【正文】 s are observed in reproductive ans of rodents in subchronic or chronic studies. All of the studies in laboratory animals show noncancer health effects at an exposure far in excess of the exposure that is effective for sedation in humans. There are no carcinogenicity data from humans. Two bioassays in rats show no increase in tumours at any site. Three separate bioassays in male mice show an increased incidence of liver tumours. The most definitive of these studies shows an increased incidence and multiplicity of liver tumours at each of three exposures. These data provide suggestive evidence of carcinogenicity in male mice but are not considered appropriate for conducting a human health risk assessment with a linear response at low 1 In a National Toxicology Program carcinogenicity bioassay in mice that became available after the Final Review Board meeting, males had an increased incidence of hepatic tumours, and females had a low increased incidence of pituitary adenomas that was of borderline statistical significance. There is an extensive database on geic toxicity. A variety of results show that chloral hydrate is a weak gene mutagen and clastogen. Chloral hydrate induces aneuploidy in a wide variety of cell types. These latter effects are thought to arise by disruption of the spindle apparatus. High concentrations of chloral hydrate are required to cause observable effects. Although these data suggest that genotoxicity may play a role in the toxicity of chloral hydrate, the data indicate that these effects require concentrations that are unlikely to occur under physiological conditions at the exposures typically encountered in the environment. Some likely candidates for the induction of liver tumours in male mice include the formation of DNA adducts caused by free radicals generated by the metabolism of chloral hydrate by cytochrome P450 2E1 (CYP2E1) and through cytotoxicity leading to pensatory hyperplasia. The tolerable intake for noncancer health effects of mg/kg body weight per day was estimated from the lowestobservedadverseeffect level (LOAEL) for sedation in humans of mg/kg body weight per day using a total uncertainty factor of 100. Only limited data are available on environmental effects. Methanotrophs can convert chloral hydrate to trichloroethanol and trichloroacetic acid. Chloral hydrate also undergoes abiotic degradation under some conditions. Limited data are available on the inhibition of growth of bacteria, algae, and protozoa and developmental effects in sea urchins. Insufficient data are available with which to assess the risk to the environment from chloral hydrate. 2. IDENTITY AND PHYSICAL/CHEMICAL PROPERTIES Chloral hydrate (CAS No. 302170) is synthesized by the chlorination of ethanol. The structural formula is given in section 7. The CAS name is 2,2,2trichloro1,1ethanediol. Synonyms include chloral monohydrate, trichloroacetaldehyde hydrate, trichloroacetaldehyde monohydrate, and 1,1,1trichloro2,2dihydroxyethane. The relative molecular mass is 。 ments into account and revise their draft, if necessary. The resulting second draft is submitted to a Final Review Board together with the reviewers39。CHLORAL HYDRATE INTERORGANIZATION PROGRAMME FOR THE SOUND MANAGEMENT OF CHEMICALS A cooperative agreement among UNEP, ILO, FAO, WHO, UNIDO, UNITAR and OECD This report contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the United Nations Environment Programme, the International Labour Organization, or the World Health Organization. First draft prepared by Dr R. Benson, Region VIII, Environmental Protection Agency, Denver, CO, USA Published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organization, and the World Health Organization, and produced within the framework of the InterOrganization Programme for the Sound Management of Chemicals. World Health Organization Geneva, 20xx The International Programme on Chemical Safety (IPCS), established in 1980, is a joint venture of the United Nations Environment Programme (UNEP), the International Labour Organization (ILO), and the World Health Organization (WHO). The overall objectives of the IPCS are to establish the scientific basis for assessment of the risk to human health and the environment from exposure to chemicals, through international peer review processes, as a prerequisite for the promotion of chemical safety, and to provide technical assistance in strengthening national capacities for the sound management of chemicals. The InterOrganization Programme for the Sound Management of Chemicals (IOMC) was established in 1995 by UNEP, ILO, the Food and Agriculture Organization of the United Nations, WHO, the United Nations Industrial Development Organization, the United Nations Institute for Training and Research, and the Organisation for Economic Cooperation and Development (Participating Organizations), following remendations made by the 1992 UN Conference on Environment and Development to strengthen cooperation and increase coordination in the field of chemical safety. The purpose of the IOMC is to promote coordination of the policies and activities pursued by the Participating Organization