Current understanding of perfluoroalkyl acid toxicology

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The perfluoroalkyl acids (PFAAs) are a family of organic chemicals consisting of a perfluorinated carbon backbone (4-14 carbons in length) and an anionic head group (sulfonate, carboxylate or phosphonate). These compounds have excellent surface-tension reducing properties and have numerous industrial and consumer applications. However, they are chemically stable, persistent in the environment, ubiquitously distributed, and present in humans and wildlife. Two issues must be considered regarding PFAA toxicology: pharmacokinetics and potency of the chemicals. The rates of PFAA clearance and their body burden accumulation are dependent on carbon-chain length and animal species. In general, the serum half-life of PFAAs increases with chain length in both rodents and humans, but the estimates in humans are markedly higher than those in laboratory animals. Recent studies with laboratory animal models have indicated a number of toxic effects of PFAAs, including tumor induction, hepatotoxicity, developmental toxicity, immunotoxicity, neurotoxicity and endocrine disruption. The modes of PFAA actions are not well understood, but are thought to involve, in part, activation of nuclear receptor signals (such as peroxisome proliferator-activated receptor-α, PPARα). Based on PPARα activation, potency of PFAAs increases with carbon-chain length, carboxylates are stronger than sulfonates, and mouse receptor is more reactive than human receptor. Adverse effects of perfluorophosphonates in mice resemble those described for sulfonates and carboxylates, although potency of this congener appears to be weaker than the other two counterparts. This abstract does not necessarily reflect US EPA policy.