Perinatal Exposure to Environmental Contaminants Detected in Canadian Arctic Human Populations Changes Bone Geometry and Biomechanical Properties in Rat Offspring

Abstract

Arctic inhabitants consume large proportions of fish and marine mammals, and are therefore continuously exposed to levels of environmental toxicants, which may produce adverse health effects. Fetuses and newborns are the most vulnerable groups. The aim of this study was to evaluate changes in bone geometry, mineral density, and biomechanical properties during development following perinatal exposure to a mixture of environmental contaminants corresponding to maternal blood levels in Canadian Arctic human populations. Sprague-Dawley rat dams were dosed with a Northern Contaminant Mixture (NCM) from gestational day 1 to postnatal day (PND) 23. NCM contains 27 contaminants comprising polychlorinated biphenyls, organochlorine pesticides, and methylmercury. Femurs were collected on PND 35, 77 and 350, and diaphysis was analyzed by peripheral quantitative computed tomography and three-point bending test, while femoral neck was assessed in an axial loading experiment. Dose-response modeling was performed to establish the benchmark dose (BMD) for the analyzed bone parameters. Exposure to the high dose of NMC resulted in short and thin femur with reduced mechanical strength in offspring at PND35. BMD of femur length, cortical area, and stiffness were 3.2, 1.6, and 0.8 mg/kg bw/d, respectively. At PND77 femur was still thin, but at PND350 no treatment-related bone differences were detected. This study provides new insights on environmental contaminants present in the maternal blood of Canadian Arctic populations, showing that perinatal exposure induces bone alterations in the young offspring. These findings could be significant from a health risk assessment point of view.

Acknowledgments

We thank Dr. Ih Chu, Environmental Health Sciences and Research Bureau, Health Canada, Ottawa, Canada, for generously providing the tissue material and Filip Rendel for his technical assistance. This study has been supported by funds from the Commission of the European Communities projects BoneTox (EU-QLK-CT-2002-02528) and CASCADE (FOOD-CT-2004-506319), Northern Contaminants Program, DIAND, Health Canada, scholarships from the Swedish Institute and the University of Khartoum, and grants from Karolinska Institute and the Swedish Research Council/Medicine.