STUDIES ON THE MUTAGENIC AND CARCINOGENIC POTENTIAL OF CHLORAL HYDRATE

Chloral hydrate (CAS 302-17-0), a widely used hypnotic and sedative ag ent, is reassessed on its mutagenic and carcinogenic potential on the evidence of recently unpublished and already published data. The compo und was administered to rats in a carcinogenicity study in the drinkin g water for 124 (males) or 128 (females) weeks at dosages of 15, 45 an d 135 mg/kg b.w./day. The administration of chloral hydrate produced n o effects on survival, appearance and behaviour. At necropsy, there wa s no evidence of treatment-related changes, histopathology revealed an increased incidence of hepatocellular hypertrophy at the high dose le vel. There was no indication for a carcinogenic potential of chloral h ydrate examined as life-time carcinogenicity study in rats. Further, i n several in vitro and in vivo test systems no indication for a mutage nic potential was detected. Still unresolved is the end-point 'aneuplo idy'. 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 f indings for man, above all, since chloral hydrate is quickly metabolis ed to trichloroethanol in man. Based on the extensive range of data av ailable, it can be concluded, that chloral hydrate has to be considere d as a safe and effective substance.