The Experts below are selected from a list of 1980 Experts worldwide ranked by ideXlab platform

Yasuhiko H. Mori - One of the best experts on this subject based on the ideXlab platform.

M. W. Anders - One of the best experts on this subject based on the ideXlab platform.

  • Invivo metabolism of the Hydrochlorofluorocarbon 1,1-dichloro-1-fluoroethane (HCFC-141b)
    Biochemical pharmacology, 1991
    Co-Authors: James W. Harris, M. W. Anders
    Abstract:

    Abstract Hydrochlorofluorocarbons (HCFCs) are being developed as substitutes for chlorofluorocarbons (CFCs) that deplete stratospheric ozone (1). 1,1-Dichloro-1-fluoroethane (HCFC-141b) is a potential substitute for CFC-11 in foam-blowing operations (2), and a mixture of HCFC-141b and HCFC-123 is an effective substitute for CFC- 113 which is used as a cleaning agent in the computer industry (3). U.S. production of CFC-11 and CFC-113 in 1986 amounted to 90,000 and 79,000 metric tons, respectively. [ 36 Cl]HCFC-141b undergoes dechlorination when incubated with rat hepatic microsomal fractions in the presence of NADPH and oxygen (4), but no organic metabolites have been identified. Because of the potential commercial importance of HCFC-141b, the accompanying potential for human exposure, and the paucity of published information about its metabolism, we have studied its in vivo metabolic fate. Also, knowledge about the metabolism of HCFC-141b may have predictive value for the metabolism of other 1,1,1-trihaloethanes that are promising CFC substitutes.

  • Metabolism and toxicity of Hydrochlorofluorocarbons: current knowledge and needs for the future.
    Environmental health perspectives, 1991
    Co-Authors: M. W. Anders
    Abstract:

    Hydrochlorofluorocarbons (HCFCs) are being developed as replacements for chlorofluorocarbons (CFCs) that deplete stratospheric ozone. The depletion of stratospheric ozone may increase the intensity...

  • Metabolism of the Hydrochlorofluorocarbon 1,2-dichloro-1,1-difluoroethane.
    Chemical research in toxicology, 1991
    Co-Authors: James W. Harris, M. W. Anders
    Abstract:

    1,2-Dichloro-1,1-difluoroethane (HCFC-132b) is a potential substitute for some ozone-depleting chlorofluorocarbons and a model for other 1,1,1,2-tetrahaloethanes under consideration as chlorofluorocarbon substitutes. Male Fischer 344 rats were given 10 mmol/kg HCFC-132b dissolved in corn oil by intraperitoneal injection. An NMR assay for covalent binding of HCFC-132b metabolites to liver proteins was negative, whereas binding was observed in halothane-treated rats. Total urinary metabolites excreted by rats given HCFC-132b during the first 24 h amounted to 1.8 +/- 0.1% of the injected dose, as determined by 19F NMR. During the first 6 h, metabolites of HCFC-132b corresponding to 2-chloro-2,2-difluoroethyl glucuronide, unknown metabolite A, chlorodifluoroacetic acid, and chlorodifluoroacetaldehyde hydrate [both free and conjugated (unknown metabolite B)] were excreted in urine in the approximate ratio 100:9:3:7, respectively. Metabolite A is apparently an O-conjugate of 2-chloro-2,2-difluoroethanol; unconjugated 2-chloro-2,2-difluoroethanol was not detected in urine. The 19F NMR spectrum of metabolite B indicates the formation of a hemiacetal of chlorodifluoroacetaldehyde. Repeated exposure of rats to HCFC-132b significantly increased both the rate of chlorodifluoroacetic acid excretion and the relative fraction of the HCFC-132b dose excreted as chlorodifluoroacetic acid in urine. Incubation of HCFC-132b with rat hepatic microsomes yielded chlorodifluoroacetaldehyde hydrate as the only fluorinated product. The in vitro metabolism of HCFC-132b was increased in microsomes from pyridine-treated rats as compared with control rats, and HCFC-132b metabolism was inhibited by p-nitrophenol, indicating that the cytochrome P-450 isoform IIE1 is largely responsible for the initial hydroxylation of HCFC-132b.

Ryo Ohmura - One of the best experts on this subject based on the ideXlab platform.

George M. Rusch - One of the best experts on this subject based on the ideXlab platform.

  • The development of environmentally acceptable fluorocarbons.
    Critical reviews in toxicology, 2018
    Co-Authors: George M. Rusch
    Abstract:

    AbstractChlorofluorocarbons (CFCs) were introduced in the 1930s as the safe replacements for the toxic and flammable refrigerants being used at that time. Subsequently, Hydrochlorofluorocarbons (HC...

