Rushing, BRBRRushingHu, QQHuFranklin, JNJNFranklinMcMahen, RRMcMahenDagnino, SSDagninoHiggins, CPCPHigginsStrynar, MJMJStrynarDeWitt, JCJCDeWitt2017-03-072017-03Toxicological Sciences, 2017, 156 (1), pp.179-1891096-6080http://hdl.handle.net/10044/1/445822,3,3,3-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.© The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Toxicological Sciences following peer review. The definitive publisher-authenticated version Blake R. Rushing, Qing Hu, Jason N. Franklin, Rebecca L. McMahen, Sonia Dagnino, Christopher P. Higgins, Mark J. Strynar, Jamie C. DeWitt; Evaluation of the Immunomodulatory Effects of 2,3,3,3-Tetrafluoro-2-(Heptafluoropropoxy)-Propanoate in C57BL/6 Mice. Toxicol Sci 2016 kfw251. doi: 10.1093/toxsci/kfw251 is available online at: https://dx.doi.org/10.1093/toxsci/kfw251Science & TechnologyLife Sciences & BiomedicineToxicologyper- and polyfluoroalkyl substances (PFASs)perfluorooctanoic acid (PFOA)immunotoxicityTDARPERFLUOROOCTANOIC ACIDPEROXISOME PROLIFERATORHUMORAL IMMUNITYSUPPRESSIONEXPOSUREIMMUNOTOXICITYINVOLVEMENTALPHAPer- and polyfluoroalkyl substances (PFASs)TDARimmunotoxicityperfluorooctanoic acid (PFOA)1115 Pharmacology and Pharmaceutical SciencesToxicologyJournal Articlehttps://www.dx.doi.org/10.1093/toxsci/kfw2511096-0929