=2.37, 95% CI 1.28 to 4.34), itchy rash (OR=2.74, 95% CI 1.33 to 5.60), doctor-diagnosed asthma and LRTI. High current ethylene thiourea (ETU) (specific metabolite of mancozeb) was somewhat associated with LRTI (OR=2.09, 95% CI 0.68 to 6.02). We obtained similar results when modelling ∑pyrethroids and ETU as continuous variables. We saw inconsistent or null associations for other pesticide exposures and health outcomes.

  Conclusions Current pyrethroid exposure may affect children’s respiratory and allergic health at 5 years of age. Current mancozeb exposure might contribute to LRTI. These findings are important as pyrethroids are broadly used in home environments and agriculture and mancozeb in agriculture.
  [Islam, J.Y. et al. (2023) Respiratory and allergic outcomes among 5-year-old children exposed to pesticides, Thorax. Available at: https://thorax.bmj.com/content/78/1/41.abstract. ]

• The association of prenatal phthalates, organophosphorus pesticides, and organophosphate esters with early child language ability in Norway.
  This study examines the influence of prenatal exposure to phthalates, organophosphate esters, and organophosphorous pesticides, on children's language ability from toddlerhood to the preschool period. This study includes 299 mother-child dyads from Norway in the Norwegian Mother, Father and Child Cohort Study (MoBa). Prenatal exposure to chemicals were assessed at 17 weeks’ gestation, and child language skills were assessed at 18 months using the Ages and Stages Questionnaire communication subscale and at preschool age using the Child Development Inventory. We ran two structural equation models to examine the simultaneous influences of chemical exposures on parent-reported and teacher-reported child language ability. Prenatal organophosphorous pesticides were negatively associated with preschool language ability through language ability at 18 months. Additionally, there was a negative association between low molecular weight phthalates and teacher-reported preschool language ability. There was no effect of prenatal organophosphate esters on child language ability at either 18 months or preschool age. This study adds to the literature on prenatal exposure to chemicals and neurodevelopment and highlights the importance of developmental pathways in early childhood.
  [Ramos, A.M., Herring, A.H., Villanger, G.D., Thomsen, C., Sakhi, A.K., Cequier, E., Aase, H. and Engel, S.M., 2023. Environmental Research, 225, p.115508.]
• Additives in Children's Nutrition-A Review of Current Events
  Additives are defined as substances added to food with the aim of preserving and improving safety, freshness, taste, texture, or appearance. While indirect additives can be found in traces in food and come from materials used for packaging, storage, and technological processing of food, direct additives are added to food with a special purpose (canning). The use of additives is justified if it is in accordance with legal regulations and does not pose a health or danger to consumers in the prescribed concentration. However, due to the specificity of the child's metabolic system, there is a greater risk that the negative effects of the additive will manifest. Considering the importance of the potential negative impact of additives on children's health and the increased interest in the control and monitoring of additives in food for children, we have reviewed the latest available literature available through PubMed, Scopus, and Google Scholar. Expert data were taken from publicly available documents published from January 2010 to April 2022 by internationally recognized professional organizations. It was found that the most frequently present additives in the food consumed by children are bisphenols, phthalates, perfluoroalkyl chemicals, perchlorates, pesticides, nitrates and nitrites, artificial food colors, monosodium glutamate, and aspartame. Increasing literacy about the presence and potential risk through continuous education of parents and young people as well as active monitoring of newly registered additives and harmonization of existing legal regulations by competent authorities can significantly prevent the unwanted effects of additives on children's health.
  [Savin, M., Vrkatić, A., Dedić, D., Vlaški, T., Vorgučin, I., Bjelanović, J. and Jevtic, M., 2022. International Journal of Environmental Research and Public Health, 19(20), p.13452.]
• Association between maternal insecticide use and otitis media in one-year-old children in the Japan Environment and Children’s Study
  Otitis media (OM) is common among young children and is related to hearing loss. We investigated the association between maternal insecticide use, from conception to the first and second/third trimesters, and OM events in children in the first year of age. Data from Japan Environment and Children's Study were used in this prospective cohort study. Characteristics of patients with and without history of OM during the first year of age were compared. The association between history of OM in the first year and insecticide use was evaluated using logistic regression analysis. The study enrolled 98,255 infants. There was no significant difference in the frequency of insecticide use between groups. Insecticide use of more than once a week from conception to the first trimester significantly increased the occurrence of OM in children in the first year (odds ratio [OR] = 1.30, 95% confidence interval [CI] 1.01–1.67). The association between OM in the first year and insecticide use from conception to the first trimester was only significant in the group without daycare attendance (OR 1.76, 95% CI 1.30–2.38). Maternal insecticide use more than once a week from conception to the first trimester significantly increased OM risk in offspring without daycare attendance.
  [Utsunomiya, T., Taniguchi, N., Taniguchi, Y., Fujino, T., Tanaka, Y., Hasunuma, H., Okuda, M., Shima, M. and Takeshima, Y. Scientific Reports, 12(1), pp.1-8.]
• Effects of prenatal and infant daily exposure to pyrethroid pesticides on the language development of 2-year-old toddlers: A prospective cohort study in rural Yunnan, China
  Prenatal and infant daily exposures to pyrethroid pesticides (PYRs), used in the elimination of harmful organisms in the family environment and agricultural activities, may have an impact on children's language development. To determine the impacts of prenatal and infant PYRs exposure on 2-year-old toddlers' language development. From January 2016 to December 2018, women in the third trimester of pregnancy, in Yunnan rural area, China, were recruited, and the development of their newborns was observed from birth till the age of two. We examined three PYRs metabolites: 3-phenoxybenzoic acid (3PBA), 4-fluoro-3-phenoxybenzoic acid (4F3PBA), and cis-2,2dibromovinyl-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA) in urine samples collected from women in the third trimester of pregnancy and their infants of 6-8 months after birth, and assessed language development of 2-year-old toddlers by the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Generalized linear models were used to analyze the impacts of exposure to PYRs on 2-year-old toddlers' language development. The median concentrations of 3PBA, 4F3PBA and DBCA creatinine-adjusted were 0.21, 0.19, and 0.15 μg/g in pregnancy, and 0.25, 0.72, and
  [Chen, S., Xiao, X., Qi, Z., Chen, L., Chen, Y., Xu, L., Zhang, L., Song, X. and Li, Y. NeuroToxicology.]
• Exposure to Contemporary and Emerging Chemicals in Commerce among Pregnant Women in the United States: The Environmental influences on Child Health Outcome (ECHO) Program
  Prenatal chemical exposures can influence maternal and child health; however, few industrial chemicals are routinely biomonitored. We assessed an extensive panel of contemporary and emerging chemicals in 171 pregnant women across the United States (U.S.) and Puerto Rico in the Environmental influences on Child Health Outcomes (ECHO) Program. We simultaneously measured urinary concentrations of 89 analytes (103 total chemicals representing 73 parent compounds) in nine chemical groups: bactericides, benzophenones, bisphenols, fungicides and herbicides, insecticides, organophosphate esters (OPEs), parabens, phthalates/alternative plasticizers, and polycyclic aromatic hydrocarbons (PAHs). We estimated associations of creatinine-adjusted concentrations with sociodemographic and specimen characteristics. Among our diverse prenatal population (60% non-Hispanic Black or Hispanic), we detected 73 of 89 analytes in ≥1 participant and 36 in >50% of participants. Five analytes not currently included in the U.S. biomonitoring were detected in ≥90% of samples: benzophenone-1, thiamethoxam, mono-2-(propyl-6-carboxy-hexyl) phthalate, monocarboxy isooctyl phthalate, and monohydroxy-iso-decyl phthalate. Many analyte concentrations were higher among women of Hispanic ethnicity compared to those of non-Hispanic White women. Concentrations of certain chemicals decreased with the calendar year, whereas concentrations of their replacements increased. Our largest study to date identified widespread exposures to prevalent and understudied chemicals in a diverse sample of pregnant women in the U.S.
  [Buckley, J.P., Kuiper, J.R., Bennett, D.H., Barrett, E.S., Bastain, T., Breton, C.V., Chinthakindi, S., Dunlop, A.L., Farzan, S.F., Herbstman, J.B. and Karagas, M.R., Environmental Science & Technology.]
• Gestational Exposure to Cyfluthrin through Endoplasmic Reticulum (ER) Stress—Mediated PERK Signaling Pathway Impairs Placental Development
  Cyfluthrin, a typical type II pyrethroid pesticide, is widely used in house hygiene and agricultural pest control. Several epidemiological investigations have found that maternal pyrethroid exposure is connected to adverse pregnancy outcomes. However, the underlying mechanisms remain to be elucidated. Thus, we evaluated the effect of cyfluthrin exposure during pregnancy on placenta development in vivo. In the current study, Pregnant SD rats were randomly divided into four groups and administered 6.25, 12.5, and 25 mg/kg body weight cyfluthrin or an equivalent volume of corn oil by gavage from GD0 to GD19. The results have shown that gestational exposure to cyfluthrin exerted no effect on the fetal birth defect, survival to PND4, or fetal resorption and death. However, live fetuses and implantation sites significantly decreased in the high-dose cyfluthrin-treated group. Moreover, a significant reduction in placenta weight and diameter was observed in rats. Correspondingly, the fetal weight and crown-rump length from dams exposed to cyfluthrin were reduced. Cyfluthrin-treat groups, the total area of the placenta, spongiotrophoblast area, and labyrinth area had abnormal changes. Meanwhile, the area of blood sinusoid and CD34-positive blood vessel numbers in the placenta were considerably reduced, as well as abnormal expression of placental pro-angiogenic and anti-angiogenic factors in dams exposed to cyfluthrin. Further observation by transmission electron microscopy revealed significant changes in the ultrastructure of the medium-dose and high-dose groups. Additional experiments showed gestational exposure to cyfluthrin inhibited proliferation and induced apoptosis of placentas, as decreased PCNA-positive cells and increased TUNEL-positive cells. Furthermore, western blot and qPCR analysis revealed that gestational exposure to medium-dose and high-dose cyfluthrin increased the expression of GRP78, and three downstream mRNA and proteins (p-eIF2α, ATF4, and CHOP) of the PERK signaling, indicating that endoplasmic reticulum (ER) stress-mediated PERK/eIF2α/ATF4/CHOP signaling pathway in rat placentas was activated. Our study demonstrated that gestational exposure to cyfluthrin leads to placental developmental disorder, which might be associated with ER stress-mediated PERK signaling pathway.
  [Ni, W. et al. (2022) Gestational exposure to cyfluthrin through endoplasmic reticulum (ER) stress-mediated perk signaling pathway impairs placental development, Toxics. Available at: https://www.mdpi.com/2305-6304/10/12/733.]
• Glyphosate exposure in early pregnancy and reduced fetal growth: a prospective observational study of high-risk pregnancies
  Prenatal glyphosate (GLY) exposure is associated with adverse reproductive outcomes in animal studies. Little is known about the effects of GLY exposure during pregnancy in the human population. This study aims to establish baseline urine GLY levels in a high-risk and racially diverse pregnancy cohort and to assess the relationship between prenatal GLY exposure and fetal development and birth outcomes. Random first trimester urine specimens were collected from high risk pregnant women between 2013 and 2016 as part of the Indiana Pregnancy Environmental Exposures Study (PEES). Demographic and clinical data were abstracted from mother and infant medical records. Urine glyphosate levels were measured as a proxy for GLY exposure and quantified using liquid chromatography-tandem mass spectrometry. Primary outcome variables included gestation-adjusted birth weight percentile (BWT%ile) and neonatal intensive care unit (NICU) admission. Relationships between primary outcome variables and GLY exposure were assessed using univariate and multivariate linear and logistic regression models. Urine GLY levels above the limit of detection (0.1 ng/mL) were found in 186 of 187 (99%) pregnant women. Further analyses were limited to 155 pregnant women with singleton live births. The mean age of participants was 29 years, and the majority were non-Hispanic white (70%) or non-Hispanic Black (21%). The mean (± SD) urine GLY level was 3.33 ± 1.67 ng/mL. Newborn BWT%iles were negatively related to GLY (adjusted slope ± SE = -0.032 + 0.014, p = 0.023). Infants born to women living outside of Indiana’s large central metropolitan area were more likely to have a lower BWT%ile associated with mother’s first trimester GLY levels (slope ± SE = -0.064 ± 0.024, p = 0.007). The adjusted odds ratio for NICU admission and maternal GLY levels was 1.16 (95% CI: 0.90, 1.67, p = 0.233). GLY was found in 99% of pregnant women in this Midwestern cohort. Higher maternal GLY levels in the first trimester were associated with lower BWT%iles and higher NICU admission risk. The results warrant further investigation on the effects of GLY exposure in human pregnancies in larger population studies.
  [Gerona, R.R., Reiter, J.L., Zakharevich, I., Proctor, C., Ying, J., Mesnage, R., Antoniou, M. and Winchester, P.D., 2022. Environmental Health, 21(1), pp.1-12.]
• Prenatal ambient pesticide exposure and childhood retinoblastoma
  Retinoblastoma is a rare tumor of the retina, most commonly found in young children. Due to the rarity of this childhood cancer, few studies have been able to examine prenatal pesticide exposure as a risk factor. To examine the relationship between childhood retinoblastoma and prenatal exposure to pesticides through residential proximity to agricultural pesticide applications. We conducted a population-based case-control study using cases aged 5 and younger identified from the California Cancer Registry, and controls randomly selected from California birth certificates. Frequency matching cases to controls by age resulted in 221 cases of unilateral retinoblastoma and 114 cases of bilateral retinoblastoma, totaling 335 cases and 123,166 controls. Based on addresses from birth certificates we employed Pesticide Use Reports and land use information within a geographic information system approach to individually assess exposures to specific pesticides within 4000 m of the residence reported on birth certificates. The associations between retinoblastoma (all types combined and stratified by laterality) and individual pesticides were expressed as odds ratios estimates obtained from unconditional logistic regression models including a single pesticide, and from a hierarchical logistic regression model including all pesticides. We found that exposures to acephate (OR: 1.70, 95% CI: 1.20, 2.41) and bromacil (OR: 1.87, 95% CI: 1.07, 3.26) were associated with increased risk for unilateral retinoblastoma. In addition to acephate, we found that pymetrozine (OR: 1.45, 95% CI: 1.00, 2.08) and kresoxim-methyl (OR: 1.60, 95% CI: 1.00, 2.56) were associated with retinoblastoma (all types combined). Our findings suggest that certain types of prenatal ambient pesticide exposure from residing near agricultural fields may play a role in the development of childhood retinoblastoma.
  [Thompson, S., Ritz, B., Cockburn, M. and Heck, J.E., 2022. International Journal of Hygiene and Environmental Health, 245, p.114025.]
• Prenatal ambient pesticide exposure and childhood retinoblastoma
  Retinoblastoma is a rare tumor of the retina, most commonly found in young children. Due to the rarity of this childhood cancer, few studies have been able to examine prenatal pesticide exposure as a risk factor. To examine the relationship between childhood retinoblastoma and prenatal exposure to pesticides through residential proximity to agricultural pesticide applications. We conducted a population-based case-control study using cases aged 5 and younger identified from the California Cancer Registry, and controls randomly selected from California birth certificates. Frequency matching cases to controls by age resulted in 221 cases of unilateral retinoblastoma and 114 cases of bilateral retinoblastoma, totaling 335 cases and 123,166 controls. Based on addresses from birth certificates we employed Pesticide Use Reports and land use information within a geographic information system approach to individually assess exposures to specific pesticides within 4000 m of the residence reported on birth certificates. The associations between retinoblastoma (all types combined and stratified by laterality) and individual pesticides were expressed as odds ratios estimates obtained from unconditional logistic regression models including a single pesticide, and from a hierarchical logistic regression model including all pesticides. We found that exposures to acephate (OR: 1.70, 95% CI: 1.20, 2.41) and bromacil (OR: 1.87, 95% CI: 1.07, 3.26) were associated with increased risk for unilateral retinoblastoma. In addition to acephate, we found that pymetrozine (OR: 1.45, 95% CI: 1.00, 2.08) and kresoxim-methyl (OR: 1.60, 95% CI: 1.00, 2.56) were associated with retinoblastoma (all types combined). Our findings suggest that certain types of prenatal ambient pesticide exposure from residing near agricultural fields may play a role in the development of childhood retinoblastoma.
  [Thompson, S., Ritz, B., Cockburn, M. and Heck, J.E., 2022. International Journal of Hygiene and Environmental Health, 245, p.114025.]
• Residential proximity to croplands at birth and childhood leukemia
  Domestic and parental occupational pesticide exposures are suspected of involvement in the occurrence of childhood acute leukaemia (AL), but the role of exposure to agricultural activities is little known. In a previous ecological study conducted in France, we observed an increase in acute lymphoblastic leukaemia (ALL) incidence rate with increasing viticulture density in the municipalities of residence at diagnosis. This study aimed to test the hypothesis that residential proximity to croplands at birth increases the risk of childhood AL, with a particular focus on vineyards. We identified all the primary AL cases diagnosed before the age of 15 years in the cohorts of children born in the French municipalities between 1990 and 2015. We estimated crop densities in each municipality of residence at birth using agricultural census data, for ten crop types. Variations in standardized incidence ratios (SIR) were evaluated with Poisson regression models, for all AL, ALL and acute myeloid leukaemia (AML), separately. Among the 19,809,700 children born and residing in mainland France at birth in 1990–2015, 8,747 AL cases (7,236 ALL and 1,335 AML) were diagnosed over the period. We did not evidence any statistically significant positive association between total crop density or any specific crop density in the municipality of residence at birth and all AL, ALL or AML. Interestingly, we observed a higher ALL incidence rate in the municipalities with the highest viticulture densities (SIR = 1.25 95%CI [1.01–1.54]). Adjusting for the main potential confounders did not change the results. Our study does not support the hypothesis that residential proximity to croplands, particularly vineyards, around birth plays a role in childhood leukaemia. The slightly higher ALL incidence rate in children born in the municipalities with the highest viticulture densities may reflect the previously-observed association at diagnosis.
  [Bamouni, S., Hémon, D., Faure, L., Clavel, J. and Goujon, S., 2022. Environ Health 21, 103 (2022). ]
• Exposure to pesticides and childhood leukemia risk: A systematic review and meta-analysis
  Despite the abundance of epidemiological evidence concerning the association between pesticide exposure and adverse health outcomes including acute childhood leukemia (AL), evidence remains inconclusive, and is inherently limited by heterogeneous exposure assessment and multiple statistical testing. We performed a literature search of peer-reviewed studies, published until January 2021, without language restrictions. Summary odds ratios (OR) and 95% confidence intervals (CI) were derived from stratified random-effects meta-analyses by type of exposure and outcome, exposed populations and window of exposure to address the large heterogeneity of existing literature. Heterogeneity and small-study effects were also assessed. We identified 55 eligible studies (n = 48 case-control and n = 7 cohorts) from over 30 countries assessing >200 different exposures of pesticides (n = 160,924 participants). The summary OR for maternal environmental exposure to pesticides (broad term) during pregnancy and AL was 1.88 (95%CI: 1.15–3.08), reaching 2.51 for acute lymphoblastic leukemia (ALL; 95%CI: 1.39–4.55). Analysis by pesticide subtype yielded an increased risk for maternal herbicide (OR: 1.41, 95%CI: 1.00–1.99) and insecticide (OR: 1.60, 95%CI: 1.11–2.29) exposure during pregnancy and AL without heterogeneity (p = 0.12–0.34). Meta-analyses of infant leukemia were only feasible for maternal exposure to pesticides during pregnancy. Higher magnitude risks were observed for maternal pesticide exposure and infant ALL (OR: 2.18, 95%CI: 1.44–3.29), and the highest for infant acute myeloid leukemia (OR: 3.42, 95%CI: 1.98–5.91). Overall, the associations were stronger for maternal exposure during pregnancy compared to childhood exposure. For occupational or mixed exposures, parental, and specifically paternal, pesticide exposure was significantly associated with increased risk of AL (ORparental: 1.75, 95%CI: 1.08–2.85; ORpaternal: 1.20, 95%CI: 1.07–1.35). The epidemiological evidence, supported by mechanistic studies, suggests that pesticide exposure, mainly during pregnancy, increases the risk of childhood leukemia, particularly among infants. Sufficiently powered studies using repeated biomarker analyses are needed to confirm whether there is public health merit in reducing prenatal pesticide exposure.

