COMPARATIVE TOXICITY OF 4 CHLORINATED DIBENZO-P-DIOXINS (CDDS) AND THEIR MIXTURE .4. DETERMINATION OF LIVER CONCENTRATIONS

Groups of male Sprague-Dawley rats were administered orally the follow ing chlorinated dibenzo-p-dioxins (CDDs) in corn oil/acetone (95/5; v/ v): 30-60 mu g/kg 2,3,7,8-tetrachlorodibenzo-dioxin (tetra-CDD), 160-2 70 mu g/kg 1,2,3,7,8-pentachlorodibenzo-p-dioxins (penta-CDD), 630-124 9 mu g/kg 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (hexa-CDD) and 5000-8 000 mu g/kg 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (hepta-CDD) or a mixture of the four homologues such that each was present in the mixt ure at one quarter of its dose as a single compound. Animals were kill ed at 2 and 8 days after dosing. Livers were immediately removed, and aliquots frozen in liquid nitrogen. Storage occurred at -80 degrees C until further use. About 0.2 g of each lyophilized rat liver was extra cted, the extract purified by column chromatography and analyzed by GC /MS for CDD content. Results obtained suggest that the absorption of C DDs after oral administration decreases in the order of tetra-CDD grea ter than or equal to penta-CDD > hexa-CDD > hepta-CDD, indicating that the dose was an incomplete surrogate of exposure in parts I-III of th is publication series (Stahl et al. 1992; Weber et al. 1992a,b). Moreo ver, data also support the notion that the pharmacokinetics of CDD mix tures at high doses are somewhat different from those expected based o n single compound exposures. Our findings suggest that the intrinsic r elative potency in terms of toxic equivalents (TEQ) of the higher chlo rinated homologues is slightly greater (about a factor of 2) than sugg ested by Stahl et al. (1992), because of reduced absorption, whereas t he contribution to total potency of the lower chlorinated homologues i n mixtures is slightly higher (about a factor of 2) because of increas ed relative liver concentrations. This later finding appears to be due to altered pharmacokinetics of mixtures of CDDs, probably originating in changes of partial solubility of the lower chlorinated homologues in fat under conditions of near saturation.