Opportunities for improving techniques for interspecies extrapolation in the risk assessment process

Journal Article · Fri Apr 01 04:00:00 EST 1988 · Environ. Health Perspect.; (United States)

DOI:https://doi.org/10.1289/ehp.887799· OSTI ID:6345420

Gibson, J E; Starr, T B

Quantitative estimates of human carcinogenic risk from chemical exposure are currently derived primarily from linearized multistage model analyses of the tumor response as observed in chronic laboratory animal bioassays versus administered dose. The numerous ad hoc assumptions that provide a rationale for this generic approach to carcinogenic risk assessment can only be evaluated critically when mechanistic data directly relevant to the low-dose and interspecies extrapolation problems are available. Clear needs exist to develop such ancillary data bases and the mean for explicitly incorporating them into the risk estimation process. Target site dosimetry provides one useful organizing concept. Physiological response modeling can account systematically for interspecies variations in the distribution and disposition of chemicals in relation to external measures of exposure. Direct measurements of interactions of chemicals and their metabolites with specific target macromolecules can provide sensitive and biologically meaningful exposure indices. Alternatively, quantitation of toxic effects such as altered cell regulation and differentiation can serve the same purpose. Virus and oncogene activation, DNA damage and repair, and enhanced cell proliferation provide additional biological markers of exposure. They may also comprise critical elements of the carcinogenic process. Identification of the actual mechanisms involved should eventually lead to the development of risk assessment models that adequately reflect the unique biological and toxicological characteristics of different species-chemical combinations.

• Research Organization: Institute of Toxicology, Research Triangle Park, NC (USA)
• OSTI ID: 6345420
• Journal Information: Environ. Health Perspect.; (United States), Journal Name: Environ. Health Perspect.; (United States) Vol. 77; ISSN EVHPA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
ALDEHYDES
BIOLOGICAL PATHWAYS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CARCINOGENESIS
DNA REPAIR
DOSE-RESPONSE RELATIONSHIPS
FORMALDEHYDE
FUELS
GASOLINE
HYDROXY COMPOUNDS
LIQUID FUELS
MATHEMATICAL MODELS
METABOLITES
METHANOL
ORGANIC COMPOUNDS
PATHOGENESIS
PETROLEUM PRODUCTS
RECOVERY
REPAIR
RISK ASSESSMENT
SPECIES DIVERSITY
UNLEADED GASOLINE