SAFETY EVALUATION OF TOOTHPASTE CONTAINING CHLOROFORM .1. LONG-TERM STUDIES IN MICE

  • 1 January 1979
    • journal article
    • research article
    • Vol. 2  (3) , 799-819
Abstract
In 3 experiments, chloroform was administered to mice by gavage in a toothpaste base or in arachis oil, in doses up to 60 mg/kg per day on 6 days/wk for 80 wk. Control groups were left untreated or given vehicle only. In general, there were more survivors in chloroform-treated groups than in the controls. In the case of the males of 3 strains (C57BL, CBA and CF/1), treatment was associated with no adverse affect on the incidence of any type of neoplasm or any other parameter. In the males but not the females of a 4th strain (lCl) and in doses of 60 mg/kg per day but not of 17 mg/kg per day, exposure to chloroform in toothpaste base as a vehicle was associated with increased incidence of epithelial tumors of the kidney. A more pronounced effect of the same kind was seen in mice given 60 mg CHCl3/kg per day in an arachis oil vehicle. This treatment was also associated with a higher incidence and severity of non-neoplastic renal disease. The mechanisms underlying the peculiar strain- and sex-specific susceptibility of lCl male mice to renal tumor development when exposed to chloroform remain obscure. Spontaneous renal tumors were also seen in vehicle control mice and possible ways in which this tendency may be enhanced by chloroform treatment are discussed. At the dose levels tested, namely 113 and 400 times average human exposure levels from the use of toothpaste (with 3.5% chloroform content), no adverse affect was seen in the liver and there was no increased incidence of liver tumors even in the higher liver tumor susceptible CBA strain. At the 17 mg CHCl3/kg per day level, equivalent to 113 times average human exposure from toothpast use, no excess of renal tumors was seen even in males of the peculiarly susceptible lCl strain.