Male and female Sprague Dawley rats were injected intraperitoneally for 4 weeks with ammonium trichloro (dioxyethylene-0-0'-) tellurate, an immunomodulating drug at doses ranging from 3 to 24 mg/kg/week. Routine laboratory examinations included body weight, food consumption, clinical chemistry and hematological examinations. At termination of the experiment, all rats were sacrificed and subjected to a detailed necropsy. Few mortalities were recorded during the course of the study. Clinical signs included hind limb paresis and paraphimosis. A garlic odor pervaded the room. Body weight and food consumption were adversely affected in a dose-related manner. Effects were elicited on the hematological system; changes being noted in the platelet and leukocyte counts as well. Clinical chemistry evaluation revealed signs of hepatoxicity, especially in the female treated groups. The level of beta-globulin was increased. At necropsy organs were found to have a grayish-blue discoloration. Tellurium related histopathological changes were observed in the eyes, liver, thymus, bone marrow, heart and kidneys. An attempt has been made to compare the toxicity of this drug with other tellurium-containing compounds. A good correlation was found. Novel effects of the drug were retinopathy and replacement of bone marrow by bony or fibrous tissue. The possibility that some of the effects may have been elicited due to selenium-vitamin E deficiency has been considered.
Subchronic oral exposure of dogs to Oxodipine, a new calcium channel blocker of the dihydropyridine-type, resulted in dose-related gingival hyperplastic changes. The doses at which an effect was elicited were 24 and 73 times the intended therapeutic dose for man. The effects were first noted after 7 weeks of treatment, and were limited to the high and intermediate dose groups of both sexes. Macroscopically, a generalized enlargement of the maxillary and mandibular facial and lingual gingivae were noted. The histological changes were similar to those described in man for Nifedipine and hydantoin-related drugs. An increase in the activity of alkaline phosphatase and a decrease in alanine aminotransferase was demonstrated. This article is the first to describe gingival hyperplasia in dogs induced in a dose-dependent manner by a calcium channel blocker.
The microscopic features of a spontaneous uterine granular cell tumour in a Fischer 344 rat are described. The location of the tumour is novel for the rat. The neoplasm is characterized by the presence of cells with cytoplasmic granules which were PAS positive and diastase resistant. Electron microscopy and immunohistochemistry results are presented and the origin of the tumour is discussed.
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