N,N,-diethyl-m-toluamide (DEET) suppresses humoral immunological function in B6C3F1 mice.
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.
Keil
Deborah E
DE
Clinical Laboratory Sciences, University of Nevada-Las Vegas, Las Vegas, Nevada 89154, USA. deborah.keil@unlv.edu
McGuinn
W David
WD
Dudley
Andrew C
AC
EuDaly
Jackie G
JG
Gilkeson
Gary S
GS
Peden-Adams
Margie M
MM
D000704:Analysis of Variance; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000276:immunology; D001682:Biological Availability; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003671:DEET / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D008658:Inactivation, Metabolic; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007302:Insect Repellents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D051379:Mice; D023421:Models, Animal; D018923:Persian Gulf Syndrome; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology
D007166:Immunosuppressive Agents; D007302:Insect Repellents; D003671:DEET