Characterizing biopersistence potential of the metabolite 5:3 fluorotelomer carboxylic acid after repeated oral exposure to the 6:2 fluorotelomer alcohol.

ABSTRACT

Our previous report on pharmacokinetic (PK) evaluation of 62 fluorotelomer alcohol (62 FTOH) examined the biopersistence potential of its metabolites based on data published from single inhalation and occupational 62 FTOH exposure studies. We calculated internal exposure estimates of three key metabolites of 62 FTOH, of which 53 fluorotelomer carboxylic acid (53 acid) had the highest internal exposure and the slowest clearance. No oral repeated 62 FTOH exposure data were available at the time to fully characterize the biopersistence potential of the metabolite 53 acid. We recently received additional data on 62 FTOH and 53 acid, which included a 90-day toxicokinetic study report on repeated oral 62 FTOH exposure to rats. We reviewed the study and analyzed the reported 53 acid concentrations in plasma, liver, and fat using one-compartment PK modeling and calculated elimination rate constants (kel), elimination half-lives (t1/2) and times to steady state (tss) of 53 acid at three 62 FTOH doses. Our results showed that tss of 53 acid in plasma and evaluated tissues were approximately close to 1 year, such that the majority of highest values were observed at the lowest 62 FTOH dose, indicating its association with the biopersistence of 62 FTOH. The results of our PK analysis are the first to characterize biopersistence potential of the 53 acid after repeated oral exposure to the parent compound 62 FTOH based on steady state PK parameters, and therefore, may have an impact on future study designs when conducting toxicity assays for such compounds.