Toxicity and distribution of 2,3,7,8-tetrachlorodibenzofuran in male guinea pigs.

The toxicity of 2,3,7,8-tetrachlorodibenzofuran (TCDF) was studied in male Hartley guinea pigs after single or multiple oral treatment. In each animal studied, adipose tissue, liver, and skin were the major depots of TCDF and accounted for 50-74% of the total dose. The whole-body half-life of TCDF in guinea pigs was estimated to be approximately 40 d. This slow clearance of TCDF by guinea pigs may explain the high toxicity of TCDF for this species even when very low repeated doses were administered. Intervals of 1, 2, or 4 wk between doses had little effect on TCDF lethality, but did have an effect on the pattern of toxicity. Treatment of mature animals with high single doses of TCDF (10 or 15 micrograms/kg body weight) resulted in the immediate loss of weight and the eventual death of all treated animals within 2-4 wk after the loss of approximately 35% of their initial body weight. Treatment of immature animals with low multiple doses totaling cumulative doses of between 4 and 12 micrograms/kg resulted in the death of 75% of these animals, with the deaths occurring between 7 and 19 d after the initial appearance of quantitative toxic symptoms (loss of weight); however, weight loss was less dramatic following repeated low doses than after acute high doses. Concentration of TCDF in adipose tissue was generally proportional to dose of TCDF. With increasing time after dosage, there was a shift in distribution from adipose tissue to liver.