Chronic toxic effects teratogenesis

It is important to note at the outset that several of the chronic toxic effects of concern, such as carcinogenesis, mutagenesis, and teratogenesis, differ in a fundamental way from acute toxic effects since their pathological endpoints are detectable only after the proliferation of a population of cells which are derived from the target cells. These self replicating chronic effects may differ... 

A review of reproductive and developmental toxicity studies of methyl salicylate indicated that, under conditions of sufficient exposure, there is a pattern of embryotoxicity and teratogenesis that is similar to that caused by comparable doses of salicylic acid. The abnormalities included neural tube defects and malformations of the skeleton and viscera. Studies of orally administered methyl salicylate indicated that the no-observed-adverse-effect level (NOAEL) for reproductive toxicity is 75-100 mg/kg daily, which is a level consistent with data from subchronic and chronic toxicity studies and is also consistent with the reproductive NOAEL for salicylic acid, which has been reported as 80 mg/kg daily (Belsito et al. 2007). 

In 1977, the NAS Safe Drinking Water Committee outlined four principles that it said should be useful in dealing with the assessment of hazards that involve chronic irreversible toxicity or the effects of longterm exposure (20). These principles (paraphrased as follows) were intended to apply primarily to cancer risks from substances whose mechanisms involve somatic mutations and may also be applicable to mutagenesis and teratogenesis ... 

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