  Despite the abundance of epidemiological evidence concerning the association between pesticide exposure and adverse health outcomes including acute childhood leukemia (AL), evidence remains inconclusive, and is inherently limited by heterogeneous exposure assessment and multiple statistical testing. We performed a literature search of peer-reviewed studies, published until January 2021, without language restrictions. Summary odds ratios (OR) and 95% confidence intervals (CI) were derived from stratified random-effects meta-analyses by type of exposure and outcome, exposed populations and window of exposure to address the large heterogeneity of existing literature. Heterogeneity and small-study effects were also assessed. We identified 55 eligible studies (n = 48 case-control and n = 7 cohorts) from over 30 countries assessing >200 different exposures of pesticides (n = 160,924 participants). The summary OR for maternal environmental exposure to pesticides (broad term) during pregnancy and AL was 1.88 (95%CI: 1.15–3.08), reaching 2.51 for acute lymphoblastic leukemia (ALL; 95%CI: 1.39–4.55). Analysis by pesticide subtype yielded an increased risk for maternal herbicide (OR: 1.41, 95%CI: 1.00–1.99) and insecticide (OR: 1.60, 95%CI: 1.11–2.29) exposure during pregnancy and AL without heterogeneity (p = 0.12–0.34). Meta-analyses of infant leukemia were only feasible for maternal exposure to pesticides during pregnancy. Higher magnitude risks were observed for maternal pesticide exposure and infant ALL (OR: 2.18, 95%CI: 1.44–3.29), and the highest for infant acute myeloid leukemia (OR: 3.42, 95%CI: 1.98–5.91). Overall, the associations were stronger for maternal exposure during pregnancy compared to childhood exposure. For occupational or mixed exposures, parental, and specifically paternal, pesticide exposure was significantly associated with increased risk of AL (ORparental: 1.75, 95%CI: 1.08–2.85; ORpaternal: 1.20, 95%CI: 1.07–1.35). The epidemiological evidence, supported by mechanistic studies, suggests that pesticide exposure, mainly during pregnancy, increases the risk of childhood leukemia, particularly among infants. Sufficiently powered studies using repeated biomarker analyses are needed to confirm whether there is public health merit in reducing prenatal pesticide exposure.
  [Karalexi, M.A., Tagkas, C.F., Markozannes, G., Tseretopoulou, X., Hernández, A.F., Schüz, J., Halldorsson, T.I., Psaltopoulou, T., Petridou, E.T., Tzoulaki, I. and Ntzani, E.E. Environmental Pollution, p.117376.]

• Gestational and childhood exposure to per- and polyfluoroalkyl substances and cardiometabolic risk at age 12 years
  Background
  Per- and polyfluoroalkyl substances (PFAS) may adversely influence cardiometabolic risk. However, few studies have examined if the timing of early life PFAS exposure modifies their relation to cardiometabolic risk. We examined the influence of gestational and childhood PFAS exposure on adolescents’ cardiometabolic risk.

  Methods
  We quantified concentrations of four PFAS (perfluorooctanoate [PFOA], perfluorooctane sulfonate [PFOS], perfluorononanoate [PFNA], and perfluorohexane sulfonate [PFHxS]) in sera collected during pregnancy, at birth, and at ages 3, 8, and 12 years from 221 mother–child pairs in the HOME Study (enrolled 2003–06, Cincinnati, Ohio). We measured cardiometabolic risk factors using physical examinations, fasting serum biomarkers, and dual-energy X-ray absorptiometry scans at age 12 years. Cardiometabolic risk summary scores were calculated by summing age- and sex-standardized z-scores for individual cardiometabolic risk factors. We used multiple informant models to estimate covariate-adjusted associations of serum PFAS concentrations (log2-transformed) at each visit with cardiometabolic risk scores and their individual components, and tested for differences in associations across visits.

  Results
  The associations of serum PFOA concentrations with cardiometabolic risk scores differed across visits (P for heterogeneity = 0.03). Gestational and cord serum PFOA concentrations were positively associated with cardiometabolic risk scores (βs and 95% confidence intervals [95% CIs]: gestational 0.8 [0.0, 1.6]; cord 0.9 [-0.1, 1.9] per interquartile range increase). These positive associations were primarily driven by homeostatic model assessment for insulin resistance index (β = 0.3 [0.1, 0.5]) and adiponectin to leptin ratio (β = -0.5 [-1.0, 0.0]). Other individual cardiometabolic risk factors associated with gestational PFOA included insulin and waist circumference. Gestational and cord PFHxS were also associated with higher cardiometabolic risk scores (βs: gestational 0.9 [0.2, 1.6]; cord 0.9 [0.1, 1.7]).

  Conclusion
  In this cohort of children with higher gestational PFOA exposure, fetal exposure to PFOA and PFHxS was associated with unfavorable cardiometabolic risk in adolescence.
  [Li, N. et al. (2021) Gestational and childhood exposure to per- and polyfluoroalkyl substances and cardiometabolic risk at age 12 years, Environment International. Available at: https://www.sciencedirect.com/science/article/pii/S0160412020322996?via%3Dihub. ]

• Household pesticide exposures and infant gross motor development in the MADRES cohort
  The development of motor skills in infancy is a vital neurodevelopmental milestone. Although previous studies have explored the neurotoxic effects of agricultural pesticides on infants’ motor development, limited research has examined early postnatal household pesticide use on infants’ motor development, particularly among urban communities. This study examined the association between early postnatal household pesticide use and infants’ gross and fine motor development at 6 months of age. Questionnaires were administered via telephone to 296 mother–infant dyads in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort. Early life household pesticide use was assessed via questionnaire administered when infants turned 3 months old and gross and fine motor development was assessed by the Ages and Stages Questionnaire (ASQ-3) at 6 months old. Infant gross motor scores were reverse coded so that higher scores indicated lower gross motor performance. Negative binomial regressions were performed to assess the relationship between household pesticide use and infant gross motor development. Infants were predominantly Hispanic (78.7%) and full term (gestational age at birth: 39.0 ± 1.9 weeks), with 22.3% of maternal participants reporting household use of rodent and insect pesticides. Adjusting for recruitment site, maternal age, ethnicity, household income, education, infant corrected age, infant sex, and home type, infants with maternal-reported household use of rodent and insect pesticides had 1.30 times higher expected gross motor scores (95% confiidence interval 1.05, 1.61) than infants with no reported use of household pesticides, with higher scores indicating reduced gross motor performance. Our results suggest household use of rodent and insect pesticides may harm infants’ gross motor development in early childhood. Future research should evaluate the impact of specific household chemicals in infant biospecimens and their associations with infant motor development to confirm these findings.
  [Hernandez‐Castro, I., Eckel, S.P., Chavez, T., Johnson, M., Lerner, D., Grubbs, B., Toledo‐Corral, C.M., Farzan, S.F., Habre, R., Dunton, G.F. and Breton, C.V. Paediatric and perinatal epidemiology.]
• Mixtures of persistent organic pollutants are found in vital organs of late gestation human fetuses
  Persistent organic pollutants (POPs) are industrial chemicals with long half-lives. Early life exposure to POPs has been associated with adverse effects. Fetal exposure is typically estimated based on concentrations in maternal serum or placenta and little is known on the actual fetal exposure. We measured the concentrations of nine organochlorine pesticides (OCPs), ten polychlorinated biphenyl (PCB) congeners, and polybrominated diphenyl ether (PBDE) congeners by gas chromatography – tandem mass spectrometry in maternal serum, placenta, and fetal tissues (adipose tissue, liver, heart, lung and brain) in 20 pregnancies that ended in stillbirth (gestational weeks 36–41). The data were combined with our earlier data on perfluoroalkyl substances (PFASs) in the same cohort (Mamsen et al. 2019). HCB, p,p’-DDE, PCB 138 and PCB 153 were quantified in all samples of maternal serum, placenta and fetal tissues. All 22 POPs were detected in all fetal adipose tissue samples, even in cases where they could not be detected in maternal serum or placenta. Tissue:serum ratios were significantly higher in later gestations, male fetuses, and pregnancies with normal placental function. OCPs showed the highest tissue:serum ratios and PFAS the lowest. The highest chemical burden was found in adipose tissue and lowest in the brain. Overall, all studied human fetuses were intrinsically exposed to mixtures of POPs. Tissue:serum ratios were significantly modified by gestational age, fetal sex and placental function. Importantly, more chemicals were detected in fetal tissues compared to maternal serum and placenta, implying that these proxy samples may provide a misleading picture of actual fetal exposures.
  [Björvang, R.D., Vinnars, M.T., Papadogiannakis, N., Gidlöf, S., Mamsen, L.S., Mucs, D., Kiviranta, H., Rantakokko, P., Ruokojärvi, P., Lindh, C.H. and Andersen, C.Y. Chemosphere, p.131125.]
• Prenatal exposure to per- and polyfluoroalkyl substances, fetal thyroid hormones, and infant neurodevelopment
  Background
  Per- and polyfluoroalkyl substances (PFAS) are believed to impair early neurodevelopment and disrupt thyroid hormone (TH) levels. However, there are limited epidemiological data on the neurodevelopmental effects in infancy of prenatal PFAS exposure and the potential mediating effects of TH.
  Objectives
  To evaluate potential associations between prenatal PFAS exposure and early neurodevelopmental deficiencies, and assess mediator effects of TH.
  Methods
  From 2010 to 2013, 274 mother-infant pairs were recruited to the Laizhou Wan Birth Cohort in China. Ten PFAS and five TH were measured in cord serum. Developmental quotient (DQ) from 5 domains (adaptive, social, language, gross and fine motor) was assessed using Gesell Developmental Schedules for each child at 1 year of age. The associations between PFAS and DQs were evaluated using multivariable linear regressions. TH-mediated effects of PFAS on DQs were calculated by mediation analyses.
  Results
  Among our study population, PFAS exposures were common and associated with DQ decrement in infants. For each 10-fold increase in PFBS concentrations, gross motor and adaptive DQ decreased by 8.56 (95%CI: −15.15, −1.97) and 5.87 (95%CI: −8.07, −3.67) points, respectively. TSH mediated 12.90% of the association of PFBS with gross motor DQ and FT4 explained 19.63% of the association of PFBS with adaptive DQ. The negative association was also found between PFHxS exposure and gross motor DQ (β = 8.14, 95%CI: −15.39, −0.98).
  Conclusions
  PFBS and PFHxS were negatively associated with early neurodevelopment, especially consistent in gross motor domain. The associations were partly explained by TSH and FT4.
  [Yao, Q. et al. (2021) Prenatal exposure to per- and polyfluoroalkyl substances, fetal thyroid hormones, and infant neurodevelopment, Environmental Research. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0013935121018624. ]
• Agricultural crop density in the municipalities of France and incidence of childhood leukemia: An ecological study
  Pesticide exposure is suspected to play a role in the etiology of childhood leukemia (AL). Various sources of exposure have been explored, but few studies have investigated the risk of childhood AL in relation to residential exposure to agricultural pesticides. Since around 50% of France is agricultural land, with marked pesticide use, France is a suitable location to investigate for an association. We aimed to analyze the association between the agricultural crop density in the municipalities of France and the incidence of childhood AL between 1990 and 2014. 11,487 cases of AL diagnosed in children aged 0–14 years were registered by the French National Registry of Childhood Hematological Malignancies over 1990–2014. National agricultural census data for 1990, 2000 and 2010 were used to estimate the densities of the most common crops in France. The incidence of AL was estimated in the 35,512 municipalities, by age and gender, and 3 observation periods, and expressed as the standardized incidence ratio (SIR). We observed a moderate log-linear association between viticulture density and the incidence of AL, with a 3% increase in SIR for a 10% increase in viticulture density (SIRR = 1.03; 95%CI [1.00–1.06]). The association remained for lymphoblastic AL but not for myeloid AL. The association was stable after stratification by geographic area, age and period, and after adjustment on UV radiation and a French deprivation index. No consistent association was observed for other crop types. This nationwide study shows a moderate increase in incidence of childhood AL in municipalities where viticulture is common. Future individual studies are needed to know whether this observation is confirmed and related to particular use of pesticides.
  [Coste, A., Goujon, S., Faure, L., Hémon, D. and Clavel, J., 2020. Environmental Research, p.109517.]
• Application of the Food Quality Protection Act children’s health safety factor in the U.S. EPA pesticide risk assessments
  Background
  The Food Quality Protection Act of 1996, or FQPA, required the Environmental Protection Agency to set allowable levels for pesticides in a way that would “ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue.” The act stipulated that an additional tenfold margin of safety for pesticide risk assessments shall be applied to account for pre- and postnatal toxicity and for any data gaps regarding pesticide exposure and toxicity, unless there are reliable data to demonstrate that a different margin would be safe for infants and children.

  Discussion
  To examine the implementation of the FQPA-mandated additional margin of safety, this analysis reviews 59 pesticide risk assessments published by the EPA between 2011 and 2019. The list includes 12 pesticides used in the largest amount in the U.S.; a group of 35 pesticides detected on fruits and vegetables; and 12 organophosphate pesticides. For the non-organophosphate pesticides reviewed here, the EPA applied an additional children’s health safety factor in 13% of acute dietary exposure scenarios and 12% of chronic dietary exposure scenarios. For incidental oral, dermal and inhalation exposures, additional FQPA factors were applied for 15, 31, and 41%, respectively, of the non-organophosphate pesticides, primarily due to data uncertainties. For the organophosphate pesticides as a group, a tenfold children’s health safety factor was proposed in 2015. Notably, in 2017 that decision was reversed for chlorpyrifos.

  Conclusions
  For the majority of pesticides reviewed in this study, the EPA did not apply an additional FQPA safety factor, missing an opportunity to fully use the FQPA authority for protecting children’s health.
  [Naidenko, O.V. (2020) Application of the Food Quality Protection Act Children’s health safety factor in the U.S. EPA pesticide risk assessments, Environmental Health. Available at: https://ehjournal.biomedcentral.com/articles/10.1186/s12940-020-0571-6. ]

• Environmental Exposures Related to Parental Habits in the Perinatal Period and the Risk of Wilms' Tumor in Children
  Wilms' tumor is the most frequently diagnosed renal tumor in children. Little is known about its etiology. The aim of this study was to investigate the potential role of specific exposures related to parental habits such as parental smoking, maternal alcohol consumption and the use of household pesticides during pregnancy. The ESTELLE study was a nationwide case-control study that included 117 Wilms' tumor cases and 1100 control children from the general French population, frequency-matched by age and gender. Unconditional logistic regression was used to estimate odds ratios and 95 % confidence intervals. After controlling for matching variables and potential confounders, the maternal use of any type of pesticide during pregnancy was associated with the risk of Wilms' tumor in children (OR 1.6 [95 % CI 1.1-2.3]). Insecticides were the most commonly reported type of pesticide and there was a positive association with their use (OR 1.7 [95 % CI 1.1-2.6]. The association was stronger when they were used more often than once a month (OR 1.9 [95 % CI 1.2-3.0]. Neither maternal smoking during pregnancy nor paternal smoking during preconception/pregnancy was associated with a risk of Wilms' tumor (ORs 1.1[95 % CI 0.7-1.8] and 1.1 [95 % CI 0.7-1.7], respectively). No association was observed with maternal alcohol intake during pregnancy (OR 1.2 [95 % CI 0.8-2.0]). Our findings suggest an association between the maternal use of household pesticides during pregnancy and the risk of Wilms' tumor.
  [Rios, P., Bauer, H., Schleiermacher, G., Pasqualini, C., Boulanger, C., Thebaud, E., Gandemer, V., Pellier, I., Verschuur, A., Sudour-Bonnange, H. and Coulomb-l'Hermine, A., 2020. Cancer Epidemiology, 66, p.101706.]
• Nationwide Biomonitoring of Neonicotinoid Insecticides in Breast Milk and Health Risk Assessment to Nursing Infants in the Chinese Population
  Presently, the potential health risks of neonicotinoid insecticides (neonics) are now receiving much attention, but no data regarding the exposure of infants to neonics via human breast milk intake have been reported. In this study, a nationwide survey was conducted during the period of 2017–2019, wherein 97 pooled breast milk samples were collected from 3570 lactating women of 23 provinces in China. Nationally, acetamiprid-N-desmethyl was the most predominant compound, accounting for 61.2% of the total amount of neonics, followed by imidacloprid (15.6%). The concentration of the sum of acetamiprid and its metabolite acetamiprid-N-desmethyl in breast milk was positively correlated with corresponding dietary exposure, while no statistically significant association between the other neonic levels in breast milk and dietary exposure was found. The cumulative daily intakes of neonics (9.40–249 ng kg–1 of body weight day–1) were estimated for breastfed infants, indicating a minuscule risk to Chinese infants from neonic exposure via breastfeeding.
  [Chen, D. et al. (2020) Nationwide Biomonitoring of Neonicotinoid Insecticides in Breast Milk and Health Risk Assessment to Nursing Infants in the Chinese Population, Journal of Agricultural and Food Chemistry. Available at: https://pubs.acs.org/doi/10.1021/acs.jafc.0c05769. ]
• Prenatal pesticide exposure and childhood leukemia – A California statewide case-control study
  A number of epidemiologic studies with a variety of exposure assessment approaches have implicated pesticides as risk factors for childhood cancers. Here we explore the association of pesticide exposure in pregnancy and early childhood with childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) utilizing land use and pesticide use data in a sophisticated GIS tool. We identified cancer cases less than 6 years of age from the California Cancer Registry and cancer-free controls from birth certificates. Analyses were restricted to those living in rural areas and born 1998–2011, resulting in 162 cases of childhood leukemia and 9,805 controls. Possible carcinogens were selected from the Environmental Protection Agency's classifications and pesticide use was collected from the California Department of Pesticide Regulation's (CDPR) Pesticide Use Reporting (PUR) system and linked to land-use surveys. Exposures for subjects were assessed using a 4000m buffer around the geocoded residential addresses at birth. Unconditional logistic and hierarchical regression models were used to assess individual pesticide and pesticide class associations. We observed elevated risks for ALL with exposure to any carcinogenic pesticide (adjusted Odds Ratio (aOR): 2.83, 95% CI: 1.67–4.82), diuron (Single-pesticide model, adjusted (OR): 2.38, 95% CI: 1.57–3.60), phosmet (OR: 2.10, 95% CI: 1.46–3.02), kresoxim-methyl (OR: 1.77, 95% CI: 1.14–2.75), and propanil (OR: 2.58, 95% CI: 1.44–4.63). Analyses based on chemical classes showed elevated risks for the group of 2,6-dinitroanilines (OR: 2.50, 95% CI: 1.56–3.99), anilides (OR: 2.16, 95% CI: 1.38–3.36), and ureas (OR: 2.18, 95% CI: 1.42–3.34). Our findings suggest that in rural areas of California exposure to certain pesticides or pesticide classes during pregnancy due to residential proximity to agricultural applications may increase the risk of childhood ALL and AML. Future studies into the mechanisms of carcinogenicity of these pesticides may be beneficial.
  [Park, A.S., Ritz, B., Yu, F., Cockburn, M. and Heck, J.E., 2020. International journal of hygiene and environmental health, 226, p.113486.]
• Urinary organophosphate metabolites and oxidative stress in children living in agricultural and urban communities
  Exposure to organophosphate (OP) pesticides in children may increase oxidative stress, resulting in the development of chronic diseases. This study aims to compare urinary OP metabolites and oxidative stress between children in agricultural and urban communities. The study also investigated the factors associated with urinary OP metabolites among children. Urine samples were collected from children for measuring levels of OP metabolites, glutathione (GSH), and malondialdehyde (MDA). The remarkable findings were that total dialkylphosphate (DAP) levels detected among children in this agricultural community were significantly higher than those from the urban community (P = 0.001). Multiple linear regression showed that total diethylphosphate (DEP) levels among children in the agricultural community were negatively associated with distances from children’s residence to the agricultural fields (β ± SE. = − 1.535 ± 0.334, 95%CI = − 2.202, − 0.863) and positively associated with playing on farms (β ± SE. = 0.720 ± 0.342, 95%CI = 0.036, 1.405). In addition, total dimethylphosphate (DMP) levels were positively associated with children working on farms (β ± SE. = 0.619 ± 0.264, 95%CI = 0.091, 1.147). Importantly, GSH levels among children in the agricultural community were significantly lower than those in the urban community (P < 0.001), but MDA levels did not differ. These results therefore suggest that children can be exposed to OPs both outdoors and indoors. Our results also provide supporting evidence that OP exposure can cause oxidative stress in children. As oxidative stress contributes to several chronic diseases, a good proposed strategy for the future would include measurement of oxidative stress biomarkers among children exposed to OPs as an early warning of chronic diseases.
  [Sapbamrer, R., Hongsibsong, S. and Khacha-Ananda, S. (2020) Urinary organophosphate metabolites and oxidative stress in children living in agricultural and urban communities, Environmental Science and Pollution Research. Available at: https://link.springer.com/article/10.1007/s11356-020-09037-z. ]
• Pollution and children's health
  Findings
  The Lancet Commission on Pollution and Health found that pollution – air, water, soil, and chemical pollution - was responsible in 2016 for 940,000 deaths in children worldwide, two-thirds of them in children under the age of 5. Pollution is inequitably distributed, and the overwhelming majority of pollution-related deaths in children occurred in low- and middle-income countries (LMICs). Most were due to respiratory and gastrointestinal diseases caused by polluted air and water.

