Quantitative structure–activity–activity and quantitative structure–activity investigations of human and rodent toxicity

Acute toxicity in different biological systems, including humans and rodents in vivo, and human and rodent cell lines in vitro, was investigated. The data were taken from the MEIC (Multicentre Evaluation of In Vitro Cytotoxicity) programme. Quantitative structure–activity–activity relationship (QSAAR) models were developed for the in vivo human and rodent toxicity including a combination of toxicity endpoint and structural descriptors as predictor variables. The human peak blood/serum LC50 concentrations were most strongly related to human liver cell toxicity, while the in vivo oral human lethal doses were most closely related to the in vivo rodent LD50 values. The QSAARs included structural descriptors encoding electronic/reactivity properties, presence of H-bond donors, compound aromaticity, and size/shape properties. Quantitative structure–activity relationships (QSARs) were derived by using structural descriptors accounting for molecular hydrophobicity, size and shape, and electronic properties. These models have the potential to provide useful insights in the development of non-animal (in vitro and in silico) methods for predicting human and mammalian toxicity.