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Toxicology and Industrial Health
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The Statistical Analysis of a Carcinogen Mixture Experiment. III. Carcinogens With Different Target Systems, Aflatoxin B1, N-Butyl-N-(4-Hydroxybutyl)Nitrosamine, Lead Acetate, and Thiouracil

Thomas R. Fears

Biostatistics Branch National Cancer Institute Washington, D.C.

Robert M. Elashoff

Department of Biomathematics University of California Los Angeles, California

Marvin A. Schneiderman

National Academy of Sciences National Research Council Washington, D.C.

This paper describes factorial experiments designed to determine whether two carcinogens that lead to cancers in different organ systems act synergistically to produce cancers in Fischer 344 rats. Four carcinogens, aflatoxin B1 (AFLA), N-butyl-n-(4-hydroxybutyl)nitrosamine (NBBN), lead acetate (LA), and thiouracil (THIO) were studied in pairwise combinations. Each of the six possible pairs were studied by means of a 4 X 4 factorial experiment, each agent being fed at zero and at three non-zero doses. Methods of analysis designed explicitly for this study were derived to study interaction. These methods were supplemented by standard statistical methods appropriate for single agent studies. Neither synergism nor antagonism was demonstrated in these combined exposure studies. Findings for male and female animals were consistent.

Key Words: aflatoxin B1 • lead acetate • N-butyl-n-(4-hydroxybutyl)nitrosamine • statistical analysis • thiouracil.

Toxicology and Industrial Health, Vol. 5, No. 1, 1-23 (1989)
DOI: 10.1177/074823378900500101
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