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Maternally Mediated Developmental Toxicity
Citation:
Rogers, J. Maternally Mediated Developmental Toxicity. Chapter 5, Charlene McQueen (ed.), Comprehensive Toxicology 3rd Edition. ELSEVIER, AMSTERDAM, Holland, , 86-99, (2018).
Impact/Purpose:
The current practice for the assessment of an agent’s potential effects on the developing embryo/fetus includes administration of high, maternally toxic doses to pregnant laboratory animals. For most agents evaluated, developmental effects occur concomitant with maternal toxicity, raising the question as to whether or not the developmental effects are secondary to maternal toxicity. This chapter reviews current knowledge on the relationship between specific manifestations of maternal toxicity and their resulting impact on the developing embryo or fetus.
Description:
The current practice for the assessment of an agent’s potential effects on the developing embryo/fetus includes administration of high, maternally toxic doses to pregnant laboratory animals. For most agents evaluated, developmental effects occur concomitant with maternal toxicity, raising the question as to whether or not the developmental effects are secondary to maternal toxicity. This chapter reviews current knowledge on the relationship between specific manifestations of maternal toxicity and their resulting impact on the developing embryo or fetus. Departing from past approaches that have tended to be more phenomenological in nature, the approach taken here is to delve into the physiology of maternal toxicity by characterizing the key stressors presented to the conceptus, and then assessing the conceptus’s ability to cope with such changes. The severity of the maternal effect and its timing during pregnancy are discussed as critical determinants of maternally mediated development toxicity. The chapter closes with some guidance and examples for interpreting data relevant to the maternal toxicity–developmental toxicity relationship, and outlines some newer concepts related to selection of doses for testing.
