20
Nov
Hazardous Compounds Formed with Pesticide Use, Studies Find, But Overlooked in Safety Reviews
(Beyond Pesticides, November 20, 2025) Recent scientific literature finds heightened toxicity associated with pesticide metabolites, the transformation/breakdown products of the parent compounds, that threaten the health of the soil, wildlife, and humans. This research stresses the importance of the U.S. Environmental Protection Agency (EPA) evaluating metabolites, which is currently insufficiently included in regulatory processes.
In a literature review in Global Change Biology, the researchers point out multiple areas in which regulations fail to address key criteria, including metabolites, saying: “Pesticide risk assessments currently rely on surrogate species and focus primarily on acute lethality metrics, failing to capture the broader impacts on non-target organisms and thus biodiversity. Under the directives of regulatory agencies worldwide, this traditional approach overlooks the complex interactions between multiple stressors, including climate change, land-use shifts, and pesticide transformation products. Pesticide risk assessments must therefore undergo a paradigm shift to account for these complex interactions, which disproportionately affect insect pollinators, other non-target species, and biodiversity at large.â€
A metabolite is a breakdown product that forms when a pesticide is used in the environment and mixes with air, water, soil, or living organisms. All metabolites fall under the category of transformation products, which is the broader term for any product resulting from the structural change of a parent compound. Metabolites are specifically formed through biological processes, while degradation products are another type of transformation product that are formed through non-biological processes in the environment.
Research on Contaminants of Concern
As previously covered by Beyond Pesticides, a study published earlier this year on sewage sludge (biosolids) used as fertilizers finds serious concerns about the range of contaminants within the treated sludge. The researchers identify 414 contaminants of emerging concern (CECs), including metabolites, in soils, untreated and treated sewage sludge, and dust, across 151 peer-reviewed studies released between 2018 and 2023—emphasizing the range of potential exposure pathways across various products, including classes of pesticides like neonicotinoid insecticides.
One of the researchers, Emile Habimana, M.S., is a speaker for the upcoming second session of the 42nd National Forum Series—The Pesticide Threat to Environmental Health: Advancing Holistic Solutions Aligned with Nature. A doctoral candidate specializing in Environmental Analytical Chemistry at the Université de Montréal, Quebec, Canada, Mr. Habimana holds a Master of Science in Chemical Engineering Integrated Chemical and Environmental Technology from Hankyong National University in South Korea, a Bachelor of Science in Chemistry from the National University of Rwanda, and has a background working in environmental management for the Ministry of Natural Resources in Kigali, Rwanda. His research, working with Sébastien Sauvé, PhD, professor of environmental chemistry, focuses on the development of advanced analytical methodologies for profiling and quantifying emerging contaminants within environmental matrices, as well as evaluating the risks they pose to both ecosystems and human health. Learn more about Mr. Habimana and the other Forum speakers here.
Neonicotinoid Metabolites
Neonicotinoids (neonics) are a class of insecticides that share a common mode of action that affects the central nervous system of insects, resulting in paralysis and death. Studies show that neonicotinoid residues accumulate in the pollen and nectar of treated plants and are a threat to the health of pollinators. Neonicotinoids are also persistent in the environment and are so toxic that as little as one neonic-treated seed is enough to kill a songbird. This class of pesticides is also known to contaminate waterways, posing additional risks as these compounds are highly toxic to aquatic organisms.
One transformation product of concern is desnitro-imidacloprid, a metabolite of imidacloprid, with recent research showing that it is more toxic than the parent compound. There is a wide body of science connecting the use of imidacloprid as a neonicotinoid insecticide to toxicity in humans, with neurological, cardiovascular, and respiratory effects, among others, as well as toxicity to birds, bees, and aquatic organisms. (See the Gateway on Pesticide Hazards and Safe Pest Management database for more information on imidacloprid here.)
