Pesticide-Induced Diseases: Birth / Fetal Effects
In 2005, the births of three babies born in Florida with severe birth defects to mothers who all worked for Ag-Mart Produce, a company that produces chemically-treated tomatoes and other agricultural products, brought the connection between birth defects and pesticide exposure into the public consciousness. Birth defects are structural or functional abnormalities present at birth that cause physical or mental disabilities, ranging from mild to fatal. Researchers have identified thousands of different types of birth defects. Currently, birth defects are the leading cause of death for infants during the first year of life.
- Assessment of Glyphosate Induced Epigenetic Transgenerational Inheritance of Pathologies and Sperm Epimutations: Generational Toxicology
Ancestral environmental exposures to a variety of factors and toxicants have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. One of the most widely used agricultural pesticides worldwide is the herbicide glyphosate (N-(phosphonomethyl)glycine), commonly known as Roundup. There are an increasing number of conflicting reports regarding the direct exposure toxicity (risk) of glyphosate, but no rigorous investigations on the generational actions. The current study using a transient exposure of gestating F0 generation female rats found negligible impacts of glyphosate on the directly exposed F0 generation, or F1 generation offspring pathology. In contrast, dramatic increases in pathologies in the F2 generation grand-offspring, and F3 transgenerational great-grand-offspring were observed. The transgenerational pathologies observed include prostate disease, obesity, kidney disease, ovarian disease, and parturition (birth) abnormalities. Epigenetic analysis of the F1, F2 and F3 generation sperm identified differential DNA methylation regions (DMRs). A number of DMR associated genes were identified and previously shown to be involved in pathologies. Therefore, we propose glyphosate can induce the transgenerational inheritance of disease and germline (e.g. sperm) epimutations. Observations suggest the generational toxicology of glyphosate needs to be considered in the disease etiology of future generations.
[Kubsad, D., Nilsson, E.E., King, S.E., Sadler-Riggleman, I., Beck, D. and Skinner, M.K., 2019. Scientific reports, 9(1), pp.1-17.]
- Mixed "Antiandrogenic" Chemicals at Low Individual Doses Produce Reproductive Tract Malformations in the Male Rat.
Biomonitoring efforts have clearly shown that all humans are exposed to chemical mixtures. Of concern is whether or not exposure to mixtures during pregnancy contributes to congenital abnormalities in children even when each chemical is at an individual dose that does not affect the fetus. Here, we hypothesized that in utero exposure to a mixture of chemicals covering multiple "antiandrogenic" mechanisms of action at doses that individually have no adverse effect would result in permanent reproductive tract alterations in the male rat after birth. Pregnant dams were exposed to a range of dilutions (100%, 50%, 25%, 12.5%, 6.25%, or vehicle control) of a mixture containing pesticides, phthalates, and drugs (p, p'-DDE, linuron, prochloraz, procymidone, pyrifluquinazon, vinclozolin, finasteride, flutamide, simvastatin, and 9 phthalates [dipentyl, dicyclohexyl, di-2-ethylhexyl, dibutyl, benzyl butyl, diisobutyl, diisoheptyl, dihexyl, and diheptyl]). The top dose contained each chemical at 20% of its lowest observed adverse effect level (LOAEL) for the most sensitive male reproductive alteration following in utero exposure. We found that male rat offspring displayed a variety of neonatal, pubertal, and permanent adult effects across all dose levels. Even at the lowest dose (each chemical approximately 80-fold below lowest observed adverse effect level) there were permanent reductions in several reproductive tract tissue weights. In the top dose group, 100% of male offspring displayed permanent severe birth defects including genital malformations. Despite acting via 5 different molecular initiating events, a mixture of 18 chemicals can combine to produce additive effects even when each compound is at is at a relatively low dose.
[Conley JM, Lambright CS, Evans N, Cardon M, et al. Toxicol Sci. 164(1):166-178]
- Prenatal Exposure to Ambient Pesticides and Preterm Birth and Term Low Birthweight in Agricultural Regions of California.
Findings from studies of prenatal exposure to pesticides and adverse birth outcomes have been equivocal so far. We examined prenatal exposure to agricultural pesticides in relation to preterm birth and term low birthweight, respectively, in children born between 1998 and 2010, randomly selected from California birth records. We estimated residential exposure to agriculturally applied pesticides within 2 km of residential addresses at birth by pregnancy trimester for 17 individual pesticides and three chemical classes (organophosphates, pyrethroids, and carbamates). Among maternal addresses located within 2 km of any agricultural pesticide application, we identified 24,693 preterm and 220,297 term births, and 4412 term low birthweight and 194,732 term normal birthweight infants. First or second trimester exposure to individual pesticides (e.g., glyphosates, paraquat, imidacloprid) or exposure to 2 or more pesticides in the three chemical classes were associated with a small increase (3⁻7%) in risk for preterm birth; associations were stronger for female offspring. We did not find associations between term low birthweight and exposure to pesticides other than myclobutanil (OR: 1.11; 95% CI: 1.04⁻1.20) and possibly the pyrethroids class. Our improved exposure assessment revealed that first and second trimester exposure to pesticides is associated with preterm delivery but is rarely linked with term low birthweight.
[Ling C, Liew Z, von Ehrenstein OS, Heck JE, et al. 2018. Toxics. 6(3). pii: E41]
- Agricultural pesticide use and adverse birth outcomes in the San Joaquin Valley of California
Virtually all agricultural communities worldwide are exposed to agricultural pesticides. Yet, the health consequences of such exposure are poorly understood, and the scientific literature remains ambiguous. Using individual birth and demographic characteristics for over 500 000 birth observations between 1997–2011 in the agriculturally dominated San Joaquin Valley, California, we statistically investigate if residential agricultural pesticide exposure during gestation, by trimester, and by toxicity influences birth weight, gestational length, or birth abnormalities. Overall, our analysis indicates that agricultural pesticide exposure increases adverse birth outcomes by 5–9%, but only among the population exposed to very high quantities of pesticides (e.g., top 5th percentile, i.e., ~4200 kg applied over gestation). Thus, policies and interventions targeting the extreme right tail of the pesticide distribution near human habitation could largely eliminate the adverse birth outcomes associated with agricultural pesticide exposure documented in this study.