  • Inhalation toxicity and genotoxicity of Hydrochlorofluorocarbon (HCFC)-225ca and HCFC-225cb.
    Journal of applied toxicology : JAT, 1999
    Co-Authors: William J. Brock, George M. Rusch, Seiji Shin-ya, Colin J. Hardy, Henry J. Trochimowicz
    Abstract:

    The acute, subchronic and genetic toxicity of the Hydrochlorofluorocarbons HCFC-225ca and HCFC-225cb were evaluated to assist in establishing proper handling guides. In acute inhalation studies, rats were exposed for 4h to various concentrations of each isomer. Based on the mortality incidence, the LC 50 value for HCFC-225cb for males and females (combined) was 36 800 ppm. For HCFC-225ca, the LC 50 for males and females (combined) was 37 300 ppm. Narcotic-like effects, e.g. prostration, incoordination and reduced motor activity, were observed during exposure to either isomer, but these signs were not evident 15 min after termination of exposure. Histopathological examination of the liver revealed an increase in mitotic figures with vacuolation of hepatocytes and fluid-filled, congested hepatic sinusoids. In cardiac sensitization studies, HCFC-225cb induced a cardiac sensitization response at 20000 ppm, with one fatal response, whereas a blend of the two isomers (45% HCFC-225ca/55% HCFC-225cb) produced a cardiac sensitization response at 15 000 ppm. In 4-week subchronic inhalation studies, male and female rats were whole-body exposed to HCFC-225cb at concentrations of 0, 1000, 5000 or 15 000 ppm for 6 h a day, 5 days per week. Similarly, male and female rats were whole-body exposed to HCFC-225ca concentrations of 0, 50, 500 or 5000 ppm for 6h a day, 5 days per week. During exposure, narcotic-like and irritant effects were observed. A dose-related decrease in cholesterol and triglycerides was observed in the treated rats, with males being affected more than females. Increases in liver weight were observed in most male and female rats exposed to either isomer. The increase in liver weight was consistent in male rats with microscopic evidence of hepatocyte hypertrophy. Although liver weight was increased in female rats, no hepatocyte enlargement was observed in treated female rats. Increases in cytochrome P-450 and β-oxidation activities were also observed in male and female rats exposed to either isomer. Neither of the HCFC-225 isomers was mutagenic in the Ames reverse mutation assay, or clastogenic in the chromosomal aberration assay with Chinese hamster lung cells. Also, neither isomer induced unscheduled DNA synthesis in liver cells. However, both isomers were clastogenic in the chromosomal aberration assay with human lymphocytes in the absence of S-9. No increases in aberrant cells were observed in activated cells exposed to either isomer.

  • Two-Year Inhalation Toxicity Study in Rats with Hydrochlorofluorocarbon 123
    Fundamental and applied toxicology : official journal of the Society of Toxicology, 1995
    Co-Authors: Linda A. Malley, David P. Kelly, George M. Rusch, Michael C. Carakostas, John F. Hansen, Henry J. Trochimowicz
    Abstract:

    Abstract Two-Year Inhalation Toxicity Study in Rats with Hydrochlorofluorocarbon 123. Malley, L. A., Carakostas, M., Hansen, J. F., Rusch, G. M., Kelly, D. P., and Trochimowicz, H. J. (1995). Fundam. Appl. Toxicol. 25, 101-114. 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.

  • Subchronic Inhalation Toxicity Studies with Hydrochlorofluorocarbon 123 (HCFC 123)
    Toxicological Sciences, 1994
    Co-Authors: George M. Rusch, John C. Peckham, Henry J. Trochimowicz, Linda J. Malley, David P. Kelly, John E. Hansen, Joel B. Charm
    Abstract:

    Abstract Subchronic Inhalation Toxicity Studies with Hydrochlorofluorocarbon 123 (HCFC 123). Rusch, G. M., Trochimowicz, H. J., Malley, L. J., Kelly, D. P., Peckham, J., Hansen, J., and Charm, J. B. (1994). Fundam. Appl. Toxicol. 23, 169-178. Hydrochlorofluorocarbon 123 (HCFC 123) is one of the chemicals being considered as a replacement for the chlorofluorocarbons. Four subchronic inhalation toxicity studies from 1 to 3 months in duration have been conducted with HCFC 123. One study utilized rats and dogs, while the others were limited to rats only. The exposure levels have ranged from 300 ppm up to 20,000 ppm. Although the studies were conducted over a 14-year period, the results were consistent. In all studies, increases in liver weights were seen at 1000 ppm and above; additionally, one showed this effect at 500 ppm. Histopathological findings were minimal, consisting primarily of focal necrosis in the liver of the dogs at 10,000 ppm. Induction of peroxisomal activity, lowering of serum cholesterol and triglyceride levels, and an increase in urinary fluoride levels were also seen. The 4-hr LC 50 in the rat has been reported as 35,000 ppm. At 20,000 ppm for 6 hr, the total daily dose on a concentration times time basis is almost equal to the LC 50 , yet, in the 4-week study, with 20 exposures at this level, there was no mortality or even marked signs of toxicity. There appeared to be no evidence for cumulative toxicity from multiple exposures in these studies. Overall, HCFC 123 appears to have a low level of toxicity by the inhalation route.

Mikio Ogawa - One of the best experts on this subject based on the ideXlab platform.