Gadolinium chloride toxicity in the rat.
Groups of 10 male and 10 female Sprague-Dawley rats were given a single intravenous injection of gadolinium chloride solution at dosages of 0 (saline vehicle), 0.07, 0.14, and 0.35 mmol/kg. Apart from 1 top-dose female, which died during dosing, 5 rats/sex/ group were necropsied 48 hr postdose, and the remaining 5 rats/sex/group were necropsied 14 days postdose. Macroscopic, hematological, and clinical chemistry analyses were undertaken on all animals that were necropsied. Histopathological examination was undertaken on all organs from high-dose and control animals necropsied 48 hr postdose and on tissues that showed treatment-related changes from all other rats necropsied either 48 hr or 14 days postdose. Major lesions related to gadolinium chloride administration consisted of mineral deposition in capillary beds (particularly lung and kidney), phagocytosis of mineral by the mononuclear phagocytic system, hepatocellular and splenic necrosis followed by dystrophic mineralization, mineralization of the fundic glandular mucosa in the absence of necrosis followed by mucous cell hyperplasia, decreased platelet numbers and increased prothrombin time, and activated partial thromboplastin time. Electron microscopy and x-ray microanalysis of the spleen and liver revealed electron-dense deposits in splenic macrophages, Kupffer cells, and hepatocytes composed of gadolinium, calcium, and phosphate.
Spencer
A J
AJ
Sanofi Research Division, Alnwick Research Centre, Northumberland, United Kingdom.
Wilson
S A
SA
Batchelor
J
J
Reid
A
A
Rees
J
J
Harpur
E
E
D000311:Adrenal Glands / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002319:Cardiovascular System / Q000187:drug effects / Q000473:pathology; D003287:Contrast Media / Q000633:toxicity*; D005260:Female; D005682:Gadolinium / Q000633:toxicity*; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology; D014551:Urinary Tract / Q000187:drug effects / Q000473:pathology
D003287:Contrast Media; D005682:Gadolinium; C038958:gadolinium chloride