Antagonism—No Synergism—in Pairwise Tests of Carcinogens in Rats

In the mid-1970s, the National Cancer Institute issued a contract for the testing of a dozen chemicals, most of them known to be carcinogenic in animals, in pairwise combinations. Those tests, which involved 918 pairwise tests and over 14,500 laboratory rats, produced no good evidence for any synergistic interactions in which exposure to two chemicals resulted in a number of tumors greater than the number produced by exposure to either chemical alone. A number of tests resulted in antagonism, in which the number of tumors in animals exposed to a pair of carcinogens was less than the number seen after exposure to either carcinogen by itself. More generally, the results indicate that synergism is an unlikely consequence when animals are exposed to pairs of chemicals, even when both chemicals are carcinogens.