Experimental design of bioassays for screening and low dose extrapolation

Journal Article · Fri Mar 01 04:00:00 EST 1985 · Risk Anal.; (United States)

DOI:https://doi.org/10.1111/j.1539-6924.1985.tb00147.x· OSTI ID:6932832

Gaylor, D W; Chen, J J; Kodell, R L

Relatively high doses of chemicals generally are employed in animal bioassays to detect potential carcinogens with relatively small numbers of animals. The problem investigated here is the development of experimental designs which are effective for high to low dose extrapolation for tumor incidence as well as for screening (detecting) carcinogens. Several experimental designs are compared over a wide range of different dose response curves. Linear extrapolation is used below the experimental data range to establish an upper bound on carcinogenic risk at low doses. The goal is to find experimental designs which minimize the upper bound on low dose risk estimates (i.e., maximize the allowable dose for a given level of risk). The maximum tolerated dose (MTD) is employed for screening purposes. Among the designs investigated, experiments with doses at the MTD, 1/2 MTD, 1/4 MTD, and controls generally provide relatively good data for low dose extrapolation with relatively good power for detecting carcinogens. For this design, equal numbers of animals per dose level perform as well as unequal allocations.

• Research Organization: National Center for Toxicological Research, US Food and Drug Admin., Jefferson, AR
• OSTI ID: 6932832
• Journal Information: Risk Anal.; (United States), Journal Name: Risk Anal.; (United States) Vol. 5:1; ISSN RIAND
• 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.
ANIMALS
BIOASSAY
BIOLOGICAL EFFECTS
CARCINOGEN SCREENING
CARCINOGENS
DOSE LIMITS
DOSE-RESPONSE RELATIONSHIPS
EXPERIMENT PLANNING
EXTRAPOLATION
HYDROCARBONS
NUMERICAL SOLUTION
ORGANIC COMPOUNDS
PETROCHEMICALS
PETROLEUM PRODUCTS
PLANNING
RISK ASSESSMENT
SAFETY STANDARDS
SCREENING
STANDARDS