  Pollution is linked also to multiple non-communicable diseases (NCDs) in children including low birth weight, asthma, cancer and neurodevelopmental disorders, and these diseases are on the rise. The full impact of pollution, especially chemical pollution on the global burden of pediatric disease is not yet known, but almost certainly is undercounted because patterns of chemical exposure are not well charted and the potential toxicity of many chemical pollutants has not been characterized. The list of pediatric NCDs attributed to pollution will likely expand as the health effects of newer chemical pollutants are better defined and additional associations between pollution and disease are discovered.

  Conclusion
  Pollution prevention presents a major, largely unexploited opportunity to improve children's health and prevent NCDs, especially in LMICs. Failure to incorporate pollution prevention into NCD control programs is a major missed opportunity for disease prevention.
  [Landrigan, P. et al. (2019) ‘Pollution and children’s health’, Science of The Total Environment, 650, pp. 2389–2394. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0048969718338543?via%3Dihub. ]

• Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study
  Data from California state mandated Pesticide Use Reporting were integrated into a geographic information system tool to estimate prenatal and infant exposures to pesticides (measured as pounds of pesticides applied per acre/month within 2000 m from the maternal residence). 11 high use pesticides were selected for examination a priori according to previous evidence of neurodevelopmental toxicity in vivo or in vitro (exposure defined as ever v never for each pesticide during specific developmental periods). Risk of autism spectrum disorder was associated with prenatal exposure to glyphosate (odds ratio 1.16, 95% confidence interval 1.06 to 1.27), chlorpyrifos (1.13, 1.05 to 1.23), diazinon (1.11, 1.01 to 1.21), malathion (1.11, 1.01 to 1.22), avermectin (1.12, 1.04 to 1.22), and permethrin (1.10, 1.01 to 1.20). For autism spectrum disorder with intellectual disability, estimated odds ratios were higher (by about 30%) for prenatal exposure to glyphosate (1.33, 1.05 to 1.69), chlorpyrifos (1.27, 1.04 to 1.56), diazinon (1.41, 1.15 to 1.73), permethrin (1.46, 1.20 to 1.78), methyl bromide (1.33, 1.07 to 1.64), and myclobutanil (1.32, 1.09 to 1.60); exposure in the first year of life increased the odds for the disorder with comorbid intellectual disability by up to 50% for some pesticide substances. 
  [von Ehrenstein, et al. 2019. BMJ 2019;364:l962 ]
• A Pilot Study Evaluating Organochlorine and Organophosphate Pesticide Exposure in Children and Adolescents of Mexican Descent Residing in Hidalgo County, Texas.
  Children and adolescents of Mexican descent residing in Hidalgo County (TX) were evaluated for exposure to organochlorine (OC) and organophosphate (OP) pesticides. A convenience sample of 60 participants enrolled in our pilot study. The lipid-adjusted serum concentrations of nine OC metabolites and creatinine-adjusted urinary concentrations of six OP metabolites were measured and compared with data from the Centers for Disease Control and Prevention's Fourth Report on Human Exposure to Environmental Chemicals. Descriptive statistics were used to summarize the concentration levels for each metabolite. Study participants were aged 5-18 years. For most of the OC and OP metabolites, our findings showed that participants had concentration levels within the distributional range of the national data. However, notable outlying levels (greater than the 95th percentile in the Fourth Report) were identified for the following OC metabolites: gamma-hexachlorocyclohexane, p,p'-dichlorodiphenyldichloroethene, and p,p'-dichlorodiphenyltrichloroethane. Among the children aged 5-11 years, one child had an outlying value for the OP metabolite: dimethylphosphate. Our findings on the levels of OC and OP pesticide exposure enhances the credibility of national estimates, and can serve as baselines for children and adolescents of Mexican descent residing in Lower Rio Grande Valley. Furthermore, our study contributes to the lacunae of knowledge regarding environmental exposures and presses further investigation of outlying OC and OP exposure levels.
  [Hernandez M, Hernández-Valero MA, García-Prieto C, et al. 2018. J Immigr Minor Health. doi: 10.1007/s10903-018-0791-9.]
• Glyphosate exposure in pregnancy and shortened gestational length: a prospective Indiana birth cohort study
  Glyphosate (GLY) is the most heavily used herbicide worldwide but the extent of exposure in human pregnancy remains unknown. Its residues are found in the environment, major crops, and food items that humans, including pregnant women, consume daily. Since GLY exposure in pregnancy may also increase fetal exposure risk, we designed a birth-cohort study to determine exposure frequency, potential exposure pathways, and associations with fetal growth indicators and pregnancy length. Urine and residential drinking water samples were obtained from 71 women with singleton pregnancies living in Central Indiana while they received routine prenatal care. Maternal risk factors and neonatal outcomes were abstracted from medical records. Correlation analyses were used to assess relationships of urine GLY levels with fetal growth indicators and gestational length. The mean age of participants was 29 years, and the majority were Caucasian. Ninety three percent of the pregnant women had GLY levels above the limit of detection (0.1 ng/mL). Mean urinary GLY was 3.40 ng/mL (range 0.5-7.20 ng/mL). Higher GLY levels were found in women who lived in rural areas (p = 0.02), and in those who consumed > 24 oz. of caffeinated beverages per day (p = 0.004). None of the drinking water samples had detectable GLY levels. We observed no correlations with fetal growth indicators such as birth weight percentile and head circumference. However, higher GLY urine levels were significantly correlated with shortened gestational lengths. This is the first study of GLY exposure in US pregnant women using urine specimens as a direct measure of exposure. We found that > 90% of pregnant women had detectable GLY levels and that these levels correlated significantly with shortened pregnancy lengths. Although our study cohort was small and regional and had limited racial/ethnic diversity, it provides direct evidence of maternal GLY exposure and a significant correlation with shortened pregnancy. Further investigations in a more geographically and racially diverse cohort would be necessary before these findings could be generalized.
  [Parvez S, Gerona RR, Proctor C, Friesen M, Ashby JL, Reiter JL, Lui Z, Winchester PD. 2018. Environ Health. 17(1):23. doi: 10.1186/s12940-018-0367-0.]
• Impact of childhood wheezing on lung function in adulthood: A meta-analysis
  Background
  A growing body of evidence shows that childhood wheezing may lead to recurrent or persistent symptoms in adulthood, such that persistent wheezing associated with lung function deficits often have their roots in the first few years of life.

  Objectives
  We summarized information from several prospective cohort studies following children with or without wheezing into adulthood, to estimate the effect of childhood wheezing on adulthood lung function.

  Methods
  Medical literatures were searched in the Medline, PubMed, ScienceDirect, Web of Science and Embase databases up to October 31, 2016. The adulthood lung function was selected as primary outcome, and chronic obstructive pulmonary disease (COPD) prevalence was selected as secondary outcome. The meta-analysis was performed with the Stata Version 14.0. A random-effects model was applied to estimate standardized mean difference (SMD) of lung function, and relative risk (RR) of COPD.

  Results
  Six articles enrolling 1141 and 1005 children with and without wheezing, respectively. Meta-analysis showed that childhood wheezing decreased adulthood lung function as compared with no-wheezing subjects (SMD = -0.365, 95% confidence interval (CI): -0.569~-0.161, P = 0.000). Subgroup analyses indicated that childhood atopic wheezing reduced adulthood FEV1/FVC and FEV1%pred when compared with no-wheezing subjects. In addition, childhood atopic wheezing was significantly associated with COPD prevalence (RR = 5.307, 95% CI:1.033~27.271, P = 0.046).

  Conclusions
  Our meta-analysis suggests that childhood wheezing may induce ongoing declined lung function that extends into adult life, as well as an increased risk of COPD prevalence when accompanied with atopy.
  [Ma, H. et al. (2018) Impact of childhood wheezing on lung function in adulthood: A meta-analysis, PLoS ONE. Available at: https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0192390.]

