Toxicity factor, susceptibility

Hurst (19) discusses the similarity in action of the pyrethrins and of DDT as indicated by a dispersant action on the lipids of insect cuticle and internal tissue. He has developed an elaborate theory of contact insecticidal action but provides no experimental data. Hurst believes that the susceptibility to insecticides depends partially on the cuticular permeability, but more fundamentally on the effects on internal tissue receptors which control oxidative metabolism or oxidative enzyme systems. The access of pyrethrins to insects, for example, is facilitated by adsorption and storage in the lipophilic layers of the epicuticle. The epicuticle is to be regarded as a lipoprotein mosaic consisting of alternating patches of lipid and protein receptors which are sites of oxidase activity. Such a condition exists in both the hydrophilic type of cuticle found in larvae of Calliphora and Phormia and in the waxy cuticle of Tenebrio larvae. Hurst explains pyrethrinization as a preliminary narcosis or knockdown phase in which oxidase action is blocked by adsorption of the insecticide on the lipoprotein tissue components, followed by death when further dispersant action of the insecticide results in an irreversible increase in the phenoloxidase activity as a result of the displacement of protective lipids. This increase in phenoloxidase activity is accompanied by the accumulation of toxic quinoid metabolites in the blood and tissues—for example, O-quinones which would block substrate access to normal enzyme systems. The varying degrees of susceptibility shown by different insect species to an insecticide may be explainable not only in terms of differences in cuticle make-up but also as internal factors associated with the stability of oxidase systems. 

Unusually susceptible populations are those groups of individuals who respond more quickly or at lower exposure levels than the general population to the toxic effects of methyl parathion. These responses may be genetic in origin or may be due to differences in development or life style factors such as nutrition or behavior, or due to preexisting disease states. 

Nelson LM Stanford University, Stanford, CA Investigate the role of environmental toxicants and genetic susceptibility factors in the etiology of ALS National Institute of Environmental Health Sciences... 

Native Americans may be more susceptible to MCS because of a P450 enzyme deficiency this enzyme is needed to break down toxic chemicals in the body. Another factor that contributes to poor health in Indian communities is that more toxic wastes are dumped on reservations than anywhere else in the United States. 

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