Estimation of maximum tolerated dose for long-term bioassays from acute lethal dose and structure by QSAR

Journal Article · Sun Sep 01 00:00:00 EDT 1991 · Risk Analysis; (United States)

DOI:https://doi.org/10.1111/j.1539-6924.1991.tb00636.x· OSTI ID:6097349

Gombar, V K; Enslein, K; Hart, J B; Blake, B W; Borgstedt, H H

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).

• OSTI ID: 6097349
• Journal Information: Risk Analysis; (United States), Vol. 11:3, Issue 3; ISSN 0272-4332
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
STRUCTURE-ACTIVITY RELATIONSHIPS
MATHEMATICAL MODELS
XENOBIOTICS
CARCINOGENS
MAXIMUM PERMISSIBLE EXPOSURE
ORAL ADMINISTRATION
RATS
ANIMALS
MAMMALS
RODENTS
SAFETY STANDARDS
STANDARDS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology