(Beyond Pesticides, December 21, 2023) A new study published in Environmental Toxicology and Pharmacology adds to prior research indicating glyphosate promotes the occurrence of nonalcoholic fatty liver disease (NAFLD) through diet by causing liver inflammation and oxidative stress. More importantly, the predisposition for NAFLD occurred at levels within toxicological limits, which are doses of glyphosate classified as causing no adverse effects or No Observed Adverse Effect Level (NOAEL). NAFLD is a condition that causes swelling of the liver and can eventually lead to cirrhosis, cancer, or liver failure. This study highlights the Westernized diet (WD), comprised of foods enriched in saturated fats, cholesterol, and simple carbohydrates (e.g., fructose, glucose, and sucrose), plays a role in the nearly 40 percent increased risk of NAFLD. Although glyphosate disrupts gut microbes and induces liver inflammation, oxidative stress, and fatty acid levels that promote NAFLD, the combination of WD and glyphosate reduces the threshold risk for NAFLD development. NAFLD is a growing worldwide epidemic, becoming the most prevalent form of liver disease and impacting at least 25 percent of the globe. Therefore, studies like this shed light on how diet and chemical exposure can work synergistically (together) to exacerbate disease risk. The study evaluates whether choric […]

(Beyond Pesticides, December 19, 2023) Last week, farmworker organizations and Beyond Pesticides, represented by the Center for Food Safety, filed a petition with the U.S. Environmental Protection Agency (EPA) urging that the weed killer glyphosate be removed from the market. The petition cites 200 studies, which represent a fraction of the independent scientific literature on the hazards of glyphosate and formulation ingredients of glyphosate products. This action follows previous litigation in 2022 in which a federal court of appeals struck down EPA’s human health assessment, finding that the agency wrongfully dismissed glyphosate’s cancer risk. The farmworker groups petitioning include Farmworker Association of Florida, Organización en California de Lideres Campesinas, Alianza Nacional de Campesinas, and the Rural Coalition.   Meanwhile, verdicts against glyphosate’s manufacturer, Bayer, continue to pile up with a December jury verdict in Pennsylvania awarding $3.5 million and a November jury in Missouri ordering $1.56 billion to be paid to four plaintiffs. All link their cancer to use of the Roundup. Bayer has lost almost all of the cases filed against it for compensation and punitive damages associated with plaintiffs’ charge that its product (previously manufactured by Monsanto) caused them harm.  The petition summarizes its purpose and justification as […]

(Beyond Pesticides, December 13, 2023) A study published in Environmental Health finds occupational (work-related) exposure to pesticides increases the risk of endometrial (uterine) cancer development. Endometrial cancer is the most common cancer of the female reproductive system and the fourth most common cancer among women, primarily affecting the uterine lining rather than the uterus itself, like uterine sarcoma. Despite data predicting the disease rate to increase, few studies evaluate the connection environmental contaminants have on endometrial cancer occurrence. Like most cancers, non-genetic factors account for a majority of endometrial cancer risk, including diabetes, age, contraceptive (birth-control) use, and hormone (endocrine) disruption. However, three percent of all cases are hereditary, primarily from Lynch syndrome. The study notes, “Identifying other modifiable risk factors may help develop strategies to reduce the expected increasing incidence of these neoplasms.” Many pesticides have a long history associated with endocrine-disrupting properties that induce various molecular changes, prompting disease development. The International Agency for Research on Cancer (IARC) classifies many of these chemicals as potent carcinogens in animal studies. Cancer development also depends on genetic susceptibility, as impaired genes responsible for xenobiotic detoxification (elimination) increase disease risk sensitivity. Adding to the science, a review published in Environmental Exposure, Biomonitoring, and Exposure […]

(Beyond Pesticides, December 12, 2023) A review published in Nature Reviews Microbiology finds pesticides can disrupt honeybee (Apis mellifera) microbiota (bacteria) in their gut, altering the immune system, metabolism, behavior, and development. Many studies emphasize chemical-driven agricultural systems dependent upon pollinators and products that harm or kill off these sensitive species. Previous studies have linked adverse impacts to bee microbiome to pesticide exposure. Toxic (manufactured poison) pesticides readily contaminate the ecosystem with residues pervasive in food and water commodities. In addition to this study, the scientific literature commonly associates pesticides with human, biotic, and ecosystem harm, as a doubling of toxic effects on invertebrates, like pollinators, has been recorded since 2004.  Pollinator declines directly affect the environment, society, and the economy. Many agricultural and nonagricultural plant species will decline or cease to exist without pollinators. In turn, the economy will take a hit, since much of the economy (65%) depends upon the strength of the agricultural sector. As the science shows, pesticides are one of the most significant stressors for pollinators. Additionally, pesticides have a devastating impact on bees and other pollinators and the larger context of what has been called by scientists as the “insect apocalypse.” In a world where habitat loss and fragmentation show no sign […]

