Toxicity endpoints also neurotoxicity

A critique of this issue is beyond the scope of this book but not irrelevant to its goals. It is valid and useful to ask whether class-stratified lead exposures in ancient cultures and societies defined macroscale dose—population responses for toxic endpoints and to define such endpoints at the higher end of the entire dose—response spectrum. Lead-associated impairments of function at executive and other levels would be consistent with, if not the sole basis of, the political and anthropological histories of the Imperial era. One can also argue that even a contributory role for lead reproductive and other systemic toxicity as a risk factor in the survival of lead-exposed populations merits consideration. At minimum, lead would be a serious risk factor for multiple reproductive, developmental neurotoxic, immunotoxic, and endocrinological effects. 

Additionally, there are specialized studies designed to address endpoints of concern for almost all drugs (carcinogenicity, reproductive or developmental toxicity) or concerns specific to a compound or family of compounds (local irritation, neurotoxicity, or immunotoxicity, for example). When these are done, timing also requires careful consideration. It must always be kept in mind that the intention is to ensure the safety of people in whom the drug is to be evaluated (clinical trials) or used therapeutically. An understanding of special concerns for both populations should be considered essential. 

Repeat-dose neurotoxicity studies may identify behavioral effects or impaired nerve functions that can interfere with mating or maternal care. Developmental neurotoxicity studies have been conducted for specific pesticide classes, following requirements of US-EPA. If such a study is available it can be examined not only for the study-specific endpoints on the developing brain but also compared to the prenatal toxicity study and the two-generation smdy with respect to general endpoints of pre- and postnatal development, respectively. 

Phycotoxins, also named shellfish toxins, are produced by free-living micro-algae upon which the shellfish feed. The toxins are concentrated in the shellfish, which act as a vector transferring the toxic compounds to the food chain. Control of the presence of these toxins in food is required as they can cause neurotoxic, diarrhetic, paralytic, or amnesic poisoning. LC methods with fluorescence detection are now available for the determination of some of these compounds, such as domoic acid, saxitoxins, okadaic acid, and ciguatoxins. Also, an enzyme inhibition assay has been described for the determination of okadaic acid in mussels using fluorescent endpoint detection. 

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