Comparison of chronic toxicity and carcinogenicity of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) in 2‐year bioassays in female Sprague‐Dawley rats

Abstract

The cancer bioassay for 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) conducted by the Dow Chemical company in the mid 70s has been used extensively for conducting quantitative cancer risk assessments for human exposure to TCDD. More recently the National Toxicology Program (NTP) conducted a cancer bioassay of similar design as part of its evaluation of the dioxin toxic equivalency factor methodology. This report compares the design and the results of these two cancer bioassays. This comparison confirms, in most cases, previously published and widely used carcinogenic response characteristics with respect to dose, time course, organ selectivity, tumor type and maximum intensity of TCDD‐induced carcinogenicity and toxicity in the Sprague‐Dawley rat. Specifically, increases in the incidences of neoplasms were seen in both studies in the liver, lung and oral mucosa. The most notable difference was the significant increase in the incidence of cholangiocarcinoma of the liver seen in the NTP study but not in the Dow study. The experimental designs for the two studies are similar but some protocol parameters differed, such as vehicle, dosing schedule, diet and rat sub‐strain utilized. Differences in the shapes of the dose response curves for several neoplasms were noted between the studies, with the NTP study showing non‐linearity for all neoplasms. This may result from differences in the experimental protocols as well as divergence in the biological behavior of the different stocks of Sprague‐Dawley rat strains used.