Studies on the mutagenic and carcinogenic potential of chloral hydrate.

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used hypnotic and sedative agent, is reassessed on its mutagenic and carcinogenic potential on the evidence of recently unpublished and already published data.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.