[Larsen, A.E., Gaines, S.D. and Deschênes, O., 2017. 8(1), pp.1-9.]
- Association of reproductive disorders and male congenital anomalies with environmental exposure to endocrine active pesticides.
There is growing evidence that environmental exposure to pesticides may increase the risk of developing reproductive and developmental disorders. This study determined the prevalence and risk of developing gestational disorders and male congenital genitourinary malformations in areas with distinct exposure to pesticides, many of them with potential endocrine disrupting properties. A population-based case-control study was carried out on pregnant women and male children living in ten health districts of Andalusia classified as areas of high and low environmental exposure to pesticides according to agronomic criteria. The study population included 45,050 cases and 950,620 controls matched for age and health district. Data were collected from computerized hospital records between 1998 and 2005. Prevalence rates and risk of miscarriage, low birth weight, hypospadias, cryptorchidism and micropenis were significantly greater in areas with higher use of pesticides in relation to those with lower use, thus supporting and extending previous information.
[García J, Ventura MI, Requena M, Hernández AF, et al. 2017. Reprod Toxicol. 71:95-100.]
- Combined exposure to low doses of pesticides causes decreased birth weights in rats
Decreased birth weight is a common effect of many pesticides in reproductive toxicity studies, but there are no empirical data on how pesticides act in combination on this endpoint. We hypothesized that a mixture of six pesticides (cyromazine, MCPB, pirimicarb, quinoclamine, thiram, and ziram) would decrease birth weight, and that these mixture effects could be predicted by the Dose Addition model. Data for the predictions were obtained from the Draft Assessment Reports of the individual pesticides. A mixture of equi-effective doses of these pesticides was tested in two studies in Wistar rats, showing mixture effects in good agreement with the additivity predictions. Significantly lower birth weights were observed when compounds were present at individual doses below their no-observed adverse effect levels (NOAELs). These results emphasize the need for cumulative risk assessment of pesticides to avoid potentially serious impact of mixed exposure on prenatal development and pregnancy in humans.
[Hass U, Christiansen S, Axelstad M, Scholze M, Boberg J. 2017. Reprod Toxicol. 72:97-105]
- Exposure to PFOA and PFOS and fetal growth: a critical merging of toxicological and epidemiological data.
Toxicological and epidemiological evidence on the association between perfluorooctanoic acid (PFOA) or perfluorooctane sulfonic acid (PFOS) and birth/fetal weight was assessed. An extensive search for toxicological information in rats and mice, and a systematic search for epidemiological evidence were conducted. The linear regression coefficient (LRC) of birth weight (BrthW) on PFOA/PFOS was considered, and separate random effects meta-analyses for untransformed (i.e. not mathematically transformed) and log-transformed values were performed. Toxicological evidence: PFOA: 12 studies (21 datasets) in mice showed statistically significant lower birth/fetal weights from 5 mg/kg body weight per day. PFOS: most of the 13 studies (19 datasets) showed lower birth/fetal weights following in utero exposure. Epidemiological evidence: Sixteen articles were considered. The pooled LRC for a 1 ng/mL increase in untransformed PFOA (12 studies) in maternal plasma/serum was -12.8 g (95% CI -23.2; 2.4), and -27.1 g (95% CI -50.6; -3.6) for an increase of 1 loge ng/mL PFOA (nine studies). The pooled LRC for untransformed PFOS (eight studies) was -0.92 g (95%CI -3.4; 1.6), and for an increase of 1 loge ng/mL was -46.1(95% CI -80.3; -11.9). No consistent pattern emerged for study location or timing of blood sampling. Epidemiological and toxicological evidence suggests that PFOA and PFOS elicit a decrease in BrthW both in humans and rodents. However, the effective animal extrapolated serum concentrations are 102-103 times higher than those in humans. Thus, there is no quantitative toxicological evidence to support the epidemiological association, thus reducing the biological plausibility of a causal relationship.
[Negri E, Metruccio F, Guercio V, Tosti L, et al. 2017. Crit Rev Toxicol. 47(6):482-508]
- Glyphosate and Paraquat in Maternal and Fetal Serums in Thai Women
This longitudinal study measured the glyphosate and paraquat concentrations found in maternal and umbilical cord serum in 82 pregnant women who gave birth in three provinces of Thailand.Through questionnaires and biological samples collected at childbirth, factors such as personal characteristics, family members occupation, agricultural activities, and herbicide use in agricultural work were evaluated as predictors of glyphosate and paraquat levels in the pregnant women. Statistical analysis used univariate and binary multiple logistic regression, where the outcome was the probability of exposure to paraquat or glyphosate above the limit of detection associated with occupation and household factors.The glyphosate concentrations in the pregnant women's serum at childbirth (median: 17.5, range: 0.2-189.1 ng/mL) were significantly higher (P < .007) than those in the umbilical cord serum (median: 0.2, range: 0.2-94.9 ng/mL). However, the paraquat concentrations in the serum of the pregnant women at childbirth (83% ≤limit of detection [LOD], with maximum of 58.3 ng/mL) were similar to those in the umbilical cord serum (80% <LOD, with maximum of 47.6 ng/mL). Women with glyphosate levels >LOD in serum at childbirth were 11.9 times more likely to report work as an agriculturist (P < .001), 3.7 times more likely to live near agricultural areas (P = .006), and 5.9 times more likely to have a family member who worked in agriculture (P < .001). The only factors affecting paraquat exposures in pregnant women at childbirth were reporting the agricultural activity of digging in farm soil and working in the agricultural fields in the third trimester of pregnancy.These results show that pregnant women who work in agriculture or live in families that work in agriculture have higher exposures to the herbicides glyphosate and paraquat. The potential for long-term health impacts of these prenatal exposures to children should be evaluated, and greater regulation of the sale and use of herbicides should be considered in Thailand.
