Acute Effects of an Insect Repellent, N,N-Diethyl-m-toluamide, on Cholinesterase Inhibition Induced by Pyridostigmine Bromide in Rats

Chaney, Leslie A.; Wineman, Robert W.; Rockhold, Robin W.; Hume, Arthur S.

doi:10.1006/taap.2000.8936

Cited by 30 publications

(13 citation statements)

References 44 publications

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“…Recent studies have demonstrated that PYR administered in combination with DEET results in decreased brain ChE activity while PYR alone does not alter brain ChE (Chaney et al, 2000). This is consistent with other reports indicating that DEET modulates the permeability of PYR into the central nervous system (Lallement et al, 1998;Grauer et al, 2000).…”

Section: Introductionsupporting

confidence: 79%

Evaluation of immunotoxicity induced by single or concurrent exposure to N, N-diethyl-m-toluamide (DEET), pyridostigmine bromide (PYR), and JP-8 jet fuel

Peden‐Adams

Eudaly

et al. 2001

Toxicol Ind Health

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Approximately 5,000 to 80,000 of the US service personnel involved in the Persian Gulf War have complained of a variety of nonspecific symptoms since their return in 1991. These symptoms have been collectively labeled Gulf War Illness and include muscle fatigue, general malaise, myalgia, impaired cognition, ataxia, headaches, fever, joint pain, skin rash, gastrointestinal disturbances, sleep disturbances, and respiratory difficulties. Exposures of military and service personnel were diverse and included the prescribed anti-nerve gas agent pyridostigmine bromide (PYR), N.N-diethyl-m-toluamide (DEET) insect repellent, and environmental exposures to jet fuel. Thus, studies in our laboratory were undertaken to determine if concurrent exposure to these agents, singly or in combination, would contribute to significant alterations in immunological function and disease susceptibility. To assess immune status, eight-week old B6C3F1 female mice were exposed for 14 days to single compounds or tertiary mixtures of 15.5 mg/kg DEET, 2 mg/kg PYR, and 500 mg/kg JP-8 (termed low dose), or 31 mg/kg DEET, 5 mg/kg PYR, and 1,000 mg/kg JP-8 (termed high dose). Immunosuppression was assessed 24 h after the last exposure. No remarkable alterations were evident in hematological parameters, spleen and thymus organ weight and total cellularity, natural killer (NK) cell activity, cytotoxic T-cell activity, or mitogen-induced lymphocyte proliferation after exposure to either single or tertiary mixtures at low or high doses. A few changes in CD4/CD8 flow cytometric lymphocyte subpopulations were detected after exposure to the tertiary mixture at the high dose. Delayed type hypersensitivity (DTH) was decreased by 88% after exposure to the high-dose mixture, and suppression of antibody-specific IgM immune responses (plaque-forming cell, PFC) occurred after exposure to all single and tertiary mixtures at both dose levels. In the PFC response, antagonism was apparent in the mixture, while coexposure to these agents resulted in a synergistic effect in the DTH response. Susceptibility to B16F10 tumor or Listeria monocytogenes challenge was not affected after single or tertiary exposures. These data suggest that combined exposure to DEET, PYR, and JP-8 does not profoundly alter many immunological endpoints, but does selectively target functional endpoints such as the PFC and DTH response. This should be considered when assessing human health risks in the military environment.

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Section: Introductionsupporting

confidence: 79%

Evaluation of immunotoxicity induced by single or concurrent exposure to N, N-diethyl-m-toluamide (DEET), pyridostigmine bromide (PYR), and JP-8 jet fuel

Peden‐Adams

Eudaly

et al. 2001

Toxicol Ind Health

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“…The chemical DEET is the most commonly used insect repellant (Veltri et al, 1994). Although the precise target of DEET is unknown, extensive and repeated topical application of DEET leads to human poisoning including death (Chaney et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Mood and Memory Deficits in a Model of Gulf War Illness Are Linked with Reduced Neurogenesis, Partial Neuron Loss, and Mild Inflammation in the Hippocampus

