6:2 Fluorotelomer iodide in vitro metabolism by rat liver microsomes: Comparison with [1,2-14C] 6:2 fluorotelomer alcohol

Abstract

6:2 Fluorotelomer iodide [6:2 FTI, F(CF2)6CH2CH2I] is the industrial raw material used to manufacture 6:2 fluorotelomer alcohol [6:2 FTOH, F(CF2)6CH2CH2OH] and 6:2 FTOH-based products. During its manufacture and industrial use, workers may be exposed to via oral, dermal or inhalation of 6:2 FTI. Therefore it is useful to understand how 6:2 FTI may be metabolized and into what transformation products. 6:2 FTI in vitro rat liver microsomal metabolism was explored for the first time to compare its biotransformation potential with that of [1,2-14C] 6:2 FTOH [F(CF2)614CH214CH2OH]. 6:2 FTI and 6:2 FTOH metabolite yields were determined in closed-bottle systems using Sprague Dawley and Wistar Han rat microsomes after incubation at 37°C for up to 6h with NADPH (reduced form of nicotinamide adenine dinucleotide phosphate)-addition and NADPH-regenerating systems, respectively. 5:3 acid [F(CF2)5CH2CH2COOH] was the most abundant metabolite for 6:2 FTI (3.3–6.3mol%) and 6:2 FTOH (9–12mol%). Perfluorobutanoic acid (PFBA), perfluoropentanoic acid (PFPeA), and perfluorohexanoic acid (PFHxA) in sum accounted for 1.3–2.2mol% from 6:2 FTI and 2.7–4.4mol% from 6:2 FTOH biotransformation. Perfluoroheptanoic acid (PFHpA) accounted for 0.14–0.36mol% from 6:2 FTI but only 0.01–0.06mol% from 6:2 FTOH biotransformation. These results suggest that mammalian systems exposed to 6:2 FTI or 6:2 FTOH would form 5:3 acid, PFBA, PFPeA, PFHxA as the primary stable metabolites, whereas more PFHpA would be expected from 6:2 FTI biotransformation.