Abstracts
Dichlorodifluoromethane (Freon 12)
CAS No. 75-71-8
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Adverse Effects

NTIS Reports

ACTIVITY: Insecticide, Fungicide Propellant, EPA List 2 Inert (Halogenated organic)

Also known as Freon 12

Structure:

•• See FAN's compilation of reports from
The National Technical Information Service (NTIS)


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11405255&dopt=Abstract

Neurotoxicology. 2001 Apr;22(2):233-48.

Acute neurobehavioral effects in rats from exposure to HFC 134a or CFC 12.

Ritchie GD, Kimmel EC, Bowen LE, Reboulet JE, Rossi J 3rd.

Geo-Centers, Inc., Wright-Patterson Air Force Base (WPAFB), OH 45433-7903, USA. glenn.ritchie@wpafb.af.mil

1,1,1,2-Tetrafluoroethane (HFC 134a), a chlorine-free hydrofluoroalkane, is internationally replacing billions of pounds of dichlorodifluoromethane (CFC 12) for coolant, refrigerant and aerosol propellant applications. The ALC50 for HFC 134a in rats is 567,000 ppm for 4 h; its potential for cardiac epinephrine sensitization in beagle dogs is acceptable (75,000 ppm); and its capacity to induce carcinogenicity or developmental disorders in animals is minimal. HFC 134a, with a serum half life estimated at 4-11 min, has been accepted for use as a propellant in metered-dose inhalant products, implying a low human toxicity risk from periodic brief exposures. There has been little published human or animal research evaluating possible neurobehavioral toxicity from longer HFC 134a exposures, as may be expected to occur in operational scenarios. In this study, male Wistar rats were exposed to various concentrations of HFC 134a or CFC 12 for up to 30 min while performing in either a rotarod/motorized running wheel apparatus or in an operant chamber The relative neurobehavioral toxicity of CFC 12 and its ozone-depleting substance replacement HFC 134a was assessed by comparing both gross motor system incapacitation and more subtle changes in ability to perform an operant discrimination task. It was shown that exposure to HFC 134a or CFC 12 concentrations from 40,000 to 470,000 ppm, for up to 30 min, induced neurobehavioral deficits in every subject, ranging from reduced operant efficiency to apparent anesthesia. For neurobehavioral endpoints examined in these experiments, HFC 134a inhalation was shown to induce deficits more rapidly, and at lower concentrations when compared to CFC 12 exposure.

PMID: 11405255 [PubMed - indexed for MEDLINE]


From Dart Special at Toxnet

TOXICOL APPL PHARMACOL 29:152,1974

ORAL TOXICOLOGY OF DICHLORODIFLUOROMETHANE

SHERMAN H, BARNES JR, STULA EF

Taxonomic Name: RATTUS

Test Object: MAMMAL, RAT

Name of Agent (CAS RN):
DICHLORODIFLUOROMETHANE ( 75-71-8 )

Assay Method:
VIABILITY, FERTILITY AND MORTALITY
NO ABNORMALITIES OBSERVED


GEBURTSHILFE FRAUENHEILKD 46:335-339,1986

EVALUATION OF EMBRYOTOXIC PROPERTIES OF INDUSTRIAL CHEMICALS

SPIELMANN H

Taxonomic Name: HOMO SAPIENS

Test Object: MAMMAL, HUMAN

Name of Agent (CAS RN): [several were listed]
DICHLORODIFLUOROMETHANE ( 75-71-8 )


EUR J TOXICOL ENVIRON HYG 9(SUPPL):385-407,1976

FLUOROCARBONS IN QUESTION

PAULET G

Taxonomic Name: RATTUS ORYCTOLAGUS

Test Object:
MAMMAL, RAT
MAMMAL, RABBIT

Name of Agent (CAS RN):
DIFLUORODICHLOROMETHANE ( 75-71-8 )
MONOFLUORODICHLOROMETHANE ( 75-43-4 )
FLUOROCARBONS


TOXICOL APPL PHARMACOL 37:151-152,1976

TRIAMCINOLONE ACETONIDE(1,4-PREGNADIENE-3,20-DIONE,9ALPHA-FLUORO-11BETA,21 DIHYDROXY 16ALPHA,17ALPHA-(ISOPROPYLIDENEDIOXY)):AEROSOL INHALATION AND TERATOLOGY STUDIES IN RABBITS

BRAR BS, JACKSON BA, TRAITOR CE, RODWELL DE, BOSHART CR. NOBLE JF

Taxonomic Name: ORYCTOLAGUS, NEW ZEALAND WHITE

Test Object: MAMMAL, RABBIT

Name of Agent (CAS RN):
TRIAMCINOLONE ACETONIDE ( 76-25-5 )
STRESS,RESTRAINT
FREON-12 ( 75-71-8 )


Chemically Induced Birth Defects 1993;2:751-75

Industrial solvents.

Schardein JL

International Research and Development Corporation, Mattawan, MI.

Medical Subject Headings (MeSH):
Pregnancy
Animal
Human
Female

Solvents/*TOXICITY
*Abnormalities, Drug-Induced

Substance (CAS Registry Number): [several were included]
Dichlorodifluoromethane (75-71-8)


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15050396

Sci Total Environ. 2004 Apr 5;321(1-3):201-17.
 
Historical trends in occurrence and atmospheric inputs of halogenated volatile organic compounds in untreated ground water used as a source of drinking water.

Shapiro SD, Busenberg E, Focazio MJ, Plummer LN.

US Geological Survey, MS 432, 12201 Sunrise Valley Drive, Reston, VA 20192, USA.

