The Statistical Analysis of a Carcinogen Mixture Experiment. Ii. Carcinogens with Different Target Organs, N-Methyl-N'-Nitro-N-Nitrosoguanidine, N-Butyl-N-(4-Hydroxybutyl)Nitrosamine, Dipentylnitrosamine, and Nitrilotriacetic Acid

Abstract

This paper describes factorial experiments designed to determine whether two carcinogens that act on different organ systems act synergistically to produce cancers in Fischer 344 rats. Four carcinogens, N-methyl-N'-nitrosoguanidine (MNNG), N-butanol-N-butylnitrosamine (NBBN), nitrilotriacetic acid (NTA), and dipentylnitrosamine (DPN) were studied in pairwise combinations. Each of the six possible pairs was studied by means of a 4 × 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. Antagonism was demonstrated in some chemical mixtures containing NTA. Other chemical mixtures did not interact. Findings for male and female animals were generally, but not always, in agreement.