The specific objectives of this investigation is to evaluate the prechronic and chronic toxicity and carcinogenicity of emodin in Fischer-344 rats and B6C3F1 mice. The following studies will be performed: Fourteen-Day Repeated-Dose Prechronic Toxicity Study: This study will characterize the toxicity associated with dietary exposure to emodin including the identification of target organs, determination of a no-effect level (if feasible), differences in sensitivity between sexes and species, and the slope of the dose-response curve. Thirteen-Week (90-Day) Subchronic Study: In addition to obtaining toxicological data as described under the 14-day repeated-dose toxicity study, this study will also help to determine the doses for each strain and species in the chronic 2-year toxicity study. This investigation includes necropsy and histopathologic evaluations, preparation of unstained blood smears (for use by the NTP in micronuleic determinations) and determination of blood concentrations of emodin in experimental animals. Two-Year Chronic Study: The two-year study will evaluate the chronic toxicity and carcinogenicity of emodin administered to male and female F344 rats and. B6C3F1 mice. All moribund animals, as well as those that survive to the end of the study, will receive a complete gross examination. All grossly visible lesions and all tissues with non-neoplastic or neoplastic lesions will receive a complete histopathologic examination.
