Urine mutagenicity and biochemical effects of the drinking water mutagen, 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX), following repeated oral administration to mice and rats

MX, a by‐product of water chlorination, lacks in vivo genotoxicity in gpt delta mice but inhibits gap junctional intercellular communication in rat WB cells

“…Despite its strong in vitro mutagenicity, MX was only marginally active at inducing nuclear anomalies in the small intestine of mice when given as a single oral dose of 0.37 mmol/ kg [Daniel et al, 1991]. Thus, it has been hypothesized that mammalian cells may effectively detoxify chlorohydroxyfuranones, including MX [Daniel et al, 1991;Meier et al, 1996]. In fact, it has been shown that MX is efficiently inactivated by endogenous defensive systems such as those involving glutathione and cysteine [LaLonde and Xie, 1993;Watanabe et al, 1994].…”

“…Most tumor promoters, both complete carcinogens and pure tumor pro- moters including non-liver tumor promoters like TPA, have the ability to inhibit cell-cell communication in WB cells [ Loewenstein, 1979;Trosko et al, 1983;Trosko and Goodman, 1994;Evans and Martin, 2002]. It has been suggested that MX might primarily affect the mucosa of the alimentary tract, when exposure levels are sufficient to overwhelm the defense capacity relying on glutathione or other factors, or when defense systems are impaired [Nishikawa et al, 1994;Meier et al, 1996]. Previously, we reported that MX induces cell proliferation in the gastric mucosa of rats even at low, nontoxic doses such as 25 ppm [Nishikawa et al, 1994] as well as at higher doses [Furihata et al, 1992].…”

MX, a by‐product of water chlorination, lacks in vivo genotoxicity in gpt delta mice but inhibits gap junctional intercellular communication in rat WB cells

“…Despite its strong in vitro mutagenicity, MX was only marginally active at inducing nuclear anomalies in the small intestine of mice when given as a single oral dose of 0.37 mmol/ kg [Daniel et al, 1991]. Thus, it has been hypothesized that mammalian cells may effectively detoxify chlorohydroxyfuranones, including MX [Daniel et al, 1991;Meier et al, 1996]. In fact, it has been shown that MX is efficiently inactivated by endogenous defensive systems such as those involving glutathione and cysteine [LaLonde and Xie, 1993;Watanabe et al, 1994].…”

“…Most tumor promoters, both complete carcinogens and pure tumor pro- moters including non-liver tumor promoters like TPA, have the ability to inhibit cell-cell communication in WB cells [ Loewenstein, 1979;Trosko et al, 1983;Trosko and Goodman, 1994;Evans and Martin, 2002]. It has been suggested that MX might primarily affect the mucosa of the alimentary tract, when exposure levels are sufficient to overwhelm the defense capacity relying on glutathione or other factors, or when defense systems are impaired [Nishikawa et al, 1994;Meier et al, 1996]. Previously, we reported that MX induces cell proliferation in the gastric mucosa of rats even at low, nontoxic doses such as 25 ppm [Nishikawa et al, 1994] as well as at higher doses [Furihata et al, 1992].…”

Lack of induction of micronuclei in bone marrow erythrocytes of rats exposed to 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) for two years in a carcinogenicity bioassay

“…Box 35, Finland. average daily doses of 0.4-5.0 mg/kg/day for males and E-mail: kjansson@ymtk.jyu.fi 0.6-6.6 mg/kg/day for females was found to induce tumors in both sexes at multiple sites, including the thyroid Received 13 March 1998; Accepted 2 May 1998 Kristian Jansson 1992]. After administration of MX to rats orally at 8-64 mg/kg/day for 14 days, none of the compound excreted in feces was in a mutagenic form [Meier et al, 1996]. mined for each animal.…”

Peer Reviewed: Analyzing Drinking Water for Disinfection Byproducts

“…Several chlorinated furanones, in addition to MX, which is by far the most mutagenic compound, were shown to form when NOM was chlorinated directly (37,38). GC/MS, GC/IR, and/or LC helped to identify these species in finished chlorinated water using functionalized resins for preconcentration.…”

“…GC/MS, GC/IR, and/or LC helped to identify these species in finished chlorinated water using functionalized resins for preconcentration. Concentrations of MX determined by GC/MS in chlorinated water were in the low parts-per-trillion range (37)(38)(39)(40)(41)(42). By contrast, THM levels in the same waters were typically 1000-fold higher.…”

MX, a by‐product of water chlorination, lacks in vivo genotoxicity in gpt delta mice but inhibits gap junctional intercellular communication in rat WB cells

“…Despite its strong in vitro mutagenicity, MX was only marginally active at inducing nuclear anomalies in the small intestine of mice when given as a single oral dose of 0.37 mmol/ kg [Daniel et al, 1991]. Thus, it has been hypothesized that mammalian cells may effectively detoxify chlorohydroxyfuranones, including MX [Daniel et al, 1991;Meier et al, 1996]. In fact, it has been shown that MX is efficiently inactivated by endogenous defensive systems such as those involving glutathione and cysteine [LaLonde and Xie, 1993;Watanabe et al, 1994].…”

