In a recently published article, Pizzurro and colleagues report several important interspecies differences in perfluoroalkyl substances (PFAS) toxicokinetics. These data represent some of the first evidence for variation in absorption, distribution, metabolism, and excretion (ADME) of PFAS across different species. For PFAS defendants, this paper provides support that pharmacokinetics must be taken into consideration when extrapolating health outcomes in animals to humans.
The main purpose of toxicokinetics is to describe systemic exposure achieved in animals and its relationship to exposure level and time course of toxicity. Extrapolation of possible health effects from animal data to humans is best done on the basis of plasma and tissue concentrations, as opposed to administered dose. However, most of the differences among species with regard to their susceptibility to the toxic effects of chemicals are related to differences in ADME processes.
Briefly, in a comprehensive review of scientific and regulatory agency data, Pizzurro et al. examined the toxicokinetic profile of five different PFAS compounds (PFOA, PFOS, PFBS, PFHxS, PFBA) in several different species. The authors found that all five PFAS compounds are relatively well-absorbed in humans and animals, systematically distributed after digestion, and do not undergo significant metabolism. In animals, PFOA, PFOS, PFBS preferentially distribute to the liver and do not cross the blood-brain barrier whereas PFHxS and PFBA distribute to the serum. However, studies in human suggest that while PFOA preferentially distributes to the liver, PFOS, PFHxS, PFBS, and PFBA may preferentially distribute to the kidney. For all species, short-chain PFAS (i.e., PFBS, PFBA) are excreted much more rapidly.
Of note, differences in placental and lactational transfer between rats and humans highlight the importance of considering toxicokinetic differences between species for risk assessment purposes. Given the same exposure level to mother or dams, the human fetus would be exposed to lower serum PFOA, PFOS, or PFHxS concentrations than the developing rat fetus. However, the newborn breastfed human infant would be exposed to higher serum PFOA concentrations than the newborn rat, but not higher PFOS levels. Substantial differences in PFAS elimination rates between humans, monkeys, and rats were also observed, with longer half-lives found in humans.
Toxicokinetic studies operative under that assumption that other organisms are accurate predictive models of toxicity in humans. However, this study revealed several important differences among different PFAS compounds regarding tissue partitioning, half-life, and transfer to offspring. Litigators need to take into consideration these differences when making risk assessments for these compounds, especially with respect to extrapolating PFAS exposure between species and across different life stages.
Citation: Pizzurro DM, Seeley M, Kerper LE, Beck BD. Interspecies differences in perfluoroalkyl substances (PFAS) toxicokinetics and application to health-based criteria. Regul Toxicol Pharmacol. 2019 May 9. pii: S0273-2300(19) 30130-8.
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