A generalized multihit dose-response model for low-dose extrapolation

Kamta Rai, John Van Ryzin

Expert InsightsPublished 1979

A quantal dose-response model based on a multihit theory of toxic response is presented. The model when spontaneous background toxic response is allowed involves three unknown parameters. The maximum likelihood equation estimators for these three parameters are given as the solution of a nonlinear iterative algorithm. The resulting three dimensional vector of estimators is shown to be asymptotically strongly consistent, asymptotically unique with probability one, and, when suitably normalized, it has asymptotically a trivariate normal distribution. Using these results, a large sample goodness-of-fit test is given. The use of this model for low-dose extrapolation is indicated. Application of the results is illustrated on three sets of toxicity data.

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Rai, Kamta and John Van Ryzin, A generalized multihit dose-response model for low-dose extrapolation. Santa Monica, CA: RAND Corporation, 1979. https://www.rand.org/pubs/papers/P6305.html.
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