ENVIRONMENTAL RISK ASSESSMENT MODEL FOR LOW-DOSE EXTRAPOLATION

Use of experimental data from animal studies to estimate human risk due to long-term exposure to very low doses of chemicals in the environment poses a number of biological and statistical problems. One of the statistical problems is to extrapolate the animal dose-response relation from the high dose levels where data are available to low dose, which humans might encounter. Here, a quantal dose-response model is developed based on a multi-hit theory of toxic response. The development of the model utilizes a weighted Lagrange-Poisson distribution for the number of hits. When spontaneous background toxic response is included, the model involves three unknown parameters. The maximum likelihood estimators for these parameters are given as the solution of a nonlinear iterative algorithm. The use of this model for low-dose extrapolation is indicated. The results are applied to nine sets of toxic response data.