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Daily News Blog

06
May

Breakdown Products (Metabolites) from Pesticides May Be More Toxic than Parent Compound, Study Finds

(Beyond Pesticides, May 6, 2021) Nearly half of all breakdown products (transformation products) from four common-use environmental pesticides produce stronger endocrine (hormone) disrupting (ED) effects than the parent compound, according to new research published in Environment International. Over 300 environmental contaminants and their byproducts—from chemicals in plastics to cosmetic/personal care products—are commonly present in water bodies, food commodities, and human blood/urine samples. These toxicants can alter hormone metabolism, producing endocrine-disrupting effects that put the health of animals, humans, and the environment at risk.

Many ecological and health risk assessments for pesticides focus on the effects of parent chemical compound products, overlooking the potential impacts of transformation products (TPs). Therefore, studies like these highlight the need to assess the implications of TPs to safeguard human, animal, and environmental health. The researchers note, “Since an increasing number of pesticide TPs have been detected in various environmental media, a more comprehensive understanding of the ecological risk of pesticide TPs is imperative for risk assessments more extensively and regulatory policy-making on pesticide restriction in the future.”

Endocrine disruptors are xenobiotics (i.e., chemical substances like toxic pesticides foreign to an organism or ecosystem), including pesticides, bisphenols, phthalates, persistent organic pollutants (POPs), and heavy metals. Past research demonstrates exposure to endocrine-disrupting chemicals can alter the natural hormones in the body responsible for conventional fertile, physical, and mental development. Numerous studies confirm the effect chemical compound exposure has on human health. However, there is a lack of research regarding the effects of breakdown products or metabolites that these chemical compounds create.

Researchers selected four widely used pesticides—pyriproxyfen (Pyr), malathion (ML), benalaxyl (BX), and fenoxaprop-ethyl (FE)—and their 21 transformation products to evaluate for endocrine-disrupting effects. Using in vitro and in silico approaches, researchers assessed estrogen receptor α, glucocorticoid receptor α, the mineralocorticoid receptor, and hormone levels in H295R cells to determine ED impacts.

The results reveal that 50 percent of TPs exhibit more powerful endocrine-disrupting effects than their respective parent compound. Pyriproxyfen (Pyr) and 5 of its TPs, one TP of malathion, one TP of benalaxyl, and two TPs of fenoxaprop-ethyl exhibit the most effects on estrogen, mimicking the binding activity of the hormone to its receptor. Malathion and its TPs, and two Pyr TPs, have weak impacts on glucocorticoid activity via hydrogen bonding. Lastly, all chemical displaying endocrine-disrupting effects increases hormone secretion and gene expression in H295R cells responsible for sex hormone production (estrogen/androgen).

Clean air, water, and healthy soils are integral to ecosystem function, interacting between Earth’s four main spheres to support life. However, toxic pesticide residues are pervasive in the ecosystem, frequently detectable in soils, water (solid and liquid), and the surrounding air at levels exceeding U.S. Environmental Protection Agency (EPA) standards. These pesticide residues undergo hydrolysis, photolysis, oxidation, and biodegradation to break down into various transformation products that are just as ubiquitous as their parent compound. For instance, 90 percent of Americans having at least one pesticide biomarker (includes parent compound and metabolites) in their body. The presence of pesticides in the body has implications for human health, especially during vulnerable life stages like childhood, puberty, pregnancy, and old age. Scientific literature demonstrates pesticides’ long history of severe adverse health effects (i.e., endocrine disruption, cancer, reproductive/birth problems, neurotoxicity, loss of biodiversity, etc.) on the environment, including wildlifebiodiversity, and human health. Therefore, exposure to pesticides and their TPs can elicit adverse health effects, including impacts on the endocrine system.

