Comparative toxicological studies on the effects of internal exposures

Age-related changes in bone metabolism of normal beagle dogs, from 3 months to 17 years of age, were examined by morphometric and serum biochemical values. From 3 months to 2 years of age, bone volume (BV/TV) and trabecular thickness (Th. Tb.) in the iliac trabecular bone, labeled with tetracycline and calcein, increased rapidly with an increase of body weight. Mineral apposition rate (MAR) and bone formation rate (BFR, equivalent to bone turnover rate) decreased. The BFR at 3 months was approximately 11 times in males and 15 times in females higher than that at 2 years when bone metabolism was of adult type. From 2 to 10 years of age, BV/TV or Th. Tb. did not remarkably change, whereas both MAR and BFR had a tendency to decrease gradually with age. Parathyroid hormone level increased from 3 months to 17 years. Testosterone level increased up to 2 years and remained almost constant thereafter. Serum osteocalcin, alkaline phosphatase, and phosphorus decreased rapidly up to 2 years, although calcium did not change with age. Effects of swimming (exercise) and lactate calcium on osteoporotic bones in rats were examined. The BV/TV and Th. Tb. increased, but the MAR and BFR were improved to be sustained. These changes were promoted by the administration of calcium and vitamin D3. Toxicological study on DTPA revealed the following results: (1) Both hypocalcemia, following an increase of blood pressure, and heart failure were observed by iv injection of Zn-DTPA, but not observed by iv injection of Ca-DTPA. When DTPA was given orally, Ca-DTPA was more toxic than Zn-DTPA. DTPA toxicity induced dysfunction of the kidney and liver, hemorrhage and congestion in the lamina propria, and vascular expansion of the small intestine. Vascular permeability was also enhanced by either Ca-DTPA or Zn-DTPA. DTPA toxicity was found to be manifested by disturbed cardiovascular system. (Namekawa, K)