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

Concern of the toxic effects and bioaccumulation of 2,3,7,8-tetrachlorodibe nzo-p-dioxin (TCDD) and polychlorinated biphenyls in the environment contin ues to be a focus of research in persistent organochlorine contaminants. Gr oups 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 mixtu re of PCB congeners (PCBs) at 2 or 20 mug/kg b.w./day for a period of 28 da ys. Growth suppression, increased absolute and relative liver weights, and decreased thymic weight were observed in either the 1000 ng TCDD group alon e, or the groups receiving a mixture of 1000 ng TCDD + 2 mug PCBs. The TCDD induced increases in liver and thymic weights were not altered by co-admin istration with PCBs, however, growth suppression appeared to be more pronou nced in the group receiving 1000 ng TCDD + 2 mug PCBs than with TCDD alone. Treatment with TCDD at 250 ng and 1000 ng/kg resulted in a significant inc rease in hepatic microsomal methoxy resorufin-O-demethylase and ethoxy reso rufin-O-deethylase activities which were antagonized by co-administration w ith 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 mug PCBs. Other biochemical effects el icited by treatment with 1000 ng TCDD, but not affected by co-administratio n 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 interact ive effects were seen. The above results indicate that the mixture effects of PCBs and TCDD may be additive or antagonistic depending on the dose leve l and endpoints measured. For the purpose of predicting mixture effects, kn owledge of mechanisms of action and toxicokinetics is required. (C) 2001 El sevier Science Ltd. All rights reserved.