Impairment of calcium homeostasis by hexachlorobenzene (HCB) exposure in Fischer 344 rats.
Human exposure to hexachlorobenzene (HCB) has resulted in demineralization of bone and development of osteoporosis. Experiments were undertaken to investigate the effects of HCB on the homeostatic mechanism of calcium metabolism. Fischer 344 rats were dosed with 0, 0.1, 1.0, 10.0, or 25.0 mg HCB/kg body weight 5 d/wk for 5 wk while being fed normal rat diet or vitamin D3-deficient diet. Rats receiving the normal diet had a dose-related decrease in body weight gain and increased liver weight when compared to their controls. Serum cholesterol, alanine aminotransferase (ALT), 1, 25-dihydroxy-vitamin D3 [1,25-(OH)2D3], and parathyroid hormone (PTH) were significantly elevated when compared to control values. In the vitamin D3-deficient diet group, there was a dose related increase in liver weight, liver-to-body weight ratio and kidney-to-body weight ratio. Serum cholesterol and 1,25-(OH)2D3 were significantly elevated. Urinary calcium decreased significantly with increasing HCB dosage, indicating conservation of calcium. The data from this study indicate that HCB does affect calcium metabolism by altering the concentrations of two primary controlling factors in calcium homeostasis.
Andrews
J E
JE
Inhalation Toxicology Division, Health Effects Research Laboratory, Research Triangle Park, North Carolina.
Courtney
K D
KD
Donaldson
W E
WE
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002722:Chlorobenzenes / Q000633:toxicity*; D002784:Cholesterol / Q000097:blood; D006581:Hexachlorobenzene / Q000633:toxicity*; D006706:Homeostasis / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010758:Phosphorus / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014808:Vitamin D Deficiency / Q000378:metabolism*
D002722:Chlorobenzenes; D010758:Phosphorus; D006581:Hexachlorobenzene; D002784:Cholesterol; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D002118:Calcium