Second Chronological Supplement to the Carcinogenic Potency Database: Standardized Results of Animal Bioassays Published through December 1984 and by the National Toxicology Program through May 1986

Abstract

This paper is the second chronological supplement to the Carcinogenic Potency Database, published earlier in this journal (1,2,4). We report here results of carcinogenesis bioassays published in the general literature between January 1983 and December 1984, and in Technical Reports of the National Cancer Institute/National Toxicology Program between January 1983 and May 1986. This supplement includes results of 525 long-term, chronic experiments of 199 test compounds, and reports the same information about each experiment in the same plot format as the earlier papers: e.g., the species and strain of test animal, the route and duration of compound administration, dose level and other aspects of experimental protocol, histopathology and tumor incidence, TD50 (carcinogenic potency) and its statistical significance, dose response, author's opinion about carcinogenicity, and literature citation. We refer the reader to the 1984 publications for a description of the numerical index of carcinogenic potency (TD50), a guide to the plot of the database, and a discussion of the sources of data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. The three plots of the database are to be used together, since results of experiments published in earlier plots are not repeated. Taken together, the three plots include results for more than 3500 experiments on 975 chemicals. Appendix 14 is an index to all chemicals in the database and indicates which plot(s) each chemical appears in.

Structure-activity relations: maximizing the usefulness of mutagenicity and carcinogenicity databases.

“…We have performed analyses ofa number ofdifferent rodent carcinogenicity databases including the NTP rodent bioassay (9,10) and the compilation of Gold and associates (21)(22)(23) which includes TD50 values. Analyzing these databases allowed us to identify the structural features responsible for the probability of carcinogenicity (i.e., the qualitative aspect of the analysis).…”

“…Applying the QSAR CASE analysis to the database assembled by Gold et al (21)(22)(23), which includes TD50 values, indicated that the data could be used to generate QSAR relationships for individual databases (i.e., mouse and rat separately) which, in turn, can be used to project carcinogenic potencies based upon the QSAR contribution of individual biophores (Table 11). [The TD50 value is defined as the lifetime dose (milligrams per kilogram per day) that reduces by one-half the lifetime chance of remaining tumor-free (24).…”

A dichotomy in the lipophilicity of natural estrogens, xenoestrogens, and phytoestrogens.

“…This descriptor (biophore) was originally recognized during structureactivity relationship (SAR) studies of diethylstilbestrol (2) and tamoxifen and toremifene (3), using the SAR expert systems computer automated structure evaluator (CASE) and multiple case (MULTICASE). This biophore was derived from the CASE/MULTICASE learning set of murine carcinogens (4)(5)(6)(7)(8). Based on its presence in carcinogenic estrogens, we suggested that the 2D biophore represented a ligand binding site on an estrogen receptor (1).…”

Prediction of the carcinogenicity of a second group of organic chemicals undergoing carcinogenicity testing.

“…In addition to molecular fragments, MULTICASE considers two-dimensional distance descriptors. Compounds (6) and the CPDB data assembled by Gold and associates (7)(8)(9)(10)(11) …”