• Organophosphate and Pyrethroid Pesticide Exposures Measured before Conception and Associations with Time to Pregnancy in Chinese Couples Enrolled in the Shanghai Birth Cohort.
  Pesticides have been associated with reproductive disorders, but there is limited research on pesticide exposures and human fertility. We aimed to investigate the effects of preconception exposure to pesticides on time to pregnancy (TTP) and on infertility in a general population of couples planning to become pregnant in Shanghai, China. A total of 615 women who were planning a pregnancy were enrolled before conception and were prospectively followed for 1 y to observe their TTP. Preconception pesticide exposures were assessed by measuring urinary metabolites of organophosphates (OPs) and pyrethroids (PYRs). Fecundability odds ratios (FORs) and odds ratios (ORs) of infertility were estimated using Cox and logistic regression models, respectively. All analyses were repeated after restricting the sample to nulliparous women (n=569). After adjusting for age, prepregnancy BMI, current smoking, education, annual household income, age at menarche, and two items from the Perceived Stress Scale (PSS-10), women in the highest quartile of diethylthiophosphate (DETP; an OP metabolite) had significantly longer TTP [adjusted FOR=0.68 (95% CI: 0.51, 0.92)] and increased infertility [adjusted OR=2.17 (95% CI: 1.19, 3.93)] compared with women in the lowest quartile. The highest versus lowest quartile of 3-phenoxybenzoic acid (3PBA; a PYR metabolite) was associated with longer TTP and infertility, with significant associations in nulliparous women [adjusted FOR=0.72 (95% CI: 0.53, 0.98); adjusted OR for infertility=2.03 (95% CI: 1.10, 3.74)].Our study provides some of the first evidence that preconception OP and PYR exposures are associated with decreased fertility in Chinese couples. Given that OPs and PYRs are rapidly metabolized in humans, more studies are needed to confirm our findings. 
  [Hu Y, Ji L, Zhang Y, Shi R, Han W, Tse LA, et al. 2018. Environ Health Perspect. 126(7):077001]
• Organophosphate exposures during pregnancy and child neurodevelopment: Recommendations for essential policy reforms
  In a Policy Forum, Irva Hertz-Picciotto and colleagues review the scientific evidence linking organophosphate pesticides to cognitive, behavioral, and neurological deficits in children and recommend actions to reduce exposures.
  [Hertz-Picciotto, I. et al. (2018) Organophosphate exposures during pregnancy and child neurodevelopment: Recommendations for essential policy reforms, PLoS medicine. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC6200179/. ]
• Prenatal organophosphate insecticide exposure and infant sensory function.
  Occupational studies suggest that exposure to organophosphate insecticides (OPs) can lead to vision or hearing loss. Yet the effects of early-life exposure on visual and auditory function are unknown. Here we examined associations between prenatal OP exposure and grating visual acuity (VA) and auditory brainstem response (ABR) during infancy. 30 OPs were measured in umbilical cord blood using gas chromatography tandem mass spectrometry in a cohort of Chinese infants. Grating visual acuity (VA) (n = 179-200) and auditory brainstem response (ABR) (n = 139-183) were assessed at 6 weeks, 9 months, and 18 months. Outcomes included VA score, ABR wave V latency and central conduction time, and head circumference (HC). Associations between sensory outcomes during infancy and cord OPs were examined using linear mixed models. Prenatal chlorpyrifos exposure was associated with lower 9-month grating VA scores; scores were 0.64 (95% CI: -1.22, -0.06) points lower for exposed versus unexposed infants (p = 0.03). The OPs examined were not associated with infant ABR latencies, but chlorpyrifos and phorate were both significantly inversely associated with HC at 9 months; HCs were 0.41 (95% CI: 0.75, 0.6) cm and 0.44 (95% CI: 0.88, 0.1) cm smaller for chlorpyrifos (p = 0.02) and phorate (p = 0.04), respectively.We found deficits in grating VA and HC in 9-month-old infants with prenatal exposure to chlorpyrifos. The clinical significance of these small but statistically significant deficits is unclear. However, the disruption of visual or auditory pathway maturation in infancy could potentially negatively affect downstream cognitive development.
  [Silver MK, Shao J, Ji C, Zhu B, Xu L, Li M, et al. 2018. Int J Hyg Environ Health. pii: S1438-4639(17)30563-1.]
• A task-based assessment of parental occupational exposure to pesticides and childhood acute lymphoblastic leukemia.
  Associations between parental occupational pesticide exposure and childhood acute lymphoblastic leukemia (ALL) vary across studies, likely due to different exposure assessment methodologies. This study assessed parental occupational pesticide exposure from the year before pregnancy to the child's third year of life for 669 children diagnosed with ALL and 1021 controls. Authors conducted expert rating using task-based job modules (JM) to estimate exposure to pesticides among farmer workers, gardeners, agricultural packers, and pesticide applicators. Compared to complete JMs, partial JMs and JEM led to 3.1% and 9.4% of parents with pesticide exposure misclassified, respectively. Misclassification was similar in cases and controls. Using complete JMs, we observed an increased risk of ALL for paternal occupational exposure to any pesticides (OR=1.7; 95% CI=1.2, 2.5), with higher risks reported for pesticides to treat nut crops (OR=4.5; 95% CI=0.9, 23.0), and for children diagnosed before five years of age (OR=2.3; 95% CI: 1.3, 4.1). Exposure misclassification from JEM attenuated these associations by about 57%. Maternal occupational pesticide exposure before and after birth was not associated with ALL. The risk of ALL was elevated in young children with paternal occupational pesticide exposure during the perinatal period, using more detailed occupational information for exposure classification.
  [Gunier RB, Kang A, Hammond SK, Reinier K, et al. 2017. Environ Res. 156:57-62.]
• Behavioural disorders in 6-year-old children and pyrethroid insecticide exposure: the PELAGIE mother-child cohort.
  The potential impact of environmental exposure to pyrethroid insecticides on child neurodevelopment has only just started to receive attention despite their widespread use. We investigated the associations between prenatal and childhood exposure to pyrethroid insecticides and behavioural skills in 6-year-olds.The PELAGIE cohort enrolled 3421 pregnant women from Brittany, France between 2002 and 2006. 428 mothers were randomly selected for the study when their children turned 6, and 287 (67%) agreed to participate. Children's behaviour was assessed using the Strengths and Difficulties Questionnaire (SDQ). Three subscales (prosocial behaviour, internalising disorders and externalising disorders) were considered. Five pyrethroid metabolites were measured in maternal and child urine samples collected between 6 and 19 gestational weeks and at 6 years of age, respectively. Increased prenatal cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (DCCA) concentrations were associated with internalising difficulties (Cox p value=0.05). For childhood 3-phenoxybenzoic acid (PBA) concentrations, a positive association was observed with externalising difficulties (Cox p value=0.04) and high ORs were found for abnormal or borderline social behaviour (OR 2.93, 95% CI 1.27 to 6.78, and OR 1.91, 95% CI 0.80 to 4.57, for the intermediate and highest metabolite categories, respectively). High childhood trans-DCCA concentrations were associated with reduced externalising disorders (Cox p value=0.03).The present study suggests that exposure to certain pyrethroids, at environmental levels, may negatively affect neurobehavioral development by 6 years of age.
  [Viel JF, Rouget F, Warembourg C, Monfort C, et al. 2017. Occup Environ Med. 74(4):275-281.]
• Biomonitoring of Danish school children and mothers including biomarkers of PBDE and glyphosate.
  The Danish part of the large European Human biomonitoring pilot project Demonstration of a study to Coordinate and Perform Human biomonitoring on a European Scale (DEMOCOPHES) investigated the urine, hair and blood concentrations of 66 different environmental chemicals in a group of 145 Danish school children aged 6-11 years and their mothers from rural and urban areas in autumn 2011. Some - but not all - results were published; however, the concurrence of the chemicals has not been assessed. The measured concentrations of polybrominated diphenyl ethers (PBDEs) and glyphosate is assessed to complete the investigation of all 66 chemicals in DEMOCOPHES. The concentrations of PBDEs were measured in plasma samples of 143 mothers and 116 children. Glyphosate was measured in a subsample of 27 urine samples. Previously assessed chemicals were polychlorinated biphenyls (PCBs), and polyfluoroalkyl substances (PFASs) analyzed in blood samples, mercury analyzed in hair, and phthalate metabolites, parabens, phenols, cadmium, paracetamol and cotinine analyzed in urine samples. Differences in concentrations between mothers and children were assessed, and the associations between the concentrations of the different environmental chemicals. investigated by correlation analysis. PBDE47 was found in relatively high levels compared with previous Danish results in both mothers and children, with a significantly higher level in the children compared to their mothers. Glyphosate in concentrations around 1 ng/mL was detected in all 27 samples. The analyzed environmental exposures seem to follow a pattern where chemicals within the same classes are strongly correlated and where children and mothers are exposed to the same chemicals.The correlations between the measured environmental chemicals indicate that a specific exposure pattern may exist, where people who are highly exposed to one class of environmental chemicals also may be highly exposed to certain other classes. As some of the compounds were measured in higher levels in children compared to mothers, increased focus also on the exposure in young children is recommended. For more detailed investigation of specific exposure sources more studies with increased power and detailed questionnaires should be developed.
  [Knudsen LE, Hansen PW, Mizrak S, Hansen HK, Mørck TA, et al. 2017. Rev Environ Health. 32(3):279-290]
• Combined Prenatal Pesticide Exposure and Folic Acid Intake in Relation to Autism Spectrum Disorder.
  Maternal folic acid (FA) protects against developmental toxicity from certain environmental chemicals. We examined combined exposures to maternal FA and pesticides in relation to autism spectrum disorder (ASD). Participants were California children born from 2000-2007 who were enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) case-control study at age 2-5 y, were clinically confirmed to have ASD (n=296) or typical development (n=220), and had information on maternal supplemental FA and pesticide exposures. Maternal supplemental FA and household pesticide product use were retrospectively collected in telephone interviews from 2003-2011. High vs. low daily FA intake was dichotomized at 800μg (median). Mothers' addresses were linked to a statewide database of commercial applications to estimate agricultural pesticide exposure. High FA intake (≥800μg) during the first pregnancy month and no known pesticide exposure was the reference group for all analyses. Compared with this group, ASD was increased in association with <800μg FA and any indoor pesticide exposure {adjusted odds ratio [OR]=2.5 [95% confidence interval (CI): 1.3, 4.7]} compared with low FA [OR=1.2 (95% CI: 0.7, 2.2)] or indoor pesticides [OR=1.7 (95% CI: 1.1, 2.8)] alone. ORs for the combination of low FA and regular pregnancy exposure (≥6 mo) to pet pesticides or to outdoor sprays and foggers were 3.9 (95% CI: 1.4, 11.5) and 4.1 (95% CI: 1.7, 10.1), respectively. ORs for low maternal FA and agricultural pesticide exposure 3 mo before or after conception were 2.2 (95% CI: 0.7, 6.5) for chlorpyrifos, 2.3 (95% CI: 0.98, 5.3) for organophosphates, 2.1 (95% CI: 0.9, 4.8) for pyrethroids, and 1.5 (95% CI: 0.5, 4.8) for carbamates. Except for carbamates, these ORs were approximately two times greater than those for either exposure alone or for the expected ORs for combined exposures under multiplicative or additive models. In this study population, associations between pesticide exposures and ASD were attenuated among those with high versus low FA intake during the first month of pregnancy. Confirmatory and mechanistic studies are needed.
  [Schmidt RJ, Kogan V, Shelton JF, Delwiche L, Hansen RL, et al. 2017. Environ Health Perspect. 125(9):097007.]
• Elemental Sulfur Use and Associations with Pediatric Lung Function and Respiratory Symptoms in an Agricultural Community (California, USA)
  Background:
  Elemental sulfur, “the oldest of all pesticides,” is the most heavily used agricultural pesticide in California and Europe. Sulfur is considered relatively safe and is used in both conventional and organic farming systems. Adverse respiratory effects have been reported in applicators and animals, but the effect on residential populations, and especially on children living in proximity to fields treated with elemental sulfur, is not known.
  Objectives:
  We evaluated associations between residential proximity to elemental sulfur applications and respiratory symptoms and spirometry of children living in an agricultural community.
  Methods:
  Participants were enrolled in the CHAMACOS longitudinal birth cohort. We collected respiratory symptomatology for 347 children at 7 y of age and measured spirometry on a subset of 279. Of these, estimations of proximity to sulfur application and relevant covariate data were available for 237 and 205 children for whom we had symptomatology information and FEV1 measurements, respectively. Data from the California Pesticide Use Reporting System were used to estimate the amount of elemental sulfur applied within 0.5, 1, and 3km of a child’s residence during the week, month, and 12 mo prior to pulmonary evaluation. Regression models controlled for maternal smoking during pregnancy; season of birth; PM2.5 (particulate matter ≤2.5mm in aerodynamic diameter); breast feeding duration; child’s sex, age, and height; technician; and other covariates.
  Results:
  Adverse associations with respiratory outcomes were found for sulfur applications within 0.5- and 1−km radii. Specifically, asthma medication usage and respiratory symptoms increased [OR=3.51; 95% confidence interval (CI): 1.50, 8.23,
  [Raanan, R. et al. (2017) Elemental Sulfur Use and Associations with Pediatric Lung Function and Respiratory Symptoms in an Agricultural Community (California, USA), Environmental Health Perspectives. Available at: https://ehp.niehs.nih.gov/doi/full/10.1289/EHP528. ]
• Endocrine Disrupting Chemicals, Transgenerational Epigenetics and Metabolic Diseases
  Exposure to environmental chemicals can produce effects on the endocrine system through epigenetic mechanisms. These can considerably decrease or increase the sensitivity of multiple hormones depending on the dose, route, or time of exposure. The exposure of endocrine disrupting chemicals (EDCs) during the in utero period could be a critical window, altering the epigenome profile. Recently, several researchers suggest a role of EDCs in the obesity epidemic. In this
  brief review, we focused on how four EDCs (bisphenol A, dichlorodiphenyltrichloroethane, di-(2-ethylhexyl) phthalate and tributyltin) may underlay transgenerational epigenetic effects. We also discuss the adipogenesis signaling pathway and the impact of exposure to individual or mixtures of EDCs on the developing endocrine system. Understanding the molecular determinants
  of epigenetic memory across generations will provide essential insight into how environmental exposure can affect the health of individuals, as well as subsequent generations.
  [Feroe, A. et al. (2017) Endocrine disrupting chemicals, transgenerational epigenetics and metabolic diseases, EC Endocrinol Metab Res. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563023/. ]
• Interaction between prenatal pesticide exposure and a common polymorphism in the PON1 gene on DNA methylation in genes associated with cardio-metabolic disease risk-an exploratory study
  Prenatal environmental conditions may influence disease risk in later life. We previously found a gene-environment interaction between the paraoxonase 1 (PON1) Q192R genotype and prenatal pesticide exposure leading to an adverse cardio-metabolic risk profile at school age. However, the molecular mechanisms involved have not yet been resolved. It was hypothesized that epigenetics might be involved. The aim of the present study was therefore to investigate whether DNA methylation patterns in blood cells were related to prenatal pesticide exposure level, PON1 Q192R genotype, and associated metabolic effects observed in the children.Whole blood DNA methylation patterns in 48 children (6-11 years of age), whose mothers were occupationally unexposed or exposed to pesticides early in pregnancy, were determined by Illumina 450 K methylation arrays.A specific methylation profile was observed in prenatally pesticide exposed children carrying the PON1 192R-allele. Differentially methylated genes were enriched in several neuroendocrine signaling pathways including dopamine-DARPP32 feedback (appetite, reward pathways), corticotrophin releasing hormone signaling, nNOS, neuregulin signaling, mTOR signaling, and type II diabetes mellitus signaling. Furthermore, we were able to identify possible candidate genes which mediated the associations between pesticide exposure and increased leptin level, body fat percentage, and difference in BMI Z score between birth and school age.DNA methylation may be an underlying mechanism explaining an adverse cardio-metabolic health profile in children carrying the PON1 192R-allele and prenatally exposed to pesticides.
  [Declerck K, Remy S, Wohlfahrt-Veje C, Main KM, et al. 2017. Clin Epigenetics. 9:35. ]
• Persistent Environmental Toxicants in Breast Milk and Rapid Infant Growth.
  Many environmental toxicants are passed to infants in utero and through breast milk. Exposure to toxicants during the perinatal period can alter growth patterns, impairing growth or increasing obesity risk. Previous studies have focused on only a few toxicants at a time, which may confound results. We investigated levels of 26 toxicants in breast milk and their associations with rapid infant growth, a risk factor for later obesity.We used data from the Norwegian HUMIS study, a multi-center cohort of 2,606 mothers and newborns enrolled between 2002 and 2008. Milk samples collected 1 month after delivery from a subset of 789 women oversampled by overweight were analyzed for toxicants including polychlorinated biphenyls (PCBs), heavy metals, and pesticides. Growth was defined as change in weight-for-age z-score between 0 and 6 months among the HUMIS population, and rapid growth was defined as change in z-score above 0.67. We used a Bayesian variable selection method to determine the exposures that most explained variation in the outcome. Identified toxicants were included in logistic and linear regression models to estimate associations with growth, adjusting for maternal age, smoking, education, pre-pregnancy body mass index (BMI), gestational weight gain, parity, child sex, cumulative breastfeeding, birth weight, gestational age, and preterm status.Of 789 infants, 19.2% displayed rapid growth. The median maternal age was 29.6 years, and the median pre-pregnancy BMI was 24.0 kg/m2, with 45.3% of mothers overweight or obese. Rapid growers were more likely to be firstborn. Hexachlorobenzene, β-hexachlorocyclohexane (β-HCH), and PCB-74 were identified in the variable selection method. An interquartile range (IQR) increase in β-HCH exposure was associated with a lower odds of rapid growth (OR 0.63, 95% CI 0.42-0.94). Newborns exposed to high levels of β-HCH showed reduced infant growth (β = -0.03, 95% CI -0.05 to -0.01 for IQR increase in breast milk concentration). No other significant associations were found. Our results suggest that early life β-HCH exposure may be linked to slowed growth. Further research is warranted on the potential mechanism behind this association and the longer-term metabolic effects of perinatal β-HCH exposure.
  [Criswell R, Lenters V, Mandal S, Stigum H, et al. 2017. Ann Nutr Metab. 70(3):210-216. ]
• Prenatal and postnatal exposure to organophosphate pesticides and childhood neurodevelopment in Shandong, China.
  Although studies in laboratory animals demonstrate neurodevelopmental deficits caused by prenatal or postnatal organophosphate pesticide (OP) exposure, there is limited evidence on effects induced by not only prenatal but also postnatal exposure of children to OPs. We measured diethylphosphate (DE), dimethylphosphate (DM), and total dialkylphosphate (DAP) metabolites in maternal and child urine at 12 and 24months of age and examined their relationship with developmental quotients (DQs) in 12-month-old infants and 24-month-old children in Shandong, China.The median concentrations of total DAP metabolites (DAPs) in child urine [371.97nmol/g creatinine (12-month-old infants), 538.64nmol/g creatinine (24-month-old children)] were higher than those in maternal urine (352.67nmol/g creatinine). Prenatal OP exposure was negatively associated with 24-month-old children's DQs, especially among boys. A 10-fold increase in prenatal DEs and DAPs was associated with a 2.59- and 2.49-point decrease in social domain DQ scores in 24-month-old children (n=262), respectively. However, positive association of postnatal exposure to OPs and 24-month-old children's DQs was observed (n=237). Neither prenatal nor postnatal exposure to OPs was related to 12-month-old infants' DQs.These data suggested that prenatal OP exposure could adversely affect children's neurodevelopment at 24months of age, especially among boys. The prenatal period might be a critical window of OP exposure. In view of the positive association with postnatal OP exposure, it is necessary to interpret findings with caution.
  [Wang Y, Zhang Y, Ji L, Hu Y, et al. 2017. Environ Int. 108:119-126.]
• Residential Pesticide Exposures in Pregnancy and the Risk of Sporadic Retinoblastoma: A Report From the Children's Oncology Group.
  Study examined whether parental pesticide exposure contributes to the development of sporadic retinoblastoma. Data were collected by a large multicenter study of sporadic retinoblastoma in which parents of 99 unilateral and 56 bilateral age-matched case-control pairs were interviewed by telephone. Unilateral retinoblastoma was associated with parental insecticide use (odds ratio [OR], 2.8; confidence interval [CI], 1.1-6.7) and the use of professional lawn or landscape services (OR, 2.8; CI, 1.0-8.2). For bilateral disease study observed large point estimates for several exposures but the small number of cases rendered these results uninformative (ie, resulted in wide confidence intervals). Whether parents used the pesticide inside vs outside the home did not appear to modify risk estimates for unilateral retinoblastoma (OR, 2.5; CI, 0.9-7.0 vs OR, 2.5; CI, 1.0-6.5), nor did the type, frequency, timing related to pregnancy, or applicator of pesticide used influence estimates to an appreciable degree for disease. Results suggest that parental pesticide exposure before or during pregnancy may play a role in the development of childhood retinoblastoma. Retrospectively collected exposure data introduces the possibility of recall bias; therefore, results should be interpreted cautiously until additional studies are conducted.
  [Omidakhsh N, Ganguly A, Bunin GR, et al. 2017. Am J Ophthalmol. 176:166-173]
• Residential proximity to agricultural fumigant use and IQ, attention and hyperactivity in 7-year old children
  Our objective was to examine the relationship between residential proximity to agricultural fumigant use and neurodevelopment in 7-year old children. Participants were living in the agricultural Salinas Valley, California and enrolled in the Center for the Health Assessment of Mothers and Children Of Salinas (CHAMACOS) study. We administered the Wechsler Intelligence Scale for Children (4th Edition) to assess cognition and the Behavioral Assessment System for Children (2nd Edition) to assess behavior. We estimated agricultural fumigant use within 3, 5 and 8km of residences during pregnancy and from birth to age 7 using California's Pesticide Use Report data. We evaluated the association between prenatal (n = 285) and postnatal (n = 255) residential proximity to agricultural use of methyl bromide, chloropicrin, metam sodium and 1,3-dichloropropene with neurodevelopment. We observed decreases of 2.6 points (95% Confidence Interval (CI): -5.2, 0.0) and 2.4 points (95% CI: -4.7, -0.2) in Full-Scale intelligence quotient for each ten-fold increase in methyl bromide and chloropicrin use within 8km of the child's residences from birth to 7-years of age, respectively. There were no associations between residential proximity to use of other fumigants and cognition or proximity to use of any fumigant and hyperactivity or attention problems. These findings should be explored in larger studies.
  [Gunier RB, Bradman A, Castorina R, Holland NT, et al. 2017. Environ Res. 158:358-365]
• Adverse Associations of both Prenatal and Postnatal Exposure to Organophosphorous Pesticides with Infant Neurodevelopment in an Agricultural Area of Jiangsu Province, China.
  Prenatal exposure to organophosphorous (OP) pesticides has been found to be associated with adverse effects on child neurodevelopment, but evidence on potential effects induced by both prenatal and postnatal OP exposure in infants is limited.Our aim was to investigate the associations of both prenatal and postnatal OP exposure with birth outcomes and infant neurodevelopment.Exposure to OP in 310 mother-infant pairs was assessed by measuring dimethylphosphate (DM), diethylphosphate (DE), and total dialkylphosphate (DAP) metabolites in urines from pregnant women and their children at 2 years of age. The Gesell Developmental Schedules was administered to examine neurodevelopment of 2-year-old children.Based on the Gesell Developmental Schedules, the proportions of children with developmental delays were < 6%. Adverse associations between head circumference at birth and prenatal OP exposure were demonstrated. Both prenatal and postnatal OP exposure was significantly associated with increased risk of being developmentally delayed. Specifically, odds ratio (OR) value for prenatal DEs was 9.75 (95% CI: 1.28, 73.98, p = 0.028) in the adaptive area, whereas in the social area, OR values for postnatal DEs and DAPs were 9.56 (95% CI: 1.59, 57.57, p = 0.014) and 12.00 (95% CI: 1.23, 117.37, p = 0.033), respectively. Adverse associations were observed only in boys, not in girls.Both prenatal and postnatal OP exposure may adversely affect the neurodevelopment of infants living in the agricultural area. The present study adds to the accumulating evidence on associations of prenatal and postnatal OP exposure with infant neurodevelopment.
  [Liu P, Wu C, Chang X, Qi X, Zheng M, Zhou Z. 2016. Environ Health Perspect. 124(10):1637-1643.]
• Agricultural crop exposure and risk of childhood cancer: new findings from a case-control study in Spain.