[Kongtip P, Nankongnab N, Phupancharoensuk R, et al. 2017. J Agromedicine. 22(3):282-289. ]
- Neurodevelopmental disorders and pesticide exposure: the northeastern Italian experience.
Endocrine disruptors are chemical substances that can interfere with the endocrine system. They include pesticides, metals, additives or contaminants in food, and personal care products. Pesticides are the only substances intentionally released into our environment to kill living things (herbicides, insecticides, fungicides, rodenticides). There is scientific evidence that exposure to pesticides produces a growing number of human pathological conditions; among these, stillbirth is an emerging issue.
[Roncati L, Pusiol T, Piscioli F, Lavezzi AM. Arch Toxicol. 91(2):603-604.]
- Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in human breast milk and associated health risks to nursing infants in Northern Tanzania
This is the first study to report organochlorines (OCs), including chlorinated pesticides (OCPs) and polychlorinated biphenyls (PCBs) in human milk from Tanzania. The main aims of this study were to assess the level of contamination and the possible health risks related to OC exposure in nursing infants from the Northern parts of Tanzania. Ninety-five healthy mother-infant couples attending Mount Meru Regional Referral Hospital (MMRRH), Arusha, Tanzania, were assessed for associations between maternal/infant characteristics, i.e. mother's age, BMI, gestational weight gain, occupation, residence and fetal growth parameters and breast milk levels of OCPs, such as dichlorodiphenyltrichloroethane (DDT) and its metabolites, dieldrin and PCBs. p,p'-DDE and p,p'-DDT were detected in 100% and 75% of the breast milk samples, respectively, and ranged between 24 and 2400ng/g lipid weight (lw) and
[Müller MH, Polder A, Brynildsrud OB, Karimi M, et al. 2017. Environ Res. 154:425-434]
- Relationship between pesticide exposure and adverse pregnancy outcomes among reproductive couples in rural areas of China
To analyze the association between pesticide exposure and adverse pregnancy outcomes in women from the rural areas of China. Data of "National Free Preconception Health Examination Project (NFPHEP)" from January 2010 to December 2012 was used for analysis. A total of 248 501 families that were planning to deliver a baby in the next 6 months were enrolled. Data on paternal exposure to pesticides before or during pregnancy was collected through questionnaires, with related outcomes on pregnancy recorded by doctors. Among all the 248 501 participants, 1 806 (0.74%) women and 2 653 (1.09%) men reported to have been exposed to pesticide before pregnancy, with 505 (0.21%) reported of having been exposed to pesticide during the period of pregnancy. Maternal exposure to pesticide was found a risk factor related to stillbirth (OR=3.37, 95%CI: 2.05-5.55), peculiar smell pregnancy (OR=3.17, 95%CI:1.18-8.55) and low birth weight (OR=7.56, 95% CI: 5.36-10.66). Paternal exposure to pesticide was also found related to miscarriage (OR=1.37, 95% CI: 1.03-1.80), low birth weight (OR=3.65, 95% CI:1.51-8.84), or giant infant (OR=0.64, 95%CI: 0.44-0.93). Maternal exposure to pesticide during pregnancy appeared a risk factor on miscarriage (OR=4.65, 95% CI: 3.47-6.24). Other adverse outcomes on pregnancy would include premature birth and high birth weight.Parental pesticide exposure appeared a risk factor on stillbirth, peculiar smell pregnancy, low birth weight and miscarriage.
[Qu YM, Chen S, Li JJ, Jin RR, et al. 2017. Zhonghua Liu Xing Bing Xue Za Zhi. 38(6):732-736]
- Association between Exposure to Endocrine Disruptors in Drinking Water and Preterm Birth, Taking Neighborhood Deprivation into Account: A Historic Cohort Study.
The relationship between preterm birth (PTB) and endocrine disruptor exposure in drinking-water has only occasionally been studied. The objective of this work was to investigate the relation between exposure to atrazine metabolites, or atrazine/nitrate mixtures, in drinking-water during pregnancy and prevalence of PTB neonates, while taking neighborhood deprivation into account. A historic cohort study in Deux-Sèvres, France, between 2005 and 2010 with a multiple imputation model for data of exposure to atrazine metabolites and a logistic regression were carried out.Study included 13,654 mother/neonate pairs living in 279 different census districts. The prevalence of PTB was 4%. Average atrazine metabolite concentration was 0.019 ± 0.009 (0.014-0.080) µg/L and 39% of mothers lived in less deprived areas. The individual data were associated with risk of PTB. The risk of PTB when exposed to highest concentration of atrazine metabolite adjusted for confounders, was ORa 1.625 95% CI [0.975; 2.710]. Taking, or not, neighborhood deprivation into account did not change the result. Exposure to atrazine/nitrate mixtures remained non-significant.Even if we took neighborhood deprivation into account, we could not show a significant relationship between exposure to atrazine metabolites, or mixtures, in drinking-water during the second trimester of pregnancy and PTB.
[Albouy-Llaty M, Limousi F, Carles C, Dupuis A, et al. 2016. Int J Environ Res Public Health.13(8).]
