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

Abstract

Three-carbon chemicals (chlorinated and nonchlorinated, saturated and unsaturated, hydroxy- and oxo-hydrocarbons) were assayed for genotoxicity. The sister chromatid exchange test in vitro served as the test system. Without S9 mix, the nonchlorinated solvents 1-propanol, 2-propanol, and 2-propanone (acetone) did not increase the SCE frequencies. All chlorinated 3-C hydrocarbons, except 1,2,3-trichloropropane, proved to be potent SCE inducers in V79 cells without S9 mix. In the presence of S9 mix, the results obtained with the nonchlorinated solvents were also negative, whereas 1,2,3-trichloropropane was transformed to SCE-inducing metabolites. The addition of S9 mix resulted in an increased SCE rate for 2,3-dichloropropanol, whereas genotoxicity of 2,3-dichloropropene, 1,2-dichloropropane, 1,3-dichloropropene, and 1,3-dichloropropanone was reduced. 1,3-dichloropropanol, 1,3-dichloropropene, and epichlorohydrin were substantially inactivated by S9 mix in the V79/SCE test. It can be concluded that the reactivity of the saturated dichloro compounds in the SCE test depends on the degree of oxidation. There is no general difference between the reactivity of alpha, beta-dichloro and alpha, omega-dichloro compounds.

Assessment of the Genotoxicity of 1,2‐Dichloropropane and Dichloromethane after Individual and Co‐exposure by Inhalation in Mice

“…By gavage administration, 1,2-DCP induced hepatocellular adenomas in mice but not in rats 6) . In in vitro studies, 1,2-DCP exhibited weak mutagenicity at high concentrations in the Ames test 7−9) and induced sister chromatid exchange and chromosome aberration in CHO cells 10,11) . There is an unpublished report showing that the micronucleus in bone marrow cells was negative in mice administered 1,2-DCP by gavage 12) .…”

Subchronic toxicity and carcinogenicity studies of 1,2-dichloropropane inhalation to mice

“…DCP-induced sister chromatid exchange and chromosome aberrations in cultured Chinese hamster ovary cells and V79 cells in the presence and absence of metabolic activation (Galloway et al, 1987;NTP, 1986;Von der Hude et al, 1987). According to these results, DFG concluded that the available mutagenicity studies indicate that DCP has genotoxic potential in vitro; in vivo weak binding to liver DNA has been demonstrated (DFG, 1998).…”

“…Because of the lack of epidemiological data relevant to the carcinogenicity of DCP in humans and the limited evidence for carcinogenicity in experimental animals, IARC re-evaluated DCP as a group 3 agent (IARC, 1999): an agent which is not classifiable as to its carcinogenicity to humans. DCP, however, is reported to be mutagenic to Salmonella typhimurium in the presence and absence of metabolic activation (De Lorenzo et al, 1977;Principe et al, 1981) and to induce sister chromatid exchange and chromosome aberrations in cultured Chinese hamster ovary cells and V79 cells (Galloway et al, 1987;NTP, 1986;Von der Hude et al, 1987). Based on the equivocal results of carcinogenicity studies in experimental animals and the positive results of in vitro mutagenicity studies, the Deutsche Forschungsgemeinschaft (DFG) classified DCP as a Category 3B agent (DFG, 1998): an agent not conclusively but possibly carcinogenic to man.…”

1,3-Dichloropropene

“…Negative results have been obtained using an epoxidized soybean oil-stabilized mixed isomer formulation of 1,3-dichloropropene in the Chinese hamster ovary (CHO) HGPRT forward mutation and rat hepatocyte unscheduled DNA synthesis assays (Stott et al, 1992). However, similar samples of single or mixed isomeric 1,3-dichloropropene induced unscheduled DNA synthesis in HeLa cells (Schiffman et al, 1983), sister chromatid exchanges in V79 lung fibroblasts (von der Hude et al, 1987), DNA fragmentation and repair in V79 cells and rat and human hepatocytes (Dean et al, 1985;Martelli et al, 1993), chromosomal aberrations in CHL and CHO cells (Loveday et al, 1989), and mutations at the tk locus in L5178Y mouse lymphoma cells (Myhr and Caspary, 1991). However, similar samples of single or mixed isomeric 1,3-dichloropropene induced unscheduled DNA synthesis in HeLa cells (Schiffman et al, 1983), sister chromatid exchanges in V79 lung fibroblasts (von der Hude et al, 1987), DNA fragmentation and repair in V79 cells and rat and human hepatocytes (Dean et al, 1985;Martelli et al, 1993), chromosomal aberrations in CHL and CHO cells (Loveday et al, 1989), and mutations at the tk locus in L5178Y mouse lymphoma cells (Myhr and Caspary, 1991).…”