Role of time and concentration on carbon tetrachloride toxicity in rats

The hepatotoxic effect of different exposure schemes to carbon tetrachloride (CCl4) was studied in inhalation experiments in rats. The duration of exposures at different concentrations of CCl4 vapours in air was changed in such a way as to give a constant product of concentration and time (CT). The animals were exposed for 4 successive days a week. A concentration of 1,625 mg/m3 (250 ppm) CCl4 for 72 min (CT = 300 ppm x h) caused a higher increase in SGPT activity than the exposure to 325 mg/m3 (50 ppm) for 6 h (CT = 300); the effect of 6,500 mg/m3 (1,000 ppm) for 3 min six times at 1-h intervals (CT = 300) had a much smaller effect than the exposure to 6,500 mg/m3 (1,000 ppm) for 18 min (again CT = 300) (1 ppm CCl4 = 6.5 mg/m3). Similar results were obtained at other concentrations and by increasing the number of exposures up to 18; the effects were also confirmed by other biochemical changes in blood serum and liver and by histological examination of the liver. The results indicate that the severity of liver lesions is more influenced by the concentration of CCl4 in the inhaled air (and accordingly in the blood entering the liver) than by the total inhaled (and absorbed) amount of CCl4. This also explains the differences between the two types of exposure in the concentration of 6,500 mg/m3 (1,000 ppm): blood cannot be saturated with CCl4 to the same level within 3 min as within 18 min of exposure.