title: Simulation of chemical metabolism for fate and hazard assessment. V. Mammalian hazard assessment.
abstract: Animals and humans are exposed to a wide array of xenobiotics and have developed complex enzymatic mechanisms to detoxify these chemicals. Detoxification pathways involve a number of biotransformations, such as oxidation, reduction, hydrolysis and conjugation reactions. The intermediate substances created during the detoxification process can be extremely toxic compared with the original toxins, hence metabolism should be accounted for when hazard effects of chemicals are assessed. Alternatively, metabolic transformations could detoxify chemicals that are toxic as parents. The aim of the present paper is to describe specificity of eukaryotic metabolism and its simulation and incorporation in models for predicting skin sensitization, mutagenicity, chromosomal aberration, micronuclei formation and estrogen receptor binding affinity implemented in the TIMES software platform. The current progress in model refinement, data used to parameterize models, logic of simulating metabolism, applicability domain and interpretation of predictions are discussed. Examples illustrating the model predictions are also provided.
authors.affiliation: Laboratory of Mathematical Chemistry, University "Prof. As. Zlatarov", Bourgas, Bulgaria. omekenya@btu.bg
authors.forename: O
authors.initials: O
authors.lastname: Mekenyan
authors.forename: S
authors.initials: S
authors.lastname: Dimitrov
authors.forename: T
authors.initials: T
authors.lastname: Pavlov
authors.forename: G
authors.initials: G
authors.lastname: Dimitrova
authors.forename: M
authors.initials: M
authors.lastname: Todorov
authors.forename: P
authors.initials: P
authors.lastname: Petkov
authors.forename: S
authors.initials: S
authors.lastname: Kotov
mesh_terms: D000818:Animals; D001711:Biotransformation; D003198:Computer Simulation; D006801:Humans; D008322:Mammals / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D015233:Models, Statistical; D021281:Quantitative Structure-Activity Relationship; D018570:Risk Assessment; D015262:Xenobiotics / Q000378:metabolism* / Q000633:toxicity*
chemical_list: D015262:Xenobiotics