DISTRIBUTION, EXCRETION, AND METABOLISM OF 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN IN C57BL/6J, DBA/2J, AND B6D2F1/J MICE

Abstract

The strains of mice, C57BL/6J, DBA/2J and B6D2F1/J, were used as models to study the mechanism of action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The distribution, excretion and metabolism of this compound was studied in male C57BL/6J, DBA/2J and B6D2F1/J mice following i.p. administration of 10 .mu.g/kg radiolabeled TCDD. In all strains, the liver and adipose tissue were the major sites for the accumulation of 3H-TCDD, with more 3H-TCDD being distributed to the livers of the C57BL/6J and B6D2F1/J strains as compared to the DBA/2J strain. While in all strains the feces were the major route of elimination, the total amount of 3H-TCDD-derived radioactivity excreted in the feces amounted to .apprx. 72% of the original dose in the C57BL/6J and B6D2F1/J strains; this was only 54% in the DBA/2J strain. The half-lives for the cumulative excretion of radioactivity in the feces were similar in all strains. The half-life for the excretion of radioactivity in the urine was considerably greater in the DBA/2J strain as compared to the C57BL/6J and B6D2F1/J strains. The estimated half-lives for the total cumulative excretion of 3H-TCDD-derived radioactivity by all routes was 11.0, 24.4 and 12.6 days for the C57BL/6J. DBA/2J and B6D2F1/J strains, respectively. Total radioactivity (> 85%) excreted in urine, bile and feces from all 3 mouse strains was present as metabolites of TCDD. The DBA/2J strain possessed .apprx. 1.9- and 2.3-fold greater adipose tissue stores than the C57BL/6J and B6D2F1/J strains, respectively. The sequestering of lipophilic TCDD in the adipose tissue stores of the DBA/2J strain may have contributed to the altered distribution and elimination of TCDD, and decreased sensitivity of this strain to the biochemical and biological effects of this compound as compared to the C57BL/6J and B6D2F1/J mouse strains.