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ToxSci Advance Access published online on February 5, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn015
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© The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

GESTATIONAL EXPOSURE TO PERFLUOROOCTANE SULFONATE (PFOS) SUPPRESSES IMMUNE FUNCTION IN B6C3F1 MICE

Deborah E. Keil*,{dagger}, Tracey Mehlmann{dagger}, Leon Butterworth{dagger} and Margie M. Peden-Adams{Delta}

{dagger} National Institute for Occupational Safety and Health, Morgantown, WV, USA * Clinical Laboratory Sciences, University of Nevada, Las Vegas, NV USA {Delta} Department of Pediatrics and the Marine Biomedicine and Environmental Science Center, Medical University of South Carolina, Charleston, SC, USA

Author to Whom Correspondence should be addressed: Deborah E. Keil, Ph.D., Clinical Laboratory Sciences, University of Nevada, 4505 Maryland Pkwy, Box 453021, Las Vegas, NV 89154-3021, Phone: 702-895-0973, Fax: 702-895-3872, Email: deborah.keil{at}unlv.edu

Received October 5, 2007; revision received January 2, 2008; accepted January 5, 2008


  Abstract

Perfluorinated alkyl acids (PFAAs) are used in a multitude of applications and are categorized as high-production volume (HPVs) chemicals produced in quantities exceeding 10,000 lbs/yr. As a result, widespread exposure has been documented in adults, children and infants. It is generally accepted that children are more sensitive to the effects of xenobiotic exposures during fetal and post-natal periods of development; therefore, considerable efforts are required to investigate the potential impact of a model PFAA, perfluorooctanesulfonate (PFOS) on children's immunological health. Using the pairing of female C57BL/6N mice with male C3H/HeJ, developmental immunotoxicity was evaluated in B6C3F1 pups following oral maternal exposure to PFOS on gestations days (GD) 1-17. Exposure levels included 0.1, 1 and 5 mg/kg/day PFOS. Natural killer (NK) cell activity, SRBC IgM plaque assay, CD4/8 lymphocytic subpopulations, nitrite production in peritoneal macrophages, and body/organ weights were evaluated at 4 and 8 weeks of age in F1 pups. No significant dose-responsive changes in maternal or pup body weights, flow cytometry, or macrophage function were observed, yet hepatomegaly was indicated in F1 male pups at 4 weeks of age. Functional deficits were not evident until 8 weeks of age when NK cell function and IgM production were significantly decreased. When compared to females, male pups were more sensitive to the effects of PFOS thereby establishing a no observed adverse effect level (NOAEL) and low observed adverse effect level (LOAEL) of 0.1 and 1.0 mg/kg/day (males only) following maternal PFOS exposure level, respectively. This study establishes that the developing immune system is sensitive to the effects of PFOS and results in functional deficits in innate and humoral immunity detectable at adulthood.

Key Words: Developmental immunotoxicity; PFOS; perfluorinated compounds.


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