Recommendation 2. The committee recommends that it is important to study how the new information about development and developmental toxicity can address the uncertainties in quantitative and qualitative risk assessment.

  • Qualitative: Testing a larger variety of chemicals and chemical mixtures.

  • Qualitative: Assessing toxicant effects across all stages of development.

  • Quantitative: Toxicokinetic differences of test animals and humans should be characterized in order to improve extrapolations.

  • Quantitative: Toxicodynamic differences of test animals and humans should be characterized to improve extrapolations.

  • Quantitative: Low-dose effects of toxicants and chemical mixtures should be better detected and characterized.

    • Low-dose cellular responses as reflected in molecular-stress and checkpoint pathways.

    • Genetically sensitized animals should be tested for low-dose toxicant effects.

  • Quantitative: Modeling the extrapolation from test animals to humans

Recommendation 3. To improve the interdisciplinary advances in developmental toxicology, the committee recommends that the databases of developmental toxicology, developmental biology, and genomics be better linked on the Internet, and that multidisciplinary outreach programs be established for the effective exchange of information and techniques related to the analysis of developmental defects and to the assessment of toxicity for risk assessment.

  • Development of cross-disciplinary, linked databases of relevance for developmental toxicity.

  • Enhancement of multidisciplinary research interactions.

entiation, and transcription. The components of signaling pathways and genetic regulatory circuits are key components to investigate. Further arguments for emphasizing these components as potential targets are the following:

  • When signaling is interrupted in mutant animals, development is affected, with specific effects depending on the component that is inactivated.

  • A few toxicants currently are known to affect signaling in mammals, such as cyclopamine (the Hedgehog signaling pathway; Chapter 4), retinoic acid and its many derivatives (the nuclear hormone signaling pathway and transcriptional

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