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 (QSAA...

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Bibliographic Details
Published in:Chemosphere (Oxford) 2006-12, Vol.65 (10), p.1878-1887
Main Authors: Lessigiarska, Iglika, Worth, Andrew P., Netzeva, Tatiana I., Dearden, John C., Cronin, Mark T.D.
Format: Article
Language:English
Subjects:
Acute toxicity
Animal, plant and microbial ecology
Animals
Applied ecology
Biological and medical sciences
Cells, Cultured
Ecotoxicology, biological effects of pollution
Fundamental and applied biological sciences. Psychology
General aspects
Hepatocytes - drug effects
Human toxicity
Humans
Lethal Dose 50
Liver - drug effects
Mammalia
MEIC programme
Mice
QSAAR
QSAR
Quantitative Structure-Activity Relationship
Rats
Reproducibility of Results
Rodent toxicity
Species Specificity
Toxicity Tests - methods
Vertebrates: general zoology, morphology, phylogeny, systematics, cytogenetics, geographical distribution
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Summary: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 LC 50 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 LD 50 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.
ISSN:0045-6535
1879-1298
DOI:10.1016/j.chemosphere.2006.03.067