Legacy and replacement plasticizers: associations of DEHP, DINCH, and DEHTP with HbA1c in US adults

Plasticizer exposure is widespread, but the metabolic safety of newer replacement plasticizers remains unclear. This study compared the associations of legacy and replacement plasticizer exposure with glycemic control in US adults. Using cross-sectional NHANES 2017–2018 data, this study examined associations between legacy di(2-ethylhexyl) phthalate (DEHP)-derived and replacement 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) or di(2-ethylhexyl) terephthalate (DEHTP)-derived plasticizer exposure indices and HbA1c (glycated hemoglobin) among 1,614 US adults aged ≥ 20 years. Exposure indices were calculated as molar sums of urinary metabolites and analyzed using survey-weighted linear regression, adjusted for demographic, lifestyle, socioeconomic, BMI, and urinary creatinine covariates. Analyses were conducted in 2026. In the fully adjusted model, none of the three indices was significantly associated with HbA1c after correction for multiple testing (DEHP: β = 0.0639; 95% CI: −0.0004, 0.1283; Holm-adjusted p = 0.1534; DINCH: β = 0.0354; 95% CI: −0.0292, 0.1001; Holm-adjusted p = 0.5159; DEHTP: β = 0.0105; 95% CI: −0.0258, 0.0468; Holm-adjusted p = 0.5425). Mixture and interaction analyses were exploratory. These findings do not show that DEHP has stronger metabolic effects than the replacements or that the replacements are safe; longitudinal studies with repeated exposure measurements are needed.