  Childhood cancer is the main cause of disease-related death in children in Spain. Although little is known about the etiology, environmental factors are potential explanations for a fraction of the cases. Previous studies have shown pesticides to be associated with childhood cancer. The difficulty of collecting personal environmental exposure data is an important limitation; this lack of information about pesticides motivates the development of new methods to subrogate this exposure. We developed a crop exposure index based on geographic information to study the relationship between exposure to different types of crops and risk of childhood tumors.We conducted a population-based case-control study of childhood cancer covering 3350 cases and 20,365 controls in two Spanish regions. We found excess of risk among children living in the proximity of crops. For total crops our results showed excesses of risk for almost all diagnostic groups and increasing risk with increasing crop index value. Analyses by region and individual type of crop also showed excess of risk.The results suggest that living in the proximity of cultivated land could be a risk factor for several types of cancer in children.
  [Gómez-Barroso D, García-Pérez J, López-Abente G, et al. 2016. Int J Health Geogr. 15(1):18]
• An Observational Study to Evaluate Associations Between Low-Level Gestational Exposure to Organophosphate Pesticides and Cognition During Early Childhood.
  Prenatal exposure to organophosphate pesticides, which is ubiquitous, may be detrimental to neurological development. We examined 327 mother/infant pairs in Cincinnati, Ohio, between 2003 and 2006 to determine associations between prenatal exposure to organophosphate pesticides and neurodevelopment. Twice during pregnancy urinary concentrations of 6 common dialkylphosphates, nonspecific metabolites of organophosphate pesticides, were measured. Aggregate concentrations of diethylphosphates, dimethylphosphates, and total dialkylphosphates were calculated. Bayley Scales of Infant Development, Second Edition-Mental and Psychomotor Developmental indices were administered at ages 1, 2, and 3 years, the Clinical Evaluation of Language Fundamentals-Preschool, Second Edition, at age 4, and the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, at age 5. Mothers with higher urinary total dialkylphosphate concentrations reported higher levels of socioeconomic status and increased fresh fruit and vegetable intake. We found no associations between prenatal exposure to organophosphate pesticides and cognition at 1-5 years of age. In our cohort, exposure to organophosphate pesticides during pregnancy was not associated with cognition during early childhood. It is possible that a higher socioeconomic status and healthier diet may protect the fetus from potential adverse associations with gestational organophosphate pesticide exposure, or that dietary exposure to the metabolites is innocuous and not an ideal measure of exposure to the parent compound.
  [Donauer S, Altaye M, Xu Y, Sucharew H, et al. 2016. Am J Epidemiol. 184(5):410-8. ]
• Effect of Prenatal Exposure to Pesticides on Children's Health.
  The aim of this study was to summarize the current state of knowledge on pesticide-related fertility problems and disadventeges of childrens due to prenatal pesticides exposure. Available literature was analyzed. Due to the extent of the issue, the study focuses on epidemiological studies conducted in humans, despite evidence from in vitro and animal studies. It seems certain that exposure to harmful chemicals is one of the factors that may cause a decline in fertility and problems with conceiving, whereas exposure during pregnancy can impair foetal development. Prenatal exposure may also result in the occurrence of childhood cancer and neurobehavioral disorders. The meaning of the project is to summarize the role of pesticides in the process of reproduction. This applies especially to people working in agriculture, since they might be occupationally exposed to pesticides.
  [Matysiak M, Kruszewski M, Jodlowska-Jedrych B, Kapka-Skrzypczak L. 2016. J Environ Pathol Toxicol Oncol. 35(4):375-386.]
• Environmental pollutants and child health-A review of recent concerns
  In recent years, many new studies have evaluated associations between environmental pollutants and child health. This review aims to provide a broad summary of this literature, comparing the state of epidemiological evidence for the effects of a wide range of environmental contaminants (air pollutants, heavy metals, organochlorine compounds, perfluoroalkyl substances, polybrominated diphenyl ethers, pesticides, phthalates and bisphenol A) on child health outcomes. The review addresses effects on foetal growth and prematurity, neurodevelopment, respiratory and immune health, and childhood growth and obesity. Findings of recent prospective studies and meta-analyses have corroborated previous good evidence, often at lower exposure levels, for effects on foetal growth of air pollution and polychlorinated biphenyls (PCBs), for neurotoxic effects of lead, methylmercury, PCBs and organophosphate pesticides, and for respiratory health effects of air pollution. Moderate evidence has emerged for a potential role of environmental pollutants in attention deficit hyperactivity disorder and autism (lead, PCBs, air pollution), respiratory and immune health (dichlorodiphenyldichloroethylene - DDE - and PCBs), and obesity (DDE). In addition, there is now moderate evidence that certain chemicals of relatively recent concern may be associated with adverse child health outcomes, specifically perfluorooctanoate and foetal growth, and polybrominated diphenyl ethers and neurodevelopment. For other chemicals of recent concern, such as phthalates and bisphenol A, the literature is characterised by large inconsistencies preventing strong conclusions. In conclusion, since most of the recent literature evaluates common exposures in the general population, and not particularly high exposure situations, this accumulating body of evidence suggests that the unborn and young child require more protection than is currently provided. Large, coordinated research efforts are needed to improve understanding of long-term effects of complex chemical mixtures.
  [Vrijheid M, Casas M, Gascon M, Valvi D, Nieuwenhuijsen M. 2016. Int J Hyg Environ Health. 219(4-5):331-42]
• Exposure to pyrethroid pesticides and the risk of childhood brain tumors in East China
  Pesticide exposure is hypothesized as one of the risk factors for the development of childhood brain tumors (CBT). This hospital-based case-control study evaluated the association of pyrethroid pesticide exposure with the risk for CBT in a children population in East China. In total, 161 CBT cases and 170 controls were recruited from 2 children's medical centers in Shanghai (Xinhua Hospital and Shanghai Children's Medical Center) between September 2012 and June 2015. The cases and controls were matched for age, sex, and province of residence. Pyrethroid pesticide exposure was evaluated by urinalysis of 3 nonspecific metabolites of pyrethroids (cis-DCCA, trans-DCCA, and 3-PBA) using gas chromatography-mass spectrometry (GC-MS) detection and by administering a questionnaire. Unconditional logistic regression showed that trans-DCCA, 3-PBA, and total metabolites (sum of the 3 metabolites) were positively associated with the increased risk of CBT. Children in the highest quartile had a nearly 3-fold increased risk of CBT compared with those in the lowest quartile after adjusting for confounding factors (trans-DCCA, odds ratio (OR) = 2.58, 95% confidence interval (CI), 1.38-4.80, p = 0.003; 3-PBA, OR = 3.26, 95% CI, 1.73-6.14, p < 0.0001; total metabolites, OR = 3.60, 95% CI, 1.87-6.93, p < 0.0001). We also found that exposure to both mosquitocide and cockroach killer was related to the increased risk of CBT (mosquitocide, OR = 1.68, 95% CI, 1.06-2.67, p = 0.027; cockroach killer, OR = 1.83, 95% CI, 1.13-2.95, p = 0.013). These findings indicate that exposure to pyrethroid pesticides might be associated with increased risk of CBT. Prospective cohort studies with larger sample sizes are required to confirm this conclusion
  [Chen S, Gu S, Wang Y, Yao Y, et al. 2016. Environ Pollut. 218:1128-1134.]
• Increased risk of attention-deficit/hyperactivity disorder associated with exposure to organophosphate pesticide in Taiwanese children.
  Attention-deficit/hyperactivity disorder (ADHD) is male predominated, and the etiology of this disorder remains unclear. Past studies have assessed the association of low-level organophosphate pesticide exposure with childhood ADHD cross-sectionally and prospectively. However, the results have been inconsistent. A first case-control study was performed to investigate the relationship between organophosphate pesticide exposure and ADHD with adjusted covariates. We recruited 97 doctor-diagnosed ADHD cases and 110 non-ADHD controls who were 4-15 years of age. Exposure was assessed using urinary levels of dialkylphosphate metabolites, which are biomarkers of OP pesticide exposure. Blood lead levels and polymorphisms of two commonly verified dopaminergic-related genes (the D4 dopamine receptor gene DRD4 and the dopamine transporter gene DAT1) were also analyzed. The sociodemographics and lifestyles of the children and of the mothers during pregnancy were collected using a questionnaire. The blood lead levels of both groups were similar (1.57 ± 0.73 vs. 1.73 ± 0.77 μg/dL, p = 0.15). Significant urinary concentration differences in one of the six dialkylphosphate metabolites, dimethylphosphate (DMP), were found between ADHD and control subjects (322.92 ± 315.68 vs. 224.37 ± 156.58 nmol/g cr., p < 0.01). A dose-response relationship was found between urinary concentrations of DMP and ADHD in both crude and adjusted analyses (p for trend<0.05). Children with higher urinary DMP concentrations may have a twofold to threefold increased risk of being diagnosed with ADHD. We report a dose-response relationship between child DMP levels and ADHD. Organophosphate pesticide exposure may have deleterious effects on children's neurodevelopment, particularly the development of ADHD.
  [Yu CJ, Du JC, Chiou HC, Chung MY, et al. 2016. Andrology. 4(4):695-705.]
• Negative Role of the Environmental Endocrine Disruptors in the Human Neurodevelopment
  The endocrine disruptors (EDs) are able to influence the endocrine system, mimicking or antagonizing hormonal molecules. They are bio-persistent for their degradation resistance in the environment. Our research group has investigated by gas chromatography-mass spectrometry (GC-MS) the EDs presence in 35 brain samples, coming from 27 cases of sudden intrauterine unexplained death syndrome (SIUDS) and 8 cases of sudden infant death syndrome (SIDS), collected by centralization in the last year (2015). More in detail, a mixture of 25 EDs has been subjected to analytical procedure, following standard protocols. Among the target analytes, some organochlorine pesticides, that is α-chlordane, γ-chlordane, heptachlor, p,p-DDE, p,p-DDT, and the two most commonly used organophosphorus pesticides (OPPs), chlorpyrifos and chlorfenvinfos, have been found in seven and three samples, respectively. The analytical procedure used to detect the presence of environmental EDs in cortex samples has been successfully implemented on SIUDS and SIDS victims. The environmental EDs have been found to be able to overcome the placental barrier, reaching also the basal ganglia assigned to the control of the vital functions. This finding, related to the OPPs bio-persistence, implies a conceptual redefinition of the fetal-placental and fetal blood-brain barriers: not real safety barriers but simply time-deferral mechanisms of absorption.
  [Roncati L, Termopoli V, Pusiol T. 2016. Front Neurol. 7:143.]
• Passive exposure to agricultural pesticides and risk of childhood leukemia in an Italian community.
  Exposure to pesticides has been suggested as a risk factor for childhood leukemia, but definitive evidence on this relation and the specific pesticides involved is still not clear.We carried out a population-based case-control study in a Northern Italy community to assess the possible relation between passive exposure to agricultural pesticides and risk of acute childhood leukemia.We assessed passive pesticide exposure of 111 childhood leukemia cases and 444 matched controls by determining density and type of agricultural land use within a 100-m radius buffer around children's homes. We focused on four common crop types, arable, orchard, vineyard and vegetable, characterized by the use of specific pesticides that are potentially involved in childhood induced leukemia. The use of these pesticides was validated within the present study. We computed the odds ratios (OR) of the disease and their 95% confidence intervals (CI) according to type and density of crops around the children's homes, also taking into account traffic pollution and high-voltage power line magnetic field exposure. Childhood leukemia risk did not increase in relation with any of the crop types with the exception of arable crops, characterized by the use of 2.4-D, MCPA, glyphosate, dicamba, triazine and cypermethrin. The very few children (n=11) residing close to arable crops had an OR for childhood leukemia of 2.04 (95% CI 0.50-8.35), and such excess risk was further enhanced among children aged
  [Malagoli C, Costanzini S, Heck JE, Malavolti M, et al. 2016. Int J Hyg Environ Health. 219(8):742-748.]
• Pesticide exposure and neurodevelopment in children aged 6-9 years from Talamanca, Costa Rica.
  Certain pesticides may affect children's neurodevelopment. We assessed whether pesticide exposure was associated with impaired neurobehavioral outcomes in children aged 6-9 years. We conducted a cross-sectional study in 140 children living near banana plantations and plantain farms in the Talamanca County, Costa Rica and assessed their neurobehavioral performance. Exposure was determined by analyzing urinary metabolites of chlorpyrifos (3,5,6-trichloro-2-pyridinol, TCPy), mancozeb (ethylenethiourea, ETU), and pyrethroids (3-phenoxybenzoic acid, 3-PBA). Repeated urine samples were obtained for 36 children. We estimated associations of pesticide concentrations with neurobehavioral outcomes using multivariable linear and logistic regression models. Median (25th-75th percentiles) TCPy, ETU, and 3-PBA concentrations were 1.4 (.7-3.1), 1.2 (.7-3.0), and .8 (.5-1.5) μg/L, respectively. Intraclass correlation coefficients (ICC) ranged between .32 and .67. After adjustment for potential confounders, higher urinary TCPy concentrations were associated with poorer working memory in boys (n = 59) (β per 10-fold increase in TCPy concentrations = -7.5, 95% CI: -14.4, -.7); poorer visual motor coordination (β = -1.4, 95% CI: -2.7, -.1); increased prevalence of parent-reported cognitive problems/inattention (adjusted OR per 10-fold increase in urinary concentrations = 5.8, 95% CI: 1.6, 22.9), oppositional disorders (aOR = 3.9, 95% CI: 1.0, 16.0), and ADHD (aOR = 6.8, 95% CI: 1.8, 28.6), and; decreased ability to discriminate colors (aOR = 6.6, 95% CI: 1.6, 30.3; the higher the score the worse). Higher ETU concentrations were associated with poorer verbal learning outcomes (β = -7.0, 95% CI: -12.7, -1.3). Higher 3-PBA concentrations were associated with poorer processing speed scores, particularly in girls (β = -8.8, 95% CI: -16.1, -1.4). Our findings indicate that children living near banana and plantain plantations are exposed to pesticides that may affect their neurodevelopment, which for certain domains may differ between boys and girls. We recommend the implementation of measures to reduce pesticide exposure in children living nearby banana plantations.
  [van Wendel de Joode B, Mora AM, Lindh CH, et al. 2016. Cortex. 85:137-150. ]
• Potential role of organochlorine pesticides in the pathogenesis of neurodevelopmental, neurodegenerative, and neurobehavioral disorders: A review.
  Organochlorine pesticides (OCPs) are persistent and bioaccumulative environmental contaminants with potential neurotoxic effects. The growing body of evidence has demonstrated that prenatal exposure to organochlorines (OCs) is associated with impairment of neuropsychological development. The hypothesis is consistent with recent studies emphasizing the correlation of environmental as well as genetic factors to the pathophysiology of neurodevelopmental and neurobehavioral defects. It has been suggested that maternal exposure to OCPs results in impaired motor and cognitive development in newborns and infants. Moreover, in utero exposure to these compounds contributes to the etiology of autism. Although impaired neurodevelopment occurs through prenatal exposure to OCs, breastfeeding causes postnatal toxicity in the infants. Parkinson's disease (PD) is another neurological disorder, which has been associated with exposure to OCs, leading to α-synuclein accumulation and depletion of dopaminergic neurons. The study aimed to review the potential association between pre- and post-natal exposure to OCs and impaired neurodevelopmental processes during pregnancy and neuropsychological diseases such as PD, behavioral alterations, seizures and autism.
  [Saeedi Saravi SS, Dehpour AR. 2016. Life Sci.145:255-64.]
• Prenatal exposure to multiple pesticides is associated with auditory brainstem response at 9months in a cohort study of Chinese infants
  Pesticides are associated with poorer neurodevelopmental outcomes, but little is known about the effects on sensory functioning.Auditory brainstem response (ABR) and pesticide data were available for 27 healthy, full-term 9-month-old infants participating in a larger study of early iron deficiency and neurodevelopment. Cord blood was analyzed by gas chromatography-mass spectrometry for levels of 20 common pesticides. The ABR forward-masking condition consisted of a click stimulus (masker) delivered via ear canal transducers followed by an identical stimulus delayed by 8, 16, or 64 milliseconds (ms). ABR peak latencies were evaluated as a function of masker-stimulus time interval. Shorter wave latencies reflect faster neural conduction, more mature auditory pathways, and greater degree of myelination. Linear regression models were used to evaluate associations between total number of pesticides detected and ABR outcomes. We considered an additive or synergistic effect of poor iron status by stratifying our analysis by newborn ferritin (based on median split).Infants in the sample were highly exposed to pesticides; a mean of 4.1 pesticides were detected (range 0-9). ABR Wave V latency and central conduction time (CCT) were associated with the number of pesticides detected in cord blood for the 64ms and non-masker conditions. A similar pattern seen for CCT from the 8ms and 16ms conditions, although statistical significance was not reached. Increased pesticide exposure was associated with longer latency. The relation between number of pesticides detected in cord blood and CCT depended on the infant's cord blood ferritin level. Specifically, the relation was present in the lower cord blood ferritin group but not the higher cord blood ferritin group.ABR processing was slower in infants with greater prenatal pesticide exposure, indicating impaired neuromaturation. Infants with lower cord blood ferritin appeared to be more sensitive to the effects of prenatal pesticide exposure on ABR latency delay, suggesting an additive or multiplicative effect.
  [Sturza J, Silver MK, Xu L, Li M, et al. 2016. Environ Int.92-93:478-85.]
• Prenatal Organophosphorus Pesticide Exposure and Child Neurodevelopment at 24 Months: An Analysis of Four Birth Cohorts.
  Organophosphorus pesticides (OPs) are used in agriculture worldwide. Residential use was common in the United States before 2001.We conducted a pooled analysis of four birth cohorts (children's centers; n = 936) to evaluate associations of prenatal exposure to OPs with child development at 24 months. Using general linear models, we computed site-specific and pooled estimates of the association of total dialkyl (ΣDAP), diethyl (ΣDEP), and dimethylphosphate (ΣDMP) metabolite concentrations in maternal prenatal urine with mental and psychomotor development indices (MDI/PDI) and evaluated heterogeneity by children's center, race/ethnicity, and PON1 genotype.There was significant heterogeneity in the center-specific estimates of association for ΣDAP and ΣDMP and the MDI (p = 0.09, and p = 0.05, respectively), as well as heterogeneity in the race/ethnicity-specific estimates for ΣDAP (p = 0.06) and ΣDMP (p = 0.02) and the MDI. Strong MDI associations in the CHAMACOS population per 10-fold increase in ΣDAP (β = -4.17; 95% CI: -7.00, -1.33) and ΣDMP (β = -3.64; 95% CI: -5.97, -1.32) were influential, as were associations among Hispanics (β per 10-fold increase in ΣDAP = -2.91; 95% CI: -4.71, -1.12). We generally found stronger negative associations of ΣDAP and ΣDEP with the 24-month MDI for carriers of the 192Q PON1 allele, particularly among blacks and Hispanics. Data pooling was complicated by center-related differences in subject characteristics, eligibility, and changes in regulations governing residential use of OPs during the study periods. Pooled summary estimates of prenatal exposure to OPs and neurodevelopment should be interpreted with caution because of significant heterogeneity in associations by center, race/ethnicity, and PON1 genotype. Subgroups with unique exposure profiles or susceptibilities may be at higher risk for adverse neurodevelopment following prenatal exposure.
  [Engel SM, Bradman A, Wolff MS, Rauh VA, Harley KG, Yang JH, Hoepner LA, et al. 2016. Environ Health Perspect. 124(6):822-30]
• Prenatal Triclosan Exposure and Anthropometric Measures Including Anogenital Distance in Danish Infants.
  Prenatal triclosan exposure is associated with reduced head circumference, a trait linked to cognitive impairment.
  [Lassen et al. 2016. Environmental Health Perspectives doi: 10.1289/ehp.1409637.]
• Research Review: Environmental exposures, neurodevelopment, and child mental health - new paradigms for the study of brain and behavioral effects.
  Environmental exposures play a critical role in the genesis of some child mental health problems.We open with a discussion of children's vulnerability to neurotoxic substances, changes in the distribution of toxic exposures, and cooccurrence of social and physical exposures. We address trends in prevalence of mental health disorders, and approaches to the definition of disorders that are sensitive to the subtle effects of toxic exposures. We suggest broadening outcomes to include dimensional measures of autism spectrum disorders, attention-deficit hyperactivity disorder, and child learning capacity, as well as direct assessment of brain function.We consider the impact of two important exposures on children's mental health: lead and pesticides. We argue that longitudinal research designs may capture the cascading effects of exposures across biological systems and the full-range of neuropsychological endpoints. Neuroimaging is a valuable tool for observing brain maturation under varying environmental conditions. A dimensional approach to measurement may be sensitive to subtle subclinical toxic effects, permitting the development of exposure-related profiles and testing of complex functional relationships between brain and behavior. Questions about the neurotoxic effects of chemicals become more pressing when viewed through the lens of environmental justice.Reduction in the burden of child mental health disorders will require longitudinal study of neurotoxic exposures, incorporating dimensional approaches to outcome assessment, and measures of brain function. Research that seeks to identify links between toxic exposures and mental health outcomes has enormous public health and societal value.
  [Rauh VA, Margolis AE. 2016. J Child Psychol Psychiatry. 57(7):775-93.]
• Residential proximity to organophosphate and carbamate pesticide use during pregnancy, poverty during childhood, and cognitive functioning in 10-year-old children.
  Low-income communities and communities of color have been shown to experience disproportionate exposure to agricultural pesticides, which have been linked to poorer neurobehavioral outcomes in infants and children. Few studies have assessed health impacts of pesticide mixtures in the context of socioeconomic adversity.We evaluated associations between both nearby agricultural pesticide use and poverty measures and cognitive abilities in 10-year-old children (n = 501) using data from a longitudinal birth cohort study linked with data from the California Pesticide Use Reporting system and the American Community Survey. Associations were assessed using multivariable linear regression.Children of mothers in the highest quartile compared to the lowest quartile of proximal pesticide use had lower performance on Full Scale IQ [β = -3.0; 95% Confidence Interval (CI) = (-5.6, -0.3)], Perceptual Reasoning [β = -4.0; (-7.6, -0.4)], and Working Memory [β = -2.8; (-5.6, -0.1)]. Belonging to a household earning an income at or below the poverty threshold was associated with approximately two point lower scores on Full Scale IQ, Verbal Comprehension, and Working Memory. Living in the highest quartile of neighborhood poverty at age 10 was associated with approximately four point lower performance on Full Scale IQ, Verbal Comprehension, Perceptual Reasoning, and Working memory.Residential proximity to OP and carbamate pesticide use during pregnancy and both household- and neighborhood-level poverty during childhood were independently associated with poorer cognitive functioning in children at 10 years of age.
  [Rowe C, Gunier R, Bradman A, Harley KG, et al. 2016. Environ Res.150:128-37.]
• Chronic adverse effects of long-term exposure of children to dichlorodiphenyltrichloroethane (DDT) through indoor residual spraying: A systematic review.
  Malaria remains a significant public health problem in endemic regions of the world, most especially in sub-Saharan Africa. As part of the global efforts to control malaria, dichlorodiphenyltrichloroethane (DDT), a cheap and effective chemical, was endorsed by the World Health Organization for use in indoor residual spraying (IRS). However, in the light of evidence on the acute toxicity of DDT, concerns have grown about the safety or the possible chronic health effects from the continued use of this persistent chemical, generating much debate and research efforts over the years. The purpose of this study was to identify, appraise and synthesise evidence about the chronic adverse effects of long-term exposure to DDT in children, 0-18 years, in zones where IRS is practised, in order to contribute to informing policy decisions.Twenty-seven electronic databases were systematically searched using pre-defined inclusion/exclusion criteria. Two were trial registers while 25 others indexed studies of various designs. Only nine studies met the inclusion/exclusion criteria out of 3281 hits generated. Five of the studies are of high quality while four are of moderate quality. For the three studies on neurodevelopment, evidence suggestive of negative impact of DDT was found. For the three studies on endocrine/congenital disorders, ambivalent evidence existed. In the case of the immunity-related outcome, there was growing but insufficient evidence of negative effect. The only study on survival outcome was inconclusive. Empirically, insufficient evidence exists with regard to the chronic adverse effects of long-term exposure of children to DDT through IRS. Considering the dearth of studies and the fact that many adverse effects might take much longer time to manifest, inferences drawn are weak. It would therefore require a series of well-coordinated observational studies done in the context of IRS to adequately address this evidence gap in the future.
  [Osunkentan AO, Evans D. 2015. Rural Remote Health.15(2):2889.]
• DDT Exposure in Utero and Breast Cancer
  Context: Currently no direct evidence links in utero dichlorodiphenyltrichloroethane (DDT) exposure to human breast cancer. However, in utero exposure to another xenoestrogen, diethylstilbestrol, predicts an increased breast cancer risk. If this finding extends to DDT, it could have far-reaching consequences. Many women were heavily exposed in utero during widespread DDT use in the 1960s. They are now reaching the age of heightened breast cancer risk. DDT exposure persists and use continues in Africa and Asia without clear knowledge of the consequences for the next generation.

