Reconstruction of phthalate exposure and DINCH metabolites from biomonitoring data from the EXHES cohort of Tarragona, Spain: A case study on estimated vs reconstructed DEHP using the PBPK model

Abstract

Phthalates are known endocrine disruptors (EDs) and are associated with potential diseases, such as obesity and diabetes. In 2002, the plasticizer 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) was introduced as an alternative to phthalates in the European market. The objective of this study was to evaluate the total exposure to phthalate and DINCH metabolites from EXHES Tarragona, Spain cohort of pregnant women. On the one hand, the analytical determination of phthalate and DINCH metabolites in urine was carried out. On the other hand, the reconstructed exposure was calculated for phthalates and DINCH using their metabolites concentration measured in the urine. Thirteen different phthalate metabolites and two metabolites of DINCH were measured and detected in almost all pregnant women's urine samples (n = 60). There were significant correlations between metabolites of the same parent compounds, and also between DEHP and MBzP metabolites, DiNP and BBZP metabolites, and DEHP and DiNP metabolites respectively. The exposure of pregnant women to phthalate and DINCH parent compounds were also back calculated using the levels of each metabolite found in pregnant women urine (reconstructed exposure). Besides, to demonstrate the utility of this approach, the physiologically based pharmacokinetic (PBPK) model was used to predict the cumulative amount of MEHP (a principal metabolite of DEHP in urine). To proceed with that, DEHP reconstructed exposure and estimated exposure from the same cohort (previously studied by the same authors) were simulated using the PBPK model. Results showed that the reconstructed-PBPK simulation was closer to the 24 h biomonitoring data than the estimated PBPK-simulation., This clearly shows that the combination of reconstructed exposure with the PBPK model is a good tool to predict chemicals exposure. However, some discrepancies between simulated and biomonitored values were found. This can be associated with other sources that contribute to the total exposure and emphasises the need to consider multi-routes exposure for the widely distributed chemicals like phthalates and DINCH.