ToxSci Advance Access published online on June 16, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn113
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Evaluation of the Immune System in Rats and Mice Administered Linear Ammonium Perfluorooctanoate (APFO)
DuPont Haskell Laboratory for Health and Environment Sciences, Newark, DE, 19714
* To whom correspondence should be addressed at DuPont Haskell Laboratory, P.O. Box 50, Elkton Rd, Newark, DE 19714-0050. Email: scott.e.loveless{at}usa.dupont.com Telephone 302-451-4806; Fax 302-366-6420
Received February 22, 2008; revision received June 2, 2008; accepted June 2, 2008
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Abstract |
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Repeated high doses of APFO have been reported to affect immune system function in mice. To examine dose response characteristics in both rats and mice, male CD rats and CD-1 mice were dosed by oral gavage with 0.3 to 30 mg/kg/day of linear ammonium perfluorooctanoate (APFO) for 29 days. Anti-sheep red blood cell (SRBC) IgM levels, clinical signs, body weights, selected hematology and lipid parameters, liver weights, spleen and thymus weights and cell number, selected histopathology, and serum corticosterone concentrations were evaluated. In rats, linear APFO had no effect on production of anti-SRBC antibodies. Ten and 30 mg/kg/day resulted in systemic toxicity as evidenced by decreases in body weight gain to 74 and 37%, and increases in serum corticosterone levels to 135 and 196% of control, respectively. In mice dosed with 10 and 30 mg/kg/day, marked systemic toxicity and stress was observed, as evidenced by a loss in body weight of 3.8 and 6.6g, respectively (despite a tripling of liver weight), 
230% increase in serum corticosterone, and increases in absolute numbers of peripheral blood neutrophils and monocytes with an accompanying decrease in absolute lymphocyte numbers. Immune-related findings at 10 and 30 mg/kg/day that likely represent secondary responses to the systemic toxicity and stress observed at these doses include: decreased IgM antibody production at 10 (20% suppression) and 30 mg/kg/day (28% suppression); decreased spleen and thymus weights and cell numbers; microscopic depletion/atrophy of lymphoid tissue at 10 mg/kg/day (thymus) and 30 mg/kg/day (spleen). In summary, no immune-related changes occurred in rats, even at doses causing systemic toxicity. In mice, immune-related changes occurred only at doses causing significant and profound systemic toxicity and stress.
Key Words: APFO; PFOA; immunotoxicity; immunomodulation.
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