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2 Toxicology
Pages 26-46

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From page 26...
... Because sarin md cycloSaTm have the same mechanism of action and toxic effects, differing mainly in potency, data on the two compounds are discussed together. PHYSICAL AND CHEMICAL PROPERTIES As discussed in GWI aoM.
From page 27...
... . Distribution and Elimination Animal data obtained by using radioactively labeled sarin indicate that sarin rapidly (within I min)
From page 28...
... . A recent study in guinea pigs indicated that sarin stereoisomers reach the blood rapidly after nose-only exposures and then gradually decline (Spruit et al., 2000)
From page 29...
... Recovery of AChE function occurs only with synthesis of new enzyme. Most of the effects of SaTm, including the acute cholinergic syndrome, are thought to be mediated by the excess ACh at the synapse.
From page 30...
... If death occurs, it is due to respiratory failure, usually as a result of a combmation of the autonomic effects mediated by the muscarinic ~md nicotmic ACh receptors ~md the effects of ACh at CNS receptors. Those effects c m include excessive fluid in the respiratory tract, paralysis of the respiratory muscles, md depression of the respiratory centers of the CNS.
From page 31...
... . Organophosphorus-lnduced Delayed Neuropathy Another type of toxicity caused by a few OP compounds is a progressive, i reversible delayed neuropathy termed org~mophosphate-mduced delayed neuropathy (OPIDN)
From page 32...
... .i Those high doses produce the acute cholinergic syndrome, in many cases necessitate pharmacologic intervention to prevent death, and are not useful in distinguishing between primary damage caused by the compound and secondary damage caused by hypoxic events after convulsions. There is no evidence that any Gulf War soldiers had the acute cholinergic syndrome, so studies of acute, high-dose exposure to sann or cyclosarin are only briefly mentioned, and this section focuses more on studies published since the preparation of GW2 of the long-term effects of low-dose exposures to compounds that are more relevant to the situation in the Gulf War.
From page 33...
... As discussed in Gym, short-term behavioral effects have been examined in the marmoset, a nonhuman primate. Doses at 33-55% of the LDso disrupted the perfomlaulce of animals' food-reinforced visually guided reaching response.
From page 34...
... studied locomotor activity md body temperature in rats exposed only intr masally to sarm (0.2 or 0.4 mg/m3 of air for I h/day for 1, 5, or 10 days) in the presence or absence of heat stress (32° C)
From page 35...
... No changes were seen on day I after 5 days of treatment, but a decrease in Ml receptors was seen in the olfactory tubercle 30 days after the highest dose. With heat stress, there were also dose-dependent decreases in Ml receptor density in the frontal cerebral cortex, olfactory tubercle, anterior olfactory nucleus, striatum, dentate gyrus, and CAI region of the hippocatnpus 30 days after treatment.
From page 36...
... Delayed Neurotoxicity As discussed previously, exposure to some organophosphates produces a delayed neurotoxic syndrome known as organophosphate-induced delayed neuropathy. In some animal models, massive doses of sarin can cause delayed neurotoxicity, which is manifested in ataxia and paralysis days to weeks after a single high exposure or multiple lower exposures (Somani, 1992; Lotti, 2000; Spencer et al., 2000)
From page 37...
... Genotoxicity A study of the genotoxicity of sarin showed no evidence of genotoxicity (mutagenesis, chromosome damage, unscheduled DNA synthesis, or sister chromatid exchange) (Goldman et al., 1988)
From page 38...
... 38 TABLE 2-:3 Delayed Neurotoxicity of Sarin Route of I r~4u~ncy Species Dow. pox Administrations and/orDurtoon Chicken 25 ( Ds0)
From page 39...
... . Because human serum PONI catalyzes the hydrolysis of OP insecticides md nerve gases such as sarm, those polytnotp hi tin i might subst~mtially alter a person's susceptibility to the toxicity of the chemicals.
From page 40...
... (2003) did not find my differences m PONI activity between symptomatic and asymptomatic Gulf War veterans Those researchers studied symptomatic Gulf War veterans, healthy Gulf War veterans, symptomatic Bosnia peacekeeping veterims, and symptomatic nondeployed military controls.
From page 41...
... 1997. AppEcahon of lignid chtomatography- tmospheflc pnesstite chemical ionisanon mass specrtometty, tnd tandem mass specmomet y, tn the tnalysis tnd ideBtineahon of degradabonptodttcts of chemical wa~fate agems.
From page 42...
... 1995. Trace detetminahon of a kyl methylphosphonic acids in envffomment d ald biological stmples using gas chtomatographyhteganve ion chemical ioninttion mass specttometty ald taBdem mass specttomeoy.
From page 43...
... Response of mrs to low levels of satin. Taxitalaky smd Applid d Phatmm a/ogy 184(2)
From page 44...
... 2001 a. Long term effects of low level sarin inhalation exposttre on the spatial memoty of rats in a T-mtee.
From page 45...
... 1992. Chemical Warfare Ageniz.
From page 46...
... 1996. Identiflcahon of alkyl methylphosphonic acids by thermospmy t mdem mass specm~metty.


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