08
Sep
Scientific Studies Identify EPA Deficiency in Evaluating Safety of Toxic Chemical Interactions
(Beyond Pesticides, September 8, 2025) Beyond Pesticides today called on Congress to require the U.S. Environmental Protection Agency (EPA) to incorporate real world science into its evaluation of pesticide safety calculations by recognizing that daily exposure involves multiple chemicals and synergistic interactions— a magnified effect greater than the individual chemical effects added together. The organization cites numerous scientific studies that call public attention to this issue; that a realistic assessment of the human and environmental harm potentially caused by pesticides cannot be evaluated based on single-chemical, single-species tests. Given the numerous complexities associated with this type of assessment, the group points to organic land management in agriculture and residential areas as a more cost-effective approach, sending this message to Congress: EPA must consider the effects of pesticides in the context in which they are used and with reference to the organic alternative.
A recent study, covered by Beyond Pesticides in its Daily News, found that the presence of Varroa mites in combination with the neonicotinoid insecticide imidacloprid increases the risk of bee mortality and disrupts the larval gut microbiome. The study found synergy (a greater combined effect) between Varroa destructor, a parasitic mite that attacks and feeds on honey bees, and imidacloprid. The findings were published last month in Pesticide Biochemistry and Physiology, and reinforces the important findings of a study published earlier this year. While there has been debate on whether neonicotinoid (neonic) insecticides or Varroa mites (Varroa destructor) are more detrimental to the survival of bees, evidence suggests that neonicotinoids are not only harmful individually but can increase vulnerability to parasitism from mites in western honey bees (Apis mellifera) and bumblebees.
Other examples of synergistic effects of pesticides abound. A review in Clinical and Experimental Obstetrics & Gynecology analyzes studies linking exposure to environmental contaminants with adverse effects on women’s reproductive health. The chemical classes within the review include plasticizers, PFAS, heavy metals, pesticides, organophosphate flame retardants (OPFRs), polychlorinated biphenyls (PCBs), volatile organic compounds (VOCs), microplastics, quaternary ammonium compounds (QACs), and polycyclic aromatic hydrocarbons (PAHs), many of which are related to chemical-intensive land management and can exacerbate health effects through additive or synergistic effects, like microplastics when in contact with petrochemical pesticides and synthetic fertilizers.
The scientific literature shows that microplastics (MPs) and pesticides, both ubiquitous throughout the environment, have synergistic effects that threaten aquatic organisms. The most recent study to demonstrate this, published in Ecotoxicology, focuses on the impacts of MPs and chlorpyrifos (CPF), a widely used organophosphate insecticide, on cladocerans, a group of microcrustaceans. A literature review of over 90 scientific articles in Agriculture documents MPs’ increase in the bioavailability, persistence, and toxicity of pesticides used in agriculture. In analyzing the interactions between neonicotinoid pesticides (NNPs) and MPs, a recent study in The Science of The Total Environment finds that neonicotinoids such as thiacloprid (THI) become more bioavailable in soils containing traditional and biodegradable plastics. Increased bioavailability, which quantifies the extent to which organisms are exposed to chemicals in soil or sediment, puts soil microbiota at risk and leaves all consumers susceptible to adverse effects in contaminated food crops.
A study in Royal Society Open Science shows intraspecific differences (genetic differences of individuals of a species) in wild bumblebees (Bombus vosnesenskii) exposed to an herbicide (glyphosate), a fungicide (tebuconazole), and an insecticide (imidacloprid), with gut microbiome health as a factor. The authors conclude, “These findings suggest that site-specific factors influence pesticide sensitivity and should be considered in ecotoxicological studies of wild bees.”
Researchers studying a mass mortality event of approximately 200 monarch butterflies (Danaus plexippus plexippus) in Pacific Grove, California, point out, there are additional issues in assessing risks to species since “available toxicity values are based on exposure to a single active ingredient, whereas all the sampled monarchs contained residues of multiple pesticides.” Exposure to multiple pesticides can result in additive or synergistic effects, which then enhance toxicity, as has been demonstrated in many studies of pollinator species.
A common soil arthropod has clearly illustrated how this convergence creates synergistic effects: warming increases pesticide toxicity; pesticide toxicity triggers antibiotic resistance; antibiotic resistance spreads through horizontal gene transfer (movement through the environment to people) and predation.
