Dose-response modeling for developmental neurotoxicity data

The fact that maternal exposures to some chemicals during pregnancy can adversely affect the structure and function of the nervous system in the offspring is well established. Government agencies have for a long time been concerned with regulation of developmental neurotoxicants and safe perinatal exposures. However, despite this concern, current guidelines provide only broad and nonspecific recommendations and lack clear directions for a model based approach to risk estimation. In this paper we propose a dose-response model for the nonquantal data obtained from developmental neurotoxicological experiments. To account for the critical issue of the correlation among responses from pups in the same litter, the so called intralitter correlation, 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 estimates is derived. An example is used to illustrate the results.