Emerging investigator series: human CYP2A6 catalyzes the oxidation of 6:2 fluorotelomer alcohol.

The biotransformation of 6:2 fluorotelomer alcohol (6:2 FTOH) results in the production of bioactive and persistent metabolites, including perfluorinated carboxylic acids (PFCAs). While the products of 6:2 FTOH metabolism have been elucidated in several animal models, the responsible cytochrome P450 (CYP) isoform(s) have not been reported. Here, we characterized the in vitro oxidation of 6:2 FTOH using human liver microsomes and recombinant human CYPs. Six major xenobiotic metabolizing CYPs were screened for their capacity to catalyze 6:2 FTOH oxidation using chemical inhibitors selective towards CYP isoforms. Of the CYP isoforms investigated, CYP2A6 was the only enzyme capable of catalyzing 6:2 FTOH in human liver microsomes, with KM and Vmax values of 4076 ng mL-1 and 69 ng mL-1 min-1, respectively. We further probed the metabolic mechanism by plotting the 6:2 FTOH kinetic profile and extrapolating data to several possible kinetic models. 6:2 FTOH oxidation followed the typical one-site Michaelis-Menten kinetic model. This study also reports that 6:2 FTOH loss is associated with active CYP2A6 by incubating microsomes with the selective CYP2A6 inhibitor tranylcypromine, which bound competitively to the enzyme as determined by an increased KM (8796 ng mL-1) but unchanged Vmax value. Collectively, these findings provide a mechanistic perspective on the potential importance of CYP2A6 in the metabolic activation and phase I elimination of 6:2 FTOH and indirect human exposure to PFCAs.

Absorption of polycyclic aromatic hydrocarbons by a highly absorptive polymeric medium.

The efficacy of a lightly cross-linked polymeric bead to absorb polycyclic aromatic hydrocarbons (PAHs) from the surface of fresh- and salt-water in a simulated oil-spill scenario was assessed in this study. A layer of PAHs at the water surface was created by first preparing the PAHs in hexane and then carefully spiking this mixture onto the surface of water. Beads were then applied to the surface of the organic phase and the amount of hydrocarbons absorbed by the beads was examined at prescribed time intervals and at different temperatures. Absorption of PAHs into the beads was exhaustive with ∼86 ±â€¯4% being selectively removed from the organic phase by 120 s. First order reaction rates best described the uptake kinetics and absorption rates ranged from 0.0085 (naphthalene) to 0.0325 s-1 (dibenzo[a,h]anthracene). Absorption of PAHs into the beads was driven by molecular volume (A3). Uptake rates increased markedly for PAHs with molecular volumes between 130 A3 and 190 A3. Beyond this molecular volume there was no apparent change in the rate of uptake. This study shows that these polymeric beads have a high affinity for PAHs and can be used under various environmental conditions with negligible difference in absorptive efficacy.