Published in Environmental Pollution, a study of commercial dry pet products finds dietary pesticide residues in dog and cat food, “highlighting the urgent need for improved regulatory frameworks to address the presence of non-approved pesticides in pet food.” Additionally, the researchers point out: “Current regulatory frameworks primarily assess the toxicity of individual pesticide compounds, yet real-world exposure involves complex mixtures that may lead to additive or synergistic effects. The presence of multiple residues in a single sample suggests that companion animals may be subjected to combined toxicological burdens that are not yet fully understood.”
A recent study published in Foods assesses the ability of the fungicide azoxystrobin (AZX) and naturally occurring toxins produced by certain fungi, known as mycotoxins, to display effects of cytotoxicity (cell damage). These effects were evaluated using three common mycotoxins found in food, including ochratoxin A, deoxynivalenol, and T-2 toxin, as mixtures with AZX within human hepatocarcinoma cell cultures. In analyzing combinations of these compounds at sublethal concentrations, the authors find modified toxicological behavior and synergistic effects that highlight the complexities of chemical mixtures and potential threats to liver health through dietary exposure to both toxicants and toxins, which are not adequately regulated for their interactions.
Study results published in Pesticide Biochemistry and Physiology “suggest that combined [pesticide] exposure may further amplify the toxicity and compromise the intestinal barrier.”
A study in GeoHealth of pediatric cancers in Nebraska links exposure to agricultural mixtures with the occurrence of these diseases. The authors find statistically significant positive associations between pesticide usage rates and children with cancer, specifically brain and central nervous system (CNS) cancers and leukemia.
A study in Chemosphere, conducted by researchers from the Institute of Biochemistry and Molecular Biology in Germany, reveals the varied lethal and sublethal effects of different mixtures of the weed killer glyphosate through tests on the South African clawed frog (Xenopus laevis). After exposing embryos to four glyphosate formulations, mortality, morphological defects, altered heartbeat rate, and impaired heart-specific gene expression are observed.
In their recent publication in Environmental Pollution, researchers from the Helmholtz Centre for Environmental Research in Leipzig, Germany, find the greatest synergistic effects when Daphnia magna are subjected to the insecticide esfenvalerate under conditions experienced with climate change.
In a study published in Biomedicines, the authors conducted a multi-behavioral evaluation of the effects of three pesticides, both individually and as mixtures, on larvae. The authors state, “Even at low concentrations, pesticides can negatively affect organisms, altering important behaviors that can have repercussions at the population level.” By analyzing effects on individual zebrafish with single compounds and mixtures, this study shows the dangers of pesticides in aquatic systems regarding synergy and the ripples created throughout entire ecosystems.
Other studies highlight the need for a broader overhaul of the current regulatory review to address critical flaws in EPA’s current ecological risk assessment process. A November 2023 European study published in Nature demonstrates that relying on testing one active ingredient in a laboratory setting misses real-world impacts of pesticides on bees, nontarget pollinators, and a “landscape-level” study finds that typical risk assessment reviews used by EPA and European regulators fail to “safeguard bees and other pollinators that support agricultural production and wild plant pollination.” The authors’ conclusions challenge “the current assumption of pesticide regulation—that chemicals that individually pass laboratory tests and semifield trials are considered environmentally benign” and call into question EPA’s current regulatory assessments based on the western honey bee and its failure to adequately regulate mixtures of chemicals to which organisms are exposed in the real world as well as the actual devastating impacts to pollinators from the ubiquitous neonicotinoids.
A study published in Conservation Letters, a journal of the Society for Conservation Biology, exposes critical shortcomings in the U.S. Environmental Protection Agency’s (EPA) ecological risk assessment (ERA) process for modeling the risks that pesticides pose to bees and other pollinators. For the study, “Risk assessments underestimate threat of pesticides to wild bees,” researchers conducted a meta-analysis of toxicity data in EPA’s ECOTOX knowledgebase (ECOTOX), an EPA-hosted, publicly available resource with information on adverse effects of single chemical stressors to certain aquatic and terrestrial species. The meta-analysis found that the agency’s approach, which relies heavily on honey bee data from controlled laboratory studies, drastically underestimates the real-world threats from neonicotinoid insecticides (and likely other pesticides) to native bees and other pollinators. The study “challenges the reliability of surrogate species as predictors when extrapolating pesticide toxicity data to wild pollinators and recommends solutions to address the (a)biotic interactions occurring in nature that make such extrapolations unreliable in the ERA process.”
