Erythrocyte and Plasma Cholinesterase Activity in Male and Female Rhesus Monkeys before and after Exposure to Sarin

Woodard, Claude L.; Calamaio, C.A.; Kaminskis, Andris; Anderson, Dana R.; Harris, Larrel W.; Martin, Dale G.

doi:10.1006/faat.1994.1114

Cited by 18 publications

(3 citation statements)

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“…Specifically as it relates to the field of OP toxicity, the sensitivity of nonhuman primates to different OPs closely resembles that of humans. For example, the intravenous LD 50 of sarin in Rhesus monkeys and humans are 15 and 14 mg/kg, respectively (Woodard et al, 1994; http://www.iom. edu/~/media/Files/Report%20Files/2007/Long-Term-HealthEffects-of-Participation-in-Project-SHAD-Shipboard-Hazardand-Defense/SARINNERVEAGENT.pdf).…”

Section: Animal Models Of Op Intoxicationmentioning

confidence: 99%

Animal Models That Best Reproduce the Clinical Manifestations of Human Intoxication with Organophosphorus Compounds

Pereira

Aracava

DeTolla

et al. 2014

J Pharmacol Exp Ther

104

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The translational capacity of data generated in preclinical toxicological studies is contingent upon several factors, including the appropriateness of the animal model. The primary objectives of this article are: 1) to analyze the natural history of acute and delayed signs and symptoms that develop following an acute exposure of humans to organophosphorus (OP) compounds, with an emphasis on nerve agents; 2) to identify animal models of the clinical manifestations of human exposure to OPs; and 3) to review the mechanisms that contribute to the immediate and delayed OP neurotoxicity. As discussed in this study, clinical manifestations of an acute exposure of humans to OP compounds can be faithfully reproduced in rodents and nonhuman primates. These manifestations include an acute cholinergic crisis in addition to signs of neurotoxicity that develop long after the OP exposure, particularly chronic neurologic deficits consisting of anxiety-related behavior and cognitive deficits, structural brain damage, and increased slow electroencephalographic frequencies. Because guinea pigs and nonhuman primates, like humans, have low levels of circulating carboxylesterases-the enzymes that metabolize and inactivate OP compounds-they stand out as appropriate animal models for studies of OP intoxication. These are critical points for the development of safe and effective therapeutic interventions against OP poisoning because approval of such therapies by the Food and Drug Administration is likely to rely on the Animal Efficacy Rule, which allows exclusive use of animal data as evidence of the effectiveness of a drug against pathologic conditions that cannot be ethically or feasibly tested in humans.

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Section: Animal Models Of Op Intoxicationmentioning

confidence: 99%

Animal Models That Best Reproduce the Clinical Manifestations of Human Intoxication with Organophosphorus Compounds

Pereira

Aracava

DeTolla

et al. 2014

J Pharmacol Exp Ther

104

View full text Add to dashboard Cite

show abstract

“…It is most rapidly absorbed into the body via the respiratory tract and mucous membranes, which are highly vascularised. 1,7,9,27 The toxin then inhibits the enzyme acetyl cholinesterase, preventing it from degrading the neurotransmitter acetylcholine, causing hyperstimulation at the nicotinic neuromuscular junction and the muscarinic parasympathetic junction, resulting in muscle fasciculations and cholinergic hyperstimulation. 1,25,27,28 Toxicity is largely dependent on the degree and method of exposure.…”

Section: Mechanism Of Action and Clinical Findingsmentioning

confidence: 99%

“…There is no maximum dose in the emergency treatment of sarin or other organophosphate compounds, but doses of 20 to 30 mg were recorded as being required in the Japanese subway attacks. 1,2,6,7,14,15,[26][27][28] Atropine crosses the blood-brain barrier, and may cause central nervous system toxicity in high doses or after prolonged periods of administration. Central nervous system toxicity symptoms from atropine administration include dilated and nonreactive pupils, hallucinations, restlessness, delirium, and coma.…”

Section: Decontaminationmentioning

confidence: 99%

Essential Lessons in a Potential Sarin Attack Disaster Plan for a Resource-Constrained Environment

Watermeyer

Dippenaar

Simo

et al. 2017

Disaster med. public health prep.

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Sarin is a potent nerve agent chemical weapon that was originally designed for military purposes as a fast-acting anti-personnel weapon that would kill or disable large numbers of enemy troops. Its potent toxicity, ease of deployment, and rapid degradation allow for rapid deployment by an attacking force, who can safely enter the area of deployment a short while after its release. Sarin has been produced and stockpiled by a number of countries, and large quantities of it still exist despite collective agreements to cease manufacture and destroy stockpiles. Sarin's ease of synthesis, which is easily disseminated across the Internet, increases the risk that terrorist organizations may use sarin to attack civilians. Sarin has been used in a number of terrorist attacks in Japan, and more recently in attacks in the Middle East, where nonmilitary organizations have led much of the disaster relief and provision of medical care. In the present article, we examine and discuss the available literature on sarin's historical use, delivery methods, chemical properties, mechanism of action, decontamination process, and treatment. We present a management guideline to assist with the recognition of an attack and management of victims by medical professionals and disaster relief organizations, specifically in resource-constrained and austere environments. (Disaster Med Public Health Preparedness. 2018;12:249-256).

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Chemical Warfare Agents: Estimating Oral Reference Doses

Opresko

Young

Faust

et al. 1998

Reviews of Environmental Contamination and Toxicology

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Erythrocyte and Plasma Cholinesterase Activity in Male and Female Rhesus Monkeys before and after Exposure to Sarin

Cited by 18 publications

References 0 publications

Animal Models That Best Reproduce the Clinical Manifestations of Human Intoxication with Organophosphorus Compounds

Animal Models That Best Reproduce the Clinical Manifestations of Human Intoxication with Organophosphorus Compounds

Essential Lessons in a Potential Sarin Attack Disaster Plan for a Resource-Constrained Environment

Chemical Warfare Agents: Estimating Oral Reference Doses

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