Perfluoroalkyl phosphinic acids (PFPiAs) are a lesser studied class of perfluoroalkyl acids (e.g. PFOA, PFOS) that have been used directly as surfactants for wetting purposes and as anti-foaming additives to pesticides, and have been detected in various environmentally matrices including human blood. In our previous work, PFPiAs were efficiently transformed to 1H-perfluoroalkanes (1H-PFAs) and perfluoroalkyl phosphonic acids (PFPAs) in rats, with over 70% biotransformation after two weeks. The novel transformation of PFPiAs was surprising because there are no known enzymes reported to cleave carbon-phosphorus bonds in humans. Although formed in a 1:1 ratio, the concentrations of 1H-PFAs were higher than PFPAs, likely due to faster excretion of the persistent PFPAs. 1H-PFAs may be potentially long-lived toxic intermediates, however the occurrence and fate of these 6-12 carbon 1H-PFA metabolites is not understood. To test this, 1H-perfluorodecane (1H-PFD) was incubated with rat liver S9 fraction for two hours. Analysis using negative electrospray ionization liquid chromatography-tandem mass spectrometry showed the formation of perfluorodecanoic acid (PFDA), and negative chemical ionization gas chromatography-mass spectrometry was used to determine the decrease in 1H-PFD concentration. An 80% decrease in 1H-PFD was observed in the active experiment compared to the control, decreasing from 7000 ± 1300 nM to 1300 ± 90 nM. After 2 hours, 4.2 ± 0.1 nM PFDA formed, which was 60% above control levels. The formation of PFDA from 1H-PFD only accounted for 0.028% of the 1H-PFD lost over the 2 hours, implying that PFDA was not the only metabolic fate. Literature on 1H-perfluoroethane, a CFC replacements, suggests that these longer 1H-PFAs may be metabolized by CYP 450 oxidation to an acyl fluoride intermediate that may also react with biological nucleophiles. Currently, work is being done to assess the extent of reactions with proteins using characterization via chemical proteomics and total organofluorine combustion ion chromatography. Understanding the reactivity of 1H-PFAs and their acyl fluoride metabolites will help better understand human exposure to lesser studied PFASs.

Investigating the metabolic fate of 1H-perfluoroalkanes

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.