Effects of Daily Dermal Application of Deet and Permethrin, Alone and in Combination, on Sensorimotor Performance, Blood-Brain Barrier, and Blood-Testis Barrier in Rats

Abou‐Donia, Mohamed B.; Goldstein, Larry B.; Dechovskaia, A; Bullman, Sarah; Jones, Katherine H.; Herrick, E A; Abdel-Rahman, Ali; Khan, Waris

doi:10.1080/152873901300007824

Cited by 51 publications

(11 citation statements)

References 33 publications

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“…Such permeabilization will be expected of course to increase chemical access to the CNS and thus increase chemical sensitivity generated in the CNS. Increased blood-brain barrier permeability in response to chemical exposure has been reported by Abou-Donia and co-workers in a rat model of MCS (119). Evidence suggesting such increased permeability has been reviewed for the related conditions of PTSD (29) and CFS (120).…”

Section: Two Accessory Mechanisms In Mcs: Increased Blood-brain Barrimentioning

confidence: 89%

NMDA sensitization and stimulation by peroxynitrite, nitric oxide, and organic solvents as the mechanism of chemical sensitivity in multiple chemical sensitivity

Pall

2002

FASEB j.

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Multiple chemical sensitivity (MCS) is a condition where previous exposure to hydrophobic organic solvents or pesticides appears to render people hypersensitive to a wide range of chemicals, including organic solvents. The hypersensitivity is often exquisite, with MCS individuals showing sensitivity that appears to be at least two orders of magnitude greater than that of normal individuals. This paper presents a plausible set of interacting mechanisms to explain such heightened sensitivity. It is based on two earlier theories of MCS: the elevated nitric oxide/peroxynitrite theory and the neural sensitization theory. It is also based on evidence implicating excessive NMDA activity in MCS. Four sensitization mechanisms are proposed to act synergistically, each based on known physiological mechanisms: Nitric oxide-mediated stimulation of neurotransmitter (glutamate) release; peroxynitrite-mediated ATP depletion and consequent hypersensitivity of NMDA receptors; peroxynitrite-mediated increased permeability of the blood-brain barrier, producing increased accessibility of organic chemicals to the central nervous system; and nitric oxide inhibition of cytochrome P450 metabolism. Evidence for each of these mechanisms, which may also be involved in Parkinson's disease, is reviewed. These interacting mechanisms provide explanations for diverse aspects of MCS and a framework for hypothesis-driven MCS research.

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Section: Two Accessory Mechanisms In Mcs: Increased Blood-brain Barrimentioning

confidence: 89%

NMDA sensitization and stimulation by peroxynitrite, nitric oxide, and organic solvents as the mechanism of chemical sensitivity in multiple chemical sensitivity

Pall

2002

FASEB j.

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“…Early animal models of PB established that this drug can adversely affect nerve function ( Drake-Baumann & Seil, 1999 ; Hudson, Foster, & Kahng, 1985 ) and can also have gastrointestinal ( Kluwe, Page, Toft, Ridder, & Chung, 1990 ), muscular ( Adler, Deshpande, Foster, Maxwell, & Albuquerque, 1992 ), immune ( Peden-Adams et al, 2004 ) and cardiovascular ( Bernatova, Babal, Grubbs, & Morris, 2006 ) effects. Rodents given PB over time showed a number of locomotor, learning and behavioral deficits ( Abou-Donia, Dechkovskaia, Goldstein, Bullman, & Khan, 2002 ; Abou-Donia et al, 2001 ; van Haaren et al, 2001 ), despite showing no overt signs of cholinergic toxicity or illness. Three studies in rodent models found that the adverse effects of PB were enhanced by stressors ( Abdel-Rahman, Abou-Donia, El-Masry, Shetty, & Abou-Donia, 2004 ; Abdel-Rahman, Shetty, & Abou-Donia, 2002 ; Friedman et al, 1996 ).…”

Section: Animal Models Of Gwi Etiology and Pathologymentioning

confidence: 99%

Recent research on Gulf War illness and other health problems in veterans of the 1991 Gulf War: Effects of toxicant exposures during deployment