- Glyphosate and adverse pregnancy outcomes, a systematic review of observational studies
A study in frog and chicken embryos, and reports of a high incidence of birth defects in regions of intensive GM-soy planting have raised concerns on the teratogenic potential of glyphosate-based herbicides. These public concerns prompted us to conduct a systematic review of the epidemiological studies testing hypotheses of associations between glyphosate exposure and adverse pregnancy outcomes including birth defects.A case-control study on the association between pesticides and congenital malformations in areas of extensive GM soy crops in South America, and reports on the occurrence of birth defects in these regions were reviewed. The search found ten studies testing associations between glyphosate and birth defects, abortions, pre-term deliveries, small for gestational date births, childhood diseases or altered sex ratios. Two additional studies examined changes of time-to-pregnancy in glyphosate-exposed populations. Except for an excess of Attention Deficit Hyperactivity Disorder - ADHD (OR = 3.6, 1.3-9.6) among children born to glyphosate appliers, no significant associations between this herbicide and adverse pregnancy outcomes were described. Evidence that in South American regions of intensive GM-soy planting incidence of birth defects is high remains elusive.Current epidemiological evidence, albeit limited to a few studies using non-quantitative and indirect estimates and dichotomous analysis of exposures, does not lend support to public concerns that glyphosate-based pesticides might pose developmental risks to the unborn child. Nonetheless, owing to methodological limitations of existing analytical observational studies, and particularly to a lack of a direct measurement (urine and/or blood levels), or an indirect estimation of exposure that has proven valid, these negative findings cannot be taken as definitive evidence that GLY, at current levels of occupational and environmental exposures, brings no risk for human development and reproduction.
[de Araujo JS, Delgado IF, Paumgartten FJ. 2016. BMC Public Health. 16:472]
- Is Hypospadias Associated with Prenatal Exposure to Endocrine Disruptors? A French Collaborative Controlled Study of a Cohort of 300 Consecutive Children Without Genetic Defect.
This study's aim was to identify the role of occupational and environmental exposures to EDCs in nongenetic isolated hypospadias. A total of 408 consecutive children with isolated hypospadias and 302 normal boys were prospectively included (2009-2014) in a multi-institutional study in the south of France, the area of the country with the highest prevalence of hypospadias surgery. In patients without AR, SRD5A2, and MAMLD1 mutations, parental occupational and professional exposures to EDCs were evaluated based on European questionnaire QLK4-1999-01422 and a validated job-exposure matrix for EDCs.Fetal exposure to EDCs around the window of genital differentiation was more frequent in the case of hypospadias. The substances were paints/solvents/adhesives (16.0%), detergents (11.0%), pesticides (9.0%), cosmetics (5.6%), and industrial chemicals (4.0%). Jobs with exposure were more frequent in mothers of hypospadiac boys, especially cleaners, hairdressers, beauticians, and laboratory workers. Paternal job exposure was more frequent in the cases of hypospadias. Industrial areas, incinerators, and waste areas were more frequent within a 3-km radius for mothers of hypospadiac boys . Association of occupational and environmental exposures increases this risk.This multicenter prospective controlled study with a homogeneous cohort of hypospadiac boys without genetic defects strongly suggests that EDCs are a risk factor for hypospadias through occupational and environmental exposure during fetal life. The association of various types of exposures may increase this risk.
[Kalfa N, Paris F, Philibert P, Orsini M, et al.2015. Eur Urol.pii: S0302-2838(15)00409-1]
- Maternal occupational pesticide exposure and risk of congenital heart defects in the national birth defects prevention study.
Congenital heart defects (CHDs) are common birth defects, affecting approximately 1% of live births. Pesticide exposure has been suggested as an etiologic factor for CHDs, but previous results were inconsistent.Study examined maternal occupational exposure to fungicides, insecticides, and herbicides for 3328 infants with CHDs and 2988 unaffected control infants of employed mothers using data for 1997 through 2002 births from the National Birth Defects Prevention Study, a population-based multisite case-control study. Maternal occupational exposure to pesticides was not associated with CHDs overall. In examining specific CHD subtypes compared with controls, some novel associations were observed with higher estimated pesticide exposure: insecticides only and secundum atrial septal defect; both insecticides and herbicides and hypoplastic left heart syndrome, as well as pulmonary valve stenosis; and insecticides, herbicides, and fungicides and tetralogy of Fallot (TOF). Broad pesticide exposure categories were not associated with CHDs overall, but examining specific CHD subtypes revealed some increased odds ratios. These results highlight the importance of examining specific CHDs separately. Because of multiple comparisons, additional work is needed to verify these associations.
[Rocheleau CM, Bertke SJ, Lawson CC, et al. 2015. Birth Defects Res A Clin Mol Teratol.103(10):823-33.]
- Early pregnancy agricultural pesticide exposures and risk of gastroschisis among offspring in the San Joaquin Valley of California.
Prevalence of gastroschisis has inexplicably been increasing over the past few decades.The intent of this study was to explore whether early gestational exposures to pesticides were associated with risk of gastroschisis. Authors used population-based data, accompanied by detailed information from maternal interviews as well as information on residential proximity to a large number of commercial pesticide applications during early pregnancy. The study population derived from the San Joaquin Valley of California (). Cases were 156 infants/fetuses with gastroschisis and controls were 785 infants without birth defects. Among 22 chemical pesticide groups analyzed, none had an elevated odds ratio with an associated confidence interval that excluded 1.0, although exposure to the triazine group showed borderline significance. Among 36 specific pesticide chemicals analyzed, only exposure to petroleum distillates was associated with an elevated risk, odds ratio = 2.5 (1.1-5.6). In general, a substantially different inference was not derived when analyses were stratified by maternal age or when risk estimation included adjustment for race/ethnicity, body mass index, folic acid supplement use, and smoking.
