Biomonitoring-Based Risk Assessment of Pyrethroid Exposure in the U.S. Population: Application of High-Throughput and Physiologically Based Kinetic Models

Pyrethroid insecticides have been extensively utilized in agriculture and residential areas in the United States. This study evaluated the exposure risk by age using available biomonitoring data. We analyzed pyrethroid metabolite concentrations in urine using the National Health and Nutrition Examination Survey (NHANES) data. Reverse dosimetry was conducted with a high-throughput model and a physiologically based kinetic (PBK) model integrated with a Bayesian inference framework. We further derived Benchmark Dose (BMD) values and systemic points of departure in rats using Bayesian BMD and PBK models. Margins of exposure (MOE) were calculated to assess neurotoxic risk based on estimated daily oral intake and dose metrics in plasma and brain. Results from both models indicated that young children have higher pyrethroid exposure compared to other age groups. All estimated risk values were within acceptable levels of acute neurotoxic effect. Additionally, MOEs calculated from oral doses were lower than those derived from internal doses, highlighting that traditional external exposure assessments tend to overestimate risk compared to advanced internal dose-based techniques. In conclusion, combining high-throughput and PBK approaches enhances the understanding of human health risks associated with pyrethroid exposures, demonstrating their potential for future applications in exposure tracking and health risk assessment.