Marvin A. Schneiderman

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:

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.

The effective number of cigarettes inhaled daily by passive smokers: are epidemiologic and dosimetric estimates consistent?

Abstract Since the early 1980s, a number of epidemiologic studies have implicated environmental tobacco smoke (ETS) as a cause of lung cancer among non-smokers passively exposed to other peoples tobacco smoke. A recent National Academy of Science Report on environmental tobacco smoke (NAS, 1986) summarized 13 such studies. Each study provided an estimate of the ratio of the lung cancer mortality rate among non-smokers with smoking spouses to the mortality rate among those with non-smoking spouses. The weighted average of the 13 study-specific rate ratios was roughly 1.3. In this paper, we show that if this summary rate ratio is causally related to ETS and not to bias then the estimated number of lung cancer deaths attributable to ETS exposure occurring in U.S. non-smokers in 1985 lies in the range 2500–5000. Further, we examine whether the summary rate ratio of 1.3 is consistent with the existing epidemiologic data on active smokers and the dosimetric measurements that have been made on mainstream and environmental tobacco smoke. If consistent with this other data, the hypothesis that the rate ratio of 1.3 is causally related to ETS exposure will be strengthened.