  Hypothesis: In utero exposure to DDT is associated with an increased risk of breast cancer.

  Design: This was a case-control study nested in a prospective 54-year follow-up of 9300 daughters in the Child Health and Development Studies pregnancy cohort (n = 118 breast cancer cases, diagnosed by age 52 y and 354 controls matched on birth year).

  Setting and participants: Kaiser Foundation Health Plan members who received obstetric care in Alameda County, California, from 1959 to 1967, and their adult daughters participated in the study.

  Main outcome measure: Daughters' breast cancer diagnosed by age 52 years as of 2012 was measured.

  Results: Maternal o,p'-DDT predicted daughters' breast cancer (odds ratio fourth quartile vs first = 3.7, 95% confidence interval 1.5-9.0). Mothers' lipids, weight, race, age, and breast cancer history did not explain the findings.

  Conclusions: This prospective human study links measured DDT exposure in utero to risk of breast cancer. Experimental studies are essential to confirm results and discover causal mechanisms. Findings support classification of DDT as an endocrine disruptor, a predictor of breast cancer, and a marker of high risk.
  [Cohn, B. et al. (2015) DDT exposure in utero and breast cancer, The Journal of Clinical Endocrinology and Metabolism. Available at: https://pubmed.ncbi.nlm.nih.gov/26079774/. ]

• Elucidating the Links Between Endocrine Disruptors and Neurodevelopment
  Recent data indicate that approximately 12% of children in the United States are affected by neurodevelopmental disorders, including attention deficit hyperactivity disorder, learning disorders, intellectual disabilities, and autism spectrum disorders. Accumulating evidence indicates a multifactorial etiology for these disorders, with social, physical, genetic susceptibility, nutritional factors, and chemical toxicants acting together to influence risk. Exposure to endocrine-disrupting chemicals during the early stages of life can disrupt normal patterns of development and thus alter brain function and disease susceptibility later in life. This article highlights research efforts and pinpoints approaches that could shed light on the possible associations between environmental chemicals that act on the endocrine system and compromised neurodevelopmental outcomes.
  [Schug TT, Blawas AM, Gray K, et al. 2015. Endocrinology. 156(6):1941-51.]
• Maternal Chemical and Drug Intolerances: Potential Risk Factors for Autism and Attention Deficit Hyperactivity Disorder (ADHD)
  Purpose: The aim of this study was to assess whether chemically intolerant women are at greater risk for having a child with autism spectrum disorders (ASD) or attention deficit hyperactivity disorder (ADHD).

  Methods: We conducted a case–control study of chemical intolerance among mothers of children with ASD (n = 282) or ADHD (n = 258) and children without these disorders (n = 154). Mothers participated in an online survey consisting of a validated chemical intolerance screening instrument, the Quick Environmental Exposure and Sensitivity Inventory (QEESI). Cases and controls were characterized by parental report of a professional diagnosis. We used a one-way, unbalanced analysis of variance to compare means across the 3 groups.

  Results: Both mothers of children with ASD or ADHD had significantly higher mean chemical intolerance scores than did mothers of controls, and they were more likely to report adverse reactions to drugs. Chemically intolerant mothers were 3 times more likely (odds ratio, 3.01; 95% confidence interval, 1.50–6.02) to report having a child with autism or 2.3 times more likely (odds ratio, 2.3; 95% confidence interval, 1.12–5.04) to report a child with ADHD. Relative to controls, these mothers report their children are more prone to allergies (P < .02), have strong food preferences or cravings (P < .003), and have greater sensitivity to noxious odors (P < .04).

  Conclusion: These findings suggest a potential association between maternal chemical intolerance and a diagnosis of ADHD or ASD in their offspring.
  [Heilbrun, L.P. et al. (2015) Maternal chemical and drug intolerances: Potential risk factors for autism and attention deficit hyperactivity disorder (ADHD), The Journal of the American Board of Family Medicine. Available at: https://www.jabfm.org/content/28/4/461. ]

• Organic Compounds Detected in Deciduous Teeth: A Replication Study from Children with Autism in Two Samples
  Biological samples are an important part of investigating toxic exposures and disease outcomes. However, blood, urine, saliva, or hair can only reflect relatively recent exposures. Alternatively, deciduous teeth have served as a biomarker of early developmental exposure to heavy metals, but little has been done to assess organic toxic exposures such as pesticides, plastics, or medications. The purpose of our study was to determine if organic chemicals previously detected in a sample of typically developing children could be detected in teeth from a sample of children with autism. Eighty-three deciduous teeth from children with autism spectrum disorders (ASD) were chosen from our tooth repository. Organic compounds were assessed using liquid chromatography tandem mass spectrometry and gas chromatography methods. Consistent with a prior report from Camann et al., (2013), we have demonstrated that specific semivolatile organic chemicals relevant to autism etiology can be detected in deciduous teeth. This report provides evidence that teeth can be useful biomarkers of early life exposure for use in epidemiologic case-control studies seeking to identify differential unbiased exposures during development between those with and without specific disorders such as autism.
  [Palmer RF, Heilbrun L, Camann D, Yau A, et al. 2015. J Environ Public Health. 2015:862414.]
• Pre- and postnatal exposures to pesticides and neurodevelopmental effects in children living in agricultural communities from South-Eastern Spain.
  Childrens exposure to neurotoxic compounds poses a major problem to public health because oftheir actively developing brain that makes them highly vulnerable. However, limited information is available on neuropsychological effects in children associated with pre- and postnatal exposures to pesticides.Study's aim was to evaluate the association between current and pre- and postnatal exposures to pesticides and their effects on neurodevelopment in children aged 6–11 years living in agricultural communities from South-Eastern Spain.An ambispective study was conducted on 305 children aged 6–11 years randomly selected from public schools of the study area. Current exposure to organophosphate pesticides was assessed measuring children's urinary levels of dialkylphosphates (DAPs). Both prenatal and postnatal residential exposure to pesticides was estimated by developing a geographical information system (GIS) technology-based index that integrated distance-weighted measure of agricultural surface, time-series of crop areas per municipality and year, and land-use maps. Neuropsychological performance was evaluated with the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV).Greater urinary DAP levels were associated with a poorer performance on intelligence quotient and verbal comprehension domain, with effects being more prominent in boys than in girls. The influence of an increase in 10 ha per year in crop surface around the child's residence during the postnatal period was associated with decreased intelligence quotient, processing speed and verbal comprehension scores. As regards prenatal exposure to pesticides, a poor processing speed performance was observed. These effects were also more prominent in boys than in girls.Our results suggest that postnatal exposure to pesticides can negatively affect children's neuropsychological performance. Prenatal exposure was weakly associated to neurodevelopment impairment.
  [González-Alzaga B, Hernández AF, Rodríguez-Barranco M, et al. 2015. Environ Int. 85:229-37. ]
• Prenatal DDT and DDE exposure and child IQ in the CHAMACOS cohort.
  Although banned in most countries, dichlorodiphenyl-trichloroethane (DDT) continues to be used for vector control in some malaria endemic areas. Previous findings from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort study found increased prenatal levels of DDT and its breakdown product dichlorodiphenyl-dichloroethylene (DDE) to be associated with altered neurodevelopment in children at 1 and 2years of age. In this study, we combined the measured maternal DDT/E concentrations during pregnancy obtained for the prospective birth cohort with predicted prenatal DDT and DDE levels estimated for a retrospective birth cohort. Using generalized estimating equation (GEE) and linear regression models, we evaluated the relationship of prenatal maternal DDT and DDE serum concentrations with children's cognition at ages 7 and 10.5years as assessed using the Full Scale Intelligence Quotient (IQ) and 4 subtest scores (Working Memory, Perceptual Reasoning, Verbal Comprehension, and Processing Speed) of the Wechsler Intelligence Scale for Children (WISC). In GEE analyses incorporating both age 7 and 10.5 scores (n=619), we found prenatal DDT and DDE levels were not associated with Full Scale IQ or any of the WISC subscales (p-value>0.05). In linear regression analyses assessing each time point separately, prenatal DDT levels were inversely associated with Processing Speed at age 7years (n=316), but prenatal DDT and DDE levels were not associated with Full Scale IQ or any of the WISC subscales at age 10.5years (n=595). We found evidence for effect modification by sex. In girls, but not boys, prenatal DDE levels were inversely associated with Full Scale IQ and Processing Speed at age 7years. We conclude that prenatal DDT levels may be associated with delayed Processing Speed in children at age 7years and the relationship between prenatal DDE levels and children's cognitive development may be modified by sex, with girls being more adversely affected.
  [Gaspar FW, Harley KG, Kogut K, Chevrier J, et al. 2015. Environ Int. 85:206-12]
• Prenatal exposure to the organophosphate pesticide chlorpyrifos and childhood tremor.
  The organophosphate insecticide chlorpyrifos (CPF), widely used for agricultural purposes, has been linked to neurodevelopmental deficits. Possible motor effects at low to moderate levels of exposure have not been evaluated.Prenatal exposure to CPF was measured in umbilical cord blood in a sample of 263 inner-city minority children, who were followed prospectively. At approximately 11 years of age (mean age 10.9 ± 0.85 years, range=9.0-13.9), during a neuropsychological assessment, children were asked to draw Archimedes spirals. These were rated by a senior neurologist specializing in movement disorders who was blind to CPF exposure level.Compared to all other children, those with prenatal CPF exposure in the upper quartile range (n=43) were more likely to exhibit mild or mild to moderate tremor (≥ 1) in either arm (p=0.03), both arms (p=0.02), the dominant arm (p=0.01), and the non-dominant arm (p=0.055). Logistic regression analyses showed significant CPF effects on tremor in both arms, either arm, the dominant arm (p-values <0.05), and the non-dominant arm (p=0.06), after adjustment for sex, age at testing, ethnicity, and medication. Prenatal CPF exposure is associated with tremor in middle childhood, which may be a sign of the insecticide's effects on nervous system function.
  [Rauh VA, Garcia WE, Whyatt RM, Horton MK, et al. 2015. Neurotoxicology. 51:80-6. ]
• Pyrethroid insecticide exposure and cognitive developmental disabilities in children: The PELAGIE mother-child cohort.
  Pyrethroid insecticides are widely used in agriculture and in homes. Despite the neurotoxicity of these insecticides at high doses, few studies have examined whether lower-level exposures could adversely affect children's neurodevelopment. The PELAGIE cohort included 3421 pregnant women from Brittany, France between 2002 and 2006. When their children reached their sixth birthday, 428 mothers from the cohort were randomly selected, successfully contacted and found eligible. A total of 287 (67%) mothers agreed to participate with their children in the neuropsychological follow-up. Two cognitive domains were assessed by the Wechsler Intelligence Scale for Children: verbal comprehension and working memory. Five pyrethroid and two organophosphate insecticide metabolites were measured in maternal and child first-void urine samples collected between 6 and 19 gestational weeks and at 6years of age, respectively. Linear regression models were used to estimate associations between cognitive scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders. Maternal prenatal pyrethroid metabolite concentrations were not consistently associated with any children's cognitive scores. By contrast, childhood 3-PBA and cis-DBCA concentrations were both negatively associated with verbal comprehension scores (P-trend=0.04 and P-trend<0.01, respectively) and with working memory scores (P-trend=0.05 and P-trend<0.01, respectively). No associations were observed for the three other childhood pyrethroid metabolite concentrations (4-F-3-PBA, cis-DCCA, and trans-DCCA). Low-level childhood exposures to deltamethrin (as cis-DBCA is its principal and selective metabolite), in particular, and to pyrethroid insecticides, in general (as reflected in levels of the 3-PBA metabolite) may negatively affect neurocognitive development by 6years of age. Whatever their etiology, these cognitive deficits may be of importance educationally, because cognitive impairments in children interfere with learning and social development. Potential causes that can be prevented are of paramount public health importance.
  [Viel JF, Warembourg C, Le Maner-Idrissi G, Lacroix A, et al. 2015. Environ Int. 82:69-75.]
• Serum Biomarkers of Exposure to Perfluoroalkyl Substances in Relation to Serum Testosterone and Measures of Thyroid Function among Adults and Adolescents from NHANES 2011–2012
  Perfluoroalkyl substances (PFASs) are a group of environmentally-persistent chemicals that have been widely used in many industrial applications. There is human and animal evidence that PFASs may alter levels of reproductive and thyroid-related hormones. However, human studies on the potential age-related effects of PFASs on these outcomes among males and females are limited. We explored the relationship between serum PFASs and serum total testosterone (T), thyroid stimulating hormone (TSH), and free and total triiodothyronine (FT3, TT3) and thyroxine (FT4, TT4) among males and females 12 to 80 years of age from the 2011–2012 cycle of the National Health and Nutrition Examination Survey. Associations were assessed using multiple linear regression models that were stratified on sex and age categories. Effect estimates from the majority of the adjusted models were not statistically significant. However, exposure to PFASs may be associated with increases in FT3, TT3, and FT4 among adult females, but during adolescence, PFASs may be related to increases in TSH among males and decreases in TSH among females. No significant relationships were observed between PFASs and T in any of the models. These findings suggest that exposure to PFASs may disrupt thyroid hormone homeostasis.
  [Lewis, R.C., Johns, L.E. and Meeker, J.D. (2015) Serum biomarkers of exposure to perfluoroalkyl substances in relation to serum testosterone and measures of thyroid function among adults and adolescents from NHANES 2011-2012, International journal of environmental research and public health. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483690/. ]
• Exposures of 129 Preschool Children to Organochlorines, Organophosphates, Pyrethroids, and Acid Herbicides at Their Homes and Daycares in North Carolina
  Few data exist on the concurrent exposures of young children to past-use and current-use pesticides in their everyday environments. In this further analysis of study data, we quantified the potential exposures and intake doses of 129 preschool children, ages 20 to 66 months, to 16 pesticides (eight organochlorines, two organophosphates, three pyrethroids, and three acid herbicides). Environmental samples (soil, dust, outdoor air, and indoor air) and personal samples (hand wipes, solid food, and liquid food) were collected at 129 homes and 13 daycare centers in six counties in North Carolina between 2000 and 2001. α-Chlordane, γ-chlordane, heptachlor, chlorpyrifos, diazinon, cis-permethrin, trans-permethrin, and 2,4-dichlorophenoxyacetic acid (2,4-D) were detected ≥50% in two or more media in both settings. Of these pesticides, the children’s estimated median potential intake doses through dietary ingestion, nondietary ingestion, and inhalation routes were the highest for 2,4-D and cis/trans-permethrin (both 4.84 ng/kg/day), cis/trans-permethrin (2.39 ng/kg/day), and heptachlor (1.71 ng/kg/day), respectively. The children’s estimated median potential aggregate intake doses by all three routes were quantifiable for chlorpyrifos (4.6 ng/kg/day), cis/trans-permethrin (12.5 ng/kg/day), and 2,4-D (4.9 ng/kg/day). In conclusion, these children were likely exposed daily to several pesticides from several sources and routes at their homes and daycares.
  [Morgan, M.K., Wilson, N.K. and Chuang, J.C. (2014) Exposures of 129 Preschool Children to Organochlorines, Organophosphates, Pyrethroids, and Acid Herbicides at Their Homes and Daycares in North Carolina, International Journal of Environmental Research and Public Health. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC4025031/.]
• Health Status of Children of Migrant Farm Workers: Farm Worker Family Health Program, Moultrie, Georgia
  Objectives. We evaluated the health status of migrant farmworkers’ children served by the Farm Worker Family Health Program (FWFHP) in Moultrie, Georgia.

  Methods. We analyzed data from children aged 0 to 16 years examined through the FWFHP from 2003 to 2011 (n across years = 179–415). We compared their prevalence of overweight, obesity, elevated blood pressure, anemia, and stunting with that of children in the United States and Mexico.

  Results. Across study years, prevalence of overweight, obesity, elevated blood pressure, anemia, and stunting ranged from 13.5% to 21.8%, 24.0% to 37.4%, 4.1% to 20.2%, 10.1% to 23.9%, and 1% to 6.4%, respectively. Children in the FWFHP had a higher prevalence of obesity than children in all comparison groups, and FWFHP children aged 6 to 12 years had a higher prevalence of elevated blood pressure than all comparison groups. Older FWFHP children had a higher prevalence of anemia than US children and Mexican children. Children in FWFHP had a higher prevalence of stunting than US and Mexican American children.

