Evaluation and interpretation of maternal toxicity in Segment II studies: Issues, some answers, and data needs

John M. Rogers, Neil Chernoff, Carl L Keen, George P. Daston

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Biologically rational regulatory policies with regards to developmental toxicity are often based on the extrapolation of standard laboratory rodent bioassay results to the human population. Significantly contributing to the difficulty of this task is the possibility that general toxic effects on the maternal organism may affect the developing conceptus. This review examines maternal factors which may bear directly or indirectly upon developmental outcome, with emphasis on those of greatest relevance to the hazard assessment process. Standard teratology testing protocols call for top dosage levels that induce overt maternal toxicity, and the developmental effects of this toxicity (both alone, and with concurrent embryo/fetal insult) continue to present regulators with considerable interpretive difficulties. In response to these problems, there have been both research and literature review efforts dealing with the relationship of maternal and developmental toxicity. Maternally mediated developmental toxicity occurs with a number of agents, and toxicant-induced alterations in maternal physiology may affect the conceptus at dosages not causing overt maternal toxicity. Relevant studies are reviewed here, and suggestions for avenues of future research are offered including the identification of any syndromes of developmental effects occurring at maternally toxic levels irrespective of the causative agent, and experimental approaches for the characterization of maternal toxicity.

Original languageEnglish (US)
JournalToxicology and Applied Pharmacology
Volume207
Issue number2 SUPPL.
DOIs
StatePublished - Sep 1 2005

Keywords

  • Fetal toxicity
  • Hazard evaluation
  • Maternal stress
  • Maternal toxicity
  • Teratology

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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