Carcinogenicity of Isosters of Epoxides and Lactones: Aziridine Ethanol, Propane Sultone, and Related Compounds<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>

Abstract

Thirteen compounds of low molecular weight were tested for carcinogenic activity by lifetime subcutaneous injection in ICR/Ha Swiss mice. The compounds tested were epoxides, their nitrogen or sulfur analogs, a polymeric aldehyde, and an acetal. The compounds were selected for bioassay on the basis of their chemical reactivity and the relationship of chemical structure to carcinogenic activity. Two of these compounds, propane sultone (1-propanesulfonic acid-3-hydroxy-γ-sultone) and aziridine ethanol (β-hydroxy-1-ethylaziridine), induced sarcomas and other tumors at the injection site. Propane sultone injections resulted in 21/30 mice with tumors (12 sarcomas, 1 carcinoma, 7 adenoacanthomas, and 1 papilloma) at the site of injection; aziridine ethanol administration resulted in 10/30 mice with sarcomas at the injection site. The following compounds induced a low incidence of tumors at the injection site: 3,4-epoxysulfolane, 1,2-epoxybutyronitrile, 3,4-dihydroxy-3-cyclobutene-1,2-dione, ethyl-2,3-epoxybutyrate, tetramethyl-1,3-cyclobutanedione, perchloro-2-cyclobutene-1-one, and polymeric dialdehyde. The following compounds were inactive when injected subcutaneously: 3-sulfolene, 3,4-epoxybutanal diethyl-acetal, 5,6-epoxyhexanal diethylacetal, and N,N-dimethylformamide dimethylacetal. The incidences of distant tumors were the same for test and control groups.