The European Union and endocrine disruptor expert (deceased) Theo Colborn, Ph.D., classify more than 50 pesticide active ingredients as endocrine disruptors (EDs), including chemicals in household products like detergents, disinfectants, plastics, and pesticides. Research demonstrates endocrine disruption is prevalent among many pesticide products like herbicides atrazine and 2,4-D, pet insecticide fipronil, and manufacturing by-product dioxin (TCDD). These chemical ingredients can enter the body, disrupting hormones and causing adverse developmental, disease, and reproductive problems. The endocrine system consists of glands (thyroid, gonads, adrenal, and pituitary) and the hormones they produce (thyroxine, estrogen, testosterone, and adrenaline). These glands and their respective hormones guide the development, growth, reproduction, and behavior of animals, including humans. Endocrine disruption is an ever-present, growing issue that plagues the global population. Hence, advocates maintain that policies should enforce stricter pesticide regulations and increase research on the long-term impacts of pesticide exposure.

This study is one of many to recognize that pesticide breakdown products are just as, or even more, toxic than their parent compounds. Globally, pyriproxyfen (Pyr) is widely used for mosquito control and the only pesticide that the World Health Organization (WHO) approves for controlling mosquitoes in drinking water containers. However, almost all seven TPs of Pyr generate estrogen-disrupting activity in the blood, kidneys, and liver. Malathion is a popular insecticide that inhibits acetylcholinesterase (AChE) activities in the nervous tissue. Inhibition of AChE can cause a buildup of acetylcholine (a chemical neurotransmitter responsible for brain and muscle function). This chemical buildup can lead to acute impacts, such as uncontrolled, rapid twitching of some muscles, paralyzed breathing, convulsions, and, in extreme cases, death. However, the inhibition AChE is non-specific, making dispersal of malathion a severe threat to wildlife and public health. Hence, the study finds two TPs of malathion to have endocrine-disrupting effects on gene expression, hormone secretion, and glucocorticoid metabolism (carbohydrates, proteins, fats). The rapid degradation of pesticide fenoxaprop-ethyl produces two highly toxic TPs that upregulate gene expression 5.8 to 12-fold and have a greater impact on estrogenic activities. Lastly, the primary TP of benalaxyl persists longer in the environment than the parent compound, acting antagonistically toward estrogen receptor α and upregulates gene expression 3-fold. The four pesticides in this study are not the only chemicals of concern; many other pesticides also produce toxic breakdown products. Numerous banned pesticides, older pesticide compounds, newer pesticide compounds, and chemical manufacturing by-products create toxic TPs that contaminate the body and ecosystem.

Banned insecticide DDT, and its major metabolite DDE, remain in the environment decades after use ended, with the U.S. Environmental Protection Agency (EPA) finding chemical concentrations that exceed acceptable levels. Although DDT and DDE dissolve into body fat and linger for many years, DDE remains in the body longer. A Centers for Disease Control (CDC) investigation finds DDE contaminates the bodies of 99 percent of study participants. As in endocrine disruptor, exposure to DDT increases risks associated with diabetesearly onset menopausereduced sperm countendometriosisbirth abnormalitiesautismvitamin D deficiency, non-Hodgkin’s Lymphoma, and obesity. However, studies find that DDE is even more toxic than its parent compound. This metabolite can produce multi-generational health effects on obesity and diabetes and uniquely augmenting multi-generational breast cancer occurrences. Some older generations of pesticides, including organophosphates like malathion, originate from the same compounds as World War II nerve agents (Agent Orange), producing adverse effects on the nervous system. Triclosan, an antimicrobial pesticide product banned from many products, persists in the environment and produces carcinogenic breakdown products like chloroform and 2,8-dichlorodibenzo-p-dioxin (2,8-DCDD).

Newer generation” of chemicals, including glyphosate and neonicotinoids (neonics), are fast-acting, with quick breakdown times, thus less likely to readily accumulate. However, studies find lower concentrations of these chemicals are more toxic than their older counterparts, requiring several kilograms less. Therefore, the breakdown products of these chemicals can produce similar or more severe toxicological effects. Studies indicate that herbicide glyphosate transforms into toxic metabolic AMPA, which alters gene expression. Furthermore, neonic metabolites, such as desnitro-imidacloprid and descyano-thiacloprid, are more than 300 and ~200 times toxic to mammals, respectively, than the parent compound imidacloprid. According to the U.S. Geographical Survey, these metabolites readily contaminate streams. Thus, experts warn that these breakdown products may morph into new forms of chlorinated disinfection byproducts (DBPs)—with unfamiliar/undiscovered health risks—during routine water treatment (chlorination) processes.

