Blood serum concentrations of PFCAs in industrial countries (e.g. USA, Europe, selleck compound and Japan) are similar, and profiles and temporal trends are also similar (Vestergren and Cousins, 2009). This suggests similar exposure to PFAAs in these countries. In order to determine which parameters were most influential in the intake estimations, the sensitivity (S) is calculated as the change in the output (ΔO/O) as a result of changing input values (I) by a small fixed amount (ΔI). Every input parameter is increased by 1%, thus (ΔI/I) = 0.01. S=ΔO/OΔI/I The following human exposure pathways are included in this study: ingestion of dust, food, and drinking water,

and inhalation click here of air. Vestergren et al. (2008) considered additional exposure pathways associated with consumer products such as contact with treated clothes and impregnation sprays, however, these pathways played an insignificant role in the overall exposure to PFOS, PFOA, and their precursors and are therefore not considered in the present study. For each of the pathways considered, intakes are estimated on a per-day basis normalized to body weight (i.e. intakes in units of pg/kg/d). To calculate the contribution of precursors to total PFAA exposure, concentrations of precursors are converted to their respective PFAAs on a molar basis, and in the case of a diPAP with twice the

same chain length (e.g., 6:2/6:2 diPAP) the molar concentration is multiplied by two. A summary of the employed literature data of PFAA and precursor concentrations (5th percentile, median, and 95th percentile) measured in dust, air, food, and drinking water

can be found in Tables S2–S6. A detailed description of the intake estimations for each Janus kinase (JAK) exposure pathway can also be found in the Supplementary data. Gastrointestinal (GI) uptake factors are based on rodent studies and were calculated as the fraction of an oral dose recovered in tissues or blood. Uptake factors for the low-, intermediate-, and high-exposure scenarios were previously estimated to be 0.66, 0.80, and 0.91, respectively, for PFOA and PFOS (Trudel et al., 2008). These uptake factors were used for PFOS precursors by Vestergren et al. (2008) due to lack of rodent data for PFOS precursors and are used in the present study. Uptake factors for FTOH were previously reported as 0.27, 0.38, and 0.56, respectively (based on various in vivo and in vitro studies), for the three exposure scenarios (Vestergren et al., 2008) and these values are used in the present study. Due to lack of information for other PFCAs, we use the same uptake factors as for PFOS and PFOA. For diPAPs, the bioavailability in rats was reported to be highly variable depending on the chain length (D’Eon and Mabury, 2011).