Early life exposure to phthalates and risk assessment: are we doing enough?

Background and Objective: Phthalates, potential endocrine disruptors with antiandrogenic effects, are widely used in several everyday products and are ubiquitous pollutants. Since 1999 European Authorities enacted several regulations to limit phthalate use and prevent exposure, mainly for more susceptible populations such as infants. This study aims to evaluate the estimated daily intake (EDI) of phthalates and to perform risk assessment evaluation in an Italian pediatric cohort. Methods: Between 2019 and 2020, 197 mother-child couples were enrolled in a prospective cohort study at the University Hospital of Modena (Italy). Urine samples were collected at birth, 3 and 6-months. 8 phthalates metabolites were analyzed. EDI was estimated and Risk quotients (RQ) were calculated using tolerable daily intake levels, (RQ(TDI)) as determined by the European Food Safety Authority, and the revised reference doses for anti-androgenicity RQ(RfD-AA), recently proposed. Finally, combined Hazard Indexes (HI) were calculated to assess synergic effect of different phthalates. Results: Most EDI and RQ(TDI) were lower than the acceptable values. The highest levels were found for Diethyl-phthalate (DEP), followed by Di-2-ethylhexyl-phthlate (DEHP). Newborns showed the highest values, followed by 6-months infants. Values exceeding the risk levels were observed for DEHP or di-n-butyl-phthalate (DnBP) in 5.5% and 10% of the newborns, respectively for RQ(RfDAA) and HI. Overall, HI higher values than threshold were observed at each follow-up visit. Conclusion: Since the European Union has a strict regulation policy regarding the most critical phthalates, these findings raise concern: exposure affecting children in Modena is still spread and includes phthalates banned in childcare products, such as DEHP and DnBP. Notably, few infants (especially newborns) exceeded the risk threshold for antiandrogenic effects. Further, exposure patterns seem to change over time during their first months of life. More extensive public health measures need to be planned to efficiently protect the most sensitive subgroups, including infants.