OBJECTIVE: Inhalation risk assessments that do not account for human relevant particle size distributions (PSDs) in the inhalation dosimetry adjustment can overestimate risk. This stems from a mismatch between animal toxicity studies that use small particle sizes for hazard identification and the larger PSDs characteristic of agricultural spray application exposures. METHODS: This work introduces a novel approach employing Multiple-Path Particle Dosimetry (MPPD) software to derive human equivalent concentrations (HECs) that incorporate a Particle-size Adjustment Factor (PAF) in addition to the dosimetric adjustment factor (DAF), which is the traditional approach to derive the inhalation risk assessment endpoint. While the DAF accounts for the differences in rat and human respiratory physiology, the PAF accounts for differences in aerosol PSDs between occupational exposure scenarios and rodent inhalation studies. The MPPD model was used to derive the DAF and PAFs for different pesticide application methods to generate HECs for use in risk assessments. RESULTS/DISCUSSION: The results demonstrate that PAF integration results in refined exposure-relevant and scenario-specific risk assessments and identified scenarios with negligible potential for exceeding the inhalation exposure hazard thresholds. While more data on human-relevant PSDs for several pesticide application scenarios are needed, this method, coupled with new approach methods (NAMs) to predict portal of entry effects, and dosimetry and kinetic modeling to understand systemic dose, supports existing weight-of-evidence frameworks for reducing animal studies in pesticide registration. Advancing exposure assessment using the best available methods ensures robust human health protection while reducing animal usage.
Pecquet et al. (Wed,) studied this question.