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Biomedical subjects

P E Owen

Publications and source records attributed to P E Owen.

5 recordsLinked to original sources

Inhalation toxicity and carcinogenicity of 1,3-butadiene in Sprague-Dawley rats.

A 2-year inhalation study was conducted in Sprague-Dawley rats with 1,3-butadiene. Groups of 110 male and 110 female rats inhaled 1,3-butadiene at 0, 1000, or 8000 ppm for 6hr/day, 5 days/week. Interim clinical pathology, neuromuscular, and histopathology investigations were carried out. The study terminated at 20 to 25% survival (105 weeks for females, 111 weeks for males). Following exposure to 1,3-butadiene there were no effects on hematology, blood chemistry, urine analysis, and neuromuscular function that definitely could be associated with treatment. Treatment was associated with changes in clinical condition, suppression of body weight gain, reduced survival, and increases in certain organ weights and in both common and uncommon tumor types. Although the biological interpretation of the significance of some of the tumor types is equivocal, the evidence suggests that the test article is an oncogen to the rat under the conditions of exposure used in this study, and the mechanism is more likely to be an indirect effect through the endocrine system, rather than a direct effect through the production of reactive metabolites.

Air Pollutants, Occupational↗

Inhalation toxicity studies with 1,3-butadiene. 3. Two year toxicity/carcinogenicity study in rats.

Groups of 110 male and 110 female CD (Sprague-Dawley) rats were exposed to atmospheres containing 0 (control), 1000 or 8000 ppm v/v butadiene for 6 hr/day and 5 days/week. Ten of each sex from each group were killed at 52 weeks. The study was terminated when it was predicted that survival would drop to 20% to 25% (105 weeks for females and 111 weeks for males). High dose rats had wet, ruffled fur and showed slight incoordination during the first exposure each week. During the second year, mortality in both treated female groups was increased because of humanitarian sacrifice of animals with large subcutaneous masses, while increased mortality in the high dose males was accompanied by an increase of the severity of nephropathy. Body weight was slightly lower than controls in both sexes at the high dose, but statistically significant only over the first 12 weeks. There were no effects in hematological analyses or tests of neuromuscular function that definitely could be associated with treatment. Liver weights at both doses were increased in both sexes with no associated pathological change. Kidney weight was increased in males at the high dose, together with an increase in the severity of nephrosis. There were increases in the incidences of pancreatic exocrine adenoma (high dose, male); uterine sarcoma (both doses, female); Zymbal gland carcinoma (high dose, female); mammary tumors (both doses, female); thyroid follicular cell tumors; and testis Leydig-cell tumors (high dose). These data suggest that butadiene is a weak oncogen to the rat under the conditions of exposure used in this study.

Administration, Inhalation↗

Subchronic inhalation toxicology of carbon fibers.

Male Sprague Dawley rats were exposed to carbon fibers 7 microns in diameter and 20 to 60 microns in length, for six hours a day and five days a week for up to 16 weeks at an average chamber concentration of 20 mg/m3. Rats were killed at 4, 8, 12, and 16 weeks of exposure and after a 32-week postexposure recovery period. A similar number of control rats exposed only to air were killed at the same times. Pulmonary function tests, conducted just prior to the animals' death, did not demonstrate any significant or consistent changes. The only pulmonary finding that could be causally related to the subchronic inhalation of carbon fibers was phagocytosis of the inhaled particles by alveolar macrophages. This physiologic response was not accompanied by any local reactive pulmonary inflammation or fibrosis.

Animals↗

Determination of ranitidine and its metabolites in human urine by reversed-phase ion-pair high-performance liquid chromatography.

A method using ion-pair high-performance liquid chromatography is presented for determining ranitidine, ranitidine N-oxide, ranitidine S-oxide and desmethyl ranitidine in the urine from four volunteers, given on separate occasions an intravenous and oral dose of 100 mg ranitidine. This method has been used to study the metabolism and pharmacokinetics of ranitidine by man. It was found that the elimination half-life of ranitidine ranged from 110-246 min. The mean renal clearance of ranitidine in these four volunteers was 512 ml/min.

Chromatography, High Pressure Liquid↗