Effects of environmentally-relevant levels of perfluorooctane sulfonate on clinical parameters and immunological functions in B6C3F1 mice.
In the first part of a series of studies to account for perfluorooctane sulfonate (PFOS)-induced sheep red blood cell (SRBC)-specific immunoglobulin M (IgM) antibody suppression in mice, a survey of clinical and immunotoxicological endpoints was examined. Adult female B₆C₃F₁ mice were exposed orally for 28 days to a total administered dose (TAD) of 0, 0.1, 0.5, 1, or 5 mg PFOS/kg. Uterus wet weight was significantly decreased compared with control at the 5 mg/kg dose. No indications of wasting syndrome, malnutrition, alteration of thyroid homeostasis, or signs of overt toxicity were observed. Numbers of splenic CD19+/CD21⁻, CD19+/CD21+, B220+/CD40+, CD4+/CD154⁻, CD4+/CD154+, and MHC-II+ cells were not altered. Additionally, ex vivo interleukin-4 (IL-4), IL-5, and IL-6 production by in vitro anti-CD3- or phorbol myristate acetate-stimulated CD4+ T-cells was not affected. Ex vivo IL-6 production by B-cells was significantly increased by in vitro stimulation with either anti-CD40 or lipopolysaccharide. Increased IL-6 production by B-cells was the most sensitive endpoint assessed resulting in alterations at the lowest dose tested (0.1 mg/kg TAD) following anti-CD40 stimulation. Further studies are required to characterize effects on inflammatory markers such as IL-6 at environmentally relevant concentrations of PFOS and to determine the key events associated with PFOS-induced IgM suppression to address potential human health risks.
National Oceanic and Atmospheric Administration, National Ocean Service, Center for Coastal Environmental Health & Biomolecular Research, Charleston, SC, USA.
Patricia A
PA
Fair
Erin
E
Driscoll
Meagan A M
MA
Mollenhauer
Sarah G
SG
Bradshaw
Se Hun
SH
Yun
Kurunthachalam
K
Kannan
Gregory D
GD
Bossart
Deborah E
DE
Keil
Margie M
MM
Peden-Adams
D017738:Alkanesulfonic Acids / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005466:Fluorocarbons / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013963:Thyroid Hormones / Q000097:blood; D014018:Tissue Distribution
D017738:Alkanesulfonic Acids; D015703:Antigens, CD; D004785:Environmental Pollutants; D005466:Fluorocarbons; D007075:Immunoglobulin M; D015850:Interleukin-6; D013963:Thyroid Hormones; C076994:perfluorooctane sulfonic acid
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