ORIGINAL ABSTRACT

BACKGROUND: The SPRINT project is an EU-funded initiative aimed at promoting a transition toward more sustainable plant protection. Growing evidence shows that combined pesticide exposures might have additive or synergistic toxic effects. OBJECTIVE(S): We conducted an in vivo rodent study on three widely used pesticides-glyphosate, tebuconazole, and acetamiprid-and their mixture, focusing on prenatal exposure at doses considered safe, to better understand long-term health risks. METHODS: Three pesticides (glyphosate, tebuconazole, acetamiprid) were administered in drinking water to male and female Sprague-Dawley rats, starting from prenatal life until 13 weeks after weaning. The main toxicological endpoints were evaluated, including hematological, biochemical, endocrine development parameters, and histopathological analysis. FINDINGS: In males a statistically significant increased trend in aspartate aminotransferase was observed in tebuconazole, acetamiprid and mixtures, while in females a trend of increased aspartate aminotransferase was observed in glyphosate and mixture. Other increases in lesions were observed in the cardiocirculatory system and genital system. CONCLUSIONS: In our present study an important design characteristic was the prenatal exposure. We observed adverse effects at doses currently considered "safe", namely equal or lower than the No Observed Adverse Effect Level in rodents and other animal models for glyphosate, acetamiprid, tebuconazole and their mixture. Based on our results, a mixture approach indicated additivity in toxicity and no signs of synergism nor antagonism were observed.