(Beyond Pesticides, December 6, 2023) A study published in Antioxidants finds prenatal and early life exposure, usually after birth (perinatal), to glyphosate-based herbicides (GBH) induce oxidative stress in the brain, causing damage and negatively affecting melatonin levels. Melatonin is a hormone responsible for regulating circadian rhythm to mitigate sleep disorders. Disruption of melatonin levels also has implications for the development of age-associated neurodegenerative diseases, as melatonin is a neuroprotector against neurodegenerative diseases associated with aging. Additionally, GBH can alter molecules in the pineal gland in the brain, resulting in neurodegenerative diseases like Alzheimer’s disease (AD) and Parkinson’s disease (PD). Levels of inadequate sleep patterns are rising among the global population. Reports find variability in sleep duration results in higher rates of depression, anxiety, and fatigue. Since sleep is an essential factor in normal brain development, disturbance in sleep patterns, such as sleeping too much or too little, can result in long-term associations with the brain’s white matter integrity (responsible for age-dependent cognitive function). The study warns, “Since decreased levels of the important antioxidant and neuroprotector melatonin have been associated with an increased risk of developing neurodegenerative disorders, this demonstrates the need to consider the melatonin hormone system as a central […]

Upcoming EPA Review of Nitrates in Waterways Raises Health and Environmental Questions About Synthetic Nitrogen Fertilizer Use. In  a quiet reversal of a 2018 Trump administration decision, EPA is resuming an evaluation of the health impacts of nitrate in water, reflecting the long-standing and mounting evidence of synthetic nitrogen’s adverse effects on human health and the environment, particularly in vulnerable communities.

(Beyond Pesticides, December 4, 2023) With a history of neglect of farmworker protection in the workplace, advocates are pointing to the need for ensuring stringent enforcement of regulations that are expected to take effect under the Pregnant Workers Fairness Act (PWFA) this month. In addition to weak laws and protections that typically exempt farmworkers, enforcement for farmworker protections that do exist has been lacking. A report on enforcement of wage and hour law under Wage and Hour Division of the U.S. Department of Labor (DOL) has documented diminished capacity to detect and enforce against violations. A report by the Economic Policy Institute (2020) shows the dramatic failures of DOL, which is underfunded and understaffed to enforce the law. As the agency charged with operationalizing the new law to protect farmworkers, the Equal Employment Opportunity Commission (EEOC) will be up against a federal pesticide law enforcement system that is dependent by agreements with state agencies, mostly departments of agriculture, that have a history of failing to enforce the limited protections provided for farmworkers. The EEOC is headquartered in Washington, D.C. and operates 53 field offices in every part of the country. Farmworkers have endured a long history of discrimination in the United […]

(Beyond Pesticides, November 30, 2023) Scientists at Minami Kyushu University in Japan have made a groundbreaking discovery of a new biological control for a target insect. They have identified a virus in tobacco cutworms that kills males, creating all-female generations. The discovery was described in a recent issue of the Proceedings of the National Academies of Sciences and The New York Times as evidence that multiple viruses have evolved to kill male insects. This “male-killing” virus could be added to the growing attempts to control unwanted insects with biological, as distinguished from genetically engineered (GE) solutions. Efforts range from the introduction of natural predators, to radiation-based sterilization of insects, CRISPR-based genetic mutations, and other techniques. While the GE approach has run into controversy because of unanswered questions associated with their release into natural ecosystems, some approaches have also run into resistance problems. Nearly a decade ago, researchers found armyworm resistance to Bacillus thuringiensis (Bt)-incorporated genetically engineered (GE) maize in the southeastern region of the U.S., calling this evolution of insect resistance to a naturally occurring soil bacterium engineered into crops “a serious threat to the sustainability of this technology.” The general population knows to avoid eating raw eggs because the bacteria salmonella, […]

