Protein binding associated with exposure to fluorotelomer alcohols (FTOHs) and polyfluoroalkyl phosphate esters (PAPs) in rats.
The biotransformation of fluorotelomer-based compounds such as fluorotelomer alcohols (FTOHs) and polyfluoroalkyl phosphate esters (PAPs) are sources of exposure to perfluorinated carboxylates (PFCAs), leading in part to the observation of significant concentrations of PFCAs in human blood. The biotransformation of FTOHs and PAPs yield intermediate metabolites that have been observed to covalently modify proteins. In the current investigation, the extent of covalent protein binding in Sprague-Dawley rats upon exposure to 8:2 FTOH and the 6:2 polyfluoroalkyl phosphate diester (6:2 diPAP) was quantified. The animals were administered a single dose of 8:2 FTOH or 6:2 diPAP at 100 mg/kg by oral gavage to monitor biotransformation and extent of protein binding within the liver, kidney, and plasma. In the 8:2 FTOH-dosed animals, perfluorooctanoate (PFOA) was produced as the primary PFCA, at 623.13 ± 59.3, 459.5 ± 171.8, and 397.3 ± 133.0 ng/g in the plasma, liver, and kidney, respectively. For the animals exposed to 6:2 diPAPs, perfluorohexanoate (PFHxA) was the primary PFCA produced, with maximum concentrations of 57.4 ± 6.5, 9.0 ± 1.2, and 25.3 ± 1.2 ng/g in the plasma, liver, and kidney, respectively. Protein binding was observed in the plasma, liver, and kidney after 8:2 FTOH and 6:2 diPAP exposure, with the most significant binding occurring in the liver (>100 nmol/g protein). This is the first study to link the exposure and in vivo biotransformation of fluorotelomer-based compounds to covalent protein binding.
University of Toronto , Department of Chemistry, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada.
Amy A
AA
Rand
Scott A
SA
Mabury
D000818:Animals; D001711:Biotransformation; D004781:Environmental Exposure / Q000032:analysis*; D004952:Esters / Q000378:metabolism*; D005466:Fluorocarbons / Q000378:metabolism*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000097:blood / Q000378:metabolism*; D007668:Kidney; D008099:Liver / Q000378:metabolism; D008297:Male; D050217:Metabolic Detoxication, Phase II; D010710:Phosphates / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley
D004952:Esters; D005466:Fluorocarbons; D006845:Hydrocarbons, Fluorinated; D010710:Phosphates; C033729:fluorotelomer alcohols