Risk based ranking of prioritized pesticides: where the exposome meets comparative toxicogenomics

Pesticides play an essential role in modern agricultural systems by enhancing crop yields and controlling pest-related losses and are applied extensively across the globe. However, their pervasive use has led to widespread environmental contamination, including accumulation in household and environmental dust, a significant yet understudied pathway of human exposure. Despite growing evidence that dust ingestion serves as a critical route for pesticide uptake, the associated health hazards remain poorly quantified and understood. We developed a Reverse Dosimetry Evaluation System (RDES) to estimate internal exposure levels from urine (EDI_u) and dust (EDI_d) samples and analyzed their association across various populations and seasons. Our study focused on eight key pesticides with high exposure risks through dust ingestion and identified risks to 12 human body systems. Notably, cypermethrin and deltamethrin were related to increased risks of asthma, lung injury, pulmonary fibrosis, and lung tumors, particularly affecting the respiratory system. A cross-regional analysis involving 13 countries using RDES and databases such as Tox21 and CTD, revealed that exposure-based health risks were highest in Korea, followed by Costa Rica/South Africa, China, Belgium, Poland, and the USA. This study introduced a standardized framework for Exposure Source identification-Internal Exposure assessment-Health Risk prediction (ESIEHR), for assessing emerging pollutants and highlights the necessity for targeted interventions to reduce health impacts.