Dose-response modeling for developmental neurotoxicity data

The fact that maternal exposures to some chemicals during pregnancy can adv ersely affect the structure and function of the nervous system in the offsp ring is well established. Government agencies have for a long time been con cerned with regulation of developmental neurotoxicants and safe perinatal e xposures. However, despite this concern, current guidelines provide only br oad and nonspecific recommendations and lack clear directions for a model b ased approach to risk estimation. In this paper we propose a dose-response model for the nonquantal data obtained from developmental neurotoxicologica l experiments. To account for the critical issue of the correlation among r esponses from pups in the same litter, the so called intralitter correlatio n, a hierarchical distributional structure is used to derive the underlying unconditional distribution of responses. The maximum likelihood method is used to estimate model parameters and the covariance matrix of the estimate s is derived. An example is used to illustrate the results.