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A quantitative structure-activity relationship (QSAR) model has been developed to estimate maximum tolerated doses (MTD) from structural features of chemicals and the corresponding oral acute lethal doses (LD50) as determined in male rats. The model is based on a set of 269 diverse chemicals which have been tested under the National Cancer Institute/National Toxicology Program (NCI/NTP) protocols. The rat oral LD50 value was the strongest predictor. Additionally, 22 structural descriptors comprising nine substructural MOLSTAC(c) keys, three molecular connectivity indices, and sigma charges on 10 molecular fragments were identified as endpoint predictors. The model explains 76% of the variance and is significant (F = 35.7) at p less than 0.0001 with a standard error of the estimate of 0.40 in the log (1/mol) units used in Hansch-type equations. Cross-validation showed that the difference between the average deleted residual square (0.179) and the model residual square (0.160) was not significant (t = 0.98).

Four related QSAR models of teratogenesis in experimental animals have been developed: one each for heteroaromatic, carboaromatic, alicyclic and acyclic compounds. The numbers of compounds in these models range from 40 (for the alicyclic model) to 144 (for the carboaromatic model). As determined by cross‐validation using the leave‐one‐out, or jackknife, technique, the accuracy of the models in discriminating between teratogens and non‐teratogens ranges from 92.4% to 96%. A single overall assessment of experimental teratogenesis was chosen as the biological endpoint; taking into account such factors as dosage, maternal toxicity, and affected organ systems remain to be subjects of further studies.

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