28
Apr
Review Identifies Regulatory Deficiencies in the Risk Assessments of Chemical Mixtures Including Pesticides
(Beyond Pesticides, April 28, 2026) In Chemical Research in Toxicology, researchers from the Universitat Rovira i Virgili in Catalonia, Spain highlight the threats to human and environmental health with “combined exposures to multiple chemical toxicants, including industrial chemicals, heavy metals, pesticides, endocrine-disrupting chemicals (EDCs), and per- and polyfluoroalkyl substances (PFAS).†As these compounds are encountered in mixtures in real-world settings, the resulting interaction can have additive or synergistic effects that risk assessments fail to adequately capture.
As the authors point out: “This leads to a systematic underestimation of health risks, particularly for vulnerable populations. Despite robust evidence on mixture toxicity, major regulatory frameworks such as the U.S. Toxic Substances Control Act (TSCA) and the EU’s [European Union] REACH program continue to assess chemicals in isolation.â€
Importance and Background
Environmental toxicants are ubiquitous throughout nature and within all organisms. In humans, these compounds can accumulate, referred to as ‘Body Burden’, which encompasses numerous chemicals such as pesticide mixtures. “Critically, organisms are rarely exposed to a single chemical in isolation,†the researchers note. “Rather, they continuously encounter complex mixtures of contaminants whose combined effects may differ substantially from those predicted by examining each substance individually.â€
As the authors explain, regulatory agencies underestimate “the true burden attributable to chemical exposures since regulatory risk assessments and epidemiological studies have traditionally evaluated compounds one at a time.†They continue, “This single-substance paradigm fails to capture the synergistic, additive, or antagonistic interactions that arise when multiple toxicants co-occur, a phenomenon collectively referred to as mixture toxicity, leaving a critical gap in the understanding of real-world chemical risk.†The effects of chemical mixtures present disproportionate risks for vulnerable populations, including “infants and children, pregnant women, the elderly, and low-income or marginalized communities, who may experience heightened biological sensitivity alongside disproportionate exposure burdens.†(See studies here and here.)
As shared in Daily News, entitled Report Describes Complex Cumulative Risk Assessment Proposal to Implement California Law, Beyond Pesticides notes that risk assessment methodology, unless it is considered in the context of a rigorous alternatives assessment, begins with the mostly false assumption that petrochemical pesticides are needed (or are essential) to achieve cost-effective pest management, agricultural productivity and profitability, and quality of life, when, in fact, this is not the case. Therefore, improved risk calculations, while important to characterizing the harm and the gaps in fully assessing adverse effects associated with pesticide use, still impose some level of harm deemed by the government to be acceptable.
Even worse, the adverse effects of exposure cannot be fully characterized because of incomplete assessments or a lack of data on harmful endpoints, as is the case currently with endocrine-disrupting pesticides not fully evaluated by the U.S. Environmental Protection Agency (EPA), California’s Department of Pesticide Regulation (DPR), or other regulatory bodies. The lack of regulatory review persists despite the robust science that shows endocrine-disrupting pesticides to induce cancer, reproductive harm, infertility, biodiversity decline, and other life-threatening, often multigenerational, effects.
The basic standard in federal pesticide law, the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), requires protection against “unreasonable adverse effects†to people and the environment, a standard that should not, but does currently, allow for hazards or uncertainties when less- or non-toxic alternatives are available. Even so-called health-based standards reliant on risk assessments, such as the tolerance setting process in the Federal Food, Drug, and Cosmetic Act (FFDCA), accept a level of harm and uncertainty despite the availability of practices and products that eliminate the identified risk. Beyond Pesticides urges better assessment of harm, full disclosure of what is not known, and in-depth alternatives assessments that consider changes in practices so that clear-eyed decisions can be made to take meaningful precautionary steps, now available, to meet pest prevention and management challenges and tackle the current existential health, biodiversity, and climate crises.
Literature Review Methodology and Results
Within the current literature review, the researchers examine current regulatory approaches regarding toxicant mixtures. The analysis aims to “(1) evaluate the limitations of prevailing single-substance approaches, (2) highlight the scientific basis for mixture-focused risk assessment, (3) illustrate potential health and environmental consequences of limited mixture consideration, and (4) propose evidence-based policy recommendations for reform.â€
The literature search, for peer-reviewed studies, official reports, and policy documents, was conducted for the timeframe of January 1, 1980 to July 31, 2025. As a result, the authors state: “Despite decades of evolving chemical safety legislation and a growing scientific understanding of the complexities of chemical exposures, most national and international regulatory systems remain firmly anchored to a paradigm that assesses and manages chemicals as isolated, individual entities. This single-substance focus inherently fails to account for the common reality of concurrent exposures to multiple chemicals and their potential interactions.†(See research here and here.)
They continue: “This siloed, chemical-by-chemical approach across various regulatory domains fails to capture the reality of multimedia and multi-pathway exposures that characterize modern life, potentially leading to an underestimation of overall chemical risk. This persistent focus on single toxicants creates challenges in regulatory oversight, that may leave the public and the environment inadequately protected from the combined effects of the chemicals to which they are exposed daily.â€
These approaches fail to consider how humans, wildlife, and ecosystems encounter chemical mixtures in the real world, thus not adequately capturing the extent of harm they present in risk assessments. “This single-substance paradigm, therefore, may create a false sense of security and potentially lead to an underestimation of true public health and environmental risks,†the researchers share.