The organic alternative. Since, as noted by John Muir—and others as long ago as John Donne’s “No Man is an Island”—all life is interconnected, it is no surprise that synergism is the rule, rather than the exception. As noted by Maricel Maffini, PhD, and Laura Vandenberg, PhD, in a commentary in Frontiers in Toxicology, “Current approaches also rely on the assumption that testing chemicals one at a time is appropriate to understand how chemicals act under real-world conditions. Numerous mixture studies, including ones that demonstrated cumulative effects, have disproven this assumption.”
Beyond Pesticides has maintained that the only way to truly protect pollinators, insects, birds, and other species, as well as the biosphere as a whole, is to stop the use of pesticides completely. This questions the system of chemical-dependent management of crops, landscapes, and structures. In this context, it advocates the conversion of the world’s agricultural systems to organic would have a tremendous positive impact on threatened populations.
Beyond Pesticides invites the public to send the following letter to Members of Congress. (The letter can be sent by clicking HERE.)
Studies demonstrating synergistic interactions between pesticides and other stressors bring to mind John Muir’s wisdom: “When we try to pick out anything by itself, we find it hitched to everything else in the Universe.”
Recent studies show:
The presence of Varroa mites in combination with a neonicotinoid insecticide increases the risk of bee mortality and disrupts the larval gut microbiome; suggesting that neonicotinoids are not only harmful individually but can increase vulnerability to parasitism from mites in western honey bees.
Women’s reproductive health is adversely affected by exposure to environmental contaminants, many of which are related to chemical-intensive land management and can exacerbate health effects through additive or synergistic effects.
Microplastics (MPs) and pesticides have synergistic effects that threaten aquatic organisms. MPs increase the bioavailability, persistence, and toxicity of pesticides used in agriculture, putting soil microbiota at risk and leaving all consumers susceptible to adverse effects in contaminated food crops.
Individual wild bumblebees differ in their response when exposed to an herbicide (glyphosate), a fungicide (tebuconazole), and an insecticide (imidacloprid), with gut microbiome health as a factor.
Researchers studying a mass mortality event of about 200 monarch butterflies in Pacific Grove point to additional issues in assessing risks to species since “available toxicity values are based on exposure to a single active ingredient, whereas all the sampled monarchs contained residues of multiple pesticides.”
A common soil arthropod demonstrates synergistic effects: warming increases pesticide toxicity; pesticide toxicity triggers antibiotic resistance; antibiotic resistance spreads through horizontal gene transfer and predation.
The presence of multiple residues in a single sample of dog or cat food suggests that companion animals may be subjected to combined toxicological burdens that are not yet fully understood.
The interaction of a fungicide and naturally occurring mycotoxins shows synergistic effects, highlighting the complexities of chemical mixtures and potential threats to liver health through dietary exposure to both toxicants and toxins that are not regulated for their interactions.
Combined pesticide exposure may further amplify the toxicity and compromise the intestinal barrier.
Agricultural mixtures are linked to the occurrence of pediatric cancers, specifically brain and central nervous system cancers and leukemia.
Different glyphosate mixtures produce varied lethal and sublethal effects–mortality, morphological defects, altered heartbeat rate, and impaired heart-specific gene expression—on the South African clawed frog.
Daphnia magna experienced synergistic effects when subjected to esfenvalerate under conditions of climate change.
A multi-behavioral evaluation of the effects of three pesticides, both individually and as mixtures, on zebrafish larvae found, “Even at low concentrations, pesticides can negatively affect organisms, altering important behaviors that can have repercussions at the population level.”
Other studies highlight the need for a broader overhaul of the EPA’s current risk assessment process. A November 2023 European study published in Nature challenges “the current assumption of pesticide regulation—that chemicals that individually pass laboratory tests and semifield trials are considered environmentally benign.”
Since interactions and synergism are the rule, pesticides cannot be evaluated based on single-chemical, single-species tests. They must be evaluated in context—that is, the system of chemical-dependent management must itself be questioned. Fortunately, there is an alternative system—regenerative organic production and land management—suitable as a successful, comparable standard.
EPA must consider effects of pesticides in the context in which they are used and with reference to the organic alternative.
Thank you.