[Shaw GM, Yang W, Roberts E, et al. 2014. Birth Defects Res A Clin Mol Teratol.100(9):686-94]
- Hypospadias in offspring is associated with chronic exposure of parents to organophosphate and organochlorine pesticides.
Authors have currently evaluated the possible association between hypospadias and exposure to organophosphorus (OP) and organochlorine (OC) pesticides. here, they measured the dialkyl phosphate metabolites of organophosphate pesticides (DAPs) in the hair and blood, as well as OC pesticides (DDTs, HCHs) in the hair collected from children with hypospadias and their parents. The concentration of HCHs in the hair samples obtained from mothers was higher than that previously reported for people working in open cultivations, while the concentration of DDTs in the hair samples obtained from mothers, fathers and their children with hypospadias was much higher than that previously reported for occupationally exposed individuals. The DMP concentration in hair samples obtained from mothers was much higher not only from that reported for the general population, but even higher than that reported for occupationally exposed individuals. Furthermore, SUMDEPs and SUMDAPs in the hair samples obtained both from the hypospadiac boys, as well as from their parents were higher than the corresponding values previously reported for the general population. Our study supports the hypothesis that organophosphate and organochlorine pesticide exposure may be a potential risk factor for hypospadias.
[Michalakis M, Tzatzarakis MN, et al. 2014. Toxicol Lett. 230(2):139-45.]
- Maternal periconceptional occupational exposure to pesticides and selected musculoskeletal birth defects.
This population-based U.S. study investigated the association between major musculoskeletal malformations and periconceptional maternal occupational pesticide exposure for a wide range of occupations. We conducted a multi-site case-control analysis using data from the National Birth Defects Prevention Study among employed women with due dates from October 1, 1997 through December 31, 2002. Cases included 871 live-born, stillborn, or electively terminated fetuses with isolated craniosynostosis, gastroschisis, diaphragmatic hernia, or transverse limb deficiencies. Controls included 2857 live-born infants without major malformations. Using self-reported maternal occupational information, an industrial hygienist used a job-exposure matrix and expert opinion to evaluate the potential for exposure to insecticides, herbicides or fungicides for each job held during one month pre-conception through three months post-conception. Exposures analyzed included any exposure (yes/no) to pesticides, to insecticides only, to both insecticides and herbicides (I+H) and to insecticides, herbicides and fungicides (I+H+F). Occupational exposure to I+H+F was associated with gastroschisis among infants of women aged 20 years or older, but not for women under age 20. No significant associations for the other defects were found. Additional research is needed to validate these findings in a separate population.
[Kielb C, Lin S, Herdt-Losavio M, Bell E, et al. 2014. Int J Hyg Environ Health. 217(2-3):248-54.]
- Maternal periconceptional occupational pesticide exposure and neural tube defects.
Adverse associations between maternal pesticide exposure and neural tube defects (NTDs) have been suggested but not consistently observed. This study used data from the multisite National Birth Defects Prevention Study to examine associations between maternal periconceptional (1 month preconception through 2 months postconception) occupational pesticide exposure and NTDs. Mothers of 502 NTD cases and 2950 unaffected live-born control infants with estimated delivery dates from 1997 through 2002 were included. Duration, categorical intensity scores, and categorical frequency scores for pesticide classes (e.g., insecticides) were assigned using a modified, literature-based job-exposure matrix and maternal-reported occupational histories. Positive, but marginally significant or nonsignificant, aORs were observed for exposure to insecticides + herbicides for all NTD cases combined and for spina bifida alone. Similarly, positive aORs were observed for any exposure and cumulative exposure to insecticides + herbicides + fungicides and anencephaly alone and encephalocele alone. All other aORs were near unity. Pesticide exposure associations varied by NTD subtype and pesticide class. Several aORs were increased, but not significantly. Future work should continue to examine associations between pesticide classes and NTD subtypes using a detailed occupational pesticide exposure assessment and examine pesticide exposures outside the workplace.
[Makelarski JA, Romitti PA, Rocheleau CM, et al.2014. Birth Defects Res A Clin Mol Teratol.100(11):877-86.]
- Residential agricultural pesticide exposures and risk of selected congenital heart defects among offspring in the San Joaquin Valley of California.
Study examined the potential association of congenital heart defects with residential proximity to commercial agricultural pesticide applications in the San Joaquin Valley, California. Study subjects included 569 heart defect cases and 785 non-malformed controls born from 1997 to 2006 whose mothers participated in a population-based case-control study. Associations with any versus no exposure to physicochemical groups of pesticides and specific chemicals were assessed using logistic regression adjusted for relevant covariates, for 8 heart defect phenotypes that included ≥ 50 cases and pesticide exposures with ≥ 5 exposed cases and controls, which resulted in 235 comparisons. 38% of cases and controls were classified as exposed to pesticides within a 500 m radius of mother's address during a 3-month periconceptional window. Adjusted odds ratios (AORs) with 95% CIs excluding 1.0 were observed for 18 comparisons; all were >1 and ranged from 1.9 to 7.1. They included tetralogy of Fallot and neonicotinoids; hypoplastic left heart syndrome and strobins; coarctation of the aorta and pyridazinones; pulmonary valve stenosis and bipyridyliums and organophosphates; ventricular septal defects and avermectins and pyrethroids; and atrial septal defects and dichlorphenoxy acid or esters, organophosphates, organotins, and pyrethroids. No AORs met both of these criteria for d-transposition of the great arteries or heterotaxia.Most pesticides were not associated with increased risk of specific heart defect phenotypes. For the few that were associated, results should be interpreted with caution until replicated in other study populations.
[Carmichael SL, Yang W, Roberts E, et al. 2014. Environ Res. 135:133-8.]
