Mutagenicity of halogenated olefins and their derivatives

Abstract

The ability of a series of haloalkanes, haloethanols and haloacetaldehydes to induce mutations in Salmonella typhrimurium and preferentially to inhibit the growth of DNA polymerase-deficient E. coli (pol A+/pol A−) was investigated. For the haloalkanes investigated, the order of reactivities towards the E. coli pol A+/pol A−, was: 1,1,2,2-tetrabromoethane > 1,1-dibromoethane > 1,1,2,2-tetrachlorethane > 1,2-dibromoethane = 1,5 dibromopentane > 1,2-dibromo-2-methylpropane > 1-bromo-2-chloroethane > 1,2-dichloroethane. In the standard Salmonella mutagenicity assay the order of these substances was 1,2-dibromoethane = 1,5-dibromopentane > 1,2-dibromo-2-methylpropane ≥ 1-bromo-2-chloroethane > 1,1,2,2-tetrachloroethane = 1,1-dibromoethane > 1,2-dichloroethane. 1,1,2,2-Tetrabromoethane was negative in the standard assay but strongly mutagenic when tested in suspension. It would appear that the discrepancy between the two procedures is due to the fact that bactericidal mutagens cannot be scored reliably in the standard Salmonella assay. The order of reactivity of 2-haloethanols in E. coli pol. A+/pol A−, was 2-iodo > 2-bromo-> 2-chloroethanol. In the Salmonella assay the order was 2-bromo-> 2 iodo- >2-chloro-ethanol. 2-Fluoroethanol and ethanol were devoid of activity in both assays. For the 2-haloacetaldehydes the reactivities in the E. coli system were 2-bromoethylacetate > 2-bromoacetaldehyde = acetaldehyde > 2-chloroacetaldehyde while in the Salmonella system the order was 2-bromoethylacetate > 2-chloroacetaldehyde. Acetaldehyde had minimal activity, while 2-bromoacetaldehyde was without activity but strongly bactericidal. ImagesFIGURE 2. AFIGURE 2. BFIGURE 2. C

Potential carcinogenic and mutagenic industrial chemicals. I. Alkylating agents

“…The order of reactivity of 2-haloethanbls (Fig. 19) in S. typhimurium TA1530 and TA1535 is 2-bromo-> 2-iodo-> 2-chloroethanol (Rosenkranz, 1977;; in E. coli pol A + /pol A" the order of reactivity is 2-iodo-> 2-bromo-> 2-chloroethanol.…”

“…Tris-BP is mutagenic in 5. typhimurium (Blum and Ames, 1977;Prival et al, 1977) and induced lesions in the DNA of cells of human origin in culture (Rosenkranz, 1977). It is carcinogenic when fed to rats and mice (NCI, 1977) or painted on the skin of mice and produces testicular atrophy and sterility in rabbits after application to the skin (Osterberg et al, 1977).…”

“…Without metabolic activation, EDB was mutagenic in S. typhimurium G46, TA153O, TA1535, and TA100 (McCann et al, 1975b(McCann et al, , 1975cSimmon et al, 1977), £ coli (Brem et al, 1974;Rosenkranz, 1977), and Drosophila (Vogel and Chandler, 1974). It was suggested that the mutagenicity of the vicinal dibromides is a consequence of their ability to react to form highly unstable bromonium ions in solution:…”