Mutagenicity of halogenated and oxygenated three‐carbon compounds

Abstract

Four structurally related three-carbon compounds, known for their antifertility activity in the male, and the brominated derivatives of two of these compounds were tested for mutagenic activity by the Salmonella typhimurium test of Ames et al. In the presence of strain TA-100, a base-pair substituion detector strain, 1,2-dibromo-3-chloropropane (DBCP), was the most active compound tested but required enzymatic conversion by 59 microsomal preparation to an active mutagen. Three of these compounds containing an epoxide group-epichlorohydrin, epibromohydrin, and glycidol-were highly active direct mutagens, not requiring 59 for activation, alpha-Chlorohydrin was the least active compound tested; alpha-bromohydrin was 40 times more active than its chlorinated analog. Epibromohydrin was only slightly more active than epichlorohydrin, but both were highly active. With both of the halogenated epoxides, 59 preparation caused a substantial decrease in mutagenic activity at every concentration tested. All six compounds showed dose-related responsiveness for the base-pair substitution detector strains used. However, they were relatively inactive against the frameshift detector strain of S. typhimurium, TA-98. Glycerol, propylene glycol, and n-propanol, which are also three-carbon compounds containing one or more hydroxy groups, were inactive when trested at high concentrations with strain TA-100.

Evaluation of a testicular sperm head counting technique using rats exposed to dimethoxyethyl phthalate (DMEP), glycerol?-monochlorohydrin (GMCH), epichlorohydrin (ECH), formaldehyde (FA), or methyl methanesulphonate (MMS)

“…DMEP has been shown to induce dominant lethal mutations in male mice, accompanied by semi-sterility (Singh et al 1974). The two chlorohydrins (GMCH, ECH) are bacterial mutagens (Stolzenberg and Hine 1979;Silhankov~i et al 1982) but do not induce dominant lethal mutations in mice (Epstein et al 1972). Furthermore, GMCH is known to be a powerful chemosterilant in male rats and other animals, but does not cause dominant lethal mutations in rat spermatozoa (Jones et al 1969).…”

Genotoxicity of three‐carbon compounds evaluated in the SCE test in vitro

“…Addition of the S9 mix, Dean et a1 [1985]; c) Stolzenberg and Hine [1980]; d) Nakamura et al [1979]; e) Gold et al [1978]; f ) Maron et al [1981]; g) Neudecker et a1 (1980); h) Stolzenberg and Hine [1979].…”

The genetic toxicity of 1,2-dibromo-3-chloropropane, 1,2-dibromo-3- chloro-2-methylpropane, and 1,2,3-tribromo-2-methylpropane

“…Studies in a number of laboratories have clearly delineated the mutagenic activity of DBCP and its structural homologue, TBP, in the Salmonella assay (Biles et al, 1978;Blum and Ames, 1977;Prival et al, 1977;Rosenkranz, 1975;Simmon et al, 1977;Stolzenberg and Hine, 1979;Zeiger, 1987). Both materials undergo metabolic activation to form reactive intermediates most easily detected in the base-pair substitution detector strains, TA-100 and TA-1535.…”

“…DBCMP and TBMP are structurally similar to 1,2-dibromo-3-chloropropane (DBCP) and to 1,2,3-tribromopropane (TBP), which are active genotoxins both in vitro (Biles et al, 1978;Blum and Ames, 1977;Prival et al, 1977;Rosenkranz, 1975;Simmon et al, 1977;Stolzenberg and Hine, 1979;Zeiger, 1987) and in vivo (Kapp, 1979;Saito-Suzuki et al, 1982;Teramoto et al, 1980). DBCP is also a rodent carcinogen (NCI, 1978;NCI, 1980;Olson et al, 1973;Powers et al, 1975;Reznik et al, 1980;Van Duuren et al, 1979;Ward and Haberman, 1974).…”