Leuschner J, Beuscher N
LPT Laboratory of Pharmacology, Hamburg, Germany.
Arzneimittelforschung. 1998 Oct;48(10):961-8.
Chloral hydrate (CAS 302-17-0), a widely used hypnotic and sedative agent, is reassessed on its mutagenic and carcinogenic potential on the evidence of recently unpublished and already published data. The compound was administered to rats in a carcinogenicity study in the drinking water for 124 (males) or 128 (females) weeks at dosages of 15, 45 and 135 mg/kg b.w./day. The administration of chloral hydrate produced no effects on survival, appearance and behaviour. At necropsy, there was no evidence of treatment-related changes, histopathology revealed an increased incidence of hepatocellular hypertrophy at the high dose level. There was no indication for a carcinogenic potential of chloral hydrate examined as life-time carcinogenicity study in rats. Further, in several in vitro and in vivo test systems no indication for a mutagenic potential was detected. Still unresolved is the end-point 'aneuploidy'. However, no validated in vivo test systems are available at the moment to confirm the positive results observed in vitro under certain experimental conditions and to assess the relevance of the in vitro findings for man, above all, since chloral hydrate is quickly metabolised to trichloroethanol in man. Based on the extensive range of data available, it can be concluded, that chloral hydrate has to be considered as a safe and effective substance.
水合氯醛（CAS 302-17-0）是一种广泛使用的催眠镇静剂，根据最近未发表和已发表的数据证据，对其诱变和致癌潜力进行了重新评估。在一项致癌性研究中，以15、45和135毫克/千克体重/天的剂量，将该化合物添加到大鼠饮用水中，持续给药124周（雄性）或128周（雌性）。水合氯醛的给药对大鼠的存活、外观和行为没有影响。尸检时，没有发现与治疗相关的变化迹象，组织病理学显示高剂量组肝细胞肥大的发生率增加。在大鼠终身致癌性研究中，未发现水合氯醛有致癌潜力的迹象。此外，在多个体外和体内测试系统中，均未检测到诱变潜力的迹象。“非整倍体”这一终点问题仍未解决。然而，目前尚无经过验证的体内测试系统，无法证实某些实验条件下在体外观察到的阳性结果，也无法评估体外研究结果对人类的相关性，尤其是因为水合氯醛在人体内会迅速代谢为三氯乙醇。基于现有的大量数据，可以得出结论，水合氯醛必须被视为一种安全有效的物质。
