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

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Komulainen et al. ( 1 ) recently reported dose-dependent tumor incidence in seven distinct tissues of male and female Wistar rats that had consumed drinking water containing 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5 H )-furanone (MX). They suggested cautiously that MX should be studied as a candidate risk factor to explain a “possible association between consumption of chlorinated drinking water and cancer in humans,” but they noted specifically that their findings “cannot be extrapolated to humans.” However, in their accompanying editorial, Melnick et al. ( 2 ) proceeded with just such an extrapolation. They estimated potential cancer risks to humans from MX in drinking water and compared these risks with those from two other disinfection products (i.e., bromodichloromethane and chloroform). They acknowledged that their estimates were dependent on a number of assumptions about the validity of extrapolating from laboratory animals to humans, but although they state that “there is no information that would indicate that these assumptions are inappropriate,” there is little evidence that they are appropriate. Multisite carcinogenicity of putative carcinogens is not exceptional ( 3 , 4 ), and we note that that there is no generally accepted explanation as to why the tumors in rats occur at different sites. Perhaps MX affects p53 or converts different proto-oncogenes to activated oncogenes. At present, however, these speculations are unverified.