SAFETY EVALUATION OF TOOTHPASTE CONTAINING CHLOROFORM .2. LONG-TERM STUDIES IN RATS

A preliminary rangefinding 13 wk oral toxicity study and 2 longer term studies on chloroform in toothpaste base are reported. Significant changes in serum enzymes and certain hematological parameters were seen at the higher dose levels in the rangefinding study. Intercurrent disease made it necessary to terminate the 1st long term experiment prematurely after 1 yr. No evidence of serious toxicity was recorded. In the 2nd long term experiment, groups of 50 Cesarean-derived SPF Sprague-Dawley rats of each sex received either the equivalent of 60 mg CHCl3/kg per day in toothpaste base or the vehicle only, by gavage on 6 days/wk for 80 wk and were then observed for up to a further 15 wk. Chloroform-treated rats of both sexes survived better than the controls, although both groups had a high incidence of non-neoplastic respiratory and renal disease. Female rats gave a consistent finding of decrease in plasma cholinesterase, shown to be related to activity against butyrylcholine but not acetyl-.beta.-methylcholine. Tumors of various sites were seen in 39% of chloroform-treated rats of both sexes examined histologically, compared with 38% of vehicle controls. There were no treatment-related effects on the incidence of liver or kidney tumors. Histologically malignant mammary tumors were reported in more treated than control rats, but the difference in incidence was not statistically significant.