(Beyond Pesticides, November 29, 2023) A study published in Environment International finds high pesticide exposure incidence associated with shingles, a varicella-zoster virus (the same highly contagious virus that causes chickenpox) that reactivates in the body after having chicken pox. Shingles is a painful condition with a blistering rash that can lead to vision and hearing loss, brain and lung inflammation, and even death if not treated. Since shingles manifest decades after initial exposure, and the association is strongest among individuals already hospitalized for pesticide-related illnesses, researchers find the long-term/chronic effects most concerning. Although dermal pesticide exposure can cause a range of adverse reactions, including dermatitis, allergic sensitization, and cancer, any route of exposure can exacerbate dermal manifestations through immune system response, causing virus-based skin reactions like shingles. People encounter toxic chemicals daily. However, frequent use of pesticides, including the use of everyday products like cleaning supplies, personal care products, agricultural chemicals, fabrics, non-stick cookware, and general airborne pollution, exacerbate chemical exposure risks. Dermal exposure is the most common pesticide exposure route, composing 95 percent of all pesticide exposure incidents, and is a significant concern for occupational (work-related) health. The study notes, “[The] findings of elevated shingles risk associated with acute, clinically relevant pesticide exposures also highlights […]

With the elevated adverse impacts associated with pesticides and reproductive health, the Pregnant Workers Fairness Act (PWFA) law may be used to improve protections for farmworkers and other high-risk employees.

(Beyond Pesticides, November 16, 2023) A study published in the Journal of Endocrinological Investigation finds exposure to the insecticide chlorpyrifos and other organophosphates (OPs) has a positive association with the development of erectile dysfunction (ED). Erectile dysfunction, also known as impotence, is the difficulty of getting or keeping an erection. Despite occurring in males later in life (between 40 and 70 years), recent studies highlight this issue emerging among adolescents, highlighting possible hormone imbalances not associated with age. Scientists and health officials already associate pesticide exposure with a decrease in male fertility, including reduced sperm count, quality, and abnormal sperm development. Exposure to many pesticides also profoundly impacts the endocrine (hormone) system, including reproductive health. Globally, ED is increasing, with over 300 million men expected to have ED by 2025. Although age and comorbid conditions (e.g., obesity, diabetes, and hypertension) play a role in ED prognosis, studies, including this one, suggest environmental contaminant exposure can also explain the increasing trend in ED. The study notes, “Future studies are warranted to corroborate these findings, determine clinical significance, and to investigate biological mechanisms underlying these associations.” Using data from the National Health and Nutrition Examination Survey (NHANES), researchers investigated urinary levels of 3,5,6-trichloro-2-pyridinol (TCPy), […]

(Beyond Pesticides, November 14, 2023) One of the Environmental Protection Agency’s (EPA) strongest tools for avoiding responsibility is delay—a tactic that kept cancellation of the neurotoxic pesticide chlorpyrifos at bay for 21 years—until May 2021, when a three-judge panel of the Ninth Circuit Court of Appeals, responded to a petition filed in 2007 by the Natural Resources Defense Council, Pesticide Action Network, and numerous other groups. The Ninth Circuit ordered the agency to quit lollygagging and acknowledge chlorpyrifos’s threat to human health, something the agency had acknowledged already. The Ninth Circuit instructed EPA to either revoke the “safe” tolerances the agency had set for chlorpyrifos’s residue in various foods or demonstrate that they are actually safe. Finally capitulating, EPA issued a final rule in August 2021 revoking all food tolerances for the neurotoxicant. Tell your governor and mayor to adopt policies that support organic land management.  This looked like progress until February 2022, when a different set of petitioners—pesticide companies, U.S. farmer groups, and other countries’ agricultural interests—filed an action in the Eighth Circuit Court of Appeals. On November 3 of this year, a three-judge panel of the Eighth Circuit reversed EPA’s decision, thereby neutralizing the Ninth Circuit’s opinion. Chlorpyrifos, […]

