alpha-chloroepoxides. 2. Mutagenicity of 1-chlorocyclohexene oxide and its thermal isomerization product, 2-chlorocyclohexanone.

B Gold, T Leuschen

Index: Chem. Biol. Interact. 45(3) , 305-14, (1983)

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Abstract

The pseudo-first-order hydrolysis rate constants in pH 7.4 buffer-acetone solution are reported for 1-chlorocyclohexene oxide and 2-chlorocyclohexanone at 0, 25 and 37 degrees C. The rate constants, in conjunction with product studies, demonstrate that the hydrolysis of 1-chlorocyclohexane oxide quantitatively affords 2-hydroxycyclohexanone and that there is no significant isomerization of 1-chlorocyclohexene oxide to 2-chlorocyclohexanone during the hydrolysis. Both 1-chlorocyclohexene oxide and 2-chlorocyclohexanone were reacted with 2-aminopyridine, a model for adenine, to yield the same product, N-(2'-pyridyl)-2-aminocyclohexanone. The mutagenicity of 1-chlorocyclohexene oxide and 2-chlorocyclohexanone in the Ames liquid incubation assay using TA100 shows 2-chlorocyclohexanone to be slightly more active than 1-chlorocyclohexene oxide, in spite of the finding that 1-chlorocyclohexene oxide is clearly a more reactive electrophile than 2-chlorocyclohexanone. These results are interpreted to indicate the important role that hydrolysis (detoxification) plays in the in vitro evaluation of the proposed ultimate electrophilic metabolites of chloroolefins.