Polychlorinated biphenyl (aroclor 1254) induced changes in femur morphometry calcium metabolism and nephrotoxicity

Abstract

Experiments were performed to investigate the effects of polychlorinated biphenyl (PCB) on calcium metabolism, femur morphometry, and nephrotoxicity. Male Fischer 344 rats were dosed daily intragastrically (ig) for 5, 10 or 15 weeks with 0, 0.1, 1, 10 or 25 mg PCB/kg body weight. After 5, 10 and 15 weeks, liver weight and liver-to-body weight ratio were increased at the 2 higher dose levels. Overt toxicity was observed at the highest dose level after 10 and 15 weeks as evidenced by significantly smaller body weight. Urinary alkaline phosphatase and lactate dehydrogenase activities were elevated at 5, 10 and 15 weeks of PCB exposure and the kidney-to-body weight ratios were elevated at the 10 and 25 mg/kg dose levels after 10 and 15 weeks of exposure indicating nephrotoxicity. Hypercalcemia was present at the highest dose level after 5 and 10 weeks of exposure but serum calcium concentration was normal at 15 weeks. Serum triglycerides were significantly elevated after 5 weeks of exposure but were significantly decreased after 10 and 15 weeks of PCB exposure. Serum cholesterol was significantly elevated at the 2 higher dose levels at all 3 periods. Femur density was increased at the 10 mg/kg dose level after 5 weeks, at all dose levels after 10 weeks and at all dose levels which did not demonstrate overt toxicity after 15 weeks of PCB exposure. Cross-sectional, medullary and cortical areas of the midpoint of the femur were significantly decreased at the higher dose levels after 10 and 15 weeks of exposure. The percent medullary area though was significantly decreased after 10 and 15 weeks of PCB exposure indicating that not only was there a decrease in medullary size but a decrease relative to the cortical bone area. These changes in bone morphometry resulted in a significantly weaker bone after 15 weeks of exposure at the highest dose level. These results demonstrate that PCB exposure effects calcium metabolism and bone morphometry and is nephrotoxic.