title: Designing in vitro assay systems for hazard characterization. basic strategies and related technical issues.
abstract: Adverse effects of chemicals on humans are typically assessed following four steps: hazard identification, hazard characterization, exposure assessment and risk characterization. Hazard characterization is defined as the qualitative and/or quantitative evaluation of the nature of the adverse effects associated with biological, chemical and physical agents of interest. For chemical agents, hazard characterization is based on a series of in vitro and/or in vivo data obtained from mechanistic, kinetic and dose-response studies on the agent of concern, which are analyzed and integrated for extrapolation to eventually match human conditions. Thus, an accurate experimental design and the development of test methods capable of generating data relevant to hazard characterization are essential for the useful risk assessment of chemicals, including inhaled materials. It should, however, be stressed that hazard characterization has widely been limited to single chemicals. The hazard characterization of airborne mixtures therefore poses a new problem in toxicology, which calls for a novel approach to its scientific assessment. During the last three decades, a number of epidemiological and experimental studies have been conducted focusing on two kinds of inhaled complex mixtures, namely cigarette smoke and diesel exhausts. A new approach to the assessment of airborne complex mixtures may be elaborated through the appropriate, combined use of the findings of such studies. In this context, the present review article is intended to illustrate some basic strategies for and technical issues related to the hazard characterization of inhaled complex mixtures, thereby taking up representative epidemiological and experimental data from published papers on tobacco smoke.
authors.affiliation: Biological Safety Research Center, National Institute of Health Sciences, Japan. tokyo@ffcr.or.jp
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects* / Q000145:classification; D002478:Cells, Cultured / Q000187:drug effects* / Q000473:pathology; D045424:Complex Mixtures / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019570:Inhalation Exposure; D012107:Research Design; D018570:Risk Assessment / Q000379:methods*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D014029:Tobacco Use Disorder / Q000453:epidemiology / Q000209:etiology; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D000393:Air Pollutants; D045424:Complex Mixtures; D014028:Tobacco Smoke Pollution