Characterization of the toxicological findings from 90-day and 2-year repeated-dose toxicity studies of pesticides in rats

Abstract

Repeated-dose toxicity (RDT) studies in rats are crucial for assessing the risks of chemicals, including pesticides, by elucidating their toxicological properties. In this study, we collected and comprehensively analyzed the results of rat RDT studies on pesticides. For over 350 pesticides across more than 400 studies, all toxicological findings observed in 90-day and 2-year RDT/carcinogenicity studies in rats were organized into 1,092 endpoints using our previously established three-level categorization system. The liver, kidney, thyroid gland, and spleen were identified as the primary non-tumor targets in both the 90-day and 2-year studies. In the 2-year study, the liver, thyroid gland, testis, and uterus were found to be the primary tumor targets, with significant sex differences in liver and thyroid tumors. We also identified findings observed at the lowest observed adverse effect level (LOAEL) for each study. Finally, analyses by pesticide class, based on their mode of action classification, demonstrated class effects on the toxicological findings observed and the LOAEL values. Taken together, these results provide valuable insights into toxicological endpoints that should be evaluated in further mechanistic studies and considered for the safety assessment of each class of pesticides.