Distribution, localization, and pulmonary effects of yttrium chloride following intratracheal instillation into the rat.
Metabolic behavior and pulmonary toxicity of yttrium chloride (YCl3) deposited in the lung was investigated. Yttrium chloride was instilled intratracheally into rats and the time-course and dose-related changes in distribution of Y between lung tissue and bronchoalveolar lavage fluid (BALF) and pulmonary inflammatory responses were investigated. Pulmonary clearance of Y was very slow and the half-life was estimated to be 168 days. Yttrium content in the supernatant of BALF did not exceed 5 micrograms Y/lung even when a dose of 200 micrograms Y/rat was administered, suggesting that the alveolar surface fluid could retain at most 5 micrograms Y. On the other hand, Y content in the pellet of BALF changed with the number of macrophages retrieved in BALF in both time-course and dose-response experiments. Transmission electron microscopy and X-ray microanalysis suggested that Y was localized in lysosomes of alveolar and interstitial macrophages, and basement membranes. These results clearly explain the long pulmonary half-life of Y. beta-Glucuronidase activity and calcium and phosphorous contents in the supernatant of BALF increased significantly even at the lowest dose (10 micrograms Y/rat). Comparative dose-effect profiles of lactate dehydrogenase activity in BALF supernatant revealed that 1 mol of YCl3 is equivalent to about one-third mole of cadmium compounds and about 3 mol of zinc oxide in the potency for acute pulmonary toxicity.
Hirano
S
S
National Institute for Environmental Studies, Ibaraki, Japan.
Kodama
N
N
Shibata
K
K
Suzuki
K T
KT
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis / Q000201:enzymology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005966:Glucuronidase / Q000378:metabolism; D006207:Half-Life; D007442:Intubation, Intratracheal; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008264:Macrophages / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009504:Neutrophils / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D015019:Yttrium / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity
C064782:yttrium chloride; D015019:Yttrium; D007770:L-Lactate Dehydrogenase; D005966:Glucuronidase