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Metabolism and Pharmacokinetics

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Part of the book series: Molecular and Integrative Toxicology ((MOLECUL))

Abstract

Perfluoroalkyl acids (PFAAs) are highly persistent and widely spread in the environment. PFAAs were detected in various wildlife and human after 1960s and the levels gradually elevated to 2000. In addition to the production of perfluorocarboxylic acids (PFCAs) themselves, fluorotelomer-based compounds were potential source of PFCAs. Fluorotelomer-based compounds can degrade through atmospheric oxidation and biodegradation to form PFCAs. The biological half-lives (t1/2) of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), major contaminants in the environment, were calculated to be 3.5 and 8.5 years in human, respectively. To elucidate the mechanisms by which PFAAs accumulate in human, pharmacokinetics have been studied in experimental animals, however, in rats, mice, monkeys and other animals, half-life (T1/2) were hours to days, therefore, great species-difference exist in t1/2 between experimental animals and human. Recent studies identified partially the biological molecules responsible for protein binding, transmembrane transport of PFCAs. In addition, transplacental and lactational transports are thought to be an important exposure routes of these chemicals, because developmental toxicity of PFAAs is thought to be one of primary toxic events of PFAAs. Physiologically-based pharmacokinetic (PBPK) models are proposed to understanding kinetics of PFAAs in biological systems.

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Kudo, N. (2015). Metabolism and Pharmacokinetics. In: DeWitt, J. (eds) Toxicological Effects of Perfluoroalkyl and Polyfluoroalkyl Substances. Molecular and Integrative Toxicology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-15518-0_6

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