Di-alkyl phosphate biomonitoring data: assessing cumulative exposure to organophosphate pesticides Original paper

What was studied?

This paper evaluated microbiome signatures database relevance indirectly by analyzing U.S. biomonitoring data for urinary di-alkyl phosphate (DAP) metabolites—non-specific breakdown products shared by many organophosphate (OP) pesticides—to estimate cumulative OP exposure and compare those biomonitoring-derived exposure estimates with U.S. Environmental Protection Agency (EPA) modeled “aggregate” and “cumulative” exposure assessments developed under the Food Quality Protection Act (FQPA). Using the CDC’s first National Report on Human Exposure to Environmental Chemicals (based on NHANES 1999 urine samples), the authors calculated absorbed OP dose equivalents from six urinary alkyl phosphate metabolites (DMP, DMTP, DMDTP, DEP, DETP, DEDTP) and contrasted these with exposure estimates from OP Registration Eligibility Decision (RED) documents and EPA’s preliminary OP cumulative risk assessment. The central scientific question was whether model-based regulatory exposure estimates align with population biomonitoring “ground truth,” and what methodological caveats limit interpretation of DAP metabolites as quantitative indicators of OP pesticide exposure.

Who was studied?

No new clinical cohort was recruited. The human data came from the CDC’s NHANES 1999 biomonitoring subsample: 703 individuals aged 6–59 years, with urine analyzed by GC-MS/MS using isotope-dilution methods. The paper primarily presents adult dose reconstructions (assuming 1.2 L urine/day and 70 kg body weight) because the March 2001 CDC report provided only summary statistics that limited stratification by age/sex and did not permit individualized exposure reconstruction. The authors also discuss how interpretation differs for children due to creatinine excretion variability and different physiology, emphasizing that future comparisons should explicitly contrast adult and pediatric biomonitoring patterns.

Most important findings

Across the U.S. population sample, >90% had one or more DAP metabolites detected at low limits of quantification, implying ubiquitous exposure to OPs and/or environmental DAP sources. Using geometric means, the authors estimated a total cumulative OP-equivalent dose of ~0.30 µg/kg/day, with a 90th percentile of ~1.68 µg/kg/day when summing across the six metabolites, while stressing that summing geometric means likely overestimates any individual’s true combined exposure because it assumes all metabolites are simultaneously at their mean. Importantly, EPA RED-based aggregate exposure estimates for several individual OP pesticides often exceeded EPA’s own preliminary cumulative dietary estimates and, in some comparisons, even exceeded the biomonitoring-derived cumulative estimate for the entire OP class—highlighting substantial conservatism (overestimation) in screening models, particularly drinking-water modeling. The paper also argues that DAP metabolites are non-specific and non-toxic (non–cholinesterase–inhibiting) and may reflect pre-hydrolyzed OP degradates already present in food/water or non-pesticide sources, potentially inflating inferred pesticide exposure signals. In microbiome terms, the study contains no microbial taxa data, but it is clinically relevant because OP exposure can be a confounder in microbiome studies; urinary DAPs may serve as exposure markers when interpreting pesticide–microbiome associations.

Key implications

For clinical and translational research—including microbiome-focused work—urinary DAP metabolites can provide a population-level upper-bound estimate of cumulative OP exposure and a valuable benchmark for “ground-truthing” exposure models, but they should not be interpreted as precise, pesticide-specific absorbed doses. The paper’s core caution is that non-specific metabolites can be substantially confounded by environmental degradates and non-pesticide sources, making dose reconstruction and risk inference uncertain; clinicians should therefore treat urinary DAPs as screening biomarkers and avoid over-assigning causality to specific OP pesticides without corroborating specific metabolites or contextual exposure data.

Citation

Duggan A, Charnley G, Chen W, et al. Di-alkyl phosphate biomonitoring data: assessing cumulative exposure to organophosphate pesticides. Regulatory Toxicology and Pharmacology. 2003;37(3):382-395. doi:10.1016/S0273-2300(03)00031-X