- Risk of cryptorchidism among sons of horticultural workers and farmers in Denmark
Previous studies indicate an increased risk of cryptorchidism, incomplete testicular descent, among sons of women working with pesticides. This study assessed the risk of cryptorchidism among boys of parents employed as horticultural workers and farmers using nationwide registers on occupation and cryptorchidism.The cohort consisted of >600 000 boys born in Denmark from 1980-2007 with a parent in employment during pregnancy. These boys were followed for cryptorchidism from 1980-2009 comparing risks among sons of horticultural workers and farmers with sons of parents in other occupations. Sons of maternal farmers were at increased risk of cryptorchidism compared to boys of mothers in other occupations. Paternal occupation as farmer was unrelated to the risk among sons. Maternal occupation as a horticultural worker was associated with a non-significantly increased risk. A similar association was found for paternal horticultural workers. Sons of maternal farmers or horticultural workers who likely worked in the first trimester were not at increased risk of cryptorchidism. This nationwide cohort study found a slightly increased risk of cryptorchidism in sons of maternal horticultural workers and farmers. However, subgroup analyses indicated similar findings for paternal horticultural workers, and no association for women likely working in the first trimester. The main findings should therefore be interpreted with caution.
[Jørgensen KT, Jensen MS, Toft GV,et al. 2014. Scand J Work Environ Health. 40(3):323-30]
- Hypospadias and residential proximity to pesticide applications.
Examine the association of hypospadias with residential proximity to commercial agricultural pesticide applications.The study population included male infants born from 1991 to 2004 to mothers residing in 8 California counties. Cases (n = 690) were ascertained by the California Birth Defects Monitoring Program; controls were selected randomly from the birth population (n = 2195). Authors determined early pregnancy exposure to pesticide applications within a 500-m radius of mother's residential address, using detailed data on applications and land use. Forty-one percent of cases and controls were classified as exposed to 57 chemical groups and 292 chemicals. Despite >500 statistical comparisons, there were few elevated odds ratios with confidence intervals that excluded 1 for chemical groups or specific chemicals. Those that did were for monochlorophenoxy acid or ester herbicides; the insecticides aldicarb, dimethoate, phorate, and petroleum oils; and adjuvant polyoxyethylene sorbitol among all cases; 2,6-dinitroaniline herbicides, the herbicide oxyfluorfen, and the fungicide copper sulfate among mild cases; and chloroacetanilide herbicides, polyalkyloxy compounds used as adjuvants, the insecticides aldicarb and acephate, and the adjuvant nonyl-phenoxy-poly(ethylene oxy)ethanol among moderate and severe cases. Odds ratios ranged from 1.9 to 2.9.Most pesticides were not associated with elevated hypospadias risk. For the few that were associated, results should be interpreted with caution until replicated in other study populations.
[Carmichael SL, Yang W, Roberts EM, et al. 2013. Pediatrics. 132(5):e1216-26]
- Association of selected persistent organic pollutants in the placenta with the risk of neural tube defects
Placental concentrations of polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides, polychlorinated biphenyls, and polybrominated diphenyl ethers were analyzed in 80 fetuses or newborns with neural tube defects (NTDs). A dose–response relationship was observed between PAH levels and the risk of NTDs.
[Ren, A. et al. 2011. PNAS. 108 (31) 12770-12775]
- Urinary Biomarkers of Prenatal Atrazine Exposure and Adverse Birth Outcomes in the PELAGIE Birth Cohort
This study, a case-cohort design nested in a prospective birth cohort conducted in the Brittany region from 2002 through 2006, collected maternal urine samples to examine pesticide exposure biomarkers before the 19th week of gestation. Quantifiable levels of atrazine were found in urine samples from 5.5% of 579 pregnant women, and various metabolites were identified in 20-40% of samples. The presence versus absence of quantifiable levels of atrazine or a specific atrazine metabolite was associated with fetal growth restriction and small head circumference. Head circumference was also inversely associated with the presence of the herbicide metolachlor. Daily News
[Chevrier C, Limon G, Monfort C, Rouget F, Garlantézec R, Petit C, et al. 2011. Environ Health Perspect. doi:10.1289/ehp.1002775]
- Agricultural-related chemical exposures, season of conception, and risk of gastroschisis in Washington State
Reserchers conducted a retrospective, case-controlled study using Washington State Birth Certificate and US Geological Survey databases. Cases included all live-born singleton infants with gastroschisis. Distance between a woman's residence and site of elevated exposure to agrichemicals was calculated. Gastroschisis occurred more frequently among those who resided <25 km from a site of high atrazine concentration (odds ratio, 1.6). Risk was related inversely to the distance between the maternal residence and the closest toxic atrazine site.
[Waller, S.A., Paul, K., Peterson, S.E. andHitti, J.E. . 2010. Am J Obst Gyn. 202(3): 241.e1–241.e6.]
- Correlation Between Pesticide Use in Agriculture and Adverse Birth Outcomes in Brazil: An Ecological Study
This ecological study analyzed the association between pesticide use and prematurity, low weight and congenital abnormality at birth, infant death by congenital abnormality, and fetal death in Brazil in 2001. The association between pesticide use and low birth weight and, congenital abnormality and infant death rate by congenital abnormality remained after the adjustment made by the proportion of pregnant women with a low number of prenatal care visits.
[de Siqueira, MT et al. 2010. Bull Environ Contam Toxicol. 84(6):647-51]
- Impact on fetal growth of prenatal exposure to pesticides due to agricultural activities: a prospective cohort study in Brittany, France
Pregnant women living in a municipality where peas or potatoes were grown had an increased risk of giving birth to an infant with a small head circumference. Head circumference also tended to be lower where wheat was grown, but not to statistically significant degree. The study found no association between head circumference and proximity to other crops. The study’s authors suggest that pesticides, specifically organophosphates, are a possible cause. OPs were applied to most of the area devoted to pea and potato crops, but used less frequently in areas growing corn and wheat.
