Tissue Distribution, Metabolism, and Excretion of14C‐TCDD in a TCDD‐Susceptible and a TCDD‐Resistant Rat Straina

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Abstract
A comparative study was carried out in the most TCDD‐resistant [Han/Wistar (H/W), LD50 > 3000 μg/kg] and the most TCDD‐susceptible [Long‐Evans (L‐E), LD50 about 10 μg/kg] rat strain to assess the significance of kinetic factors in TCDD toxicity. Young adult males of both strains were administered 5 μg/kg (1.9 μCi/kg)14C‐TCDD intraperitoneally. Four rats per strain were killed at 4 hr, 1, 4, 8, 16, and 32 days after exposure. A total of 22 tissues along with blood and serum were sampled for liquid scintillation counting. From half of the animals, daily urine and faeces were also analyzed. In addition, 3 rats per strain were given 50 μg/kg (19 μCi/kg)14C‐TCDD and prepared for whole‐body autoradiography after 1, 4 or 8 days. The livers of two rats per strain killed at 4 hr, 4 or 16 days, and the excreta from two rats of both strains collected on days 1‐4, 5‐8, 13‐16, and 29‐32 after exposure were analyzed for metabolites of TCDD by high pressure liquid chromatography. The label was mainly excreted in faeces as metabolites of TCDD, and the half‐life of elimination was 20.8 (L‐E) or 21.9 (H/W) days. A very similar overall distribution pattern was observed in both strains irrespective of dose, and the liver was the major site of accumulation. Practically all liver14C‐activity was found as the parent compound. Moderate strain‐related differences were observed in the thyroid, thymus, prostate, adrenals, and brown and white fat, where lower values were recorded in H/W rats. Site‐dependent variation was detected in the brain. The results do not support the view that TCDD metabolism or disposition would have a major impact on the strain difference in TCDD lethality.