Marilyn S. Arnott
Mechanism-Based Prediction of Carcinogenic Potential of Chemicals: The OncoLogic®Approach
LogiChem Inc., P.O. Box 357, Boyertown, PA 19512, USA. Tel:(610)367-1636, Fax: (610)367-1893, Email: marnott@logichem.com
OncoLogic® is a rule-based expert system that is used to predict the carcinogenic potential of chemicals. Developed in cooperation with the carcinogenesis experts on the U.S. EPA's Structure-Activity Team (SAT), the system models the mechanism-based decision-making approach that has been used to evaluate the hazard potential of nearly 30,000 chemicals. The human experts typically use SAR analysis and consider all available biological data as well. To model this, OncoLogic® contains both SAR analysis and biological data interpretation capabilities. An evaluation produces one of six levels of conern ranging from Low to High, to give a semi-quantitative assessment of carcinogenic potential. In addition to the concern level, OncoLogic® generates the line of reasoning that was used to arrive at that level, briefly explaining the scientific rationale.
The SAR analysis permits the user to evaluate a wide variety of chemicals, including fibers, polymers, metals and metal-containing compounds, in addition to approximately fifty classes of organic chemicals. The chemical class-specific approach allows the evaluations to be based on appropriate mechanisms of action. Among the characteristics considered are physicochemical properties, route of exposure, metabolic activation and detoxification, and structural features of potential electrophilic or receptor-mediated activity. The underlying principle is to identify structural features that may contribute to carcinogenic activity, and then evaluate the modifying roles of the rest of the molecule.
The functional analysis provides a mechanistic approach to integrate the results of short-term tests and noncancer toxicity observations. The tests and toxicities are organized according to their most probable contributions to the initiation, promotion and progression stages of carcinogenesis. Each test is assigned a score based on the weight of evidence, which may include considerations of lowest effective dose, severity of response, and in vivo vs. in vitro observations. The biologically-based level of concern may be used to complement or modify the level derived from SAR analysis, or may be used to evaluate the carcinogenic potential of chemicals for which no SAR analysis is available.
(Although this work was supported by the U.S. EPA, this does not constitute an official endorsement of the product.)
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