ToxSci Advance Access originally published online on January 13, 2009
Toxicological Sciences 2009 108(1):110-123; doi:10.1093/toxsci/kfp001
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N,N,-Diethyl-m-Toluamide (DEET) Suppresses Humoral Immunological Function in B6C3F1 Mice
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* Clinical Laboratory Sciences, University of Nevada-Las Vegas, Las Vegas, Nevada 89154
US-FDA, Silver Spring, Maryland 20993
Department of Pediatrics
Department of Medicine, Division of Rheumatology and Immunology
¶ Marine Biomedicine and Environmental Science Center, Medical University of South Carolina, Charleston, South Carolina 29412
|| Medical Research Service, Ralph Johnson VAMC, Charleston, South Carolina 29425
1 To whom correspondence should be addressed at Clinical Laboratory Sciences, University of Nevada, 4505 Maryland Pkwy, Box 453021, Las Vegas, NV 89154-3021. Fax: (702) 895-3872. E-mail: deborah.keil{at}unlv.edu.
Received September 15, 2008; accepted December 29, 2008
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Abstract |
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N,N-diethyl-meta-toluamide (DEET) is a particularly effective broad-spectrum insect repellent used commonly in recreational, occupational and military environments. Due to its widespread use and suggested link to Gulf War Illness, this study examined the immunotoxicity of DEET. Adult female B6C3F1 mice were injected sc for 14 days with DEET at 0, 7.7, 15.5, 31, or 62 mg/kg/day. Due to differences in the dermal absorption of DEET between mice and humans, this study eliminated this confounding factor by utilizing sc injection and measured circulating blood levels of DEET to assess bioavailability from sc administration. Effects on lymphocyte proliferation, natural killer cell activity, thymus and spleen weight and cellularity, the antibody plaque-forming cell (PFC) response, and thymic and splenic CD4/CD8 lymphocyte subpopulations were assessed 24 h after the last dose. No effect was observed in lymphocyte proliferation, natural killer cell activity, thymic weight, splenic weight, thymic cellularity, or splenic cellularity. Significant decreases were observed in the percentage of splenic CD4–/CD8– and CD4+/CD8– lymphocytes but only at the 62 mg DEET/kg/day treatment level and not in absolute numbers of these cells types. Additionally, significant decreases in the antibody PFC response were observed following treatment with 15.5, 31, or 62 mg DEET/kg/day. Pharmacokinetic (PK) data from the current study indicate 95% bioavailability of the administered dose. Therefore, it is likely that DEET exposure ranges applied in this study are comparable to currently reported occupational usage. Together, the evidence for immunosuppression and available PK data suggest a potential human health risk associated with DEET in the occupational or military environments assuming similar sensitivity between human and rodent responses.
Key Words: DEET; immune function; Gulf War Illness; PFC response; T-cell subpopulations.