title: Systems Biology and Biomarkers of Early Effects for Occupational Exposure Limit Setting.
abstract: In a recent National Research Council document, new strategies for risk assessment were described to enable more accurate and quicker assessments. This report suggested that evaluating individual responses through increased use of bio-monitoring could improve dose-response estimations. Identification of specific biomarkers may be useful for diagnostics or risk prediction as they have the potential to improve exposure assessments. This paper discusses systems biology, biomarkers of effect, and computational toxicology approaches and their relevance to the occupational exposure limit setting process. The systems biology approach evaluates the integration of biological processes and how disruption of these processes by chemicals or other hazards affects disease outcomes. This type of approach could provide information used in delineating the mode of action of the response or toxicity, and may be useful to define the low adverse and no adverse effect levels. Biomarkers of effect are changes measured in biological systems and are considered to be preclinical in nature. Advances in computational methods and experimental -omics methods that allow the simultaneous measurement of families of macromolecules such as DNA, RNA, and proteins in a single analysis have made these systems approaches feasible for broad application. The utility of the information for risk assessments from -omics approaches has shown promise and can provide information on mode of action and dose-response relationships. As these techniques evolve, estimation of internal dose and response biomarkers will be a critical test of these new technologies for application in risk assessment strategies. While proof of concept studies have been conducted that provide evidence of their value, challenges with standardization and harmonization still need to be overcome before these methods are used routinely.
authors.affiliation: a National Institute for Occupational Safety and Health, Division of Applied Research and Technology , Cincinnati , Ohio.
authors.forename: D Gayle
authors.initials: DG
authors.lastname: DeBord
authors.affiliation: b U.S. Environmental Protection Agency, Office of Research and Development, Research Triangle Park , North Carolina.
authors.forename: Lyle
authors.initials: L
authors.lastname: Burgoon
authors.affiliation: b U.S. Environmental Protection Agency, Office of Research and Development, Research Triangle Park , North Carolina.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Edwards
authors.affiliation: c Toxicology Excellence for Risk Assessment (TERA) , Cincinnati , Ohio.
authors.forename: Lynne T
authors.initials: LT
authors.lastname: Haber
authors.affiliation: a National Institute for Occupational Safety and Health, Division of Applied Research and Technology , Cincinnati , Ohio.
authors.forename: M Helen
authors.initials: MH
authors.lastname: Kanitz
authors.affiliation: d National Institute for Occupational Safety and Health, Education and Information Division , Cincinnati , Ohio.
authors.forename: Eileen
authors.initials: E
authors.lastname: Kuempel
authors.affiliation: b U.S. Environmental Protection Agency, Office of Research and Development, Research Triangle Park , North Carolina.|e The Hamner Institute for Health Sciences , Research Triangle Park, North Carolina.
authors.forename: Russell S
authors.initials: RS
authors.lastname: Thomas
authors.affiliation: f National Institute for Occupational Safety and Health, Heath Effects Laboratory Division , Morgantown , West Virginia.
authors.forename: Berran
authors.initials: B
authors.lastname: Yucesoy
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D004784:Environmental Monitoring; D006801:Humans; D016273:Occupational Exposure / Q000592:standards*; D018570:Risk Assessment; D049490:Systems Biology; D014116:Toxicology / Q000379:methods*
chemical_list: D015415:Biomarkers
keywords: biomarkers; dose-response; exposure assessment; occupational; risk assessment