Abstract
BACKGROUND: Plasticizers used in consumer products raise concerns for nephrotoxicity; while DEHP is well characterized, evidence for DEHTP and DiNP-particularly their metabolites-remains limited. We examined associations of five urinary metabolites-MEHHP/MECPP (DEHP), MEHHTP/MECPTP (DEHTP), and MONP (DiNP)-with renal endpoints in a nationally representative adult sample. METHODS: We analyzed 2,229 adults from NHANES 2015-2018 using multivariable linear and restricted cubic spline models for eGFR, and evaluated combined-exposure effects with WQS and BKMR; analyses were repeated with UACR as a secondary outcome. RESULTS: Higher MECPP and MEHHP were associated with lower eGFR, whereas positive associations for MECPTP and MEHHTP may reflect early glomerular hyperfiltration rather than benefit. As a secondary endpoint, UACR indicated early injury: MECPP increased UACR (p < 0.001) and MONP decreased UACR (p = 0.002), with mild nonlinearity. Combined-exposure models prioritized DEHP/DEHTP metabolites, with MECPTP contributing most. CONCLUSION: Urinary plasticizer metabolites are linked to altered renal endpoints. Heterogeneous exposure-response patterns support complementary outcomes and mixture methods; longitudinal and mechanistic studies are needed to clarify causality and inform risk management for emerging plasticizers.