Prediction of probability of carcinogenicity for a set of ongoing NTP bioassays

Enslein, Kurt; Blake, Benjamin W.; Borgstedt, Harold H.

doi:10.1093/mutage/5.4.305

Cited by 44 publications

(19 citation statements)

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“…Predictions using a wide variety of expert and computer-based systems were submitted, including predictions based on TOPKAT [Enslein et al, 1990]. Predictions for overall carcinogenicity, rather than for each particular animal model, were made for 28 of the NTP chemicals using the TOPKAT software available at that time.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the TOPKAT system for predicting the carcinogenicity of chemicals

Prival

2001

Environ. Mol. Mutagen.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the TOPKAT system for predicting the carcinogenicity of chemicals

Prival

2001

Environ. Mol. Mutagen.

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“…TOPKAT (Enslein et al, 1990) structural activity, physical properties, substructures 0.60 (6/10) 1 DEREK (Sanderson & Earnshaw, 1991) chemical substructures 0.50 (7/14) 2 COMPACT (Lewis et al, 1990) shape and molecular energy levels of chemical structures 0.53 (8/15) compared the predictions made by RL's rule set with those made by other computerized methods as well as those made by human experts. We also trained C4.5 on the same data using the same attributes RL used and made predictions with the decision tree for the same 24 chemicals.…”

Section: Discussionmentioning

confidence: 99%

Untitled

1998

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Abstract. In this paper, we report on a multi-year collaboration among computer scientists, toxicologists, chemists, and a statistician, in which the RL induction program was used to assist toxicologists in analyzing relationships among various features of chemical compounds and their carcinogenicity in rodents. Our investigation demonstrated the utility of knowledge-based rule induction in the problem of predicting rodent carcinogenicity and the place of rule induction in the overall process of discovery. Flexibility of the program in accepting different definitions of background knowledge and preferences was considered essential in this exploratory effort. This investigation has made significant contributions not only to predicting carcinogenicity and non-carcinogenicity in rodents, but to understanding how to extend a rule induction program into an exploratory data analysis tool.

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“…However, by careful dissection of the molecules into component parts, it is often possible to arrive at likely estimates of the toxicity. This is not the only system available for the prediction of carcinogenesis of compounds based principally on structural features (9,(21)(22)(23)(24), however, TOPKAT has the advantage of being compact enough to fit on a personal computer, and it is commercially available.…”

Section: Alternative Methods Of Evaluationmentioning

confidence: 99%

Risk and benefit evaluation in development of pharmaceutical products.

Aaron

Harbach

Mattano

et al. 1993

Environ Health Perspect

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Pharmaceutical products are intended to cure disease, reduce pain and suffering, prolong life, and correct metabolic deficits in patients. However, the potential patient population is intrinsically genetically heterogenous, and this factor complicates the evaluation of data on all aspects of safety evaluation of new drugs. Often the genetic heterogeneity is related to drug metabolizing capacity, but recent evidence suggests that heterogeniety in repair capacity as well as structural integrity of the chromatin (fragile X) have been shown to be relevant. Because drugs are biologically active and may have more than one type of effect, the evaluation of a large number of parameters is necessary in arriving at a rational estimate of potential risk. In this paper, several specific examples of risk assessments and some generic genotoxicity questions that are recurrent, including the question of the relevance of in vitro chromosomal aberration induction at high dose/sampling time, are raised. Other examples of the kinds of concerns from the safety evaluation of U-48753E, U-54461, and U-68,553B are discussed. The drug U-48753E was discovered to be slightly mutagenic in the AS52 assay, and significant efforts were expended in evaluation of the metabolism-based generation of a reactive intermediate. The drug U-54,461 was shown to be capable of breaking chromosomes in vitro but extensive in vivo data as well as a variety of other studies served to reduce the level of concern substantially. The induction of apparent chromosome breaks and gaps by U-68553B was shown to be an artifact that was restricted to a single cell line of rodent cells. These diverse examples of risk assessments illustrate the complexity of risk/benefit analysis in drug development.

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Prediction of probability of carcinogenicity for a set of ongoing NTP bioassays

Cited by 44 publications

References 0 publications

Evaluation of the TOPKAT system for predicting the carcinogenicity of chemicals

Evaluation of the TOPKAT system for predicting the carcinogenicity of chemicals

Untitled

Risk and benefit evaluation in development of pharmaceutical products.

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