Toxicological study on rats fed haloperidol: 80 week chronic toxicity test

Haloperidol (HPL) was administered by presenting HPL-admixed food to 20 male and 19 female Sprague-Dawley rats from the age of 5 weeks at a target dose of 1.0 mg/kg/day for 80 weeks. The range of the actual daily dose was 0.48-1.11 mg/kg in males and 0.34-0.73 mg/kg in females. The control rats(13 males and 13 females) were given normal food. In the present study, the general condition and locomotor activity of these rats were examined. 1. The number of HPL-treated animals that died during the administration periods (11 males and 9 females) and the symptoms observed immediately before their death were comparable to those in the control group. Vacuous chewing movement developed in HPL-treated animals (12 males and 11 females) after the 28th week of administration. These movements showed a tendency of decrease after the 68th week. Blepharitis was observed in all females and 3 males of the HPL-treated group, but in none of the controls of either sex. Subcutaneous masses in the chest and abdomen were observed in 3 HPL-treated females and 6 control females, but there was no significant difference in their incidence between the two groups. 2. The body weight gain in the HPL-treated group was suppressed in males, but was promoted and then suppressed in females. The food consumption in the HPL-treated group was similar, but the water consumption was reduced in both sexes as compared with the control groups. 3. Locomotor activity was reduced in the HPL-treated group for both males and females, and no tolerance developed. These results suggest that HPL does not have a possibility to cause death even by chronic administration at the doses examined in the present study. However, the occurrence of body weight losses and blepharitis indicated the need for particular attention to these symptoms during chronic administration.