ABSTRACT
2,3,3,3-Tetrafluoropropene (HFO-1234yf) is being developed as a refrigerant because it has a very low global warming potential (less than 10), as contrasted to the hydrofluorocarbons, which is intended to replace with values of over 500. Several toxicology studies were conducted to develop a toxicology profile for this material. There was no lethality in mice and rats receiving single 4-hour exposures up to 101,850 or 405,800 ppm, respectively. Additionally, there was no mortality or clinical signs of toxicity when rabbits were exposed to 100,000 ppm for 1 hour. Exposures up to 120,000 ppm did not induce cardiac sensitization to adrenalin in dogs. Rats were exposed to HFO-1234yf at levels of 5000, 20,000 and 50,000 ppm 6 hours/day 5 days/week for 2 weeks and at levels of 5000, 15,000 and 50,000 ppm for 4 weeks and for 90 days. No treatment-related adverse effects were noted in these studies. HFO-1234yf was not genotoxic in a mouse and a rat micronucleus assay, and unscheduled DNA synthesis assay and was not clastogenic in human lymphocytes. HFO-1234yf was mutagenic to Salmonella typhimurium TA 100 and Escherichia coli (WP2 uvrA) at concentrations of 20% and higher in the presence of metabolic activation only. There were no biologically significant effects in a rat developmental toxicity study with exposures up to 50,000 ppm.
Subject(s)
Chromosome Aberrations/chemically induced , Escherichia coli/drug effects , Fluorocarbons/toxicity , Salmonella typhimurium/drug effects , Animals , Bronchial Provocation Tests , DNA Replication/drug effects , Dogs , Dose-Response Relationship, Drug , Female , Humans , Male , Mice , Micronucleus Tests , Rabbits , Rats , Rats, Sprague-Dawley , Refrigeration/methods , Time Factors , Toxicology/methodsABSTRACT
HFO-1234ze is being developed as a refrigerant, propellant, and foam-blowing agent because it has a very low global warming potential (less than 10), as contrasted to the hydrofluorocarbons with values of over 500. Several toxicology studies were conducted to develop a toxicology profile for this material. There was no lethality in mice and rats receiving single 4-hour exposures up to 103,300 or 207,000 ppm, respectively. Exposures up to 120,000 ppm did not induce cardiac sensitization to adrenalin. Rats were exposed to HFO-1234ze at levels of 5,000, 20,000, and 50,000 ppm 6 hours/day 5 days/week for 2 weeks. Predominate findings of increased liver and kidney weights and histopathological changes in the liver and heart suggested that these organs were the targets for HFO-1234ze toxicity. In a 4-week study at 1000, 5000, 10,000, and 15,000 ppm, the only organ showing treatment-related effects was the heart. In a 90-day study with exposures of 1500, 5000, and 15,000 ppm 6 hours/day 5 days/week, again, the heart was the only target organ. The findings consisted of focal and multifocal mononuclear cell infiltrates in the heart. There was no evidence of fibrosis, and, when compared to the 2- and 4-week studies, there did not appear to be an increase in severity with length of exposure. HFO-1234ze was inactive in a mouse and rat micronucleus assay, an Ames assay, and an unscheduled DNA synthesis assay and was not clastogenic in human lymphocytes. It was also not a developmental toxin in either the rat or rabbit, even at exposure levels up to15,000 ppm.
Subject(s)
Aerosol Propellants/toxicity , Fluorocarbons/toxicity , Toxicity Tests/methods , Administration, Inhalation , Aerosol Propellants/administration & dosage , Animals , Dose-Response Relationship, Drug , Female , Fluorocarbons/administration & dosage , Global Warming , Heart/drug effects , Humans , Kidney/drug effects , Kidney/metabolism , Liver/drug effects , Liver/pathology , Lymphocytes/drug effects , Lymphocytes/metabolism , Male , Mice , Organ Size/drug effects , Rabbits , Rats , Rats, Sprague-Dawley , Species Specificity , Time FactorsABSTRACT
The effects of cyclosporin A (CY) and cyclophosphamide (CPS) on Peyer's patches (PP) were studied in Wistar rats, exposed in utero and neonatally or during adult age. In one study, pregnant dams received 5 or 15 mg/kg bw/day CY from gestation day 6 to day 21 of lactation. In two other studies, animals were exposed at young adult age: female rats received orally 5 or 20 mg/kg/day CY or 5 or 10 mg/kg bw CPS for 4 weeks; males received orally 5 mg/kg bw CPS for 4 weeks, or a single i.v. injection of 50 mg/kg bw CPS. Upon in utero and neonatal exposure, the numbers of grossly observed PP were increased in male pups from the high-dose CY dams at 70 days of age. Exposure to high-dose CY at adult age only tended to decrease the numbers of PP; germinal center development was reduced in the PP from the middle segment of the small intestines, as examined microscopically. Exposure to both doses CPS at adult age reduced the numbers of PP and reduced germinal centre development and the number of lymphocytes in all compartments of PP. It was concluded that the effects of CPS and CY could be established by counting the number of grossly visible PP and by microscopic observation of PP, provided that regional differences of PP were taken into account. Moreover, the type of effects of an immunotoxic agent may vary with age of exposure.