One study from earlier this year, published in Scientific Reports, finds impacts on human plasma protein bindings with exposure to neonicotinoid insecticides and their metabolites. The researchers report: “In the case of the phase I metabolites of neonicotinoids, some metabolites, such as descyano-thiacloprid and desnitro-imidacloprid, exhibit more toxic effects on mammals due to stronger receptor protein binding affinity than the corresponding parent compounds.â€
Another study in humans, published previously in Archives of Toxicology, analyzes the acute effects of desnitro-imidacloprid on neurons. “[I]midacloprid (IMI) and other members of this pesticide family form a set of diverse metabolites within crops,†the authors state. They continue, “Among these, desnitro-imidacloprid (DN-IMI) is of special toxicological interest, as there is evidence (i) for human dietary exposure to this metabolite, (ii) and that DN-IMI is a strong trigger of mammalian nicotinic responses.â€
As a result of the study, the researchers find that the data suggests “DN-IMI functionally affects human neurons similar to the well-established neurotoxicant nicotine†and that the metabolite “exhibits significantly higher potency and efficacy on the human nAChR [nicotinic acetylcholine receptor] subtypes than its parent compound IMI.†The authors summarize, this “showcases the role of metabolism for human neurotoxicology, as it demonstrates that a particular metabolite can be several orders of magnitude more potent as a neuronal signaling disrupter (desensitization) than its parent compound.â€
In comparing reproductive effects with exposure to imidacloprid and desnitro-imidacloprid, a study in Toxics finds that the two compounds differentially affect ovarian antral follicle growth, morphology, and hormone synthesis. The results show that desnitro-imidacloprid inhibits follicle growth, causes follicles to rupture, decreases testosterone and progesterone, and alters estradiol levels. This highlights the reproductive toxicity that occurs with neonicotinoid exposure, as well as how the mechanisms of toxicity can differ between parent compounds and their metabolites.
Published this month in Environmental Pollution, a study of transformation products of neonicotinoid (TPNNIs) examines soil and water within an agriculturally intensive basin to investigate the toxicity of the TPNNIs in comparison to their parent compounds. The results reveal that “Clothianidin-urea and desnitro-imidacloprid [DN-IMI] were the predominant TPNNIs in the topsoil and surface water, accounting for 68.2% and 47.2% of the total TPNNIs, respectively.†The authors also report: “DN-IMI exhibits greater mammalian neurotoxicity than IMI [imidacloprid] and is up to 300 times more potent than IMI in mammals. This increased toxicity is attributed to higher binding affinity of DN-IMI to mammalian nAChRs than IMI; therefore, human may face serious health risks when exposure to DN-IMI primarily through the consumption of contaminated water and food products.â€
Previous Research on Transformation Products
Additional research on transformation products and specific metabolites adds to the overall body of science on threats from these compounds. A study in Environmental Science and Pollution Research from earlier this year shares that pesticide transformation products (TPs) are frequently found in surface and groundwater as they “often present higher polarity than parent compounds, are less volatile and less biodegradable and are therefore more mobile and persistent.â€
Within their research, the authors discover transformation products of dimethachlor and chlorothalonil for the first time in drinking water in France, with concentrations exceeding the regulatory quality standards in more than one of three drinking water samples for the transformation product of chlorothalonil. “This research confirmed the benefit of focusing on TPs and parent compounds, and also to continue monitoring TPs that originate from compounds already withdrawn from the market for several years that appear to be highly persistent,†the authors conclude.
Another study in Ecotoxicology and Environmental Safety examines the association between urinary organophosphate pesticide metabolites and blood lipid levels in U.S. children enrolled in the National Health and Nutrition Examination Survey (NHANES). In analyzing the urinary concentrations of organophosphate pesticide metabolites, known as dialkylphosphates (DAPs), the results show: “Over 50 % of children had detectable levels of dimethylphosphate, diethylphosphate, dimethylthiophosphate, and diethylthiophosphate… Higher diethylthiophosphate was associated with high blood cholesterol levels.â€
In a previous Daily News, Breakdown Products (Metabolites) from Pesticides May Be More Toxic than Parent Compound, Study Finds, research published Environment International finds that nearly half of all transformation products from four common-use pesticides produce stronger endocrine-disrupting effects than the parent compound. Many ecological and health risk assessments for pesticides focus on the effects of parent chemical compound products, overlooking the potential impacts of transformation products.
