Mixture effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and polychlorinated biphenyl congeners in rats

Concern of the toxic effects and bioaccumulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls in the environment continues to be a focus of research in persistent organochlorine contaminants. Groups of five adult female S.D. rats were administered by gavage 0, 2.5, 25, 250 or 1000 ng TCDD/kg body weight/day or TCDD in combination with a mixture of PCB congeners (PCBs) at 2 or 20 microg/kg b.w./day for a period of 28 days. Growth suppression, increased absolute and relative liver weights, and decreased thymic weight were observed in either the 1000 ng TCDD group alone, or the groups receiving a mixture of 1000 ng TCDD + 2 microg PCBs. The TCDD induced increases in liver and thymic weights were not altered by co-administration with PCBs, however, growth suppression appeared to be more pronounced in the group receiving 1000 ng TCDD + 2 microg PCBs than with TCDD alone. Treatment with TCDD at 250 ng and 1000 ng/kg resulted in a significant increase in hepatic microsomal methoxy resorufin-O-demethylase and ethoxy resorufin-O-deethylase activities which were antagonized by co-administration with PCBs. Similarly, effects of 250 ng TCDD on serum cholesterol and liver UDP glucuronosyl transferase activity and ascorbic acid were significantly reduced by co-administration with 20 microg PCBs. Other biochemical effects elicited by treatment with 1000 ng TCDD, but not affected by co-administration with PCBs include the following: increased serum albumin, decreased liver vitamin A, and increased kidney vitamin A and liver microsomal glutathione-S-transferase activity. While decreased hemoglobin, platelet, packed cell volume and red cell indices were observed in TCDD treated rats, no interactive effects were seen. The above results indicate that the mixture effects of PCBs and TCDD may be additive or antagonistic depending on the dose level and endpoints measured. For the purpose of predicting mixture effects, knowledge of mechanisms of action and toxicokinetics is required.