3 and Tables S12–S14 for individual PFCAs. Direct exposure to PFBA via drinking water consumption is estimated to be the primary exposure pathway in all exposure scenarios (88–99%) (although data on PFBA in other exposure pathways, such as dietary intake, is limited). Direct exposure via food is estimated

to be the major exposure pathway for PFHxA, PFOA, PFDA and PFDoDA in the low- (41–88% of total exposure) and intermediate- (38–86%) exposure scenarios. In the high-exposure scenario, direct dietary exposure is estimated to be the major exposure pathway only for PFHxA and PFDoDA (42 and 47%, respectively), while for PFOA and PFDA precursor exposure via dust ingestion is estimated to be the dominant pathway (62% for both pathways). Apoptosis inhibitor Sensitivity

analysis reveals that the GI uptake fraction for PFCAs Neratinib mw and diPAPs is the most influential parameter affecting the calculated total exposure to all individual PFCAs in all exposure scenarios (Figs. S2–S6). However, there is a large uncertainty regarding this parameter for PFCAs as well as for diPAPs (see Section 2.2). For PFBA, the concentration in water and volume of water consumed are the most sensitive parameters in all three exposure scenarios after the GI uptake fraction. These parameters are quite well constrained. For PFHxA, PFOA, PFDA, and PFDoDA, concentrations in water, food, or air are influential parameters in the low- and intermediate-exposure scenarios, whereas levels in dust, amount of dust ingested and biotransformation factors for PAPs become more influential in the high-exposure

scenario. Levels of individual PFCAs in different exposure media and FTOHs in air can be measured with a high level of certainty. On the other hand, concentrations of diPAPs in dust, the amount of dust ingested, and biotransformation factors for diPAPs are poorly constrained. Ixazomib nmr The precursor contribution to PFCA exposure has previously only been determined for PFOA, and it should be noted that the daily exposure estimates for PFOA in the current study are roughly one order of magnitude lower for each exposure scenario compared to earlier estimates (Fig. 2) (Trudel et al., 2008 and Vestergren et al., 2008). The relative contribution of precursors to total PFOA exposure is higher in the present study in all three exposure scenarios compared to the earlier estimations (Vestergren et al., 2008). These differences between the present and earlier studies are likely the result of one or several of the following factors: i) reduced emissions over time and therewith lower levels of PFOA and its precursors in exposure media (US EPA, 2006 and Wang et al., 2014), ii) improvement of analytical methods resulting in more accurate (i.e., generally lower) PFOA concentrations in the major exposure medium, food (Vestergren et al., 2012), iii) more literature data became available on PFOA and precursors in the exposure media included in the present study (e.g.