(Beyond Pesticides, November 13, 2023) The news of a federal Appeals Court’s reversal of a U.S. Environmental Protection Agency (EPA) decision in early November calls into question the value of the basic structures, processes, and authorities of pesticide law that the public has been told are protective of health and the environment. After decades of review and litigation, this reversal, especially on a highly neurotoxic insecticide like chlorpyrifos, identifies a fundamentally flawed system that does not protect the health of people, in this case, children’s brains. >>Tell your governor and mayor to adopt policies that support organic land management.  It was EPA’s finding that chlorpyrifos was destructive of the nervous system, particularly in children, and the functioning of the brain that led to an EPA-negotiated chemical company (Corteva/Dow Chemical) settlement in 1999 (took effect in 2000) that removed residential uses of chlorpyrifos from the market. The 2020 EPA decision, 21 years later, to stop agricultural uses followed another Appeals Court decision, departing from the agency’s usually long drawn-out negotiations that ultimately compromise health and the environment. EPA banned agricultural uses of chlorpyrifos in 2016 in the Obama Administration, but the decision was reversed by the Trump Administration in 2017. Because […]

(Beyond Pesticides, November 8, 2023) A study published in Environmental Science and Pollution Research finds organophosphate pesticides (OPs) are linked to an increased asthma prevalence. The study was released just before an 8th Circuit U.S. Court of Appeals November 3 decision vacating EPA’s 2021 decision to cancel all food tolerances for chlorpyrifos and sending it back to the agency. (Required by a 9th Circuit Court of Appeals decision in April 2021 to take action, EPA issued a final rule in August, 2021—in full effect February 28, 2022—after an earlier 9th Circuit decision, concluding that, “EPA is unable to conclude that the risk from aggregate exposure from the use of chlorpyrifos meets the safety standard of the Federal Food, Drug, and Cosmetic Act (FFDCA). Accordingly, EPA is revoking all tolerances for chlorpyrifos.”  Using urinary metabolites of OPs, the study highlights that diethyl phosphate (DEP, the breakdown chemical of chlorpyrifos) has the strongest association with asthma. However, individual and combined exposure to all OPs have a significant link to respiratory disease. The respiratory system is essential to human survival, regulating gas exchange (oxygen-carbon dioxide) in the body to balance acid and base tissue cells for normal function. Damage to the respiratory system can […]

(Beyond Pesticides, November 7, 2023) Two decades after the introduction of genetically engineered, herbicide-resistant crops and the consequential exponential growth in weed killers, Brazil is seeing an increase in childhood cancer. This is the conclusion reached in a comprehensive study spanning 15 years (2004-2019), “Agriculture Intensification and Childhood Cancer in Brazil,” published in Proceedings of the National Academy of Sciences (PNAS) in October. For the past 20 years, soybean herbicides have been killing and sickening children in the Cerrado and Amazon regions–where soybean cultivation is concentrated. The study reveals a link between an increase in soy cultivation and a spike in cases of acute lymphoblastic leukemia (ALL), the most common cancer affecting children, among indirectly exposed populations. Researchers identify pesticide-contaminated drinking water as the driving force behind the increased cancer rates occurring downstream from soybean sites.  In 2003, Brazil legalized its first official genetically modified (GM) crop, welcoming the era of GM soybeans and sparking a radical transformation in its agricultural landscape–for better or worse. The introduction of Monsanto’s Roundup Ready soybean seed promised farmers an efficient and herbicide-resistant alternative to traditional crops. A significant shift occurred in the areas dedicated to soy cultivation in the Cerrado region, tripling from […]

(Beyond Pesticides, November 1, 2023) A study published in Environmental Health Perspective finds the risk of acute childhood leukemia (AL), specifically acute lymphoblastic leukemia (ALL), slightly increases with exposure to pesticides (i.e., insecticides and herbicides) from uses on vines, a crop subject to intensive pesticide use. Within 1 kilometer [km] of vineyards, the risk of ALL among children increases in areas with a higher density of vines. Although medical advancements in disease survival are more common nowadays, childhood AL remains the secondary cause of child mortality following physical injury. Furthermore, childhood leukemia survivors can suffer from chronic or long-term health complications that may be life-threatening. The etiology or cause of childhood AL involves the interaction of multiple components, including lifestyle and genetics; emerging evidence indicates that environmental contaminants (e.g., pesticides, air pollution, solvents, diet, etc.) play a role in disease. Pesticide contamination is widespread in all ecosystems, and chemical compounds can accumulate in human tissues, resulting in chronic health effects. Children are particularly vulnerable to the impacts of pesticide exposure as their developing bodies cannot adequately combat exposure effects. Already, studies find low levels of pesticide exposure during pregnancy or childhood cause adverse health effects, from metabolic disorders to mental and physical disabilities. Moreover, […]

