Risk assessment case study--chloroform and related substances.

Chlorine, used as an important disinfectant for drinking water, can react with naturally occurring organic matter to form chloroform, bromodichloromethane, chlorodibromomethane and bromoform. Chloroform and other trihalomethanes have been shown to increase tumours of the liver, kidney or large intestine in rats or mice. The risk to man from these contaminants must be assessed carefully since there is considerable benefit associated with the use of chlorine. The weight of evidence suggests that chloroform is non-genotoxic and there are data, for each site, to indicate that tumours only occur at high doses where there is also tissue damage. Bromodichloromethane has also been shown to increase liver and kidney tumours but this and bromoform have been shown to increase large intestinal tumours in rats. The weight of evidence is that they are only weak genotoxins and they do not appear to be active in vivo. It is probable that the mechanism for the liver and kidney tumours is the same as for chloroform but the mechanism for the large intestinal tumours is uncertain. However, the toxicity and carcinogenicity of these substances is profoundly affected by dosing in corn oil. New studies suggest that dosing in drinking water would not result in increases in tumours. The evidence suggests that the use of a threshold approach, based on a tolerable daily intake, would be the most appropriate way of determining safe levels in drinking water.