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M Carakostas

Publications and source records attributed to M Carakostas.

4 recordsLinked to original sources

Subchronic toxicity and teratogenicity of 2-chloro-1,1,1,2-tetrafluoroethane (HCFC-124).

Inhalation studies were conducted to determine the potential toxicity of HCFC-124. Groups of rats and mice were exposed to HCFC-124 6 hr/day, 5 days/week for 13 weeks at 0, 5000, 15,000, and 50,000 ppm. Subgroups of rats and mice were held for a 1-month recovery period. A functional observational battery (FOB) was conducted on rats at 0, 4, 13, and 16 weeks. Clinical pathology evaluations were conducted at 7, 13, and 17 weeks. Thirteen or 17 weeks after study initiation, rats and mice underwent gross and microscopic evaluation, and livers were evaluated for hepatic beta-oxidation activity. In addition, groups of female rats and rabbits were exposed to HCFC-124 by inhalation during gestation to 0, 5000, 15,000, or 50,000 ppm. Exposure of rats and mice to HCFC-124 caused minimal compound-related effects. Compound-related changes occurred in several clinical pathology parameters in rats and mice. Hepatic beta-oxidation activity was significantly higher in 5000, 15,000, and 50,000 ppm male mice; however, there were no compound-related effects on beta-oxidation activity in rats. During the daily exposures, rats, mice, and rabbits exposed to 50,000 ppm were less responsive to auditory stimuli or less active compared to controls. At the 13-week FOB, male rats exposed to 15,000 or 50,000 ppm had decreased arousal. There were no compound-related effects on mortality, clinical signs, ocular tissues, hematology parameters, organ weights, and tissue morphology at any concentration in rats or mice. Maternal toxicity in rats was evident by a significant decrease in weight gain and food consumption at 50,000 ppm. Similarly, 50,000 ppm pregnant rabbits had lower food consumption. However, for both rats and rabbits, there was no evidence of fetal toxicity at any concentration.

Administration, Inhalation↗

Two-year inhalation toxicity study in rats with hydrochlorofluorocarbon 123.

The potential chronic toxicity and oncogenicity of hydrochlorofluorocarbon 123 (HCFC-123) was evaluated by exposing male and female rats to 0, 300, 1000, or 5000 ppm HCFC-123 for 6 hr/day, 5 days/week, for 2 years. Clinical pathology was evaluated at 6, 12, 18, and 24 months. An interim termination and measurements of hepatic cell proliferation and beta-oxidation activity were conducted at 12 months. The terminal euthanization occurred at 24 months. Males and females exposed to 5000 ppm and females exposed to 300 or 1000 ppm had lower body weights and body weight gains. Serum triglyceride and glucose concentrations were significantly decreased at all exposure concentrations in both sexes. Serum cholesterol was also lower in 300, 1000, and 5000 ppm females and in 5000 ppm males. Alterations in serum protein concentrations occurred at 300, 1000, and 5000 ppm. Survival was higher in 1000 and 5000 ppm males and females. At 24 months, increased relative liver weight occurred in 5000 ppm males, and decreased absolute kidney weight occurred in 5000 ppm males and in 1000 and 5000 ppm females. Benign hepatocellular adenomas were increased in 5000 ppm males and in all test groups of females. Hepatic cholangiofibromas were also increased in 5000 ppm females. Pancreatic acinar cell adenomas were increased in all test groups of males, and acinar cell hyperplasia was increased in the 1000 and 5000 ppm males and females. Benign testicular interstitial adenomas and focal interstitial cell hyperplasia were also increased in all male test groups compared to controls. Diffuse retinal atrophy was increased in all male and female test groups, but it was considered to be an indirect compound-related effect. Hepatic beta-oxidation activity (peroxisome proliferation) was higher in 300, 1000 and 5000 ppm males and 1000 and 5000 ppm females. Compound-related differences in the rate of hepatic cell proliferation were not observed at any exposure concentration. Decreased incidences of a variety of age-related lesions occurred at 1000 and 5000 ppm.

Administration, Inhalation↗

Clinical pathology testing recommendations for nonclinical toxicity and safety studies. AACC-DACC/ASVCP Joint Task Force.

Clinical pathology testing in nonclinical toxicity and safety studies is an important part of safety assessment. In recent years, clinical laboratory testing has rapidly expanded and improved. Some government regulatory agencies provide guidelines for clinical pathology testing in nonclinical toxicity and safety studies. To improve these testing guidelines and the resultant safety assessments, the American Association for Clinical Chemistry's Division of Animal Clinical Chemistry and the American Society for Veterinary Clinical Pathology formed a joint committee to provide expert recommendations for clinical pathology testing of laboratory species involved in subchronic and chronic nonclinical toxicity and safety studies. These recommendations include technical recommendations on blood collection techniques and hematology, serum chemistry, and urinalysis tests.

Animals↗