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On the Carcinogenicity of a Single Intragastric Dose of Hydrocarbons, Nitrosamines, Aromatic Amines, Dyes, Coumarins, and Miscellaneous Chemicals in Female Sprague-Dawley Rats¹

Southern Research Institute (D. P. G., F. M. S.) and Birmingham Baptist Hospital (A. E. C.), Birmingham, Alabama, and National Cancer Institute (E. K. W., J. H. W.), Bethesda, Maryland

The carcinogenic activity of 50 compounds of various chemical classifications was determined 6 months following the p.o. administration of a single experimentally determined maximum tolerated dose of each compound in sesame oil to young female Sprague-Dawley rats.

Histologically confirmed cancer of the breast, absent in controls, was observed in rats following the feeding of: 7,12-dimethylbenz[a]anthracene; 4H-cyclopenta[def]phenanthrene; 2,3-dihydro-3-ethyl-6-methylcyclopenta[a]anthracene; 2-anthramine; dimethyl-p-styrylaniline; 4'-fluoro-4-biphenylamine; N-(7-chloro-2-fluorenyl)acetamide; 2,7-fluorenediamine; 3-methyl-2-naphthylamine hydrochloride; N-hydroxy-N-2-fluorenylacetamide; N-6-(3,4-benzocoumarinyl)acetamide; 5,5-diphenylhydantoin; 1-chloro-2,4-dinitronaphthalene; and p-ureidobenzenearsonic acid. These results confirm previous observations that mammary tissue in rats is remarkably sensitive to exogenous chemical influences, and further suggest that certain coumarins, as well as hydrocarbons and aromatic amines, are capable of inducing cancer of the breast of rats under the experimental conditions used.

Carcinoma of the kidney was seen in 1 rat each, of 20, with cyclopentaphenanthrene, 2-anthramine, 2',4',6'-trimethylacetanilide (of 40 rats), 4,4'-oxydianiline, 3-methyl-2-naphthylamine hydrochloride, N-hydroxy-N-2-fluorenylacetamide, and Colour Index Acid Blue 9 and was present in 1 control rat, of 89. Carcinoma of the lung was noted in 1 rat fed dinitrochloronaphthalene and in 1 control animal. Precancerous change in the ovary occurred in a rat fed 4,4'-sulfonyldianiline and in none of the control animals.

¹ Research performed under Contract No. PH43-64-66 from the NIH.

Received 8/ 9/65.