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

Abstract

The objective of this work was to evaluate potential interactions between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls congeners (PCBs) in rats. Groups of five adult female rats were given 0, 2.5, 25, 250, or 1000 ng TCDD/kg body weight/day or TCDD in combination with a mixture of PCB congeners at a concentration of 2 or 20 µg kg⁻¹ body weight/day by gavage for 28 days. After the 28-day treatment period, the rats were killed for the analysis of biochemical, liver enzyme activities, and hematological and pathological end points. Growth suppression, increased absolute and relative liver weights, and decreased thymic weight were observed in the 1000 ng TCDD group alone, or the groups receiving a mixture of 1000 ng TCDD and 2 and 20 µg PCBs. TCDD-increased liver and thymic weights were not altered by PCBs; however, growth suppression was more pronounced in animals receiving 1000 ng TCDD and 2 µg PCBs. Increased hepatic microsomal methoxy resorufin-O-demethylase and ethoxy resorufin-O-deethylase activities occurred in 250 and 1000 ng kg⁻¹ TCDD-treated animals, which were antagonized by PCBs. Effects of 250 ng TCDD on serum cholesterol and liver uridine diphosphate glucuronosyl transferase activity were reduced by 20 µg PCBs. Treatment with 1000 ng TCDD increased serum albumin, decreased liver vitamin A, increased kidney vitamin A, and liver microsomal glutathione-S-transferase activity, which were not affected by PCBs. Decreased hemoglobin, platelet, packet cell volume, and red cell indices were observed in TCDD-treated rats, but no interactive effects were seen. Histopathological evaluation revealed that liver, thyroid, and thymus were the target organs, but the effects of co-exposure to PCBs and TCDD were variable. These results indicate that the mixture effects of PCBs and TCDD may be additive, synergistic, or antagonistic depending on the dose level and end points measured.

Keywords:

• TCDD
• PCBs
• mixtures
• interactions
• histopathology

Acknowledgments

The authors wish to thank E. Manzoor, C. Trossvik, and Kevin Kittle for technical assistance and Wellington Laboratories, Guelph, Ontario for chemical analysis.