Add time:07/14/2019         Source:sciencedirect.com

In order to find an explanation of the low acute toxicity of di-(2-chloroethyl) aryl phosphates and their variable ataxic toxicity in sheep, the reactions of these compounds with various esterases found in sheep were studied, and compared with those of other, more toxic compounds.Di-(2-chloroethyl) aryl phosphates have been shown to form unstable di-(2-chloroethyl) phosphoryl derivatives of various esterases found in sheep. It is suggested that the instability of the cholinesterase derivative is the reason-for the low toxicity of these compounds to mammals, when compared with their diethyl analogues. The corresponding ali-esterase derivatives are also unstable, so that inhibition of these enzymes is only temporary.The rate of hydrolysis of the di-(2-chloroethyl) aryl phosphates by plasma has been shown to be much greater in some sheep than in others. This difference of activity is demonstrated as being genetically determined, and due to the presence or absence of a dominant allele, the sheep of low hydrolytic ability being the homozygous recessives. The rapid hydrolysis of di-(2-chloroethyl) aryl phosphates found in some samples of sheep plasma protects the animals from the ataxia syndrome which sometimes results when large doses (> 150 mg/kg) of these compounds are given.

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