Safety evaluation studies on oxisuran, a differential inhibitor of cell-mediated hypersensitivity
| Autor: | E. Schwartz, D. Abrutyn, J.A. Tornaben, G. Briziarelli |
|---|---|
| Rok vydání: | 1976 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Dose Pyridines Thyroid Function Tests Toxicology Thyroid function tests Median lethal dose Transaminase Iodine Radioisotopes Lethal Dose 50 Mice Dogs Internal medicine medicine Animals Pharmacology medicine.diagnostic_test business.industry Body Weight Thyroid Histology Organ Size Hyperplasia medicine.disease Rats Endocrinology medicine.anatomical_structure Female Rabbits Thyroid function business |
| Zdroj: | Toxicology and Applied Pharmacology. 36:49-64 |
| ISSN: | 0041-008X |
| DOI: | 10.1016/0041-008x(76)90026-0 |
| Popis: | Preclinical toxicity studies were conducted on oxisuran, 2-[(methylsulfinyl) acetyl]-pyridine, an immunosuppressant with selective inhibition of cell-mediated hypersensitivity. Oral LD50 values were 5280 and 6610 mg/kg in female mice and rabbits, respectively, and 6550 mg/kg in female and male rats. An LD50 could not be established in dogs because of emesis at a dose of 5000 mg/kg. Intravenous LD50 values were 2510 mg/kg for mice and 1800 mg/kg for female and male rats. Feeding the drug in the diet to rats at dosages of 20, 100, 300, and 1000 mg/kg for 13 weeks caused a slight reduction in food consumption and body weight gain at the higher dosages. At doses of 100, 300, and 1000 mg/kg, cloudy swelling and fatty infiltration of the liver and hyperplasia of the thyroid occurred in dose-related patterns (mild to moderate) in many animals. No significant changes were found in thyroid function studies which included thyroid uptake ( 125 I) and T 3 and T 4 determinations. The thyroid hyperplasia seen at 13 weeks disappeared within a few days of drug withdrawal. Oral daily administration of 20, 125, 500, and 2000 mg/kg of oxisuran to dogs for 13 weeks produced a decrease in food consumption and body weight in the latter phase of the study in the males treated with the high dose. Serum glutamic-pyruvic transaminase was mildly elevated in dogs given 2000 mg/kg. At this dose, some animals showed slightly increased thyroid and liver weights. Histologically, thyroid hyperplasia was moderate in females (2000 mg/kg) and mild to moderate in males (125, 500, and 2000 mg/kg). The liver, in the animals of the high-dose group showed a slight degree of vacuolar changes and bile retention. Thyroidal radioiodine uptake ( 125 I), PBI, TI, and serum cholesterol were slightly below normal values. The histology and function tests of the thyroid were within normal ranges at 4 weeks post-treatment. |
| Databáze: | OpenAIRE |
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