The effects of organophosphate ester exposure on metabolic syndrome: A systematic review and meta-analysis of human observational studies.

BACKGROUND

Widespread organophosphate esters (OPEs) have drawn increasing concern due to their potential metabolic toxicity. Although epidemiological studies have reported associations between OPE exposure and metabolic syndrome (MetS), the evidence remains inconclusive.

OBJECTIVE

This systematic review conducts a meta-analysis to quantitatively evaluate the associations between OPE exposure and MetS and related diseases.

METHODS

A systematic search of Web of Science, PubMed, Embase, and the Cochrane Library was conducted up to January 8, 2025. Study quality was assessed using Newcastle-Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) criteria. Pooled effect estimates were calculated for chlorinated, alkyl, and aryl-OPEs. Evidence certainty was evaluated using Office of Health Assessment and Translation (OHAT) framework.

RESULTS

A total of 19 published studies were ultimately included. Pooled estimates demonstrated that OPE metabolite mixture were significantly associated with increased risks of MetS (OR = 1.46; 95 % CI: 1.22, 1.75) and hypertension (OR = 1.18; 95 % CI: 1.00, 1.38), with a stronger association observed for hypertension in females. Additionally, OPE mixture exposure was significantly associated with an increased risk of gestational diabetes mellitus (GDM) (OR = 1.42; 95 % CI: 1.13, 1.78). Subgroup analyses identified chlorinated and alkyl-OPEs as major contributors to GDM risk, while aryl-OPEs were primarily responsible for high-density lipoprotein cholesterol (HDL-C) reduction. MetS, obesity, hypertension, and diastolic blood pressure (DBP) were found to have moderate confidence, the remaining items had low confidence.

CONCLUSION

These findings provide robust epidemiological evidence linking OPE exposure to metabolic disturbances and suggest chemical structure-specific toxicological profiles.