Comparing the potency in vivo of PFAS alternatives and their predecessors
(English)Manuscript (preprint) (Other academic)
Since the year 2000, a number of per- and polyfluoroalkyl substances (PFASs) have been introduced onto the market to replace long-chain perfluoroalkyl acids (e.g. perfluoroctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA)) and their respective precursors. The main rationale for this industrial transition is that the PFAS alternatives are less bioaccumulative and toxic than their predecessors. Here, we evaluated to what extent differences in toxicological effect thresholds for PFASs, expressed as an administered dose, were confounded by differences in their distribution and elimination kinetics. Increased liver weight was selected as the investigated endpoint based on the availability of sufficient toxicological and toxicokinetic data to enable a comparison of sub-chronic effects. Converting administered doses into equivalent serum and liver concentrations significantly reduced the variability in the dose-response curves for perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononaoic acid (PFNA) and ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate (GenX). The toxicity ranking using serum (PFNA>GenX>PFOA>PFHxA>PFBA) and liver (GenX>PFNA≈PFOA≈PFHxA≈PFBA) concentrations also indicated that some PFAS alternatives may have a higher toxic potency than their predecessors when correcting for differences in toxicokinetics. For PFOS and perfluorobutane sulfonic acid (PFBS) the conversion from administered dose to serum concentration equivalents did not change the toxicity ranking which, however, could be due to the internal dose of PFBS being too low to allow a correct comparison. This study illustrates the importance of taking toxicokinetics/internal dose into account in substitution of hazardous chemicals for independent evaluation of bioaccumulation and toxicity criteria.
PFOS, PFOA, PFAS alternatives, toxicokinetic model, potency, toxicity
Research subject Applied Environmental Science
IdentifiersURN: urn:nbn:se:su:diva-141082OAI: oai:DiVA.org:su-141082DiVA: diva2:1085755