Inhalation toxicity nerve agents

DF and its precursor, DC are organophosphonic acids. They will react with alcohols to form crude lethal nerve agents, such as crude GB. High overexposure may cause inhibition of cholinesterase activity. Although much less toxic than GB, DF and DC are toxic and corrosive materials. Because DF and DC are relatively volatile compounds, the primary route of exposure is expected to be the respiratory system. However, ingestion also results from inhalation exposures in animals and could occur in humans. DF and DC vapors have a pungent odor and may cause severe and painful irritation of the eyes, nose, throat, and lungs. Data provided is for DF only, DC has similar properties. 

Human toxicity values have not been established or have not been published. However, based on available information, this material appears to be approximately one-third as toxic as the nerve agent VX (C02-004) when inhaled, but to have a similar toxicity when injected. 

Nerve Agent Substances that interfere with the central nervous system. Organic esters of phosphoric acid used as a chemical warfare agent because of their extreme toxicity (tabun-GA, sarin-GB, soman-GD, GF, and VX). All are potent inhibitors of the enzyme, acetylcholinesterase, which is responsible for the degradation of the neurotransmitter, acetylcholine in neuronal synapses or myoneural junctions. Nerve agents are readily absorbed by inhalation and/or through intact skin. 

Bide, R.W., Risk, D.J. (2000). Inhalation toxicity of aerosolized nerve agents. 1. VX revisited. Technical Report DRES TR 2000-063. Defence Research Establishment, Suffield, Alberta, Canada. 

Nambiar, M., Gordon, N.K., Rezk, P.E., Katos, A.M., Wajda, N.A., Moran, T.S., Steele, K.E., Doctor, B.P., Sciuto, A.M. (2007). Medical countermeasures against respiratory toxicity and acute lung injury following inhalation exposure to chemical warfare nerve agent VX. Toxicol. Appl. Pharmacol. 219 142-50. 

A single exposure to another nerve agent, cyclosarin, at concentrations that do not produce convulsions or severe clinical signs of toxicity can also produce performance deficits on learned behavioral tasks. However, with repeated exposure, the deficits are not persistent and recovery is complete. In addition, exposure concentrations not producing any evaluated clinical signs of toxicity, other than temporary miosis (in the case of inhalation exposure), do not produce performance deficits on the behavioral tasks (Genovese et al, 2006). 

GA, a unitary chemical munition, inhibits AChE, the enzyme responsible for the breakdown of the neurotransmitter ACh. When inhaled, its toxicity is half that of sarin. It depresses plasma and RBC-AChE activities significantly in the blood. At 20-25% of red blood cell AChE baseline, the effect of the nerve agent becomes noticeable. There is no evidence of systemic toxicity other than the cholinesterase activity (Parker et al, 1990 Munro et al, 1994). GA has not been shown to produce OPIDN except at extremely high doses. The cardiac effect of GA conforms to OP-caused arrhythmias and AV block. 

Sarin is absorbed both through the skin and via respiration. It is more soluble in water than the other nerve agents (soman (GD) and VX) its solubility is directly related to temperature. The half-life of sarin, however, is inversely related to temperature and pH. In water the half-life of sarin is 15 min at 30°C and at pH 7.6. Nerve agents inhaled as vapors or aerosols enter the systemic circulation, resulting in toxic manifestations within seconds to 5 min of inhalation. 

Toxic effects occur within seconds to 5 min of nerve agent vapor or aerosol inhalation. The muscarinic effects include ocular (miosis, conjunctival congestion, ciliary spasm), nasal discharge, respiratory (bronchoconstriction and increased bronchial secretion), gastrointestinal (anorexia, vomiting, abdominal cramps, and diarrhea), sweating, salivation, and cardiovascular (bradycardia and hypotension) effects. The nicotinic effects include muscular fa-sciculation and paralysis. CNS effects can include ataxia, confusion, loss of reflexes, slurred speech, coma, and paralysis. 

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