Carcinogenic activity of di- and trifunctional alpha-chloro ethers and of 1,4-dichlorobutene-2 in ICR/HA swiss mice.

Four bifunctional and one trifunctional alpha-chloro ethers were tested for carcinogenicity. These compounds were bis-1,2-(chloromethoxy)ethane (Compound I), bis-1,4-(chloromethoxy)butane (Compound II), bis-1,6-(chloromethoxy) hexane (Compound III), bis-1,4-(chloromethoxy)-p-xylene (Compound IV), and tris-1,2,3-(chloromethoxy)propane (Compound V). trans-1,4-Dichlorobutene-2 (Compound VI) was tested along with the five alpha-chloro ethers. All six compounds were tested in female ICR/Ha Swiss mice for 502 to 569 days, depending on survival, by skin application or s.c. and i.p. injection. There were 30 or 50 mice/group. The i.p. and s.c. injections were given once weekly at 0.1 or 0.3 mg of compound dissolved in 0.05 ml tricaprylin for Compounds I to V and 0.05 mg/0.05 ml tricaprylin for Compound VI for the duration of the tests. The skin applications, three times weekly, were at doses of 0.3 or 1.0 mg/0.1 ml cyclohexane for the alpha-chloro ethers and 1.0 mg/0.1 ml acetone for Compound VI. Vehicle and no treatment controls were carried out together with the test compounds. Significance values (p) were calculated for all the compounds tested. Three compounds, I, IV and V, gave notable tumor incidences by all three routes of administration. Compounds II, III, and VI were either inactive by one or more routes of administration or gave low tumor yields.