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A Biologically‐Based Dose—Response Model for Developmental Toxicology

Author

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  • Brian G. Leroux
  • Wendy M. Leisenring
  • Suresh H. Moolgavkar
  • Elaine M. Faustman

Abstract

The methods currently used to evaluate the risk of developmental defects in humans from exposure to potential toxic agents do not reflect biological processes in extrapolating estimated risks to low doses and from test species to humans. We develop a mathematical model to describe aspects of the dynamic process of organogenesis, based on branching process models of cell kinetics. The biological information that can be incorporated into the model includes timing and rates of dynamic cell processes such as differentiation, migration, growth, and replication. The dose‐response models produced can explain patterns of malformation rates as a function of both dose and time of exposure, resulting in improvements in risk assessment and understanding of the underlying mechanistic processes. To illustrate the use of the model, we apply it to the prediction of the effects of methylmercury on brain development in rats.

Suggested Citation

  • Brian G. Leroux & Wendy M. Leisenring & Suresh H. Moolgavkar & Elaine M. Faustman, 1996. "A Biologically‐Based Dose—Response Model for Developmental Toxicology," Risk Analysis, John Wiley & Sons, vol. 16(4), pages 449-458, August.
    • Handle: RePEc:wly:riskan:v:16:y:1996:i:4:p:449-458
    DOI: 10.1111/j.1539-6924.1996.tb01092.x
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    References listed on IDEAS

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    1. Gregory J. Carr & Christopher J. Portier, 1991. "An Evaluation of the Rai and Van Ryzin Dose‐Response Model in Teratology," Risk Analysis, John Wiley & Sons, vol. 11(1), pages 111-120, March.
    2. Carole A. Kimmel & David W. Gaylor, 1988. "Issues in Qualitative and Quantitative Risk Analysis for Developmental Toxicology," Risk Analysis, John Wiley & Sons, vol. 8(1), pages 15-20, March.
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    Cited by:

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