Structure-Informed Comprehensive Screening and Risk Prioritization of Organophosphorus Compounds in Human Serum: Revealing the Hidden Burden and Emerging Risks

Organophosphorus
compounds (OPCs) are widely distributed environmental
contaminants for which there are increasing health concerns, yet human
internal exposure beyond a few well-studied organophosphate esters
(OPEs) remains poorly understood. In this study, a structure-informed
integrated screening and risk prioritization framework was developed
to systematically characterize the internal burden and potential risks
of OPCs in human serum. The use of machine-learning-predicted retention
times and response factors, coupled with a cross-subgroup multidimensional
weighted fragment-ion scoring system, enhanced the identification
and semiquantification of broad-spectrum OPCs in complex biological
matrices. In serum samples from 254 residents, 59 OPCs were identified,
including 33 newly detected OPCs in humans, revealing that emerging
OPCs (e.g., organophosphonates, phosphine oxides, and organothiophosphate
esters) dominate current exposure profiles. Coexposure network analysis
indicated that OPCs may occur in humans as highly interconnected mixtures.
Risk prioritization integrating computational toxicology with exposure
burden demonstrated that several emerging OPCs exhibit greater toxicological
potential than typical OPEs and predominate among high-priority chemicals.
This study provides a more comprehensive profile of the human internal
exposure landscape of OPCs and emphasizes the importance of emerging
OPCs in future exposure assessment and risk management.