Fecapentaenes from human feces have been found to be direct- acting mutagens and are therefore prime candidates as human carcinogens, especially for the large bowel. A variety of in vitro studies by other investigators have demonstrated potent mutagenic effects of fecapentaene-12 (FP-12) in bacterial cells, although cell transforming activity in vitro is low and mutagenic activity for mammalian cells is weak. Thus, animal experiments have become necessary to characterize the in vivo toxic and carcinogenic effects. We first studied the purity and stability of FP-12 to determine the most effective handling procedures during animal exposure. The chemical was moderately stable under argon but quickly decomposed after exposure to air. Vitamin E has shown promise for stabilizing fecapentaene solutions for use in carcinogenesis studies. Several types of animal experiments were performed. Skin painting studies in SENCAR mice revealed neither initiating activity nor complete carcinogenesis to the skin by repeated exposure. Intrarectal and subcutaneous administration to mice and rats have not provided convincing evidence of the carcinogenesis of FP-12, although most studies are still in progress. In a preliminary but small intrarectal mouse study, 1/15 mice has a small colonic carcinoma and 3 had foci of atypical colonic hyperplasia. Primary tumors of the colonic mucosa, confirmed histologically as polypoid adenomas, occurred in 2 of 25 rats given repeated intrarectal instillations of FP-12 in ethanol and killed 72 weeks after the first instillation. Transplacental mutagenesis by FP-12 in hamsters was not convincingly demonstrable, but mutagenesis in vivo in rats by the granuloma pouch assay was unequivocal. Carcinogenesis studies by means of the granuloma pouch assay are in progress. One N-nitrosomethylnitroguanidine (MNNG)- induced tumor has occurred. From previous reports, the bulk of MNNG tumors should start being detected in the next few months and FP-12 tumors, if they occur, should develop during the next 6 months.
