Developmental toxicants general mechanisms

TABLE 34.2. General Mechanisms and Pathogenesis of Developmental Toxicants... 

A.7.2.3.5 If appropriate information is available it is important to try to determine whether developmental toxicity is due to a specific maternally mediated mechanism or to a non-specific secondary mechanism, like maternal stress and the disruption of homeostasis. Generally, the presence of maternal toxicity should not be used to negate findings of embryo/fetal effects, unless it can be clearly demonstrated that the effects are secondary nonspecific effects. This is especially the case when the effects in the offspring are significant, e.g., irreversible effects such as structural malformations. In some situations it is reasonable to assume that reproductive toxicity is due to a secondary consequence of maternal toxicity and discount the effects, for example if the chemical is so toxic that dams fail to thrive and there is severe inanition they are incapable of nursing pups or they are prostrate or dying. 

The mechanisms of Pb developmental neurotoxicity in particular and multisystem toxicity in general are likely multiple. To date, no global, single mechanism explaining the element s toxicity, and particularly its neurotoxicity, has emerged. Rather, organ- and system-specific effects appear to be linked to specific mechanisms. In the case of neurotoxic effects, and aU other effects in general, studies have typically focused on processes at the subcel-lular and biomolecular level to explain whole-animal results. The focus of... 

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