Immune function in female B(6)C(3)F(1) mice is modulated by DE-71, a commercial polybrominated diphenyl ether mixture.
Polybrominated diphenyl ethers (PBDEs) are an important class of flame-retardants that are environmentally persistent and bioaccumulative. Toxicity of these compounds has become a concern because detectable levels of PBDEs are present in humans and wildlife and they are structurally similar to polychlorinated biphenyls (PCBs). This study examined the effects of the commercial penta-BDE mixture, DE-71, in adult female B(6)C(3)F(1) mice on hematology, serum clinical chemistry, thyroid hormones, tissue histology, and several immunotoxicity end-points (lymphocyte proliferation, NK cell activity, splenic immunophenotypes, and SRBC-specific-IgM production). Mice were exposed via oral gavage for 28 days to achieve total administered doses (TAD) of 0, 0.5, 5, 50, or 100 mg/kg. No changes in histology, clinical chemistry, body or organ weights were observed. Serum total T3 and T4 levels were not altered by any of the DE-71 treatments. Peripheral blood monocyte numbers were decreased by the 0.5, 5, and 50 mg/kg treatments, but not by the 100 mg/kg TAD concentration. Compared to controls, mitogen-stimulated T- and B-cell proliferation was increased by the 100 mg/kg TAD concentration (ED(50) = 60 mg/kg TAD [2.14 mg/kg/day] and 58 mg/kg TAD [2.57 mg/kg/day], respectively). NK cell activity was decreased compared to controls by the 100 mg/kg TAD concentration (ED(50) = 20 mg/kg TAD [0.7 mg/kg/day]). No alterations were noted in thymic T-cell populations or in SRBC-specific-IgM production. Numbers of CD19(+)CD21(-), CD19(+)CD21(+), CD4(+)CD8(-), CD4(-)CD8(+), CD4(-)CD8(-), and MHC-II(+) cells in the spleen were not affected. However, the numbers of splenic CD4(+)CD8(+) cells were decreased compared to the controls by 0.5, 5, and 100 mg/kg TAD. This study provides an assessment of the systemic toxicity and immunotoxicity of DE-71, and indicates that immune parameters are modulated at exposure concentrations lower than previously reported.
National Oceanic and Atmospheric Administration, National Ocean Services, Center for Coastal Environmental Health and Biomolecular Research, Charleston, SC 29412, USA. pat.fair@noaa.gov
Patricia A
PA
Fair
Hui-Chen
HC
Stavros
Meagan A M
MA
Mollenhauer
Jamie C
JC
DeWitt
Natasha
N
Henry
Kurunthachalam
K
Kannan
Se Hun
SH
Yun
Gregory D
GD
Bossart
Deborah E
DE
Keil
Margie M
MM
Peden-Adams
D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D005411:Flame Retardants / Q000378:metabolism / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000378:metabolism / Q000633:toxicity*; D007107:Immune System / Q000187:drug effects* / Q000276:immunology; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008099:Liver / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D018570:Risk Assessment; D012756:Sheep; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D018675:Toxicity Tests
D015415:Biomarkers; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; C086401:pentabromodiphenyl ether