Studies like these highlight the need to assess the implications of transformation products 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.â€
Regulatory Failures
As highlighted in the literature review in Global Change Biology, pesticide transformation products present a hidden risk. The authors note: “Research on pesticide risks often focuses on the effects of primary molecules and rarely considers their TPs. These TPs, generated through abiotic and biotic processes, can be equally or even more toxic than their parent compounds… Some TPs are more toxic than their parent compounds, while others exhibit reduced acute toxicity but have additive or synergistic effects to the primary pesticide molecules, including important chronic or sub-lethal effects on non-target organisms like bees, butterflies, or aquatic invertebrates.â€
The studies on the toxicity and adverse effects of metabolites raise critical deficiencies in EPA’s regulatory process for evaluating transformation products—calling into question the validity of assessments that allow pesticide uses with inadequate restrictions for the protection of health and the environment. As the Global Change Biology researchers conclude: “The ecological implications of TPs remain understudied, representing a critical frontier for pesticide risk assessments. Addressing this gap requires not only identifying major TPs in environmental matrices but also assessing their chronic and sublethal effects under realistic field conditions.â€
When EPA discusses its registration process, it includes language regarding the evaluation of pesticide metabolites, degradates, contaminants, and impurities. Critics, however, feel that EPA’s outdated data requirements, lack of inclusion of all peer-reviewed scientific literature showing adverse health and environmental effects of pesticide active ingredients, and inability to fully evaluate for endocrine disruption, synergistic effects, and the toxicity from inert ingredients, metabolites, and pesticide mixtures are insufficient and unreasonable. As the researchers from Environment International say: “[T]he toxicity assessments of the pesticide TPs are still overlooked for the registration and use approval of pesticides. Therefore, the risk of environmental pesticide TPs is not only an emerging issue but also a scientific blind spot.â€
Resources
To hear one of the study authors, Emile Habimana, M.S., speak, along with Carolina Panis, PhD, Rossella Cannarella, M.D., PhD, Génon K. Jensen, and Jabeen Taiba, PhD, join the second session of the National Forum on December 4, 2025, 1:00 – 3:30 PM Eastern (ET). âž¡ï¸ Registration and speaker backgrounds are available here.
The information in this session empowers voices for the transition to practices and products that do not accept toxic chemicals as necessary when alternative systems are available to us. The science supports the urgent call for systemic change at this moment of health, biodiversity, and climate crises, with the promise of productive and profitable alternatives. This call for foundational change is motivated by our collective understanding that the critically needed response to the crises must not be diverted by anything less than a holistic strategy—recognizing the science on adverse effects of extremely small chemical doses to all organisms, including humans, and the synergistic effects of multiple chemical exposure.
The presentations at this session support community-level understanding of the science and its relationship to debilitating and deadly disease patterns associated with toxic chemical exposure, so that all societal decisions close to home and around the globe embrace the changes that are within reach. To learn more, visit Beyond Pesticides’ resources for the Pesticide-Induced Diseases Database and the health and environmental benefits of organic land management. Â
All unattributed positions and opinions in this piece are those of Beyond Pesticides.
Sources:
Loser, D. et al. (2021) Acute effects of the imidacloprid metabolite desnitro-imidacloprid on human nACh receptors relevant for neuronal signaling, Archives of Toxicology. Available at: https://link.springer.com/article/10.1007/s00204-021-03168-z.
Morimoto, N. et al. (2025) Association between urinary organophosphate pesticide metabolites and blood lipid levels in US children, Ecotoxicology and Environmental Safety. Available at: https://www.sciencedirect.com/science/article/pii/S0147651325016756.
Mourikes, V. et al. (2023) Imidacloprid and Its Bioactive Metabolite, Desnitro-Imidacloprid, Differentially Affect Ovarian Antral Follicle Growth, Morphology, and Hormone Synthesis In Vitro, Toxics. Available at: https://www.mdpi.com/2305-6304/11/4/349.
Pasquini, L., Lardy-Fontan, S. and Rosin, C. (2025) Pesticide transformation products: a potential new source of interest for drinking water, Environmental Science and Pollution Research. Available at: https://link.springer.com/article/10.1007/s11356-025-35979-3.
Taira, K. et al. (2025) Human plasma protein bindings of neonicotinoid insecticides and metabolites, Scientific Reports. Available at: https://www.nature.com/articles/s41598-025-96812-y.
Tissier, M., Shahmohamadloo, R. and Guzman, L. (2025) Pesticide Risk Assessment in a Changing World, Global Change Biology. Available at: https://onlinelibrary.wiley.com/doi/full/10.1111/gcb.70203.
Wang, J. et al. (2025) Contamination characteristics and influencing factors of transformation products of neonicotinoid in soil and water from an agriculturally intensive basin, Northern China, Environmental Pollution. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0269749125014599.
