Quantitative cancer risk assessments for 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD)

Abstract

State-of-the-art quantitative risk assessment techniques, including consideration of new time-to-response data, have been applied to chronic animal bioassay data on the dietary intake of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD). The non-linear shapes of the dose-response relationships for the hepatocellular carcinogenic responses have been estimated, and a review of the quantitative impacts of several of the choices involved in the quantitative risk assessment considers, particularly, the definition of the carcinogenic responses of concern, the experimental data set, the pathology evaluation, a biologically effective dose scale versus the administered dose, methods of making the fitted model responsive to the data at the lower experimental doses, consistency in dose-response shapes for different data sets, fitted model values versus bounds, the utilization of time-to-response information incorporating the lateness of the carcinogenic responses, and the method of characterizing the maximum acceptable dose. The estimated virtually safe dose for an increase of 0.000001 (one in a million) in the probability of hepatocellular neoplastic nodule and/or carcinoma in a female rat is approximately 0.1 ng/kg body weight/day in the diet. The estimated mean free dose, corresponding to a reduction in the expected amount of time without hepatocellular neoplastic nodule and/or carcinoma proportional to 1 wk in 70 yr, is in the range of 1–5 ng/kg body weight/day in the diet of a female rat. No species-to-species extrapolations nor human exposure assessments have been made. However, these estimated risks correspond to dietary intakes that are at least 150 times greater than the 0.0006365 ng/kg body weight/day intake described by the Centers for Disease Control as a reasonable level to begin consideration of action to limit human exposure.