Advance Access publication September 23, 2009 Estimates of Cancer Potency of 2,3,7,8-Tetrachlorodibenzo(p)dioxin Using Linear and Nonlinear Dose-Response Modeling and

Linear and nonlinear toxicity criteria were derived for 2,3,7,8-tetrachlorodibenzo(p)dioxin (TCDD) using the recent National Toxicology Program rat cancer bioassay. Dose-response relation-ships were assessed for combined liver tumors based on lifetime average liver concentrations (LALCs) estimated with a toxicokinetic model. Rat LALCestimates at the 1%point of departure (POD)were obtained with benchmark dose (BMD) modeling to yield the BMD01 in terms of LALC. The same toxicokinetic model was used to back-extrapolate the human-equivalent external dose (HED). A linear cancer slope factor (CSF)with a value of 13 1024 per pg/kg/day was calculated as the ratio between the benchmark response rate and the HEDat the lower confidence limit of the benchmark dose (BMDL)01. A nonlinear reference dose (RfD) with a value of 100 pg/kg/day was developed from the BMD01 value by applying uncertainty factors to rat internal and human external doses. The RfD was 100 time