Bacterial and mammalian‐cell genotoxicity of mixtures of chlorohydroxyfuranones, by‐products of water chlorination

Abstract

The genotoxic responses of mixtures of four chlorohydroxyfuranones (CHFs), 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), 3,4-dichloro-5-hydroxy-2(5H)-furanone (MCA), 3-chloro- 4-(chloromethyl)-5-hydroxy-2(5H)-furanone (CMCF) and 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone (MCF), were compared with the genotoxicity of the individual compounds. Genotoxicity was evaluated in the Salmonella reversion assay (Ames test), the in vitro Chinese hamster ovary (CHO) cell Hprt mutation assay, and in the CHO chromosome aberration test. When tested individually, the concentrations of the chemicals that were chosen for the mixtures induced no or only a modest increase in the genotoxic effects, and caused little or no cytotoxicity. In the Ames test, the genotoxic responses caused by the mixtures of CHFs did not follow simple additivity. Synergism was observed with strains TA97 and TA98, and antagonism with strain TA100. In the CHO/Hprt mutation assay, the mutagenic response of the mixtures was inconsistent, with near additivity seen with a mixture of CHFs that resulted in 12% cell survival. In contrast, the four CHFs together consistently caused more structural chromosome damage (mainly chromatid-type breaks and exchanges) compared to the sum of net effects of the four CHFs tested alone. Also, a potentiating effect was consistently seen for the cytotoxicity of the CHF mixtures both in the CHO/Hprt mutation assay and the chromosome aberration test. The present results indicate that the genotoxic effects of CHF mixtures can be greater than additive. Such effects may be worth considering in the cancer risk assessment of chlorinated drinking water.

Mutagenicity in Surface Waters: Synergistic Effects of Carboline Alkaloids and Aromatic Amines

“…Deviations have been reported for high concentrations or increasing mixture complexity resulting in lower numbers of revertants than expected from additivity due to an interference of inhibiting processes . So far, mixture effects and particularly synergism in mutagenicity of water samples have been rarely reported but may be hypothesized as one of the reasons that explains why previous studies failed to identify individual compounds as the cause of mutagenicity in river waters. , For that purpose, employing different strains -such as YG1024 for aromatic amines- should be considered which is shown to act as an effective diagnostic tool to unveil not only the mutagenicity of single compounds, but also mutagenicity of mixtures involving these compound classes. Moreover, a systematic filtering of candidates using HDX, pH dependent retention time shifts and number of references improved the candidate selection significantly, suggesting this approach as useful for the identification of environmentally relevant pollutants when mass spectral libraries lack a similar entry, although biasing candidate lists toward more well-studied compounds.…”

“…Deviations have been reported for high concentrations or increasing mixture complexity resulting in lower numbers of revertants than expected from additivity due to an interference of inhibiting processes. 41 So far, mixture effects and particularly synergism in mutagenicity of water samples have been rarely reported 81 but may be hypothesized as one of the reasons that explains why previous studies failed to identify individual compounds as the cause of mutagenicity in river waters. 10,52 For that purpose, employing different strains -such as YG1024 for aromatic amines-should be considered which is shown to act as an effective diagnostic tool to unveil not only the mutagenicity of single compounds, but also mutagenicity of mixtures involving these compound classes.…”

Perturbation of cytochrome P450, generation of oxidative stress and induction of DNA damage in Cyprinus carpio exposed in situ to potable surface water

“…Both in vitro genotoxicity [17] and in vivo carcinogenicity testing [18,19] of different artificial mixtures of OBPs showed complex dose-dependent interactions that suggested an overestimation of the overall carcinogenic effect of this group of chemicals. While the current default risk assessment of chemical mixtures assumes that the carcinogenic effect of these chemicals is additive [20], long-term human exposure to OBP mixtures warrants further investigations into both the possible epigenetic and the genetic mechanisms of toxicity of these compounds.…”

Genotoxic potential of organic extracts from municipal reclaimed water in Tianjin, China

“…However, similar to the genotoxic potential of by-product in drinking water (Sycheva et al 2000;Maki-Paakkanen, Komulainen, Kronberg, 2004;Sujbert et al 2006), there appears to be a reluctance to utilize this information for extrapolation to potential human health effects. In most instances, the ambient concentration of the compounds producing this activity is below that which is readily detectable by these tests.…”