Phthalate metabolite concentrations and effects on albuminuria in the US population

The usage pattern of phthalates has changed with the introduction of new alternatives such as 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH) and di-isodecyl phthalate (DiDP). However, the concentrations of these alternatives at the population level and their effects on endothelial function are under-studied. We examined the concentrations of the new alternatives and their previous counterparts, as well as the associations between phthalate exposure and albuminuria in the general US population. In total, 2672 participants from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 were enrolled in this study, and we obtained data on 19 urinary phthalate metabolites, albumin, and creatinine. The distributions of urinary phthalates were studied by age and sex. Linear and logistic regressions were used to estimate the association between urinary phthalate metabolites and albumin. The geometric mean of the total phthalate concentrations in males and females was 124.97 and 113.09 ng/mL respectively. The detection rates of most urinary phthalate metabolites were greater than 95 %. The major phthalate metabolites found in the US population were MEP (24.20 %) and MECPTP (23.76 %). More positive relationships between phthalate and micro- plus albuminuria were found in females aged ≥ 60 years group（1.49 (95 % CI: 1.08–1.90), 1.44 (95 % CI: 1.06–1.81), 1.52 (95 % CI: 1.14–1.90), 1.41(95 % CI: 1.04–1.78), 1.29(95 % CI: 1.01–1.58), 1.60(95 % CI: 1.20–2.01), 1.45(95 % CI:1.14–1.77), and 1.55(95 % CI: 1.22–1.87) in MECPP, MEHHP, MEOHP, MEHP, MCPP, MHBP, MHNCH and MCOCH respectively）. In total population, logistic regression showed that all traditional phthalate metabolites were associated with an increased proportion of albuminuria (OR range from 1.19 to 1.40, all p < 0.05). However, three new alternatives were not associated with albuminuria (OR range from 1.01 to 1.05, all p > 0.05), and six new alternatives were associated with an increased proportion of albuminuria (OR range from 1.14 to 1.30, all p < 0.05). Children have higher metabolite concentrations than adults. Exposure to certain phthalates may disrupt albuminuria homeostasis, especially in older females. Alternative phthalates may have a lower impact on albuminuria than conventional phthalates. The safety of the new alternatives should be interpreted with caution, as more research is still required.