(Beyond Pesticides, October 31, 2023) With cooler weather setting in and people heading indoors and closing windows, the issue of COVID-19 transmission escalates, as do concerns about toxic chemicals filling the indoor ambient air. As a recent segment of 60 Minutes (October 29, 2023) stresses, COVID-19 spreads elevated public concern and understanding about the importance of ventilation, filtration, and air exchange to indoor air quality. Unfortunately, the concerns about indoor air are not limited to COVID-19 as volatile organic compounds (VOCs) invade most spaces where people live and work. These invisible toxic substances can be found in common household products, furniture, mattresses, and more, including pesticides in and around the house. Recognizing the risks associated with VOCs and the potentially hazardous off-gassing process is crucial for protecting public health.  VOCs are a group of chemicals that can easily vaporize into the air at room temperature. These compounds are found in many everyday items, including furniture, cleaning products, pesticides, cosmetics, and even air fresheners. Some household products, particularly pesticides, can introduce their own set of risks in addition to the risks they pose due to their VOC content. VOCs can range from harmless to harmful, and their presence can have a […]

(Beyond Pesticides, October 25, 2023) A study published in Environmental Pollution finds farming and organophosphate (OP) pesticide exposure are risk factors for depression, with pesticide poisoning being a risk factor for suicidal behavior. Additionally, psychiatric disorder prognosis affects men more than women, with depression and suicidal outcomes more common among pesticide-exposed males. Age also affected depression and suicidal consequences, with elevated rates among older farmers. Research on pesticide-induced diseases commonly investigates pesticide exposure concerning the development of various physical illnesses. However, previous studies show that occupational (work-related) risks of developing depression are high in agriculture, where pesticide use is widespread. Acute exposure to chemicals, including organophosphate, organochlorine, triazine, and carbamate pesticides, tends to put farmers at elevated risk. More study is needed on pesticide exposure and similar psychological (psychiatric) effects in the general population. According to the World Health Organization (WHO), depression affects 322 million people globally, with the number of diagnosed patients increasing by 18.4% from 2005 to 2015. Although the etiology of depression—and many other psychiatric disorders—is often genetic, studies suggest that other etiological factors, like pesticide exposure, play a role in depression incidents. Poor mental health has a tangible influence on physical health (e.g., depression and cardiovascular disease); therefore, the combination of pesticide exposure […]

(Beyond Pesticides, October 18, 2023) A meta-analysis published in Toxics finds an association between exposure to organophosphate pesticides (OPs) and respiratory diseases and diabetes mellitus (DM). Specifically, wheezing and asthma are the most common respiratory manifestations of OP exposure, while fluctuation in weight and fat/glucose levels are the most common metabolically related manifestations. Organophosphorus pesticides have a wide range of biological uses—from insecticides to flame retardants—that make these chemicals ubiquitous, significantly contributing to ecosystem contamination. Thus, OP compounds have a global distribution, with evaporation and precipitation facilitating long-range atmospheric transport, deposition, and bioaccumulation of hazardous chemicals in the environment. Many studies show OPs are highly toxic, and residues are consistently present in human and animal urine, blood, tissues, and milk. Considering 90 percent of Americans have at least one pesticide compound in their body, primarily stemming from dietary exposure, including food and drinking water, advocates maintain that current restrictions on their use must adequately detect and assess total chemical contaminants.  This study investigated the effects and possible mechanisms involved in adverse health outcomes associated with OP exposure. Reviewing studies from Web of Science, PubMed, Embase, OVID, and the Cochrane Library, researchers systematically searched for articles on OP exposure and respiratory, DM, and cardiovascular disease (CVD) outcomes until 2022. […]

