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

- 6:2 FTI metabolism in rat liver microsomes was explored for the first time.
- 5:3 Acid was the primary stable metabolite in the microsomes dosed with 6:2 FTI.
- 6:2 FTI metabolism in the microsomes also produced PFBA, PFPeA, and PFHxA.
- 6:2 FTOH in the microsomes produced more 5:3 acid, PFBA, PFPeA, and PFHxA.
- More PFHpA was produced from 6:2 FTI metabolism than observed from 6:2 FTOH metabolism.

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 6 h 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 (3.3-6.3 mol%) and 6:2 FTOH (9-12 mol%). Perfluorobutanoic acid (PFBA), perfluoropentanoic acid (PFPeA), and perfluorohexanoic acid (PFHxA) in sum accounted for 1.3-2.2 mol% from 6:2 FTI and 2.7-4.4 mol% from 6:2 FTOH biotransformation. Perfluoroheptanoic acid (PFHpA) accounted for 0.14-0.36 mol% from 6:2 FTI but only 0.01-0.06 mol% 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.