Toxicological Effects of In Utero and Lactational Exposure of Rats to a Mixture of Environmental Contaminants Detected in Canadian Arctic Human Populations

Abstract

As part of the program to investigate mixture effects of environmental pollutants, this study describes clinical, biochemical, and histopathological effects in rats perinatally exposed to a mixture of persistent organochlorine pollutants and methylmercury that simulates the blood contaminant profile of humans residing in the Canadian Arctic. Groups of pregnant rats were administered orally 0, 0.05, 0.5, or 5 mg/kg body weight (bw)/d of a reconstituted mixture of organochlorine pollutants (referred to as mixture hereafter) from gestational day (GD) 1 to postnatal day (PND) 23. Positive and vehicle controls were given Aroclor 1254 (Aroclor hereafter, 15 mg/kg bw) and corn oil (vehicle), respectively. After parturition, the pups were colled to 8 per litter on PND 4, and killed on PND 35, 77, or 350, when tissues were collected for analysis. Gestational and lactational exposure of rats to mixture up to 5 mg/kg bw produced adverse effects in the offspring, including growth suppression, decreased spleen and thymic weights, increased serum cholesterol and liver microsomal enzyme activities, lower liver retinoid levels, and histological changes in the liver, thyroid, and spleen. Histological changes in the liver consisted of hepatic inflammation, vacuolation, and hypertrophy, while alterations in the thyroid were characterized by hypertrophy and hyperplasia of follicles. The hepatic and thyroidal effects were mild even at the highest dose. The spleen showed a dose-dependent atrophy in the lymphoid nodules and periarteriolar lymphatic sheath regions. Aroclor produced effects similar to those seen in the highest mixture group. In summary, this study demonstrates that exposure to the reconstituted mixture at 5 mg/kg bw produced growth suppression, changes in organ weights, and biochemical and histopathological changes in liver, thyroid, and spleen. This study also demonstrated that the blood level in rats given the 5-mg/kg dose, where most of the effects were observed, is 100-fold higher than the blood level in the 0.05-mg/kg group, which is comparable to that found in humans living in the Canadian Arctic region.

Acknowledgements

The authors thank Bruce Martin, Susan Kelly, Kelly Brennan, Ron Strathern, Tanya Hoeksma, and Yasmin Dirieh for technical assistance. This study was supported in part by the Northern Contaminants Program and the European Commission project (QLK4-CT-2002-0528).