Computer analysis of toxicological data bases: Mutagenicity of aromatic amines in Salmonella tester strains

Abstract

There is an increasing problem in the world of toxicological evaluation in that, while test results of new compounds are appearing regularly, traditional methods of analysis of such data are cumbersome and slow. The new computer program CASE (computer automated structure evaluator) was designed to handle just such problems. It analyzes molecules and their associated biological activity on the basis of structural fragments found and identified by the program as being important for the activity based on statistical tests of significance. The program was used to examine mutagenicity in Salmonella typhimurium strains TA98 and TA100 (with S9 activation) of approximately 80-100 aromatic amines. The resulting structural features were then used in a predictive fashion to test the expected mutagenic properties of a smaller set of about 20 compounds.

Use of Computers in Toxicology and Chemical Design

“…CASE was developed by Klopman at Case Western Reserve University during the 1980s (23)(24)(25)(26)(27)(28) and is a statistical analysis method closely related to those already described. This program, shown schematically in Figure 2 is based upon statistical analysis of a database and as such as similar to TOPKAT.…”

Perspectives on testing for toxic agents.

“…This would suggest the consideration of a deliberate set of studies in which mathematical and computer approaches (14)(15)(16) There are currently in toxicology some simplifications which, although perhaps useful, do not instill immediate confidence that they produce accurate results. One is the relationship between toxicity and carcinogenicity (17).…”

Invited contribution: An objective approach to the development of short-term tests predictive of carcinogenicity

“…In the last several years we have been concerned with the development of procedures for accomplishing these goals. This work has resulted in the development of two independent, but complementary, computer-based methodologies: CPBS Tua, the Carcinogen Prediction and Battery Selection method , and CASE, the Computer-Automated Structure Evaluation method Frierson et al, 1986;Klopman et al, 1985). In the present report we illustrate the applicability of CPBS to the prediction of the carcinogenicity of benzo[a]pyrene (B[a]P) and benzoin, a carcinogen and non-carcinogen, respectively (Purchase et al, 1981;IARC, 1973IARC, , 1983.…”