Assessment of developmental toxicity potential of chemicals by quantitative structure-toxicity relationship models.
Statistically significant quantitative structure-toxicity relationship (QSTR) models have been developed for assessing developmental toxicity potential (DTP) of chemicals. Three submodels, one each for aliphatic, heteroaromatic and carboaromatic compounds, have been cross-validated to ascertain their robustness. The specificities of the models range from 86% to 97%, and their sensitivities between 86% and 89%. For convenient computer-assisted application, the models are installed in a toxicity assessment software package, TOPKAT, which has been recently enhanced with algorithms to identify whether or not a query structure is inside the optimum prediction space (OPS) of a QSTR model. Different functionalities of the TOPKAT program have been explained by assessing the DTP of a number of compounds not used in the model training sets. The DTP of 18 existing drugs was assessed using these models; the DT assay results were available for 5 of these. Three of these 5 molecules were identified to be inside the OPS and their TOPKAT assessment matched their experimental assignment.
Gombar
V K
VK
Health Designs, Inc., Rochester, NY 14604, USA.
Enslein
K
K
Blake
B W
BW
D000465:Algorithms; D000818:Animals; D001555:Benzene Derivatives / Q000737:chemistry / Q000633:toxicity*; D001681:Biological Assay; D003198:Computer Simulation; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D006256:Hazardous Waste / Q000009:adverse effects*; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D006838:Hydrocarbons / Q000737:chemistry / Q000633:toxicity*; D008956:Models, Chemical; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012016:Reference Values; D013329:Structure-Activity Relationship
D001555:Benzene Derivatives; D006256:Hazardous Waste; D006571:Heterocyclic Compounds; D006838:Hydrocarbons