Quantitative structure-activity relationships for human health effects: commonalities with other endpoints.
This article describes the use of quantitative structure-activity relationships (QSARs) to predict toxicity endpoints for ecologically relevant and human-surrogate species. The interrelationships between the endpoints, and the possibilities of exploring the commonalities of chemical action from one species to another as well as from one endpoint to another, are evaluated. A number of toxic endpoints are discussed including mutagenicity and carcinogenicity; developmental toxicity (teratogenicity); acute toxicity; skin sensitization; skin, eye, and sensory irritation; and the modeling of membrane permeability. A number of electrophilic molecular substructures have been identified that are common to a number of toxicities. It is postulated that if such a substructure is observed in a molecule, it may exhibit a range of toxicities. Further, there appear to be relationships between the toxicity to ecologically relevant and human-surrogate species, which may allow for appreciation and possible extrapolation in both directions. Overall, however, QSARs are limited by the paucity of available toxicological data and information.
Cronin
Mark T D
MT
School of Pharmacy and Chemistry, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, United Kingdom. m.t.cronin@livjm.ac.uk
Dearden
John C
JC
Walker
John D
JD
Worth
Andrew P
AP
D000818:Animals; D004463:Ecology; D023381:Endpoint Determination; D004785:Environmental Pollutants / Q000633:toxicity*; D005544:Forecasting; D023421:Models, Animal; D008962:Models, Theoretical; D011634:Public Health; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D018675:Toxicity Tests / Q000379:methods*
D004785:Environmental Pollutants