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Experimental Design of Bioassays for Screening and Low Dose Extrapolation

 

作者: David W. Gaylor,   James J. Chen,   Ralph L. Kodell,  

 

期刊: Risk Analysis  (WILEY Available online 1985)
卷期: Volume 5, issue 1  

页码: 9-16

 

ISSN:0272-4332

 

年代: 1985

 

DOI:10.1111/j.1539-6924.1985.tb00147.x

 

出版商: Blackwell Publishing Ltd

 

关键词: Bioassay design;low dose extrapolation

 

数据来源: WILEY

 

摘要:

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.

 

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