Parihar

Hattiangady

Shuai

et al. 2013

Neuropsychopharmacol

156

190

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Impairments in mood and cognitive function are the key brain abnormalities observed in Gulf war illness (GWI), a chronic multisymptom health problem afflicting ∼25% of veterans who served in the Persian Gulf War-1. Although the precise cause of GWI is still unknown, combined exposure to a nerve gas prophylaxis drug pyridostigmine bromide (PB) and pesticides DEET and permethrin during the war has been proposed as one of the foremost causes of GWI. We investigated the effect of 4 weeks of exposure to Gulf war illness-related (GWIR) chemicals in the absence or presence of mild stress on mood and cognitive function, dentate gyrus neurogenesis, and neurons, microglia, and astrocytes in the hippocampus. Combined exposure to low doses of GWIR chemicals PB, DEET, and permethrin induced depressive- and anxiety-like behavior and spatial learning and memory dysfunction. Application of mild stress in the period of exposure to chemicals exacerbated the extent of mood and cognitive dysfunction. Furthermore, these behavioral impairments were associated with reduced hippocampal volume and multiple cellular alterations such as chronic reductions in neural stem cell activity and neurogenesis, partial loss of principal neurons, and mild inflammation comprising sporadic occurrence of activated microglia and significant hypertrophy of astrocytes. The results show the first evidence of an association between mood and cognitive dysfunction and hippocampal pathology epitomized by decreased neurogenesis, partial loss of principal neurons, and mild inflammation in a model of GWI. Hence, treatment strategies that are efficacious for enhancing neurogenesis and suppressing inflammation may be helpful for alleviation of mood and cognitive dysfunction observed in GWI.

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“…Surprisingly, little is known about the environmental fate and effects of DEET, because as a residential‐use pesticide [7], it traditionally has been considered to have little potential for environmental effects. Previous research, however, has shown that DEET enhances the activity of cholinesterase inhibitors [8,9].…”

Section: Introductionmentioning

confidence: 99%

Widespread detection of N,N-diethyl-m-toluamide in U.S. Streams: Comparison with concentrations of pesticides, personal care products, and other organic wastewater compounds

Sandstrom

Kolpin

Thurman

et al. 2005

Environmental Toxicology and Chemistry

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One of the most frequently detected organic chemicals in a nationwide study concerning the effects of wastewater on stream water quality conducted in the year 2000 was the widely used insect repellant N,N-diethyl-m-toluamide (DEET). It was detected at levels of 0.02 microg/L or greater in 73% of the stream sites sampled, with the selection of sampling sites being biased toward streams thought to be subject to wastewater contamination (i.e., downstream from intense urbanization and livestock production). Although DEET frequently was detected at all sites, the median concentration was low (0.05 microg/L). The highest concentrations of DEET were found in streams from the urban areas (maximum concentration, 1.1 microg/L). The results of the present study suggest that the movement of DEET to streams through wastewater-treatment systems is an important mechanism that might lead to the exposure of aquatic organisms to this chemical.

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Acute Effects of an Insect Repellent, N,N-Diethyl-m-toluamide, on Cholinesterase Inhibition Induced by Pyridostigmine Bromide in Rats

Cited by 30 publications

References 44 publications

Evaluation of immunotoxicity induced by single or concurrent exposure to N, N-diethyl-m-toluamide (DEET), pyridostigmine bromide (PYR), and JP-8 jet fuel

Evaluation of immunotoxicity induced by single or concurrent exposure to N, N-diethyl-m-toluamide (DEET), pyridostigmine bromide (PYR), and JP-8 jet fuel

Mood and Memory Deficits in a Model of Gulf War Illness Are Linked with Reduced Neurogenesis, Partial Neuron Loss, and Mild Inflammation in the Hippocampus

Widespread detection of N,N-diethyl-m-toluamide in U.S. Streams: Comparison with concentrations of pesticides, personal care products, and other organic wastewater compounds

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