title: Evaluation of the immunomodulatory effects of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate in C57BL/6 mice.
abstract: 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate was designed to replace perfluorooctanoic acid (PFOA), which has been mostly phased out of U.S. production due to environmental persistence, detectable human and wildlife serum concentrations, and reports of systemic toxicity. In rodent models, PFOA exposure suppresses T cell-dependent antibody responses (TDAR) and vaccine responses in exposed humans. To determine replacement compound effects on TDAR and related parameters, male and female C57BL/6 mice were gavaged with 0, 1, 10, or 100 mg/kg/day for 28 days. Mice immunized with antigen on day 24 were evaluated for TDAR and splenic lymphocyte subpopulations five days later. Serum and urine were collected for test compound concentrations and liver peroxisome proliferation was measured. Relative liver weight at 10 and 100 mg/kg and peroxisome proliferation at 100 mg/kg were increased in both sexes. TDAR was suppressed in females at 100 mg/kg. T lymphocyte numbers were increased in males at 100 mg/kg; B lymphocyte numbers were unchanged in both sexes. Females had less serum accumulation and higher clearance than males, and males had higher urine concentrations than females at all times and doses. While this PFOA-replacement compound appears less potent at suppressing TDAR relative to PFOA, it produces detectable changes in parameters affected by PFOA; further studies are necessary to determine its full immunomodulatory profile and potential synergism with other per- and polyfluoroalkyl substances of environmental concern.
authors.affiliation: Department of Pharmacology & Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, rushingb13@students.ecu.edu; huq@ecu.edu; Franklin.Jason@epa.gov; dewittj@ecu.edu.
authors.forename: Blake R
authors.initials: BR
authors.lastname: Rushing
authors.affiliation: Department of Pharmacology & Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, rushingb13@students.ecu.edu; huq@ecu.edu; Franklin.Jason@epa.gov; dewittj@ecu.edu.
authors.forename: Qing
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Pharmacology & Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, rushingb13@students.ecu.edu; huq@ecu.edu; Franklin.Jason@epa.gov; dewittj@ecu.edu.|National Exposure Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC, 27711, Strynar.Mark@epa.gov.
authors.forename: Jason N
authors.initials: JN
authors.lastname: Franklin
authors.affiliation: Oak Ridge Institute for Science Education (ORISE) Fellows, U.S. Environmental Protection Agency, Research Triangle Park, NC,27711, McMahen.Rebecca@epa.gov; sonia.dagnino@imperial.ac.uk.
authors.forename: Rebecca
authors.initials: R
authors.lastname: McMahen
authors.affiliation: Oak Ridge Institute for Science Education (ORISE) Fellows, U.S. Environmental Protection Agency, Research Triangle Park, NC,27711, McMahen.Rebecca@epa.gov; sonia.dagnino@imperial.ac.uk.|Current address: Toxicology Assessment Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC, 27711.
authors.forename: Sonia
authors.initials: S
authors.lastname: Dagnino
authors.affiliation: Oak Ridge Institute for Science Education (ORISE) Fellows, U.S. Environmental Protection Agency, Research Triangle Park, NC,27711, McMahen.Rebecca@epa.gov; sonia.dagnino@imperial.ac.uk.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Higgins
authors.affiliation: Oak Ridge Institute for Science Education (ORISE) Fellows, U.S. Environmental Protection Agency, Research Triangle Park, NC,27711, McMahen.Rebecca@epa.gov; sonia.dagnino@imperial.ac.uk.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Strynar
authors.affiliation: Department of Pharmacology & Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, rushingb13@students.ecu.edu; huq@ecu.edu; Franklin.Jason@epa.gov; dewittj@ecu.edu. dewittj@ecu.edu.
authors.forename: Jamie C
authors.initials: JC
authors.lastname: DeWitt
keywords: Per- and polyfluoroalkyl substances (PFASs); TDAR; immunotoxicity; perfluorooctanoic acid (PFOA)