  Conclusions. We observed an elevated prevalence of obesity, anemia among older age groups, and stunting in this sample of children of migrant workers.
  [Nichols, M., Stein, A.D. and Wold, J.L. (2014) ‘Health status of children of migrant farm workers: Farm Worker Family Health Program, Moultrie, Georgia’, American Journal of Public Health, 104(2), pp. 365–370. Available at: https://ajph.aphapublications.org/doi/full/10.2105/AJPH.2013.301511. ]

• Increased risk of childhood brain tumors among children whose parents had farm-related pesticide exposures during pregnancy.
  Malignant brain tumors rank second in both incidence and mortality by cancer in children, and they are the leading cause of cancer death in children. While there are several studies which link pesticide exposure to increased risk of CBT, findings have been inconsistent. Authors performed a meta-analysis on 15 published epidemiological studies to test that in utero exposure to pesticides may be involved in the development of brain cancer in children. Findings of meta-analyses revealed a significantly increased risk of CBT among children whose mothers had farm-related exposures during pregnancy (RR=1.48, 95% CI=1.18-1.84). A dose response was recognized when this risk estimate was compared to those for risk of CBT from maternal exposure to non-agricultural pesticides (e.g., home extermination, pest strips) during pregnancy (RR=1.36, 1.10-1.68), and risk of CBT among children exposed to agricultural activities (RR=1.32, 1.04-1.67). Three studies combined for the paternal exposure to pesticides during preconception produced a calculated summary risk estimate of odds ratio (OR) = 2.29 (95% CI: 1.39-3.78). Meta-analysis of five studies of paternal exposure to pesticides during pregnancy produced a final calculated summary risk estimate of OR = 1.63 (95% CI: 1.16-2.31). The search of the CTD databases revealed association between herbicide and astrocytoma and more than 300 genes are altered by exposure to herbicide, fungicide, insecticide or pesticides. Based on the collective results of these meta-analyses, it appears that pesticide exposure may increase risk of CBT, with preconception and prenatal exposures being especially important factors in increasing risk of its development.
  [Kunkle B, Bae S, Singh KP, Roy D. 2014. JP J Biostat. 11(2):89-101]
• Maternal perchlorate levels in women with borderline thyroid function during pregnancy and the cognitive development of their offspring: data from the Controlled Antenatal Thyroid Study
  Objective: Thyroid dysfunction is associated with impaired cognitive development. Perchlorate decreases thyroidal iodine uptake, potentially reducing thyroid hormone production. It is unclear whether perchlorate exposure in early life affects neurodevelopment.

  Design: Historical cohort analysis.

  Patients: From 2002 to 2006, 21,846 women at gestational age

  Main outcome measures: Maternal urinary perchlorate, offspring IQ.

  Results: Urine perchlorate was detectable in all women (median 2.58 μg/L); iodine levels were low (median 72 μg/L). Maternal perchlorate levels in the highest 10% of the population increased the odds of offspring IQ being in the lowest 10% OR = 3.14 (95% CI 1.38, 7.13) P = .006 with a greater negative impact observed on verbal OR = 3.14 (95% CI 1.42, 6.90) P = .005 than performance IQ. Maternal levothyroxine therapy did not reduce the negative impact of perchlorate on offspring IQ.

  Conclusions: This is the first study using individual-level patient data to study maternal perchlorate exposure and offspring neurodevelopment and suggests that high-end maternal perchlorate levels in hypothyroid/hypothyroxinemic pregnant women have an adverse effect on offspring cognitive development, not affected by maternal levothyroxine therapy. These results require replication in additional studies, including in the euthyroid population.
  [Taylor, P. et al. (2014) Maternal perchlorate levels in women with borderline thyroid function during pregnancy and the cognitive development of their offspring: data from the Controlled Antenatal Thyroid Study, The Journal of Clinical Endocrinology and Metabolism. Available at: https://pubmed.ncbi.nlm.nih.gov/25057878/.]

• Chemical exposure early in life and the neurodevelopment of children--an overview of current epidemiological evidence
  A number of chemicals have been shown to demonstrate neurotoxic effects either in human or laboratory animal studies. This article aims at evaluating the impact of exposure to several chemicals including: organophosphate, organochlorine pesticides, polychlorinated biphenyls (PCBs), mercury and lead on the neurodevelopment of children by reviewing the most recent published literature, and answer the question whether any progress has been made in the epidemiology of the neurodevelopment of children induced by exposure to those chemicals. The result of the presented studies show that exposure to the above-mentioned chemicals may impair the neurodevelopment of children. Neonates exposed to organophosphate pesticides demonstrated a higher proportion of abnormal reflexes, and young children had more attention problems. Exposure to organochlorine pesticides in children was associated with alertness, quality of alert responsiveness, cost of attention and other potential attention associated measures. Because the neurotoxicants may cross the placenta and the fetal brain, exposure consideration regarding the reduction of exposure to those chemicals should be implemented.
  [Jurewicz J, Polańska K, Hanke W. 2013. Ann Agric Environ Med. 20(3):465-86]
• Exposure to pesticides and the risk of childhood brain tumors.
  Previous research has suggested positive associations between parental or childhood exposure to pesticides and risk of childhood brain tumors (CBT). This Australian case-control study of CBT investigated whether exposures to pesticides before pregnancy, during pregnancy and during childhood, were associated with an increased risk. Cases were recruited from 10 pediatric oncology centers, and controls by random-digit dialing, frequency matched on age, sex, and State of residence. The odds ratios (ORs) for professional pest control treatments in the home in the year before the index pregnancy, during the pregnancy, and after the child's birth were 1.54 (95% confidence interval (CI): 1.07, 2.22), 1.52 (95% CI: 0.99, 2.34) and 1.04 (95% CI: 0.75, 1.43), respectively. ORs for treatments exclusively before pregnancy and during pregnancy were 1.90 (95% CI: 1.08, 3.36) and 1.02 (95% CI: 0.35, 3.00), respectively. The OR for the father being home during the treatment was 1.79 (95% CI: 0.85, 3.80). The OR for paternal occupational exposure in the year before the child's conception was 1.36 (95% CI: 0.66, 2.80). ORs for prenatal home pesticide exposure were elevated for low- and high-grade gliomas; effect estimates for other CBT subtypes varied and lacked precision. These results suggest that preconception pesticide exposure, and possibly exposure during pregnancy, is associated with an increased CBT risk. It may be advisable for both parents to avoid pesticide exposure during this time.
  [Greenop KR, Peters S, Bailey HD, et al. 2013. Cancer Causes Control. 24(7):1269-78]
• Infant antibiotic exposures and early-life body mass.
  Exposure to antibiotics during the first 6 months of life is associated with consistent increases in body mass from 10 to 38 months. Exposures later in infancy (6–14 months, 15–23 months) are not consistently associated with increased body mass. Although effects of early exposures are modest at the individual level, they could have substantial consequences for population health. Given the prevalence of antibiotic exposures in infants, and in light of the growing concerns about childhood obesity, further studies are needed to isolate effects and define life-course implications for body mass and cardiovascular risks.
  [Trasande, L., Blustein, J., Liu, M., Corwin, E., Cox, L.M. and Blaser, M.J., 2013. International journal of obesity, 37(1), p.16.]
• Late life effects on rat reproductive system after developmental exposure to mixtures of endocrine disrupters
  This study examined late life effects of perinatal exposure of rats to a mixture of endocrine disrupting contaminants. Four groups of 14 time-mated Wistar rats were exposed by gavage from gestation day 7 to pup day 22 to a mixture of 13 anti-androgenic and estrogenic chemicals including phthalates, pesticides, UV-filters, bisphenol A, parabens and the drug paracetamol.Onset of puberty and estrous cyclicity at 9 and 12 months of age was assessed. Significantly fewer females showed regular estrus cyclicity at 12 months of age in the 2 exposure groups compared to controls. In 19 months old male offspring, epididymal sperm counts were lower than controls and in ventral prostate, an over-representation of findings related to hyperplasia was observed in exposed groups compared to controls particularly in the group dosed with anti-androgens. A higher incidence of pituitary adenoma at 19 months of age was found in males and females in the high dose group. Developmental exposure of rats to the highest dose of a human relevant mixture of endocrine disrupters induced adverse effects late in life manifested as earlier female reproductive senescence, reduced sperm counts, higher score for prostate atypical hyperplasia and higher incidence of pituitary tumors. These delayed effects highlight the need for further studies on the role of endocrine disrupters in hormone-related disorders in aging humans.
  [Isling LK, Boberg J, Jacobsen PR, et al. 2013. Reproduction. doi: 10.1530/REP-13-0448]
• Prenatal exposure to environmental contaminants and behavioural problems at age 7-8years
  Animal studies showed that the developing brain is particularly sensitive to chemical exposure. Human studies carried out in areas with high exposures have proven neurodevelopmental disorders in relation to e.g. lead and PCBs. Whether these chemicals are associated with behavioural problems in childhood at current environmental levels is not well known. Therefore, we assessed the association between prenatal exposure to lead, cadmium, PCBs, dioxin-like compounds, HCB and p,p'-DDE and behavioural problems in 7-8year old children. Prenatal exposure data were obtained from the Flemish mother-new-born cohort. Lead, cadmium, PCBs, dioxin-like compounds, HCB and p,p'-DDE were analysed in cord blood. When the child reached 7-8years, 270 mothers completed the Strengths and Difficulties Questionnaire assessing their children's behavioural health. We found that doubling the prenatal lead exposure (cord blood lead levels) was associated with a 3.43 times higher risk for hyperactivity in both boys and girls. In addition, total difficulties were 5.08 times more likely in the highest tertile for prenatal lead exposure compared to the lowest tertile. In girls, total difficulties were 4.92 more likely when doubling cord blood p,p'-DDE, whereas no significant association was found in boys. Further, we noted in boys a 1.53 times higher risk for emotional problems when doubling cord blood cadmium, whereas no significant association was found in girls. These results indicate that the presence of environmental contaminants influences the mental health of the next generation.
  [Sioen I, Den Hond E, Nelen V, Van de Mieroop E, et al. 2013. Environ Int. 59:225-31.]
• Does the home environment and the sex of the child modify the adverse effects of prenatal exposure to chlorpyrifos on child working memory?
  In the current paper, the authors expanded the previous work on CPF to investigate how additional biological and social environmental factors might create or explain differential neurodevelopmental susceptibility, focusing on main and moderating effects of the quality of the home environment (HOME) and child sex. The study evaluate how the quality of the home environment (specifically, parental nurturance and environmental stimulation) and child sex interact with the adverse effects of prenatal CPF exposure on working memory at child age 7years. Results found a borderline significant interaction between prenatal exposure to CPF and child sex suggesting males experience a greater decrement in working memory than females following prenatal CPF exposure. In addition, a borderline interaction between parental nurturance and child sex was detected suggesting that, in terms of working memory, males benefit more from a nurturing environment than females. This is the first investigation into factors that may inform an intervention strategy to reduce or reverse the cognitive deficits resulting from prenatal CPF exposure.
  [Horton, M.K., L.G. Kahn, F. Perera, D.B. Barr and V. Rauh. 2012. Neurotoxicology and Teratology. 34(5):534-41]
• Organophosphate pesticide levels in blood and urine of women and newborns living in an agricultural community
  Organophosphate pesticides are widely used and recent studies suggest associations of in utero exposures with adverse birth outcomes and neurodevelopment. Few studies have characterized organophosphate pesticides in human plasma or established how these levels correlate to urinary measurements. We measured organophosphate pesticide metabolites in maternal urine and chlorpyrifos and diazinon in maternal and cord plasma of subjects living in an agricultural area to compare levels in two different biological matrices. We also determined paraoxonase 1 (PON1) genotypes (PON1192 and PON1−108) and PON1 substrate-specific activities in mothers and their newborns to examine whether PON1 may affect organophosphate pesticide measurements in blood and urine.
  Chlorpyrifos levels in plasma ranged from 0–1726 ng/mL and non-zero levels were measured in 70.5% and 87.5% of maternal and cord samples, respectively. Diazinon levels were lower (0–0.5 ng/mL); non-zero levels were found in 33.3% of maternal plasma and 47.3% of cord plasma. Significant associations between organophosphate pesticide levels in blood and metabolite levels in urine were limited to models adjusting for PON1 levels. Increased maternal PON1 levels were associated with decreased odds of chlorpyrifos and diazinon detection (odds ratio(OR): 0.56 and 0.75, respectively). Blood organophosphate pesticide levels of study participants were similar in mothers and newborns and slightly higher than those reported in other populations. However, compared to their mothers, newborns have much lower quantities of the detoxifying PON1 enzyme suggesting that infants may be especially vulnerable to organophosphate pesticide exposures.
  [Huen, K. et al. (2012) Organophosphate pesticide levels in blood and urine of women and newborns living in an agricultural community, Environmental Research. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0013935112001740.]
• Dioxin Exposure and Age of Pubertal Onset among Russian Boys
  

  Animal data demonstrate associations of dioxin, furan, and polychlorinated biphenyl (PCB) exposures with altered male gonadal maturation. It is unclear whether these associations apply to human populations. We investigated the association of dioxins, furans, PCBs, and corresponding toxic equivalent (TEQ) concentrations with pubertal onset among boys in a dioxin-contaminated region. Between 2003 and 2005, 499 boys 8–9 years of age were enrolled in a longitudinal study in Chapaevsk, Russia. Pubertal onset [stage 2 or higher for genitalia (G2+) or testicular volume (TV) > 3 mL] was assessed annually between ages 8 and 12 years. Serum levels at enrollment were analyzed by the Centers for Disease Control and Prevention, Atlanta, Georgia, USA. We used Cox proportional hazards models to assess age at pubertal onset as a function of exposure adjusted for potential confounders. We conducted sensitivity analyses excluding boys with pubertal onset at enrollment. The median (range) total serum TEQ concentration was 21 (4–175) pg/g lipid, approximately three times higher than values in European children. At enrollment, boys were generally healthy and normal weight (mean body mass index, 15.9 kg/m2), with 30% having entered puberty by G2+ and 14% by TV criteria. Higher dioxin TEQs were associated with later pubertal onset by TV (hazard ratio = 0.68, 95% confidence interval, 0.49–0.95 for the highest compared with the lowest quartile). Similar associations were observed for 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin concentrations for TV but not G2+. Results were robust to sensitivity analyses. Findings support an association of higher peripubertal serum dioxin TEQs and concentrations with later male pubertal onset reflected in delayed testicular maturation.
  [Korrick, S.A., Lee, M., Williams, P., et al. 2011. Environ Health Perspect. 119 (9):1339–1344.]

• Exposure to pesticides and risk of childhood cancer: a meta-analysis of recent epidemiological studies.
  The authors performed a meta-analysis of case-control and cohort studies to clarify the possible relationship between exposure to pesticides and childhood cancers. Two cohort and 38 case-control studies were selected for the first meta-analysis. Meta-analysis of the three cohort studies did not show any positive links between parental pesticide exposure and childhood cancer incidence. However, the meta-analysis of the 40 studies with OR values showed that the risk of lymphoma and leukemia increased significantly in exposed children when their mother was exposed during the prenatal period (OR=1.53; 95% CI 1.22 to 1.91 and OR=1.48; 95% CI 1.26 to 1.75). The risk of brain cancer was correlated with paternal exposure either before or after birth (OR=1.49; 95% CI 1.23 to 1.79 and OR=1.66; 95% CI 1.11 to 2.49). The OR of leukemia and lymphoma was higher when the mother was exposed to pesticides. Despite some limitations in this study, the incidence of childhood cancer does appear to be associated with parental exposure during the prenatal period.
  [Vinson F, Merhi M, Baldi I, Raynal H, Gamet-Payrastre L. 2011. Occup Environ Med. 68(9):694-702.]
• Exposure to professional pest control treatments and the risk of childhood acute lymphoblastic leukemia.
  Previous studies suggest that exposure to pesticides increases the risk of childhood acute lymphoblastic leukemia (ALL). The aim of this analysis was to investigate whether professional pest treatments in or around the home before birth or during childhood increased the risk of childhood ALL. Data from 388 cases and 870 frequency-matched controls were analyzed using unconditional logistic regression, adjusting for study matching variables and potential confounders, to calculate odds ratios (ORs). The ORs for any professional pest control treatments were 1.19 in the year before pregnancy, 1.30 during pregnancy and 1.24 for those done after the child's birth. The ORs for exposure after birth were highest when it occurred between the ages of two and three years. ORs were elevated for termite treatments before birth. ORs were higher for pre-B than T cell ALL and for t(12;21) (ETV6-Runx-1) than other cytogenetic sub-types. Results provide some evidence of a modestly increased risk of ALL for professional pest control treatments done during the index pregnancy and possibly in the child's early years.
  [Bailey HD, Armstrong BK, de Klerk NH, et al. 2011. Int J Cancer. 129(7):1678-88]
• Internal exposure to pollutants and sexual maturation in Flemish adolescents
  Sexual maturation of adolescents (aged 14-15 years) was studied in relation to internal exposure to pollutants. Serum levels of pollutants and sex hormones were measured in 1679 participants selected as a random sample of the adolescents residing in the study areas. Data on sexual development were obtained from the medical school examination files. Self-assessment questionnaires provided information on health, use of medication and lifestyle factors. In boys, serum levels of hexachlorobenzene (HCB), p,p'-DDE and polychlorinated biphenyls (sum of marker PCB138, 153 and 180) were significantly and positively associated with pubertal staging (pubic hair and genital development). Higher levels of serum HCB and blood lead were associated with, respectively, a lower and a higher risk of gynecomastia. In girls, significant and negative associations were detected between blood lead and pubic hair development; higher exposure to PCBs was significantly associated with a delay in timing of menarche. Further understanding of toxic mode of action and sensitive windows of exposure is needed to explain the current findings.
  [Den Hond, E., Dhooge, W., Bruckers,L., Schoeters,G., et al. 2011.J Expo Sci Environ Epidemiol.21(3): 224–233.]
• Chlorpyrifos Exposure and Urban Residential Environment Characteristics as Determinants of Early Childhood Neurodevelopment
  

  We evaluated whether neighborhood characteristics correlated with early neurodevelopment and whether these characteristics confounded the previously reported association between exposure to chlorpyrifos (an organophosphate insecticide) and neurodevelopment. We obtained prenatal addresses, chlorpyrifos exposure data, and 36-month Psychomotor Development Index (PDI) and Mental Development Index (MDI) scores for a birth cohort in New York City (born 1998–2002). We used data from the 2000 US Census to estimate measures of physical infrastructure, socioeconomic status, crowding, demographic composition, and linguistic isolation for 1-kilometer network areas around each child's prenatal address. Generalized estimating equations were adjusted for demographics, maternal education and IQ, prenatal exposure to tobacco smoke, caretaking environment quality, and building dilapidation. Of 266 children included as participants, 47% were male, 59% were Dominican, and 41% were African American. For each standard deviation higher in neighborhood percent poverty, the PDI score was 2.6 points lower (95% confidence interval [CI] = −3.7, −1.5), and the MDI score was 1.7 points lower (95% CI = −2.6, −0.8). Neighborhood-level confounding of the chlorpyrifos-neurodevelopment association was not apparent. Neighborhood context and chlorpyrifos exposure were independently associated with neurodevelopment, thus providing distinct opportunities for health promotion.
  [Lovasi , G. et al. 2010. Am J Public Health. AJPH.2009.168419v1]

