Carcinogenicity of chloral hydrate administered in drinking water to the male F344/N rat and male B6C3F(1), mouse

Male B6C3F(1) mice and male F344/N rats were exposed to chloral hydrate (ch loral) in the drinking water for 2 years. Rats: Measured chloral hydrate dr inking water concentrations for the study were 0.12 g/L, 0.58 g/L, and 2.51 g/L chloral hydrate that yielded time-weighted mean daily doses (MDDs) of 7.4, 37.4, and 162.6 mg/kg per day. Water consumptions, survival, body weig hts, and organ weights were not altered in any of the chloral hydrate treat ments. Life-time exposures to chloral hydrate failed to increase the preval ence (percentage of animals with a tumor) or the multiplicity (tumors/anima l) of hepatocellular neoplasia. Chloral hydrate did not increase the preval ence of neoplasia at any other organ site. Mice: Measured chloral hydrate d rinking water concentrations for the study were 0.12 g/L, 0.58 g/L, and 1.2 8 g/L that gave MDDs of 13.5, 65.0, and 146.6 mg/kg per day. Water consumpt ions, survival, body and organ weights, were not altered from the control v alues by any of the chloral hydrate treatments. Enhanced neoplasia was obse rved only in the liver. Prevalence and multiplicity of hepatocellular carci noma (HC) were increased only for the high-dose group (84.4%; 0.72 HC/anima l; p less than or equal to 0.05). Values of 54.3%; 0.72 HC/animal and 59%; 1.03 HC/animal were observed for the 13.5- and 65.0-mg/kg per day treatment groups. Prevalence and multiplicity for the control group were 54.8%; 0.74 HC/animal. Hepatoadenoma (HA) prevalence and multiplicity were significant ly increased (p less than or equal to 0.05) at all chloral hydrate concentr ations: 43.5%; 0.65 HA/animal, 51.3%; 0.95 HA/animal and 50%; 0.72 HA/anima l at 13.5, 65.0, and 146.6 mg/kg per day chloral hydrate compared to 21.4%; 0.21 HA/animal in the untreated group. Altered foci of cells were evident in all doses tested in the mouse, but no significant differences were obser ved over the control values. Hepatocellular necrosis was minimal and did no t exceed that seen in untreated rats and mice. Chloral hydrate exposure did not alter serum chemistry and hepatocyte proliferation in rats and mice or increase hepatic palmitoyl CoA oxidase in mice at any of the time periods monitored. It was concluded that chloral hydrate was carcinogenic (hepatoce llular neoplasia) in the male mouse, but not in the rat, following a lifeti me exposure in the drinking water. Based upon the increased HA and combined tumors at all chloral hydrate doses tested, a no observed adverse effect l evel was not determined.