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Quantitative Risk Assessment for Developmental Neurotoxic Effects

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  • Mehdi Razzaghi
  • Ralph Kodell

Abstract

Developmental neurotoxicity concerns the adverse health effects of exogenous agents acting on neurodevelopment. Because human brain development is a delicate process involving many cellular events, the developing fetus is rather susceptible to compounds that can alter the structure and function of the brain. Today, there is clear evidence that early exposure to many neurotoxicants can severely damage the developing nervous system. Although in recent years, there has been much attention given to model development and risk assessment procedures for developmental toxicants, the area of developmental neurotoxicity has been largely ignored. Here, we consider the problem of risk estimation for developmental neurotoxicants from animal bioassay data. Since most responses from developmental neurotoxicity experiments are nonquantal in nature, an adverse health effect will be defined as a response that occurs with very small probability in unexposed animals. Using a two‐stage hierarchical normal dose‐response model, upper confidence limits on the excess risk due to a given level of added exposure are derived. Equivalently, the model is used to obtain lower confidence limits on dose for a small negligible level of risk. Our method is based on the asymptotic distribution of the likelihood ratio statistic (cf. Crump, 1995). An example is used to provide further illustration.

Suggested Citation

  • Mehdi Razzaghi & Ralph Kodell, 2004. "Quantitative Risk Assessment for Developmental Neurotoxic Effects," Risk Analysis, John Wiley & Sons, vol. 24(6), pages 1673-1681, December.
    • Handle: RePEc:wly:riskan:v:24:y:2004:i:6:p:1673-1681
    DOI: 10.1111/j.0272-4332.2004.00558.x
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    References listed on IDEAS

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    1. Kenny S. Crump, 1995. "Calculation of Benchmark Doses from Continuous Data," Risk Analysis, John Wiley & Sons, vol. 15(1), pages 79-89, February.
    2. Mehdi Razzaghi & Ralph L. Kodell, 2000. "Risk Assessment for Quantitative Responses Using a Mixture Model," Biometrics, The International Biometric Society, vol. 56(2), pages 519-527, June.
    3. Ralph L. Kodell & Richard B. Howe & James J. Chen & David W. Gaylor, 1991. "Mathematical Modeling of Reproductive and Developmental Toxic Effects for Quantitative Risk Assessment," Risk Analysis, John Wiley & Sons, vol. 11(4), pages 583-590, December.
    4. Ralph L. Kodell & Ronnie W. West, 1993. "Upper Confidence Limits on Excess Risk for Quantitative Responses," Risk Analysis, John Wiley & Sons, vol. 13(2), pages 177-182, April.
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    Cited by:

    1. Walter W. Piegorsch, 2010. "Translational benchmark risk analysis," Journal of Risk Research, Taylor & Francis Journals, vol. 13(5), pages 653-667, July.

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