三氯乙醛风险评估报告(编辑修改稿)

三氯乙醛风险评估报告(编辑修改稿)内容摘要：

to approve CICADs as international assessments. Board members serve in their personal capacity, not as representatives of any anization, government, or industry. They are selected because of their expertise in human and environmental toxicology or because of their experience in the regulation of chemicals. Boards are chosen according to the range of expertise required for a meeting and the need for balanced geographic representation. Board members, authors, reviewers, consultants, and advisers who participate in the preparation of a CICAD are required to declare any real or potential conflict of interest in relation to the subjects under discussion at any stage of the process. Representatives of nongovernmental anizations may be invited to observe the proceedings of the Final Review Board. Observers may participate in Board discussions only at the invitation of the Chairperson, and they may not participate in the final decisionmaking process. 1. EXECUTIVE SUMMARY This CICAD on chloral hydrate was prepared by the US Environmental Protection Agency (EPA) and is based on the US EPA39。 s Toxicological review on chloral hydrate (US EPA, 20xx). Scientific literature identified as of March 1999 was included. Information on the nature of the review processes and the availability of the source document is presented in Appendix 3. Information on the peer review of this CICAD is presented in Appendix 4. This CICAD was approved as an international assessment at a meeting of the Final Review Board, held in Sydney, Australia, on 2124 November 1999. Participants at the Final Review Board meeting are listed in Appendix 5. The International Chemical Safety Card (ICSC 0234) for chloral hydrate, produced by the International Programme on Chemical Safety, has been reproduced in Appendix 6 (IPCS, 1993). Chloral hydrate (CAS No. 302170) is synthesized by the chlorination of ethanol. It is used in human and veterinary medicine as a sedative and hypnotic drug. The anhydrous chemical, chloral (CAS No. 75876), is used as an intermediate in the synthesis of DDT, methoxychlor, naled, trichlorfon, dichlorvos, and trichloroacetic acid. The major route of exposure of the general public is from drinkingwater, as chloral hydrate is formed when drinkingwater is disinfected with chlorine. A typical concentration of chloral hydrate in a public water supply in the USA is 5 181。 g/litre. Since chloral hydrate is a metabolite of trichloroethylene and tetrachloroethylene, people will be exposed to chloral hydrate if they are exposed to these chemicals. The public will be exposed to the metabolites of chloral hydrate, trichloroacetic acid and dichloroacetic acid, as these chemicals are also formed when drinkingwater is disinfected with chlorine. In its use as a sedative for people, the usual clinical dose is 250 mg, 3 times a day (equivalent to mg/kg body weight per day). The metabolite trichloroethanol is responsible for the pharmacological effect. No quantitative information is available from occupational exposure. Chloral hydrate is irritating to the skin and mucous membranes and often causes gastric distress, nausea, and vomiting at the remended clinical dose. An acute overdose produces (in order of progression) ataxia, lethargy, deep a, respiratory depression, hypotension, and cardiac arrhythmia. There is some evidence of hepatic injury in people surviving nearlethal, acute overdoses, but no convincing evidence that hepatic injury results from the remended clinical dose. Several studies of the clinical use of chloral hydrate show a low incidence of minor sideeffects. Despite its long use in human medicine, there is no published information on toxicity in controlled studies in humans following extended exposure. Chloral hydrate is pletely absorbed and rapidly metabolized following oral administration. The major metabolites are trichloroethanol and its glucuronide and trichloroacetic acid. Some data suggest that a small amount of dichloroacetic acid may be formed. In humans, the halflife of trichloroethanol and its glucuronide is about 8 h。 the halflife of trichloroacetic acid is about 4 days. Some data suggest that the halflife of trichloroethanol is increased severalfold in preterm and fullterm infants pared with toddlers and adults. The major route of excretion of the metabolites of chloral hydrate is elimination in the urine. Chloral hydrate and its metabolites have been found in milk from women treated with chloral hydrate. The concentration of these chemicals, however, is too low to cause a pharmacological effect in the nursing infant. Acute administration of chloral hydrate to mice causes loss of coordination (ataxia) at about the same exposure as in humans for the same effect. A 90day study in mice shows no evidence of behavioural changes or other neurotoxicity. Chronic studies in rats and mice show no evidence of behavioural changes and no evidence of histopathological changes in nervous tissue. A slight decrement in humoral immunity was observed following exposure of mice for 90 days. Chloral hydrate has been tested for developmental effects in rats and mice. No structural abnormalities were observed. In a neurodevelopmental study in mice, there was a slight effect in passive avoidance learning. Although chloral hydrate has not been tested in a twogeneration reproduction study, the data on reproductive perf。