13
Mar
Study of Pesticide Mixtures and Intestinal Barrier Dysfunction Further Highlights Regulatory Deficiencies
(Beyond Pesticides, March 13, 2025) Study results published in Pesticide Biochemistry and Physiology “suggest that combined [pesticide] exposure may further amplify the toxicity and compromise the intestinal barrier.†The researchers studied the toxic effects of the insecticides abamectin and spirodiclofen, as well as the fungicide fluazinam, individually and in combination. In exposing mice and Caco-2 cells to these pesticides, the results show the disruption of intestinal functions and highlight the need to assess potential synergistic effects of pesticide mixtures as a part of the regulatory review process.Â
Effects on the intestinal barriers of mice represent a threat to “the first line of defense against the external environment,†the researchers say. The intestinal mucosal epithelial structure plays an important role in preventing harmful substances from entering the intestines and causing damage to cells.Â
[Caco-2 cells represent a human cell line, derived from a colon cancer patient’s tissue, and mimic the small intestine. These cells are vital in research as a model of the intestinal epithelial barrier.]Â
“Currently, most studies investigating the effects of pesticide residues on the barrier function of Caco-2 cells concentrate on the exposure to a single residue, while the potential toxic effects arising from the concurrent presence of multiple pesticide residues remain largely overlooked,†the authors say. As Beyond Pesticides has previously reported, scientists and advocates have urged prioritizing further studies on the effect of mixtures on organisms for many decades, given that exposure in the environment is not limited to a single pesticide at a time. Â
“[R]ecent studies have increasingly highlighted the toxic effects of abamectin on non-target organisms and human cells,†the researchers state. The combination of pesticides has been widely used due to widespread resistance among red spider mites to individual pesticides. The researchers continue: “Currently, research predominantly focuses on individual exposure to pesticides, while the interaction effects of three commonly used pesticides remain largely unexplored. Therefore, it is essential to investigate the potential interaction effects of abamectin, fluazinam, and spirodiclofen pesticides with high detection rates in actual samples on the impairment of intestinal barrier function and transepithelial transport.â€Â
The study subjected both mice and Caco-2 cells to concentrations of the three pesticides, representing acceptable daily intake (ADI) values as well as environmental exposure concentrations. After 28 days, histopathological changes in the colon of the mice were evaluated. For the Caco-2 cell cultures, viability assays and an analysis of gene expression were performed. Â
Findings from the histopathological analysis (a microscopic examination of tissues) “suggest that exposure to both individual and combined pesticides may induce structural damage to the mouse colon, with fluazinam and spirodiclofen exposure further exacerbating this damage,†the authors report. Â
Between the mouse models and cell assays, treatment with the pesticide mixtures shows compromised intestinal integrity as well as changes in the transport and uptake of the chemicals. The study reports: “[A]nalysis of mouse intestines revealed synergistic damage in those exposed to a binary mixture of abamectin, fluazinam, and spirodiclofen… The studies on the transport in Caco-2 cells revealed that the combined exposure to abamectin and spirodiclofen resulted in transport amounts that were 5.37 and 19.98 times greater than those observed with individual exposures, respectively.†These results highlight how the uptake of chemicals into cells can differ not only between single pesticides but also when exposure occurs in combination. Â
The effects of pesticide mixtures seen in this study highlight the importance of considering synergy in risk assessments. “These findings enhance our understanding of the interactions among multiple pesticide residues and further clarify the complexity of these interactions and their impact on human exposure,†the authors conclude. (See additional coverage on health effects from pesticide mixtures here and here.) Â
Additional research referenced in the study supports the findings of intestinal damage from pesticide exposure. This includes:Â
- The insecticide imidacloprid, which “induces disruption of the intestinal epithelial barrier, specifically through the down-regulation of tight junction protein complexes,†and has enhanced toxicity against the gut microbiota in mice with co-exposure to zinc oxide. (See studies here and here.)Â
- The insecticide chlorpyrifos, which is “observed to disrupt the integrity of the gut barrier in mice, resulting in increased entry of lipopolysaccharides into the body.†(See study here.)Â
- The fungicide carbendazim, which when combined with epoxiconazole or fluazinam has synergistic effects in Caco-2 cells, according to a study in Food Chemistry.Â
The findings are very concerning, given that pesticide residues in food are introduced directly to the intestines. As the researchers note, “The intestinal tract functions as a congenital barrier for homeostasis, preventing pathogenic bacteria, toxins, and other harmful substances from entering the body.†They continue: “Pesticides ingested through the diet are absorbed and transported into the human body, directly interacting with intestinal epithelial cells. This exposure results in alterations to cell permeability and integrity, ultimately compromising the barrier function of these cells.â€Â
The complex interactions among pesticide mixtures are not fully understood but represent a significant threat to human health. As previously reported by Beyond Pesticides, there is persistent failure of the U.S. Environmental Protection Agency (EPA) to adequately regulate mixtures of chemicals to which organisms are exposed in the real world. Risk assessments have been highly criticized by Beyond Pesticides as inadequately addressing the full range of adverse effects that put human health and the health of all organisms at risk. (See more on regulatory deficiencies here.)Â Â
Scientists and advocates have long asked EPA to evaluate and regulate full formulations, and their mixtures, instead of assessing active ingredients singularly. As science and the knowledge base evolve, so should the systems for assessments that are meant to inform decisions that have a wide impact on human and ecosystem health. Â
Given both the known and still unevaluated effects of pesticides, including the impact of mixtures and synergistic effects, Beyond Pesticides urges the elimination of petrochemical pesticides and synthetic fertilizers by 2032. As a holistic solution, organic land management practices offer both health and environmental benefits, with proven commercial viability and effectiveness in both agricultural and nonagricultural uses.Â
Interested in transitioning your community to organic? Become a Parks Advocate through the Parks for a Sustainable Future program. You can also help protect yourself and your family by Eating with a Conscience and making The Safer Choice to avoid hazardous home, garden, community, and food use pesticides.Â
All unattributed positions and opinions in this piece are those of Beyond Pesticides. Â
Source:Â
Liu, Z. et al. (2025) Transport mechanisms of pesticide mixtures impairing intestinal barrier function in mice, Pesticide Biochemistry and Physiology. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0048357525000690.Â