White

Steele

O’Callaghan

et al. 2016

Cortex

350

398

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Veterans of Operation Desert Storm/Desert Shield – the 1991 Gulf War (GW) – are a unique population who returned from theater with multiple health complaints and disorders. Studies in the U.S. and elsewhere have consistently concluded that approximately 25–32% of this population suffers from a disorder characterized by symptoms that vary somewhat among individuals and include fatigue, headaches, cognitive dysfunction, musculoskeletal pain, and respiratory, gastrointestinal and dermatologic complaints. Gulf War illness (GWI) is the term used to describe this disorder. In addition, brain cancer occurs at increased rates in subgroups of GW veterans, as do neuropsychological and brain imaging abnormalities.Chemical exposures have become the focus of etiologic GWI research because nervous system symptoms are prominent and many neurotoxicants were present in theater, including organophosphates (OPs), carbamates, and other pesticides; sarin/cyclosarin nerve agents, and pyridostigmine bromide (PB) medications used as prophylaxis against chemical warfare attacks. Psychiatric etiologies have been ruled out.This paper reviews the recent literature on the health of 1991 GW veterans, focusing particularly on the central nervous system and on effects of toxicant exposures. In addition, it emphasizes research published since 2008, following on an exhaustive review that was published in that year that summarizes the prior literature (RACGWI, 2008).We conclude that exposure to pesticides and/or to PB are causally associated with GWI and the neurological dysfunction in GW veterans. Exposure to sarin and cyclosarin and to oil well fire emissions are also associated with neurologically based health effects, though their contribution to development of the disorder known as GWI is less clear. Gene-environment interactions are likely to have contributed to development of GWI in deployed veterans. The health consequences of chemical exposures in the GW and other conflicts have been called “toxic wounds” by veterans. This type of injury requires further study and concentrated treatment research efforts that may also benefit other occupational groups with similar exposure-related illnesses.

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“…Abou-Donia et al (2001) observed that clinical conditions of rats treated with daily dermal applications of 4, 40, and 400 mg/kg BW DEET in ethanol were not different from the controls. There were also no differences observed in the weight of treated animals when compared to the controls Abou-Donia et al, 2001). However, Abou-Donia et al (2001) suggested that exposures to DEET at 40 and 400 mg/kg BW for 60 days decreased blood-brain barrier permeability in certain brain regions, which may have important physiological or pharmacological consequences.…”

Section: Subchronic Toxicitymentioning

confidence: 86%

Risk assessments for the insect repellents DEET and picaridin

Antwi

Shama²,

Peterson

2008

Regulatory Toxicology and Pharmacology

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a b s t r a c tFor the use of topical insect repellents, DEET and picaridin, human health risk assessments were conducted for various population subgroups. Acute, subchronic, and chronic dermal exposures were examined. No-observed-effect-levels (NOELs) of 200, 300, and 100 mg/kg body weight (BW) were used as endpoints for DEET for acute, subchronic, and chronic exposures, respectively. For picaridin, a NOEL of 2000 mg/kg BW/day for acute exposure and a NOEL of 200 mg/kg BW/day for subchronic and chronic exposures were used. Daily exposures to several population subgroups were estimated. Risks were characterized using the Margin of Exposure (MOE) method (NOEL divided by the estimated exposure), whereby estimated MOEs were compared to an MOE of 100. Estimates of daily exposures ranged from 2 to 59 mg/kg BW/day for DEET and 2 to 22 mg/kg BW/day for picaridin. Children had the lowest MOEs. However, none of the estimated exposures exceeded NOELs for either repellent. At 40% DEET for acute exposure, children 612 years had MOEs below 100. For subchronic and chronic exposures children at P25% DEET and at 15% picaridin had MOEs below 100. Therefore, we found no significant toxicological risks from typical usage of these topical insect repellents.

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Effects of Daily Dermal Application of Deet and Permethrin, Alone and in Combination, on Sensorimotor Performance, Blood-Brain Barrier, and Blood-Testis Barrier in Rats

Cited by 51 publications

References 33 publications

NMDA sensitization and stimulation by peroxynitrite, nitric oxide, and organic solvents as the mechanism of chemical sensitivity in multiple chemical sensitivity

NMDA sensitization and stimulation by peroxynitrite, nitric oxide, and organic solvents as the mechanism of chemical sensitivity in multiple chemical sensitivity

Recent research on Gulf War illness and other health problems in veterans of the 1991 Gulf War: Effects of toxicant exposures during deployment

Risk assessments for the insect repellents DEET and picaridin

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