title: Preliminary studies on model development for rodent toxicity and its interspecies correlation with aquatic toxicities of pharmaceuticals.
abstract: Environmental toxicity due to pharmaceuticals has been an issue of serious concern for long time. Development of chemometric models with reliable predictive power has been considered as an effective tool for the design of new drug agents with reduced or without ecotoxic potential. Considering a higher degree of similarity in genetic homology towards drug receptor with mammals, we have used a dataset of 194 compounds with reported rodent, fish, daphnia and algae toxicity data for extrapolation of their toxicity towards humans. Allowing for rodents as the most surrogate to human physiology, attempts have also been made to develop interspecies correlation models keeping rodent toxicity as dependent variable so that any drug without reported rodent toxicity can be predicted using fish, daphnia or algae toxicity data which can be consequently extrapolated to human toxicity. The developed models have been subjected to multiple validation strategies. Acceptable results have been obtained in both cases of direct and interspecies extrapolation quantitative structure-activity relationship models.
authors.affiliation: Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur Univeristy, Kolkata, 700 032, India.
authors.forename: Rudra Narayan
authors.initials: RN
authors.lastname: Das
authors.forename: Hans
authors.initials: H
authors.lastname: Sanderson
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Mwambo
authors.forename: Kunal
authors.initials: K
authors.lastname: Roy
mesh_terms: D000818:Animals; D000460:Chlorophyta / Q000187:drug effects / Q000254:growth & development; D003621:Daphnia / Q000187:drug effects / Q000254:growth & development; D064420:Drug-Related Side Effects and Adverse Reactions; D005399:Fishes / Q000254:growth & development; D007928:Lethal Dose 50; D051379:Mice; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D013045:Species Specificity; D014874:Water Pollutants, Chemical / Q000737:chemistry* / Q000633:toxicity*
chemical_list: D004364:Pharmaceutical Preparations; D014874:Water Pollutants, Chemical