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

Abstract

The most important criteria for the development and analysis of databases for elucidating the structural bases of toxicological activity include the integrity of the databases with respect to uniformity of the experimental protocol and interpretation ofthe test results and inclusion ofch cls representin different chemical classs and differingmechanisms of action. Within these criteria, it is de_mostrated that when the chemials are chosen at random, the larer the database, the better the pedictvity ofchemials not inlud in the learning sL It is shownhower, thatwhenchemicasare selected on the basis of structural features, that a learning set of approxmately 180 chemicals is as informative as a database consisting of 800 chemicals chosen at random.

Use of QSARs in international decision-making frameworks to predict health effects of chemical substances.

“…CASE methodology and all its variants were developed by Klopman and colleagues (Klopman 1992;Klopman and Rosenkranz 1991). There are a multitude of models for a variety of endpoints and hardware platforms [for more details, see MultiCASE Inc. (2002)].…”

The identification of toxicophores for the prediction of mutagenicity, hepatotoxicity and cardiotoxicity

“…With the help of MULTICASE, an artificial intelligence program capable of uncovering the relationship between the presence of specific substructures in a molecule and its toxicity, and TOX II, a program capable of identifying the existence of such substructures in new molecules, it is possible to predict whether a new molecule will be toxic. TOX II will uncover any functionality that was previously found to be associated with toxicity in any organic molecule [74][75][76][77][78][79][80]. The evaluation can also include automatically generated metabolites by use of the program META [74,75].…”

Use of QSARs in international decision-making frameworks to predict ecologic effects and environmental fate of chemical substances.

“…CASE methodology, and all its variants, has been developed by Klopman colleagues (Klopman 1992;Klopman and Rosenkranz 1991). There are a multitude of models available for a variety of endpoints and hardware platforms [more details are available from the manufacturer: MultiCASE Inc. (2002)].…”