Additionally, there is “significant inconsistency†between countries, or even within the same country, for chemical standards and risk assessment methodologies. As an example, the artificially narrow definition of PFAS by EPA mischaracterizes the widespread threat to health and the environment. The definition of PFAS used by the Organisation for Economic Co-operation and Development (OECD) encompasses a wide variety of fluorinated compounds (containing the element fluorine) and is “scientifically grounded, unambiguous, and well suited to identify these chemicals,†as described by scientists in a commentary published in Environmental Science & Technology Letters. As the researchers describe, excluding certain fluorinated chemical subgroups does not properly represent the scope of PFAS, which they estimate to include millions of theoretical structures, but more practically, several thousand that are actually manufactured. (See Daily News here.)
In summary, the current study authors write: “The analysis presented in this review identifies a significant misalignment between the scientific understanding of toxicant mixture exposures and the prevailing regulatory paradigms worldwide. The evidence suggests: humans and ecosystems are ubiquitously exposed to complex mixtures of chemicals, not isolated substances. These mixtures can interact in additive, synergistic, or antagonistic ways, often leading to health and environmental outcomes that are not predictable from single-substance assessments alone… Addressing this challenge will require more than incremental adjustments to existing frameworks; it necessitates a paradigm shift.â€
Previous Research
A wide body of science continues to emerge on the effects of pesticide mixtures. In a recent study covered in Daily News, researchers analyze the effect of multiple climate stressors and pesticides in the environment and published their disturbing findings of elevated harm in “Double trouble: The synergistic threat of environmental stressors and pesticide mixtures.†The authors document synergism that is up to 70 times stronger than for a single chemical assessment. This work is a follow-up to a previous study covered in Daily News in 2024.
Dire Pediatric Cancer Risk Linked to Pesticide Mixtures, Laws To Protect Children Found To Be Lax highlights a study of Nebraska pesticide use and pediatric cancer incidence by researchers from the University of Nebraska Medical Center and the University of Idaho Department of Fish and Wildlife Sciences where they found positive associations between pesticides and overall cancer, brain and central nervous system cancers, and leukemia among children (defined as under age 20). The authors’ emphasis on evaluating mixtures, and their innovative technical methods for doing so, highlight the direction environmental health research and regulation must take. Studying pesticides singly is an inadequate approach, according to the authors, because pesticides are not applied individually anymore, but very often in mixtures of herbicides, insecticides, and fungicides in spray tanks.
Daily News, entitled Study of Chemical Mixtures at Low Concentrations Again Finds Adverse Health Effects, find synergistic relationships in chemical mixtures, even with low concentrations. The findings come as no surprise to advocates who have urged an assessment of the potential synergistic impacts of pesticide mixtures in the regulation of pesticides. Additionally, a novel study mapping pesticide mixtures and cancer risk, published in Nature Health, “reveals a robust spatial association between environmental pesticide exposure risk and cancer incidence.†The team of international researchers incorporates pesticide risk modeling with Peruvian National Cancer Institute (INEN) registry data to map pesticide-induced cancer clusters in Peru, finding significant associations between pesticide mixtures and cases of carcinogenicity. The study analyzes 31 active ingredients to identify pesticide-associated cancer hotspots, none of which are classified as carcinogenic on their own by international standards. When combined as pesticide mixtures, as experienced in real-world environments, heightened risks and synergistic effects are noted. (See here.)
A Holistic Solution
While many researchers stress the need for enhanced risk assessments, this fails to acknowledge that there is not adequate information available for accurate risk assessments that include all possible cumulative, additive, and synergistic effects from pesticide mixtures for all possible health effects including cancer and endocrine disruption. Because of that, many advocates call for the adoption of the precautionary principle to protect health and the environment. (See here and here.)
As regulatory bodies are unable to sufficiently analyze the threats from environmental contaminants like pesticides, a holistic solution is urgently needed. Given the efforts captured by this paper, taken together with the extensive research in the Pesticide-Induced Diseases Database and the daily tracking of scientific studies linking pesticides to cancer, birth defects, immune system disorders, endocrine disruption, sexual and reproductive dysfunction, learning and developmental effects, and nervous system implications, among others, the public can take no comfort in ‘acceptable’ levels of pesticides in the environment.
A widespread transition to organic agriculture and land management is the path forward. Visit the Eating with a Conscience database to learn more about why food labeled “organic†is the right choice and learn more about the National Organic Standards Board Spring 2026 Meeting on the Keeping Organic Strong resource page.
All unattributed positions and opinions in this piece are those of Beyond Pesticides.
Source:
Domingo, J. and Nadal, M. (2026) Mixture Toxicity in Human Health: Integrating One Health, Exposomics, and Modern Risk Assessment Strategies, Chemical Research in Toxicology. Available at: https://pubs.acs.org/doi/full/10.1021/acs.chemrestox.5c00375.