[Petit, C., et al. 2010. Environmental Health, 9(71).]
- Maternal Pesticide Exposure and Neural Tube Defects in Mexican Americans
The relation between maternal pesticide exposures and neural tube defects (NTDs) in offspring was evaluated in 184 Mexican American case-women and 225 comparison women. women who reported using pesticides in their homes or yards were two times more likely to have NTD-affected pregnancies than women without these reported exposures. Case-women were also more likely to report living within 0.25 mile of cultivated fields than control-women. As sources of pesticide exposure opportunities increased, risk of NTDs also increased.
[Brender, JD., et al. 2010. Ann Epidemiol. 20(1):16-22]
- Parental occupational exposure to potential endocrine disrupting chemicals and risk of hypospadias in infants
The aim of this study was to investigate the association between both maternal and paternal occupational exposures to endocrine disrupting chemcials (EDCs) and hypospadias. Analysis showed a strong association with potential maternal occupational exposure to heavy metals with an over twofold increased risk of hypospadias and women exposed to phthalates were more likely to have an affected son. The risks of moderate–severe hypospadias or multiple defects were increased up to two- and fivefold, respectively, with maternal exposure to most types of EDCs. Paternal occupational exposures to polychlorinated organic and bi-phenolic compounds were also possible risk factors.
[Nassar, N. et al. 2010. Occup Environ Med. 67:585-589]
- PESTICIDES: Examining DDT’s Urogenital Effects
Review of reserach documenting a variety of urogenital malformations in male babies born to women living in an area of South Africa where the potentially endocrine-disrupting pesticide DDT is still used.
[Lubick, N. 2010. Environ Health Perspect. 118(1): A18]
- Agrichemicals in surface water and birth defects in the United States
Researchers compiled data for monthly concentrations of pesticides/nitrates and birth defect rates between 1996 and 2002, and found that the months (April-July) with the highest rates of pesticides conincided with the months with the highest rates of birth defects.
[Winchester, P., et al. 2009. Acta Paediatrica, 98(4).]
- Glyphosate Formulations Induce Apoptosis and Necrosis in Human Umbilical, Embryonic, and Placental Cells
One study found that the so-called "inert" ingredient in Roundup amplified the effects of the active, toxic ingredient, glyphosate by causing cell membranes to become more permeable and accelerating the rate of apoptosis and necrosis.
[Benachour, N., et al. 2009. Chemical Research in Toxicology, 22(1)]
- Pesticides and hypospadias: A meta-analysis
Study used meta-analytic techniques to synthesize the findings of the current body of published literature regarding the risk of hypospadias resulting from parental exposure to pesticides. Elevated but marginally significant risks of hypospadias were associated with maternal occupational exposure and paternal occupational exposure. Exposure assessment using a job-exposure matrix resulted in slightly higher estimated risk than agricultural occupation in fathers; but this effect was reversed in mothers, suggesting the importance of indirect and residential pesticide exposures in this group.
[Rocheleau CM, Romitti PA, Dennis LK. 2009. J Pediatr Urol. 5(1):17-24]
- Risk of limb birth defects and mother's home proximity to cornfields
Authors studied birth defects in relation to the area of corn or soybeans within 500 m of the mother's residence. Results found that limb birth defects increased in relation to cornfields. None of the birth defect types studied was associated with soybeans.
[Ochoa-Acuña, H. and Carbajo. C. 2009. Sci Total Environ. 407(15):4447-51]
- Use of biocides and insect repellents and risk of hypospadias
Study found an association between the use of insect repellent and total biocide score and risk of hypospadias. The use of insect repellent during the first trimester of pregnancy was associated with an 81% increased risk of hypospadias.
[Dugas J., et al. 2009. Occupational and Environmental Medicine, doi:10.1136/oem.2009.047373]
- Cryptorchidism at birth in Nice area (France) is associated with higher prenatal exposure to PCBs and DDE, as assessed by colostrum concentrations
A 2008 study finds a link between total chemical contamination in the bodies of pregnant women and the risk of cryptorchidism in their male babies. Mothers whose babies were born with the defect had the highest concentrations of persistent organic pollutants (POPs), mostly organochlorines like PCB and DDE, in their breast milk. The study compares prebirth exposure to chemicals, as measured through their mother’s milk, and the risk of undescended testicles or cryptorchidism, during a three-year period. While all subjects in the study had detectable levels of these chemicals in either their blood or breast milk, the researchers found that mothers in the highest exposure group for PCBs and DDE in breast milk had two-fold greater odds of giving birth to a boy baby with cryptorchidism, as compared to moms with low to medium exposure. The occurrence of cryptorchidism indicates that testosterone production and/or hormone signaling conditions in the womb have gone awry. Both of these conditions are related to sperm production and the risk of testicular cancer later in life. Cryptorchidism is seen in about 3% of male full-term births, 30% of premature births and is one cause of male infertility.
[Brucker-Davis F., et al. 2008. Human Reproduction, 23(8).]
- Mammary Gland Development as a Sensitive End Point after Acute Prenatal Exposure to an Atrazine Metabolite Mixture in Female Long-Evans Rats
Exposure of rats late in pregnancy to amixture of metabolites of atrazine also leads to persistent changes in mammary gland development in the pups that were exposed during gestation. These abnormalities in prenatally exposed rats persist into adulthood.
[Enoch R.R., et al. 2007. Environmental Health Perspectives, 115(4).]