• Dietary Intake and Its Contribution to Longitudinal Organophosphorus Pesticide Exposure in Urban/suburban Children.
  Study assessed young urban/suburban children's longitudinal exposure to OP pesticides in the Children's Pesticide Exposure Study (CPES).Twenty-three children 3-11 years of age who consumed only conventional diets were recruited for this 1-year study conducted in 2003-2004. Children switched to organic diets for 5 consecutive days in the summer and fall sampling seasons. Study measured specific urinary metabolites for malathion, chlorpyrifos, and other OP pesticides in urine samples collected twice daily for a period of 7, 12, or 15 consecutive days during each of the four seasons. By substituting organic fresh fruits and vegetables for corresponding conventional food items, the median urinary metabolite concentrations were reduced to nondetected or close to non-detected levels for malathion and chlorpyrifos at the end of the 5-day organic diet intervention period in both summer and fall seasons. Study also observed a seasonal effect on the OP urinary metabolite concentrations, and this seasonality corresponds to the consumption of fresh produce throughout the year. The findings from this study demonstrate that dietary intake of OP pesticides represents the major source of exposure in young children.
  [Lu C, Barr DB, Pearson MA, Waller LA. 2008. Environ Health Perspect. 216(4):537-42.]
• Childhood cancer in Texas counties with moderate to intense agricultural activity
  With few established risk factors, cancer remains the second leading cause of death for children in the U.S. Agricultural pesticide use is one of many suspected factors that may contribute to the etiology of childhood cancer. This study tests the hypothesis that birth in Texas counties with moderate to intense agricultural activity increases childhood cancer risk. This case-control study analyzed 6974 cases and controls ages 0 to 14, identified through the Texas Cancer Registry and Texas birth records, respectively. Exposure data were obtained from the Census of Agriculture. Percent cropland in the county of birth and total county-specific pesticide exposure incorporating the EPA's carcinogenicity classification served as surrogates for pesticide exposure. Cancer sites examined include: all cancers, leukemia, lymphoma, CNS tumors, and several specific subsites. Elevated, although not statistically significant, ORs for the association between birth in counties with > or =50% cropland were produced for all CNS tumors (OR = 1.3, 95% CI = 0.9-1.8), astrocytoma (OR = 1.4, 95% CI = 0.8-2.2), and PNET (OR = 1.3, 95% CI = 0.7-2.5). A similar pattern was not observed using the index of total county-specific pesticide exposure. Although imprecise, these exposure assessment methods represent novel applications of agricultural census data. Although a pattern of increased risk was observed between percent cropland and CNS tumors, this study's results do not support an association between birth in Texas counties with moderate to intense agricultural activity and childhood cancer. Due to study limitations, such an association should not be ruled out. Future research should incorporate individual-level data from various sources to increase precision and decrease misclassification in the exposure assessment.
  [Walker, K.M., et al. 2007. J Agric Saf Health 13(1):9-24.]
• Developmental exposure to pesticides zineb and/or endosulfan renders the nigrostriatal dopamine system more susceptible to these environmental chemicals later in life.
  The purpose of this study was to test the hypothesis that exposure to pesticides such as endosulfan and/or zineb during critical periods of postnatal development could result in neuronal dysfunction and enhance the impact of these pesticides during exposure as adults. Mice exposed to these pesticides as juveniles and re-exposed at 8 months of age had significantly altered striatum and brain cortex neurotransmitter levels. Thus, mice re-exposed during adulthood to zineb, endosulfan and their mixtures showed a significantly depleted striatal dopamine levels, to 22, 16 and 35% of control, respectively. Acetylcholinesterase activity in the cerebral cortex was significantly increased in all pesticide treated groups (rho< or =0.05) upon repeated exposure, and pesticide mixture treatment also significantly increased levels of normal and aggregated alpha-synuclein. Collectively, these findings support our hypothesis that exposure to pesticides such as endosulfan and zineb during critical periods of postnatal development contributes to neurotransmitter changes upon re-challenge in adulthood.
  [Jia, Z., et al. 2007. Neurotoxicology 28(4):727-735]
• A Longitudinal Approach to Assessing Urban and Suburban Children's Exposure to Pyrethroid Pesticides
  Researchers conducted a longitudinal study to assess the exposure of 23 elementary school-age children to pyrethroid pesticides, using urinary pyrethroid metabolites as exposure biomarkers. Most of the children's conventional diets were substituted with organic food items for 5 consecutive days and two daily spot urine samples wrer collected, throughout the 15-day study period. Yrine samples for five common pyrethroid metabolites were analyzed. Authors found an association between the parents' self-reported pyrethroid use in the residential environment and elevated pyrethroid metabolite levels found in their children's urine. Children were also exposed to pyrethroids through their conventional diets, although the magnitude was smaller than for the residential exposure. Children's ages appear to be significantly associated with pyrethroids exposure, which is likely attributed to the use of pyrethroids around the premises or in the facilities where older children engaged in the outdoor activities. Study concludes that residential pesticide use represents the most important risk factor for children's exposure to pyrethroid insecticides. Because of the wide use of pyrethroids in the United States, the findings of this study are important for both children's pesticide exposure assessment and environmental public health.
  [Lu C, Barr DB, Pearson M, Bartell S, Bravo R.. 2006. Environ Health Perspect. 114(9):1419-23.]
• In Utero Exposure to Dichlorodiphenyltrichloroethane (DDT) and Dichlorodiphenyldichloroethylene (DDE) and Neurodevelopment Among Young Mexican American Children
  Study investigated the relationship between prenatal exposure to dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) and neurodevelopment of Mexican farm-workers' children in California. Participants from the Center for the Health Assessment of Mothers and Children of Salinas study, a birth cohort study, included 360 singletons with maternal serum measures of p,p'-DDT, o,p'-DDT, and p,p'-DDE. Psychomotor development and mental development were assessed with the Bayley Scales of Infant Development at 6, 12, and 24 months. Results found a approximately 2-point decrease in Psychomotor Developmental Index scores with each 10-fold increase in p,p'-DDT levels at 6 and 12 months (but not 24 months) and p,p'-DDE levels at 6 months only. We found no association with mental development at 6 months but a 2- to 3-point decrease in Mental Developmental Index scores for p,p'-DDT and o,p'-DDT at 12 and 24 months, corresponding to 7- to 10-point decreases across the exposure range. Even when mothers had substantial exposure, breastfeeding was usually associated positively with Bayley scale scores. Prenatal exposure to DDT, and to a lesser extent DDE, was associated with neurodevelopmental delays during early childhood, although breastfeeding was found to be beneficial even among women with high levels of exposure. Countries considering the use of DDT should weigh its benefit in eradicating malaria against the negative associations found in this first report on DDT and human neurodevelopment.
  [Eskenazi B, Marks AR, Bradman A, Fenster L, et al. 2006. Pediatrics.118(1):233-41.]
• Early-Life Environmental Risk Factors for Asthma: Findings from the Children's Health Study
  To investigate further whether the timing of such experiences and exposures is associated with the occurrence of asthma by 5 years of age, authors conducted a prevalence case-control study nested within the Children's Health Study, a population-based study of > 4,000 school-aged children in 12 southern California communities. Asthma diagnosis before 5 years of age was associated with exposures in the first year of life to wood or oil smoke, soot, or exhaust , cockroaches , herbicides, pesticides, and farm crops, farm dust, or farm animals. The ORs for herbicide, pesticide, farm animal, and crops were largest among children with early-onset persistent asthma. The risk of asthma decreased with an increasing number of siblings. Day care attendance within the first 4 months of life was positively associated with early-onset transient wheezing.
  [Salam, MT, YF Li, B Langholz, and FD Gilliland. 2004. Environmental Health Perspectives 112 (6): 760-765]
• In Utero Pesticide Exposure, Maternal Paraoxonase Activity, and Head Circumference.
  Although the use of pesticides in inner-city homes of the United States is of considerable magnitude, little is known about the potentially adverse health effects of such exposure. Recent animal data suggest that exposure to pesticides during pregnancy and early life may impair growth and neurodevelopment in the offspring. To investigate the relationship among prenatal pesticide exposure, paraoxonase (PON1) polymorphisms and enzyme activity, and infant growth and neurodevelopment, authors conducted a prospective, multiethnic cohort study of mothers and infants delivered at Mount Sinai Hospital in New York City. In this report the effects of pesticide exposure on birth weight, length, head circumference, and gestational age among 404 births between May 1998 and May 2002 were evaluated. Pesticide exposure was assessed by a prenatal questionnaire administered to the mothers during the early third trimester as well as by analysis of maternal urinary pentachlorophenol levels and maternal metabolites of chlorpyrifos and pyrethroids. When the level of maternal PON1 activity was taken into account, maternal levels of chlorpyrifos above the limit of detection coupled with low maternal PON1 activity were associated with a significant but small reduction in head circumference. In addition, maternal PON1 levels alone, but not PON1 genetic polymorphisms, were associated with reduced head size. Because small head size has been found to be predictive of subsequent cognitive ability, these data suggest that chlorpyrifos may have a detrimental effect on fetal neurodevelopment among mothers who exhibit low PON1 activity.
  [Berkowitz GS, Wetmur JG, Birman-Deych E, Obel J, et al. 2004. Environ Health Perspect.112(3):388-91.]
• Antibiotic Resistance: What is the Impact of Agricultural Uses of Antibiotics on Children’s Health?
  Antimicrobial resistance has reached crisis stage in human medicine. The rapid acceleration of multidrug-resistant bacteria in the past 2 decades has overtaken new drug development, and patients and clinicians are faced with the prospect of untreatable infections. Although much of the problem stems from overuse and misuse of antimicrobial agents in human medicine, large-scale use of antimicrobials in agriculture also contributes to the crisis. Agricultural uses of antibiotics produce environmental exposures in a variety of reservoirs, which select for resistant microbes and microbial genes. This article presents the major lines of evidence documenting the risks to human health of some of the agricultural uses of antimicrobials. A brief review of the microbiologic antecedents of resistance is followed by a discussion of agricultural uses of antimicrobials and a targeted review of the literature, which provides the background knowledge and evidence necessary for pediatricians and other clinicians to be informed and to advocate for judicious use of antimicrobials in all sectors.
  [K.M. Shea, 2003. Pediatrics 2003;112:253–258.]
• Fatal asthma in a child after use of an animal shampoo containing pyrethrin
  This case suggests that physicians should also be alert to formulations marketed as pyrethrin. Pesticides of this class are being used with increasing frequency in homes and are easily available to the public. Manufacturers are not required by the Environmental Protection Agency to state on the label that the pyrethrum formulations are allergens. The possibility of an acute allergic reaction occurring from the use of any currently marketed pyrethrum insecticide should be considered in any case of respiratory or dermal allergy of unknown cause.
  [Wagner, SL. 2000. West J Med 173: 86-87]
• Leukemia and Non-Hodgkin's Lymphoma in Childhood and Exposure to Pesticides: Results of a Register-based Case-Control Study in Germany
  

  Previous studies have suggested an association between exposure to pesticides and different types of childhood cancer. This paper presents results from a population-based case-control interview study of parents of children less than 15 years of age, which was conducted in the states of West Germany from 1993 to 1997. Cases were 1,184 children with leukemia, 234 with non-Hodgkin's lymphoma, and 940 with a solid tumor; 2,588 controls were also included. Parental occupational exposures were found to be related to childhood cancer regardless of the time period of exposures and the type of cancer. This finding might partially be explained by different recall of past exposures by the parents of cases and controls. Residential use of insecticides was assodated with childhood lymphoma: both extermination of insects by professional pest controllers (odds ratio (OR) = 2.6, 95% confidence interval (CI): 1.2, 5.7) and frequency of parental use of household insecticides (pfor trend = 0.02) were significant risk factors for this diagnosis. The use of pesticides on farms was weakly related to childhood leukemia (OR = 1.5, 95% CI: 1.0, 2.2), while their use in gardens was not assodated with childhood leukemia (OR = 1.0, 95% CI: 0.8, 1.2). The major strengths of this study were the population base and the large number of cases and controls included; a drawback was assessment of expasure on the basis of parental interviews. The data provide some evidence for an increased leukemia risk for children living on farms and for an association between use of household pesticides and risk of childhood leukemia or lymphoma. 
  [Meinert, R., et al. 2000. American Journal of Epidemiology 151(7):639-646]

• Exposures of children to organophosphate pesticides and their potential adverse health effects.
  Recent studies show that young children can be exposed to pesticides during normal oral exploration of their environment and their level of dermal contact with floors and other surfaces. Children living in agricultural areas may be exposed to higher pesticide levels than other children because of pesticides tracked into their homes by household members, by pesticide drift, by breast milk from their farmworker mother, or by playing in nearby fields. Nevertheless, few studies have assessed the extent of children's pesticide exposure, and no studies have examined whether there are adverse health effects of chronic exposure. There is substantial toxicologic evidence that repeated low-level exposure to organophosphate (OP) pesticides may affect neurodevelopment and growth in developing animals. For example, animal studies have reported neurobehavorial effects such as impairment on maze performance, locomotion, and balance in neonates exposed (italic)in utero(/italic) and during early postnatal life. Possible mechanisms for these effects include inhibition of brain acetylcholinesterase, downregulation of muscarinic receptors, decreased brain DNA synthesis, and reduced brain weight in offspring. Research findings also suggest that it is biologically plausible that OP exposure may be related to respiratory disease in children through dysregulation of the autonomic nervous system. The University of California Berkeley Center for Children's Environmental Health Research is working to build a community-university partnership to study the environmental health of rural children. This Center for the Health Assessment of Mothers and Children of Salinas, or CHAMACOS in Monterey County, California, will assess (italic)in utero(/italic) and postnatal OP pesticide exposure and the relationship of exposure to neurodevelopment, growth, and symptoms of respiratory illness in children. The ultimate goal of the center is to translate research findings into a reduction of children's exposure to pesticides and other environmental agents, and thereby reduce the incidence of environmentally related disease.
  [Eskanazi, B, A Bradman, and R Castorina. 1999. Environmental Health Perspectives 107(Suppl 3): 409-419]
• An Anthropological Approach to the Evaluation of Preschool Children Exposed to Pesticides in Mexico
  In a comparative study in Mexico, children exposed to pesticides demonstrated decreases in stamina, coordination, memory, and the ability to draw familiar subjects.
  [Guillette, E., et al. 1998. Environmental Health Perspectives, 106(6):347-353.]
• Childhood cancer and paternal employment in agriculture: the role of pesticides
  Previous studies have suggested that the offspring of men potentially exposed to pesticides at work may be at increased risk of kidney cancer (Wilms' tumour), brain tumours, Ewing's bone sarcoma and acute leukaemia. This paper examines the association between potential occupational exposure of fathers to pesticides and offspring's death from cancer in a large national database. Records for 167703 childhood deaths occurring during 1959-63, 1970-78 and 1979-90 in England and Wales have been analysed. Among the offspring of men with potential occupational exposure to pesticides there were 5270 deaths, of which 449 were due to cancer. Associations were assessed using proportional mortality ratios (PMRs), with adjustment for age, year of death and paternal social class. Of the childhood cancers previously linked with potential paternal occupational exposure to pesticides, the only statistically significant excess was for kidney cancer (PMR=1.59, 95% CI=1.18-2.15, based on 42 deaths). Although these results offer some support for the suggestion that paternal occupational exposure to pesticides may be related to the subsequent development of kidney cancer in offspring, other explanations cannot be excluded. In the light of the findings presented here and elsewhere, further, more detailed, research into the nature of this relationship is warranted.
  [Fear, N.T., et al. 1998. Br J Cancer 77(5):825-829.]
• Farm and animal exposures and pediatric brain tumors: results from the United States West Coast Childhood Brain Tumor Study.
  Nineteen counties from San Francisco and Los Angeles, California and Seattle, Washington were the United States sites for a large population-based case-control study of childhood brain tumors (CBTs), sponsored by the National Cancer Institute. CBT patients who were < 20 years of age and were diagnosed between 1984 and 1991 were reported to each region's cancer registry. The 801 control subjects were obtained by random digit dial and were frequency-matched to the 540 CBT patients in San Francisco and Seattle (one patient to two controls) and in Los Angeles (one patient to one control). Data collected by in-person interview with subjects' mothers were analyzed to investigate an association between risk for CBTs and life on a farm, exposure to farm animals (dairy cattle, beef cattle, pigs, sheep/goats, poultry, and horses), and some cat and non-farm horse exposures. Elevated risks for CBTs were observed in association with mothers' exposure to pigs [odds ratio (OR) = 3.8, 95% confidence interval (CI) = 1.2-12] and horses (OR = 2.2, 95% CI = 1.0-4.8) on a farm during the index pregnancy. Children diagnosed with primitive neuroectodermal tumors showed elevated risks for CBTs with personal and maternal prenatal exposure to pigs (child, OR = 4.0, 95% CI = 1.2-13; mother, OR = 11.9, 95% CI = 2.8-51) and poultry (child, OR = 3.0, 95% CI = 1.1-8.0; mother, OR = 4.0, 95% CI = 1.2-14). No other animal exposures of children or mothers were found to be consistently related to CBTs. Children diagnosed with primitive neuroectodermal tumors who were on a farm for > 1 year and were first on a farm when they were < 6 months of age also had increased risk for CBTs (OR = 3.9, 95% CI = 1.2-13). A somewhat increased risk for CBTs was found for children of mothers who ever had worked on livestock farms compared with mothers who never had worked on a farm (OR = 7.4, 95% CI = 0.86-64, based on five case mothers and one control mother who worked on livestock farms during the 5 years preceding the birth of the index child). The associations are consistent with those of two previous studies in Norway (P. Kristensen et al., Int. J. Cancer, 65: 39-50, 1996) and the United States and Canada (G. R. Bunin et al., Cancer Epidemiol. Biomark. Prev., 3: 197-204, 1994) that investigated the role of farm-related exposures in the etiology of CBTs.
  [Holly, E.A., et al. 1998. Cancer Epidemiol Biomarkers Prev 7(9):797-802]
• Is the increase in asthma prevalence occurring in children without a family history of atopy?
  Study investigated the familial associations of asthma and atopic disease in a population in which the prevalence of asthma and atopy is increasing. The prevalence of reported asthma (22.5%), eczema (24%) and hayfever (20%) in the children was high but similar to previous studies in this population. Asthma was reported in 20.8% of children of parents without a history of asthma and 18% of children of parents without any history of atopic disease. In children of parents without a family history of atopic disease suggests that much of the increase in asthma prevalence is occurring in children without a significant genetic predisposition. Childhood asthma developing in what would previously have been regarded as low risk families may differ in its aetiology from classical atopic asthma.
  [Christie GL, McDougall CM, Helms PJ. 1998. Is the increase in asthma prevalence occurring in children without a family history of atopy? Scott Med J. 43 (6): 180-182]
• The disproportionate impact of environmental health threats on children of color
  Children receive greater exposures to environmental pollutants present in air, food, and water because they inhale or ingest more air, food, or water on a body-weight basis than adults do. Communities of color are disproportionately exposed to hazardous wastes, dioxin, and air pollution. Existing data demonstrate that children of color are the subgroup of the population most exposed to certain pollutants, including lead, air pollution, and pesticides. Government standards do not take into account children's differential exposures or the cumulative nature of these exposures. Federal regulations fail to protect the most highly exposed and most sensitive subgroups of the population. More often than not this group is children of color.
  [Mott, L. (1995) The disproportionate impact of environmental health threats on children of color, Environmental Health Perspectives. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1518919/. ]
• Family pesticide use and childhood brain cancer.
  The relationship between family pesticide use and childhood brain cancer was examined in a case-control study. Telephone interviews were conducted from June 1989 through March 1990 with the natural mothers of 45 childhood brain cancer cases, 85 friend controls, and 108 cancer controls. In comparisons to friend controls, significant positive associations were observed for use of pesticides to control nuisance pests in the home, no-pest-strips in the home, pesticides to control termites, Kwell shampoo, flea collars on pets, diazinon in the garden or orchard, and herbicides to control weeds in the yard. In comparisons to cancer controls, significant positive associations were observed for use of pesticide bombs in the home, pesticides to control termites, flea collars on pets, insecticides in the garden or orchard, carbaryl in the garden or orchard, and herbicides to control weeds in the yard. In general, positive associations in comparisons to one control group were supported by elevated odds ratios in comparisons to the other control group. Several potentially important associations were identified in this study. However, small sample sizes, potential recall bias, multiple comparisons, and lack of detailed exposure verification require further research to confirm these findings.
  [Davis, J., et al. 1993. Family pesticide use and childhood brain cancer. Archives of Environmental Contamination and Toxicology 24:87-92]