Titre du document / Document title

Neurotoxicity resulting from coexposure to pyridostigmine bromide, DEET, and permethrin : Implications of gulf war chemical exposures

Auteur(s) / Author(s)

ABOU-DONIA M. B. ⁽¹⁾ ; WILMARTH K. R. ⁽¹⁾ ; JENSEN K. F. ; OEHME F. W. ; KURT T. L. ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Pharmacology, Duke University Medical Center, Durham, North Carolina, ETATS-UNIS

Résumé / Abstract

Of the three-quarters of a million service personnel involved in the Persian Gulf War, approximately 30,000 have complained of neurological symptoms of unknown etiology. One contributing factor to the emergence of such symptoms may be the simultaneous exposure to multiple agents used to protect the health of service personnel, in particular, the anti-nerve agent pyridostigmine bromide (PB ; 3-dimethylaminocarbonyloxy-N-methylpyridinium bromide), the insect repellent DEET (N,N-diethyl-m-toluamide), and the insecticide permethrin (3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid (3-phenoxyphenyl)methyl ester). This study investigated neurotoxicity produced in hens by individual or simultaneous exposure to these agents (5 d/wk for 2 months to 5 mg/kg/d PB in water, po ; 500 mg/kg/d DEET, neat, sc ; and 500 mg/kg/d permethrin in corn oil, sc). At these dosages, exposure to single compounds resulted in minimal toxicity. Combinations of two agents produced greater neurotoxicity than that caused by individual agents. Neurotoxicity was further enhanced following concurrent administration of all three agents. We hypothesize that competition for liver and plasma esterases by these compounds leads to their decreased breakdown and increased transport of the parent compound to nervous tissues. Thus, carbamylation of peripheral esterases by PB reduces the hydrolysis of DEET and permethrin and increases their availability to the nervous system. In effect, PB pumps more DEET and permethrin into the central nervous system. Consistent with this hypothesis, hens exposed to the combination of the three agents exhibited neuropathological lesions with several characteristics similar to those previously reported in studies of nearlethal doses of DEET and permethrin. If this hypothesis is correct, then blood and liver esterases play an important buffering role in protecting against neurotoxicity in the population at large. It also suggests that individuals with low plasma esterase activity may be predisposed to neuro logic deficits produced by exposure to certain chemical mixtures.

Revue / Journal Title

Journal of toxicology and environmental health   ISSN 0098-4108   CODEN JTEHD6 

Source / Source

1996, vol. 48, n^o1, pp. 35-56 (2 p.1/2)

Langue / Language

Anglais

Editeur / Publisher

Taylor & Francis, London, ROYAUME-UNI  (1975-1997) (Revue)

Mots-clés anglais / English Keywords

Chemical warfare agent ; Insecticide ; Antidote ; Army ; Military ; Prevention ; Toxicity ; Human ; Toxic association ; Chicken ; Mechanism of action ; Pyrethroids ; Organic carbamate ; Permethrin ; Nervous system diseases ; Aves ; Vertebrata ;

Mots-clés français / French Keywords

Arme chimique ; Insecticide ; Antidote ; Armée ; Militaire ; Prévention ; Pyridostigmine bromure ; Diéthyltoluamide ; Toxicité ; Homme ; Association toxique ; Poulet ; Mécanisme action ; Pyréthrinoïde ; Carbamate organique ; Permethrin ; toxicité antidote ; Système nerveux pathologie ; Aves ; Vertebrata ;

Mots-clés espagnols / Spanish Keywords

Arma química ; Insecticida ; Antídoto ; Ejército ; Militar ; Prevención ; Toxicidad ; Hombre ; Asociación toxíca ; Pollo ; Mecanismo acción ; Piretrinoide ; Carbamato orgánico ; Permethrin ; Sistema nervioso patología ; Aves ; Vertebrata ;

Localisation / Location

INIST-CNRS, Cote INIST : 17099, 35400004339538.0020