(Beyond Pesticides, October 12, 2023) A new study published in Environment International finds novel environmental chemicals (i.e., piperidine insecticide, 2,4-dinitrophenol, benzo[a]carbazole, and a benzoate derivative) involved in developing breast cancer through various inflammation pathways. These new potential factors contribute to breast cancer and highlight the importance of employing epidemiological biomonitoring like exposome (total exposure from birth to death) to discover mechanisms involved in disease development that are otherwise overlooked. According to the Centers for Disease Control and Prevention (CDC), breast cancer is a disease that causes breast cells to grow out of control, with the type of breast cancer depending on the cells themselves. Several studies and reports, including U.S. Environmental Protection Agency (EPA) data, identify hundreds of chemicals as influential factors (either promoting or initiating) associated with breast cancer risk. Breast cancer is the most common cancer among women, accounting for 12 percent of all new annual cancer cases worldwide and causing the second most cancer-related deaths in the United States. Past studies suggest genetic inheritance factors influence breast cancer occurrence. However, genetic factors only play a minor role in the incidence of breast cancer, while exposure to external environmental factors (e.g., chemical exposure) appears to play a more notable role. One in […]

(Beyond Pesticides, October 11, 2023) Rachel Carson Conservation Park, a 650-acre conservation area in Montgomery County, Maryland, named in honor of the renowned scientist and author Rachel Carson, is now at the center of a controversy surrounding the use of toxic herbicides. Ms. Carson played a pivotal role in raising awareness about the harmful ecosystem and human health effects of pesticides that led to the banning of DDT. Environmentalists and concerned citizens have raised alarm over the recent spraying of “invasive weeds” with Garlon 3A, a powerful herbicide, within the park’s boundaries. Concern about pesticide use in Montgomery County is complicated by competing jurisdictions and restrictions within the county, and highlights the stark difference between nontoxic organic practices and pesticide-dependent Integrated Pest Management. (See more below on Montgomery County land management policy for local parks.) According to the Montgomery County website: “Montgomery County Parks [Maryland-National Capital Park and Planning Commission or M-NCPPC] are a State agency. M-NCPPC operates under an integrated pest management plan (IPM). Montgomery Parks manages all playgrounds, community gardens and common lawn areas within local parks without the use of pesticides. In 2016, Montgomery Parks designated ten pesticide-free parks. In September 2019, the program expanded to 45 […]

(Beyond Pesticides, October 10, 2023) In recent years, the effects of climate change have become more frequent and more severe, from extreme weather events to rising sea levels. But perhaps one of the most insidious consequences of a warming planet is the way it influences the spread of diseases, often hitting marginalized communities the hardest. This is no more evident than in the case of malaria, where the disease transmission through the Anopheles stephensi mosquito serves as a dire warning of the challenges caused by a changing climate. As this deadly vector of disease expands its territory, it is clear that pesticide-intensive approaches are poorly equipped to cope with the threat as insect resistance to chemical controls steadily grows.  Native to South Asia, the Anopheles stephensi mosquito has been on a relentless journey, crossing continents from the Arabian Peninsula to East Africa and deeper into the African continent. The mosquito’s ability to quickly adapt to new environments, bolstered by shifting climate patterns, illustrates how global warming affects disease vectors. Matthew Thomas, PhD, emphasizes, “Anopheles stephensi has higher thermal tolerance and a capacity to transmit at higher temperatures than Anopheles gambiae [another malaria-spreading mosquito]. This is significant when considering climate change […]

(Beyond Pesticides, October 4, 2023) A study published in Food and Chemical Toxicology finds acute exposure to chlordane, an organochlorine insecticide, results in decreased lipid (fat) levels, altered anti-oxidant capacity, and increased testosterone levels (pro-androgenic) in male mice, while increasing liver enzyme activation and reducing regulation of both liver identity and function in females. These findings indicate that chlordane induces toxicant-associated steatosis (fat retention) liver disease (TASLD) with underlying, sex-specific, endocrine, and metabolic effects. It is well-known that traces of legacy (past-use) pesticides, like organochlorine pesticides (OCPs), remain in the environment for decades—possibly centuries, post-final application, as OCPs have greater chemical stability and gradual attenuation. However, these chemicals have profound adverse impacts on human health, especially on the endocrine system. Obesity, insulin resistance, type 2 diabetes, and elevated liver enzymes resulting from endocrine disruption contribute to liver diseases and can lead to liver cirrhosis. Although some, but not all, manufacturing and use of specific OCPs have declined in the U.S., OCPs remain a global issue, as much of the developing world still report usage. Considering the lack of studies on OCP-induced endocrine disruption, TASLD, and other liver diseases, research like this highlights the need to understand the underlying mechanisms contributing to […]