Retrospective evaluation of repeated dose dermal toxicity studies in North American agrochemical risk assessment

Current North American pesticide regulations mandate route-specific repeated-dose dermal toxicity (RDDT) studies for dermal exposure risk assessment. To evaluate the scientific necessity of this study requirement, a proof-of-concept retrospective analysis was conducted on conventional active pesticide ingredients with Syngenta end use product registered in North America (NA) from 2001 to 2025, examining publicly available risk assessments for 51 pesticides assessed by the United States Environmental Protection Agency (US EPA) and 43 by the Health Canada Pesticides Regulatory Directorate (PRD). Most risk assessments relied on oral toxicity studies to set points of departure for dermal risk assessment (57% for US EPA; 67% for PRD), primarily because critical toxicity endpoints were not evaluated in standard RDDT studies. For cases where RDDT data were utilized, dermal equivalent doses (DEDs) were calculated based on oral studies and dermal absorption factors. The oral study-derived DEDs consistently yielded comparable or more conservative points of departure than RDDT studies. Overall, the dermal toxicity study was not utilized, or the DED was protective of the RDDT, in the majority of cases (98% of US EPA and 97% PRD assessments). These findings demonstrate that adequate human health protection for dermal risk assessment is feasible without an RDDT study, supporting broader evaluation and reasonable rationale toward the removal of the RDDT study as a mandatory data requirement for agrochemical regulation.