Abstract

Environmental safety testing typically requires procedures for extrapolating from the relatively high experimental to the very low use doses of potentially harmful substances. In the present paper, a stochastic mammillary compartmental model for environmental safety testing is proposed and extrapolation procedures based on its dose-response relationship are developed. The proposed model is a direct generalization of one of the basic safety models, the one-hit model, in that a harmful reaction is assumed to occur if at any time any of the peripheral compartments attains a specified threshold of particles. Consideration of a closed model yields an upper bound on the probability of attaining a certain threshold level, thus providing a conservative procedure for extrapolating to a low dose, while a lower bound obtained from a related open model provides a useful monitoring device as to the sharpness of the upper, bound. The extrapolation procedure is illustrated with simulated data and approximations for initial values are developed.

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