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International Agency for Research on Cancer (IARC) - Summaries & Evaluations

3-CHLORO-4-(DICHLOROMETHYL)-5-HYDROXY-2(5H)-FURANONE (MX)

(Group 2B)

For definition of Groups, see Preamble Evaluation.

VOL.: 84 (2004) (p. 441)

CAS No.: 77439-76-0

5. Summary of Data Reported and Evaluation

5.1 Exposure data

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) is a disinfection by-product that has been found at nanogram-per-litre levels in drinking-water as a result of chlorination or chloramination.

5.2 Human carcinogenicity data

Several studies were identified that analysed risk with respect to one or more measures of exposure to complex mixtures of disinfection by-products that are found in most chlorinated and chloraminated drinking-water. No data specifically on MX were available to the Working Group.

5.3 Animal carcinogenicity data

In a single bioassay, MX induced malignant and benign thyroid and mammary tumours in male and female rats. MX failed to increase the incidence of tumours in the small intestine or colon of C57BL/6J-MiN/ mice. MX promoted preneoplastic and malignant lesions in the glandular stomach but not aberrant crypt foci (preneoplastic lesions) in the colon of rats initiated with N-methyl-N-nitro-N-nitrosoguanidine.

5.4 Other relevant data

MX is well absorbed in the gastrointestinal tract of experimental animals. About 40% of the administered dose is excreted rapidly in urine almost entirely as uncharacterized metabolites. Pharmacokinetic studies suggest that MX does not accumulate upon continuous exposure.

The target organs of toxicity of MX in rats are the kidneys and the liver. It affects hepatic lipid metabolism and kidney function. At high doses, MX is highly irritating in the gastrointestinal tract. No data were available on the teratogenicity of MX in vivo.

MX is genotoxic. It is a direct-acting mutagen and causes DNA and chromosome damage in vitro and DNA damage in vivo. MX-induced liver tumours of rats contained only a few point mutations in p53 and none in ras genes. Hormonal data suggest that MX does not cause thyroid gland tumours in rats by the thyroid-stimulating hormone-mediated promotion mechanism.

5.5 Evaluation

There is inadequate evidence in humans for the carcinogenicity of MX.

There is limited evidence in experimental animals for the carcinogenicity of MX.

MX is a potent, direct-acting mutagen that induces primarily GCTA transversions in both bacterial and mammalian cells. It induces DNA damage in bacterial and mammalian cells as well as in rodents in vivo. MX is a chromosomal mutagen in mammalian cells and in rats, and it induces mammalian cell transformation in vitro. The MX-associated thyroid gland tumours in rats are caused by mechanisms other than TSH-mediated hormonal promotion.

Overall evaluation

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) is possibly carcinogenic to humans (Group 2B).

For definition of the italicized terms, see Preamble Evaluation.

Synonyms

       Chloro(dichloromethyl)-5-hydroxy-2(5H)-furanone

       MX

Last updated: 29 September 2004



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       Toxicological Abbreviations