- Differential Effects of Glyphosate and Roundup on Human Placental Cells and Aromatase
A 2005 study finds damaging endocrine effects of glyphosate (Roundup) to fetal growth at levels 10 times lower than used in agriculture. The product formulation Roundup was shown to be at least twice as toxic as the active ingredient alone. According to the researchers, the study demonstrates that Roundup acts as a disruptor of aromatase activity (, a mammalian enzyme crucial for sex steroid hormone synthesis and physiologic functions, including female and male reproduction, sex differentiation, and bone growth.) from concentrations 100 times lower than the recommended use in agriculture. The effect they report is noticeable on human placental cells after only 18 hours.
[Richard S., et al. 2005. Environmental Health Perspectives, 113(6).]
- Low-Dose Agrochemicals and Lawn-Care Pesticides Induce Developmental Toxicity in Murine Preimplantation Embryos
Lawn pesticide products containing herbicides and fertilizers (such as “weed and feed” products) tested on mice show increased risk of infertility, miscarriage and birth defects at very low dosages.
[Greenlee, A., et al. 2004. Environmental Health Perspectives, 112(6): 703-709.]
- Pesticides and children
This study examines how children are at risk for other effects of organophosphates and synthetic pyrethroids, including physical and mental retardation, alterations of the cardiovascular system and musculoskeletal defects, alterations of the menstrual cycle, obesity, and failure to develop secondary sex characteristics.
[Garry, V.F., 2004. Toxicology and Applied Pharmacology, 198(2): p. 152-163.]
- Prenatal Insecticide Exposures and Birth Weight and Length Among an Urban Minority Cohort
Insecticide exposures are widespread among minority women in New York City during pregnancy and that levels of the organophosphate chlorpyrifos in umbilical cord plasma were inversely associated with birth weight and length. Here authors analyse insecticides (the organophosphate diazinon and the carbamate propoxur), a sample size (n = 314 mother-newborn pairs), and insecticide measurements in maternal personal air during pregnancy as well as in umbilical cord plasma at delivery. Authors found no association between maternal personal air insecticide levels and birth weight, length, or head circumference. For each log unit increase in cord plasma chlorpyrifos levels, birth weight decreased by 42.6 g and birth length decreased by 0.24 cm. Combined measures of (ln)cord plasma chlorpyrifos and diazinon were also inversely associated with birth weight and length. Birth weight averaged 186.3 g less among newborns with the highest compared with lowest 26% of exposure levels. Further, the associations between birth weight and length and cord plasma chlorpyrifos and diazinon were highly significant among newborns born before the 2000-2001 U.S. Environmental Protection Agency's regulatory actions to phase out residential use of these insecticides. Among newborns born after January 2001, exposure levels were substantially lower, and no association with fetal growth was apparent. The propoxur metabolite 2-isopropoxyphenol in cord plasma was inversely associated with birth length, a finding of borderline significance after controlling for chlorpyrifos and diazinon. Results indicate that prenatal chlorpyrifos exposures have impaired fetal growth among this minority cohort and that diazinon exposures may have contributed to the effects. Findings support recent regulatory action to phase out residential uses of the insecticides.
[Whyatt RM, Rauh V, Barr DB, Camann DE, Andrews HF, et al. 2004. Environ Health Perspect.112(10):1125-32.]
- Birth Malformations and Other Adverse Perinatal Outcomes in Four U.S. Wheat-Producing States.
A 2003 EPA study suggests an association between rates of birth malformations and indirect measures of human exposure to chlorophenoxy herbicides, such as 2,4-D and MCPA, common weed killers sold commercially and used in agriculture. Combined circulatory and respiratory malformations increased by more than two-fold, and musculoskeletal malformations increased by 50%; Death rates from birth malformations among male infants were more than double; and, compared with births conceived during other months of the year, an increased chance of circulatory and respiratory (excluding heart) malformations for infants conceived from April to June, a time that more than 85% of the acreage treated with chlorophenoxy herbicides is applied on durum wheat in the states studied.
[Schreinemachers, D. 2003. Environmental Health Perspectives, 111(9).]
- Effects of Transplacental Exposure to Environmental Pollutants on Birth Outcomes in a Multiethnic Population.
A 2003 study finds that prenatal exposure to the pesticide chlorpyrifos adversely affects fetal development. The researchers examined 250 non-smoking African American and Dominican women in the New York City area for prenatal exposure to chlorpyrifos by measuring levels of the pesticide in the umbilical cord of the newborn. The results associated chlorpyrifos presence with decreased birth weight and birth length.
[Perera, F. et al. Feb. 2003. Environmental Health Perspectives, 111(2).]
- Developmental neurotoxicity of chlorpyrifos modeled in vitro: Comparative effects of metabolites and other cholinesterase inhibitors on DNA synthesis in PC12 and C6 cells.
A 2001 published study finds that organophosphate pesticides and their major metabolites can affect a fetus or newborn at concentrations that are nontoxic to adults. The study compared the effects of these pesticides in two in vitro models, using neuronotypic and gliotypic cells.
[Qiao, D. et al. 2001. Environmental Health Perspectives, 109(9):909-913.]
- Chlorpyrifos (Dursban)-associated birth defects: report of four cases.
A 1996 study of children exposed to chlorpyrifos in utero found that extensive and unusual patterns of birth defects, including brain, nervous system, eyes, ears, palate, teeth, heart, feet, nipples, and genitalia. Published literature and EPA documents contain reports that identify similarities in defects found in test animals and children exposed to chlorpyrifos.
[Sherman, J.D. 1996. Environmental Health Perspectives, 51(1).]
- Pesticide appliers, biocides, and birth defects in rural Minnesota.
A study of live births in Minnesota farming communities links the use of 2,4-D and other penoxy-acetic acid-derived herbicides to significantly higher rates of central nervous system, urogenital, circulatory/respiratory, or musculoskeletal anomalies in the children of pesticide applicators versus the average population.
[Garry, V., et al. 1996. Environmental Health Perspectives 104(4):394-399.]