Study raises concerns over “safe” pesticide mixtures and doses

New research from the Ramazzini Institute warns that exposure to three widely used agricultural pesticides—even at levels currently deemed "safe"—may pose subtle yet significant long-term health risks. The study, conducted as part of the European Union-funded SPRINT project, examined the biological impacts of the herbicide glyphosate, the fungicide tebuconazole, the insecticide acetamiprid, and a combined mixture of all three on rats exposed from prenatal life through early adulthood.

Rather than testing massive lethal doses, researchers administered the chemicals via drinking water at concentrations ranging from the European Acceptable Daily Intake (ADI) up to the No Observed Adverse Effect Level (NOAEL). Despite operating within these regulatory limits, several toxicological responses were observed.

Blood tests revealed statistically significant increases in aspartate aminotransferase (AST)—a clinical indicator of potential liver stress—across both male and female treatment groups.

Male rats exposed to individual compounds and the mixture exhibited an increased incidence of testicular lesions, including tissue inflammation, fibrosis, and tubular degeneration, which were absent in control groups.

Male rats receiving glyphosate or acetamiprid showed elevated trends of inflammatory lesions in the heart, pericardium, and ascending aorta, while high-dose tebuconazole exposure correlated with an increased incidence of exocrine pancreas lesions.

Maternal exposure to tebuconazole at low and intermediate doses significantly increased pup mortality during early lactation.

A central priority of the experiment was evaluating chemical interactions. Experts have long questioned whether combining low doses of multiple pesticides creates severe "cocktail effects".

The findings indicate that while the combined mixture did not yield hyper-amplified or synergistic harm, it produced cumulative additive toxicity. In short, multiple low-level exposures incrementally stack risks rather than canceling one another out.

While these findings offer key insights, rodent results cannot be automatically extrapolated to humans. The study was constrained by small group sizes (12 per sex), a brief monitoring window, and omitted parameters like sperm counts. Rather than proving human disease, its value stems from comparing low-dose individual pesticides directly against a mixture starting prenatally, showing that single-chemical evaluations may miss cumulative additive risks.

The study heavily emphasizes early-life exposure, aligning with the Developmental Origins of Health and Disease (DOHaD) framework. Because organ systems undergo critical development during gestation and early lactation, early-life chemical exposures can trigger physiological changes that manifest much later in life.

The authors conclude that existing regulatory safety thresholds, which typically evaluate isolated chemicals in mature models, may fail to protect against early developmental exposures and routine real-world mixtures.

Source:

Environmental International