Behavioral toxicity of chloral in mice: an approach to evaluation

The potential for behavioral toxicity of the water contaminant chloral (CHL) was ascertained from acute, 14 day and 90 days of exposure in adult mice and perinatal exposure. Acute motor incoordination produced by CHL occurred 5 min after gavage and persisted for about 2 hr. The ED50 for acute CHL effects was 84.2 mg/kg, a value less than 1/10th of the acute LD50. Exposure for 14 days to either 14.4 or 144.0 mg/kg/day of CHL by gavage did not produce any deleterious effects on body weight, behavioral observations, locomotor activity, motor coordination or swimming endurance which were measured 24-48 hr after exposure was terminated. Subchronic, 90 day exposure to 0.70 or 0.07 mg/ml CHL in drinking water (15.7 and 159.8 mg/kg/day) did not affect the palatibility of drinking water since total fluid intakes were not reduced. Mice exposed to these doses of CHL did not gain weight as rapidly as control mice. Exposure to 159.8 mg/kg/day produced a decrease in body temperature after 45 days of exposure and a second temperature measurement indicated that mice exposed to both 15.7 and 159.8 mg/kg/day were hypothermic on day 91. Mice were also evaluated on various behavioral tests and none of these measures were altered by 90 days of CHL exposure. Mice perinatally exposed to 21.3 and 204.8 mg/kg/day CHL in drinking water had normal body weights, normal development of neurobehavioral reflexes and normal motor coordination. The retention of passive avoidance learning was reduced on both the 1 hr and 24 hr retention tests for mice exposed to the higher CHL concentration. CHL did not produce motor incoordination at relatively low doses following a single acute exposure. Repetitive exposure to CHL at levels of about 1/10th and 1/100th the acute LD50 for 14 or 90 days did not produce delayed or persistent behavioral changes. Non-specific effects on body temperature and body weight gains were observed for mice exposed for 90 days. There is little evidence that exposure to CHL is likely to result in delayed or persistent behavioral toxicity to adults exposed to contaminated drinking water supplies while CHL during the prenatal and early postnatal period at levels as high as 204.8 mg/kg/day can result in detrimental behavioral effects.