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HERO ID
3859965
Reference Type
Journal Article
Title
Biotransformation of N-ethyl-N-(2-hydroxyethyl)perfluorooctanesulfonamide by rat liver microsomes, cytosol, and slices and by expressed rat and human cytochromes P450
Author(s)
Xu, L; Krenitsky, DM; Seacat, AM; Butenhoff, JL; Anders, MW
Year
2004
Is Peer Reviewed?
Yes
Journal
Chemical Research in Toxicology
ISSN:
0893-228X
EISSN:
1520-5010
Publisher
AMER CHEMICAL SOC
Location
WASHINGTON
Volume
17
Issue
6
Page Numbers
767-775
Language
English
PMID
15206897
DOI
10.1021/tx034222x
Web of Science Id
WOS:000222232500005
Abstract
Perfluorooctanesulfonic acid (PFOS) and its derivatives have been used in a range of industrial and commercial applications, including the manufacture of surfactants, adhesives, anticorrosion agents, and insecticides. PFOS is found at detectable concentrations in human and wildlife tissues and in the global environment. N-Substituted perfluorooctanesulfonamides are believed to be degraded to PFOS and, therefore, contribute to the accumulation of PFOS in the environment. N-Ethyl-N-(2-hydroxyethyl)perfluorooctanesulfonamide (N-EtFOSE) is converted to PFOS in experimental animals. The objective of this study was to elucidate the pathways for the biotransformation of N-EtFOSE, which is a major precursor and component of PFOS-based compounds. N-EtFOSE and several putative metabolites were incubated with liver microsomes and cytosol and with liver slices from male Sprague-Dawley rats. Microsomal fractions fortified with NADPH catalyzed the N-deethylation of N-EtFOSE to give N-(2-hydroxyethyl)perfluorooctanesulfonamide (FOSE alcohol) and of FOSE alcohol to give perfluorooctanesulfonamide (FOSA). These N-dealkylation reactions were catalyzed mainly by male rat P450 2C11 and P450 3A2 and by human P450 2C19 and 3A4/5. Rat liver microsomal fractions incubated with UDP-glucuronic acid catalyzed the O-glucuronidation of N-EtFOSE and FOSE alcohol and the N-glucuronidation of FOSA. Cytosolic fractions incubated with NAD(+) catalyzed the oxidation of FOSE alcohol to perfluooctanesulfonamidoacetate (FOSAA). The oxidation of N-EtFOSE to N-ethylperfluorooctanesulfonamidoacetate (N-EtFOSAA) was observed in liver slices but not in cytosolic fractions. FOSA was biotransformed in liver slices to PFOS, albeit at a low rate. These results show that the major pathway for the biotransformation of N-EtFOSE is N-dealkylation to give FOSA. The biotransformation of FOSA to PFOS explains the observation that PFOS is found in animals given N-EtFOSE.
Keywords
biotransformation; anatomy; alcohols; metabolism; rodent models
Tags
PFAS
•
Additional PFAS (formerly XAgency)
Literature Search November 2019
PubMed
Web of Science
Screened Studies
Excluded
Exclude (TIAB)
Perfluorooctanesulfonamido ethanol
•
Expanded PFAS SEM (formerly PFAS 430)
Litsearch: September 2019
Web of Science
Not prioritized for screening
Perfluorooctane
2-(N-Ethyl-perfluorooctanesulfonamido)acetate
2-(N-Ethylperfluorooctanesulfonamido)acetic acid
Perfluorooctanesulfonamido ethanol
•
NEtFOSAA
Literature Search
Pubmed
Screening Results
Excluded/Not on Topic
•
^Per- and Polyfluoroalkyl Substances (PFAS)
PFOSA (754-91-6)
Literature Search
Pubmed
WOS
NEtFOSAA (2991-50-6)
Literature Search
Pubmed
•
PFAS 150
Literature Search Update December 2020
PubMed
WOS
Literature Search August 2019
PubMed
Web of Science
Screened Studies
Supplemental
N-Ethyl-N-(2-hydroxyethyl)perfluorooctanesulfonamide
Perfluorinated compounds
Perfluorooctane
Perfluorooctanesulfonamide
Perfluorooctanesulfonamide sodium salt (1:1)
Perfluorooctanesulfonic acid
•
PFOSA
Literature Search
Pubmed
WOS
Screening Results
Excluded/Not on Topic
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