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ToxSci Advance Access published online on January 13, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp001
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© The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

N,N,-DIETHYL-M-TOLUAMIDE (DEET) SUPPRESSES HUMORAL IMMUNOLOGICAL FUNCTION IN B6C3F1 MICE

D.E. Keil*, W. D. McGuinn{dagger}, A.C. Dudley, J.G. EuDaly{ddagger},§,¶, G.S. Gilkeson§,|| and M.M. Peden-Adams{ddagger},§,¶

* Clinical Laboratory Sciences, University of Nevada-Las Vegas, Las Vegas, NV, 89154, USA {dagger} US-FDA, Silver Spring, MD, 20993, USA {ddagger} Department of Pediatrics, Medical University of South Carolina, Charleston, SC, 29412, USA § Department of Medicine, Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC, 29412, USA Marine Biomedicine and Environmental Science Center, Medical University of South Carolina, Charleston, SC, 29412, USA || Medical Research Service, Ralph Johnson VAMC, Charleston, SC, 29425, USA

Author to Whom Correspondence should be addressed: Deborah E. Keil, Ph.D., DABT, 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 September 15, 2008; revision received December 22, 2008; accepted December 29, 2008


  Abstract

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 subcutaneously (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 hours 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.


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