Carcinogenicity of the Drinking Water Mutagen 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone in the Rat

Komulainen, Hannu; Vaittinen, Sirkka-Liisa; Vartiainen, Terttu; Tuomisto, Jouko; Kosma, Veli‐Matti; Kaliste-Korhonen, Eila; Lötjönen, Simo; Tuominen, Raimo K.

doi:10.1093/jnci/89.12.848

Cited by 145 publications

(113 citation statements)

References 24 publications

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“…Chlorine dose, TOC, and pH were also associated with increased mutagenicity. Seasonal differences were observed in the MX samples-higher concentrations were found in spring (10 ng/L; 95% CI, [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] compared to fall ( Table 5). Communities that used filtration (-12 ng/L; 95% CI, -23 to -2) and chloramination (-17 ng/L; 95% CI, -27 to -6) had significantly lower MX levels compared to other methods of treatment.…”

Section: Resultsmentioning

confidence: 99%

“…Other DBPs reported to be carcinogenic in animal studies include the haloacetic acids (3), haloacetonitriles (4), bromate (5), and 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) (6). Toxicologic data have indicated that the brominated trihalomethanes (such as bromoform and bromodichloromethane) are more carcinogenic (7,8) and mutagenic (9,10) than chloroform.…”

mentioning

confidence: 99%

“…In addition to bacterial assays, MX is a direct-acting mutagen and genotoxin in vivo (17)(18)(19)(20)(21) and in mammalian cells in vitro (21)(22)(23)(24)(25)(26)(27). MX is a multisite carcinogen in male and female rats (6), with an estimated cancer potency 170 times greater than chloroform and 17 times greater than bromodichloromethane (28).…”

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confidence: 99%

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3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and mutagenic activity in Massachusetts drinking water.

Wright

Schwartz

Vartiainen

et al. 2002

Environ Health Perspect

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There is limited information on the prevalence of the potent mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in U.S. water supplies. We measured MX concentrations and mutagenic activity in tap water samples from 36 surface water systems throughout Massachusetts. We found MX levels much higher (up to 80 ng/L) than previously reported in the United States. We also evaluated the role of water treatment on mutagenic activity and disinfection by-product formation. After adjusting for other covariates, chloramination and filtration were the most important treatment options for reducing mutagenic activity and disinfection by-product formation. Multiple chlorine application (before and after filtration) was associated with increased mutagenicity. Chlorine dose, pH, and total organic carbon were also associated with mutagenicity, MX, and total trihalomethane (TTHM) concentration. Seasonal variation was evident for MX and mutagenic activity, with higher levels occurring in the spring compared to the fall. In contrast, TTHM concentrations were greater in the fall.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and mutagenic activity in Massachusetts drinking water.

Wright

Schwartz

Vartiainen

et al. 2002

Environ Health Perspect

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“…39) Several results pointing to carcinogenicity of MX have been reported. [40][41][42][43] It induces DNA single strand scissions, enhances replicative DNA synthesis and increases ornithine decarboxylase activity in the glandular stomach of rats. 40) Also, MX induces cell proliferation as well as lipid peroxidation in the gastric mucosa 41) and exerted promoting effects in two-stage glandular stomach carcinogenesis in rats.…”

Section: Discussionmentioning

confidence: 99%

Lack of Modifying Effects of Environmental Estrogenic Compounds on the Development of Thyroid Proliferative Lesions in Male Rats Pretreated with N‐Bis(2‐hydroxypropyl)nitrosamine (DHPN)

Son

Nishikawa

Ikeda

et al. 2000

Japanese Journal of Cancer Research

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“…On a molar basis MX alone can account for up to 30-50% of the mutagenicity of chlorinated water (49). It is also a potent multitarget carcinogen in the rat (50). The upper-bound cancer risk per unit dose (oral slope factor) for lifetime exposure to MX (based on thyroid follicular adenomas in the rat) was estimated (51) to be 3.7 (mg/kg-day) -1 .…”

Section: Halofuranones MX and Related Compoundsmentioning

confidence: 99%

Use of mechanism-based structure-activity relationships analysis in carcinogenic potential ranking for drinking water disinfection by-products.

Woo

Lai

McLain

et al. 2002

Environ Health Perspect

222

100

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Disinfection by-products (DBPs) are formed when disinfectants such as chlorine, chloramine, and ozone react with organic and inorganic matter in water. The observations that some DBPs such as trihalomethanes (THMs), di-/trichloroacetic acids, and 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) are carcinogenic in animal studies have raised public concern over the possible adverse health effects of DBPs. To date, several hundred DBPs have been identified. To prioritize research efforts, an in-depth, mechanism-based structure-activity relationship analysis, supplemented by extensive literature search for genotoxicity and other data, was conducted for ranking the carcinogenic potential of DBPs that met the following criteria: a) detected in actual drinking water samples, b) have insufficient cancer bioassay data for risk assessment, and c) have structural features/alerts or short-term predictive assays indicative of carcinogenic potential. A semiquantitative concern rating scale of low, marginal, low-moderate, moderate, high-moderate, and high was used along with delineation of scientific rationale. Of the 209 DBPs analyzed, 20 were of priority concern with a moderate or high-moderate rating. Of these, four were structural analogs of MX and five were haloalkanes that presumably will be controlled by existing and future THM regulations. The other eleven DBPs, which included halonitriles (6), haloketones (2), haloaldehyde (1), halonitroalkane (1), and dialdehyde (1), are suitable priority candidates for future carcinogenicity testing and/or mechanistic studies.

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Carcinogenicity of the Drinking Water Mutagen 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone in the Rat

Abstract: Although these findings cannot be extrapolated to humans, MX should be studied as a candidate risk factor in the possible association between consumption of chlorinated drinking water and cancer in humans.

Cited by 145 publications

References 24 publications

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and mutagenic activity in Massachusetts drinking water.

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and mutagenic activity in Massachusetts drinking water.

Lack of Modifying Effects of Environmental Estrogenic Compounds on the Development of Thyroid Proliferative Lesions in Male Rats Pretreated with N‐Bis(2‐hydroxypropyl)nitrosamine (DHPN)

Use of mechanism-based structure-activity relationships analysis in carcinogenic potential ranking for drinking water disinfection by-products.

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