“…Most tumor promoters, both complete carcinogens and pure tumor pro- moters including non-liver tumor promoters like TPA, have the ability to inhibit cell-cell communication in WB cells [ Loewenstein, 1979;Trosko et al, 1983;Trosko and Goodman, 1994;Evans and Martin, 2002]. It has been suggested that MX might primarily affect the mucosa of the alimentary tract, when exposure levels are sufficient to overwhelm the defense capacity relying on glutathione or other factors, or when defense systems are impaired [Nishikawa et al, 1994;Meier et al, 1996]. Previously, we reported that MX induces cell proliferation in the gastric mucosa of rats even at low, nontoxic doses such as 25 ppm [Nishikawa et al, 1994] as well as at higher doses [Furihata et al, 1992].…”

Lack of induction of micronuclei in bone marrow erythrocytes of rats exposed to 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) for two years in a carcinogenicity bioassay

“…Box 35, Finland. average daily doses of 0.4-5.0 mg/kg/day for males and E-mail: kjansson@ymtk.jyu.fi 0.6-6.6 mg/kg/day for females was found to induce tumors in both sexes at multiple sites, including the thyroid Received 13 March 1998; Accepted 2 May 1998 Kristian Jansson 1992]. After administration of MX to rats orally at 8-64 mg/kg/day for 14 days, none of the compound excreted in feces was in a mutagenic form [Meier et al, 1996]. mined for each animal.…”

Peer Reviewed: Analyzing Drinking Water for Disinfection Byproducts

“…Several chlorinated furanones, in addition to MX, which is by far the most mutagenic compound, were shown to form when NOM was chlorinated directly (37,38). GC/MS, GC/IR, and/or LC helped to identify these species in finished chlorinated water using functionalized resins for preconcentration.…”

“…GC/MS, GC/IR, and/or LC helped to identify these species in finished chlorinated water using functionalized resins for preconcentration. Concentrations of MX determined by GC/MS in chlorinated water were in the low parts-per-trillion range (37)(38)(39)(40)(41)(42). By contrast, THM levels in the same waters were typically 1000-fold higher.…”

MX, a by‐product of water chlorination, lacks in vivo genotoxicity in gpt delta mice but inhibits gap junctional intercellular communication in rat WB cells

“…Despite its strong in vitro mutagenicity, MX was only marginally active at inducing nuclear anomalies in the small intestine of mice when given as a single oral dose of 0.37 mmol/ kg [Daniel et al, 1991]. Thus, it has been hypothesized that mammalian cells may effectively detoxify chlorohydroxyfuranones, including MX [Daniel et al, 1991;Meier et al, 1996]. In fact, it has been shown that MX is efficiently inactivated by endogenous defensive systems such as those involving glutathione and cysteine [LaLonde and Xie, 1993;Watanabe et al, 1994].…”

“…Most tumor promoters, both complete carcinogens and pure tumor pro- moters including non-liver tumor promoters like TPA, have the ability to inhibit cell-cell communication in WB cells [ Loewenstein, 1979;Trosko et al, 1983;Trosko and Goodman, 1994;Evans and Martin, 2002]. It has been suggested that MX might primarily affect the mucosa of the alimentary tract, when exposure levels are sufficient to overwhelm the defense capacity relying on glutathione or other factors, or when defense systems are impaired [Nishikawa et al, 1994;Meier et al, 1996]. Previously, we reported that MX induces cell proliferation in the gastric mucosa of rats even at low, nontoxic doses such as 25 ppm [Nishikawa et al, 1994] as well as at higher doses [Furihata et al, 1992].…”

Lack of induction of micronuclei in bone marrow erythrocytes of rats exposed to 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) for two years in a carcinogenicity bioassay

“…Box 35, Finland. average daily doses of 0.4-5.0 mg/kg/day for males and E-mail: kjansson@ymtk.jyu.fi 0.6-6.6 mg/kg/day for females was found to induce tumors in both sexes at multiple sites, including the thyroid Received 13 March 1998; Accepted 2 May 1998 Kristian Jansson 1992]. After administration of MX to rats orally at 8-64 mg/kg/day for 14 days, none of the compound excreted in feces was in a mutagenic form [Meier et al, 1996]. mined for each animal.…”

Peer Reviewed: Analyzing Drinking Water for Disinfection Byproducts

“…Several chlorinated furanones, in addition to MX, which is by far the most mutagenic compound, were shown to form when NOM was chlorinated directly (37,38). GC/MS, GC/IR, and/or LC helped to identify these species in finished chlorinated water using functionalized resins for preconcentration.…”

“…GC/MS, GC/IR, and/or LC helped to identify these species in finished chlorinated water using functionalized resins for preconcentration. Concentrations of MX determined by GC/MS in chlorinated water were in the low parts-per-trillion range (37)(38)(39)(40)(41)(42). By contrast, THM levels in the same waters were typically 1000-fold higher.…”