Worldwide serum concentration-based probabilistic mixture risk assessment of perfluoroalkyl substances among pregnant women, infants, and children

[[abstract]]Pregnant women, infants, and children are particularly vulnerable to perfluoroalkyl substances (PFASs), yet little is known about related health risks. Here, we aimed to study the four main PFASs: perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS), and assess the mixture risks of co-exposure to PFASs for pregnant women and children as well as for infants associated with maternal PFAS exposure at national and global scales, based on biomonitoring data on serum. We conducted a literature search and aggregated 69 data sources across 22 countries/regions from 2010 to 2020 to profile the serum concentrations of these four PFASs in pregnant women and children. Based on toxicity assessments by regulatory authorities, we determined conservative reference levels (RfLs) in the serum for the primary adverse effects of PFASs, including hepatic, developmental, and immune effects. The cumulative hazard quotient (HQ) was combined with probabilistic analysis to compare serum levels with RfLs and to quantify mixture risks. Our analysis revealed that PFOS was the dominant PFAS in maternal and child serum worldwide, with median levels 2.5-10 times higher than those of PFOA, PFNA, and PFHxS. The estimated global median serum levels of PFOS were 6.17 ng/mL for pregnant women and 4.85 ng/mL for children, and their immune effects in pregnant women and children are concerning as their cumulative HQs could exceed 1. For infants, the cumulative HQs for both developmental and immune effects could also be > 1, suggesting that maternal exposure to PFASs during pregnancy and breastfeeding may pose concerns for infant development and immunity. Our national and global serum database and risk assessment offer additional insights into PFAS exposures and mixture risks in susceptible populations, serving as a reference for evaluating the effectiveness of ongoing regulatory mitigation measures