Pesticides and their TPs can promote higher acute and sublethal toxicity levels, which can cause chronic effects on species abundance and biodiversity. Various past and present pesticide products act similarly to other environmental contaminants, and individuals can encounter these substances simultaneously. Often, these chemical contaminants work together or synergize to produce a more severe, combined effect. Synergism is a common issue among pesticide mixture and can underestimate the toxic impacts on human, animal, and environmental health. Therefore, current ecological and human health risk assessments vastly underestimate hazardous effects from pesticide residues, metabolites, and other environmental contaminants.  

Lack of efficient pesticide testing fails to evaluate the impacts of breakdown products as many studies merely assess the effect of parent products. With newer generations of pesticide products having faster breakdown times and increased toxicity, breakdown products will pose a real problem for future ecosystem and human health. As has been previously stated: “[Beyond Pesticides] has long been critical of EPA’s risk assessment process, which fails to look at chemical mixtures—including inert ingredients—and synergistic effects in common pesticide products. Additionally, lack of awareness on specific health endpoints (such as endocrine disruption), disproportionate effects to vulnerable population groups, and regular non-compliance with product label directions hinder accurate risk assessments. These deficiencies contribute to its severe limitations in defining real-world poisoning, as captured by epidemiologic studies in Beyond Pesticides’ Pesticide-Induced Diseases Database.”

The study’s authors conclude, “ [I]t is urgent to pay more attention to the TPs in the process of environmental risk assessment of pesticides, and the profound findings of the endocrine-disrupting effects from pesticide TPs provided in this current study would be beneficial to further risk assessment and regulatory improvement of pesticide use.”

It is essential to understand the effects that endocrine-disrupting pesticides and their breakdown products may have on the health of current and future generations. There is a lack of understanding behind the etiology of pesticide-induced diseases, including predictable lag time between chemical exposure, health impacts, and epidemiological data. Therefore, lawmakers and regulators should consider taking a more precautionary approach before introducing these chemicals into the environment. With far too many diseases in the U.S. associated with pesticide exposure, reducing pesticide use is a critically important aspect of safeguarding public health. Learn more about the effects of pesticides on human health by visiting Beyond Pesticides’ Pesticide-Induced Diseases Database, supporting a shift away from pesticide dependency. This database is a fantastic resource for additional scientific literature, documenting elevated rates of Endocrine Disruption, Cancer, and other chronic diseases and illnesses among people exposed to pesticides. Beyond Pesticides believes that we must mitigate the impacts pesticides and their metabolites pose on human and animal health. Learn more about pesticides, their metabolite, and inert ingredients by visiting Beyond Pesticides’ webpage, What Is a Pesticide? 

One way to reduce human and environmental contamination from pesticides is buyinggrowing, and supporting organic. Numerous studies find that levels of pesticide metabolites in urine drop greatly when switching to an all-organic diet. Organic agriculture has many health and environmental benefits, which curtail the need for chemical-intensive agricultural practices. Adopting regenerative-organic practices and using least-toxic pest control can reduce harmful exposure to pesticides. Given the wide availability of non-pesticidal alternative strategies, families and agro-industry workers alike can apply these methods to promote a safe and healthy environment. For more information on how organic is the right choice for both consumers and the farmworkers that grow our food, see Beyond Pesticides webpage, Health Benefits of Organic Agriculture.

Help Beyond Pesticides educate and build the movement that will bring long-needed protection to humans, animals, and the entire environment by attending the National Pesticide Forum this spring. Cultivating Healthy Communities will bring together expert scientists, farmers, policymakers, and activists to discuss strategies to eliminate harms from toxic chemical use in favor of non-toxic organic solutions. It begins with a pre-conference session on Monday, May 24, and continues every Tuesday beginning May 25, June 1, June 8, and ending June 15, 2021. Registration is open today and available through the webpage on this link. It starts with US.

All unattributed positions and opinions in this piece are those of Beyond Pesticides.

Source: Environment International

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