Synergism among oral carcinogens: I. Results of the simultaneous feeding of four tumorigens to rats

A mixture of four substances, namely, Aramite, methoxychlor, DDT, and thiourea was fed to rats at a level of 50 ppm of each in the diet for a period of 24 months. This dietary concentration is considerably below the tumorigenic dosage of each of the individual compounds. Compared to the control rats, a somewhat increased incidence of liver tumors was observed in the males, and to a lesser extent the females, given the combination of the compounds. The incidences of tumors at other sites in the control and treated groups were not markedly different. A second experiment was performed using a larger number of rats in which the same four compounds were fed individually as well as in combination, at a higher dietary level (80 ppm). In this experiment the incidence of tumors of all types in the rats fed the mixture of four tumorigens was no higher than that in the rats fed single tumorigens. No liver tumor was observed in any rat receiving any of these compounds. Thus, it would seem that these four compounds do not exert a synergistic or additive tumorigenic effect when fed to rats at the levels employed.