Despite their common phosphate core, organophosphorus (OP) insecticides are structurally diverse, and this contributes to their individually distinct hazards and exposure profiles. In this review, summary data on biomonitoring for urinary levels of six alkyl phosphate (AP) metabolites of OPs reported in the March 2001, U.S. Centers for Disease Control and Prevention’s (CDC) ‘‘National Report on Human Exposure to Environmental Chemicals,’’ are analyzed for hazard and exposure relevance. Fundamentally, neutral phosphorus atom has electronic configuration of 1s2, 2s2, 2p6, 3s2, 3p3 – resulting in a total of 5 valence electrons in outermost shell. The d orbitals are vacant; however, the activation energy required to promote electrons from 3p to the vacant 3d is relatively low. This thermodynamically favored pπ-dπ interaction constitutes the fundamental basis for the nucleophilicity of phosphorus required for cholinesterase inhibition, and the generation of AP metabolites. Hence, nucleophilicity of central phosphorus core is a summation of simple inductive effect and pπ-dπ interactions with neighboring heteroatoms. The general reversibility of enzyme inhibitor process central to OP insecticidal mechanism hence cautions that evidence for exposure does not indicate biological sufficiency for exposure-induced hazard. In line with biologically sound biophase analyzed (urine) and appropriateness of assay methodology (heavy isotopes as internal standards) analyses of CDC data show very low environmental exposures to OPs, relative to earlier conclusions based on EPA’s aggregate exposure estimates (dietary, drinking water, and non-dietary residential exposures) for many individual OPs. The complexities of drawing inferences on OP exposure and hazard from biomonitoring data are minimized by the quality design of this CDC study. For example, method specificity (HR/MS with heavy AP isotopes as internal standards) minimized potential overestimates based on presence of phosphates from intermediary metabolism (endogenous phosphates). This experimental flaw seen in other AP biomonitoring studies did not apply here. In conclusion, when grounded in biologically sound kinetics and dynamics, biomonitoring studies can provide upper bound estimates for human absorbed dosages that are indispensable for rational hazard estimation, coupled with risk assessment and management decisions.

Urinary dialkyl phosphates as biomarkers of hazard and exposure: A review

254th National Meeting (2017)

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