Analyses of samples of untreated ground water from 413 community-, non-community- (such as restaurants), and domestic-supply wells throughout the US were used to determine the frequency of detection of halogenated volatile organic compounds (VOCs) in drinking-water sources. The VOC data were compiled from archived chromatograms of samples analyzed originally for chlorofluorocarbons (CFCs) by purge-and-trap gas chromatography with an electron-capture detector (GC-ECD). Concentrations of the VOCs could not be ascertained because standards were not routinely analyzed for VOCs other than trichloromonofluoromethane (CFC-11), dichlorodifluoromethane (CFC-12) and 1,1,2-trichloro-1,2,2-trifluoroethane (CFC-113). Nevertheless, the peak areas associated with the elution times of other VOCs on the chromatograms can be classified qualitatively to assess concentrations at a detection limit on the order of parts per quadrillion. Three or more VOCs were detected in 100% (percent) of the chromatograms, and 77.2% of the samples contained 10 or more VOCs. The maximum number of VOCs detected in any sample was 24. Modeled ground-water residence times, determined from concentrations of CFC-12, were used to assess historical trends in the cumulative occurrence of all VOCs detected in this analysis, as well as the occurrence of individual VOCs, such as CFC-11, carbon tetrachloride (CCl(4)), chloroform and tetrachloroethene (PCE). The detection frequency for all of the VOCs detected has remained relatively constant from approximately 1940 to 2000; however, the magnitude of the peak areas on the chromatograms for the VOCs in the water samples has increased from 1940 to 2000. For CFC-11, CCl(4), chloroform and PCE, small peaks decrease from 1940 to 2000, and large peaks increase from 1940 to 2000. The increase in peak areas on the chromatograms from analyses of more recently recharged water is consistent with reported increases in atmospheric concentrations of the VOCs. Approximately 44% and 6.7% of the CCl(4) and PCE detections, respectively, in pre-1940 water, and 68% and 62% of the CCl(4) and PCE detections, respectively, in water recharged in 2000 exceed solubility equilibrium with average atmospheric concentrations. These exceedences can be attributed to local atmospheric enrichment or direct contaminant input to ground-water flow systems. The detection of VOCs at concentrations indicative of atmospheric sources in 100% of the samples indicates that untreated drinking water from ground-water sources in the US recharged within the past 60 years has been affected by anthropogenic activity. Additional inputs from a variety of sources such as spills, underground injections and leaking landfills or storage tanks increasingly are providing additional sources of contamination to ground water used as drinking-water sources.

PMID: 15050396 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15180066

Environ Sci Technol. 2004 May 1;38(9):2685-92.

Standards development of global warming gas species: methane, nitrous oxide, trichlorofluoromethane, and dichlorodifluoromethane.

Rhoderick GC, Dorko WD.

National Institute of Standards and Technology, Analytical Chemistry Division, 100 Bureau Drive, Building 227/Room B120, Gaithersburg, Maryland 20899-8393, USA. george.rhoderick@nist.gov

Environmental scientists from federal agencies, such as the National Oceanic and Atmospheric Administration (NOAA), and academia have long suspected that increasing anthropogenic inputs of various trace gases into the atmosphere can cause changes in the earth's climate and protective ozone layer. Nitrous oxide and methane, cited in the Kyoto Protocol, as well as trichlorofluoromethane (CFC-11) and dichlorodifluoromethane (CFC-12), cited in the Montreal Protocol, are all greenhouse gases and are implicated in the destruction of the stratospheric ozone layer. The lack of national standards prompted research to determine the feasibility of preparing accurate and stable standards containing these four compounds. Development of these standards would support the measurement of these species by those in the atmospheric research community not having their own source of standards. A suite of eight primary gas standards containing methane, nitrous oxide, CFC-11, and CFC-12 in a balance of air were prepared gravimetrically to bracket the ambient atmospheric concentrations. The combined uncertainties (uc) were calculated from error propagation analysis that included the weighing data from the gravimetric preparation and other sources of error such as the purity analysis of the compounds and air matrix. The expanded uncertainties (U) for the gravimetric standards were < 0.5% as calculated from the equation U = kuc, where the coverage factor k is equal to 2 for a 95% confidence interval. Analyses of the suite of standards by gas chromatography with flame-ionization and electron capture detection resulted in average absolute residuals of < 0.25% from regression models. The NIST suite of eight gravimetric standards was used to determine the concentrations in two standardsfrom NOAA. Those analyses resulted in bias across the two laboratories of < or = 2.1%.

PMID: 15180066 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11516020&dopt=Abstract

Environ Monit Assess. 2001 Jul;70(1-2):47-56.

Background monitoring and long-range transport of atmospheric CFC-11 and CFC-12 at Kosan, Korea.

Kim J, Oh SN, Cho HM, Park MK, Kim KR, Elkins JW.

Applied Meteorology Research Laboratory, Meterological Research Institute, Seoul, Korea. jykim@metri.re.kr

The background concentrations of atmospheric CFC-11 and CFC-12 were monitored to assess their impact on stratospheric ozone depletion and global warming from September 1995 to March 1999 at Kosan, Korea, located at eastern margin of the Asian Continent. The concentrations of atmospheric CFC-11 at Kosan have decreased slightly, at a rate of -2.5 pptv yr(-1), over the period in response to the Montreal Protocol. The CFC-12 mixing ratio at Kosan continues to increase in the atmosphere at a rate of 5.7 pptv yr(-1) despite international regulations, because of its extreme atmosphere persistence. Recent trends of these two chlorofluorocarbons at Kosan, Korea were concordant with those of the northern hemispheric background monitored unit at Mauna Loa, Hawaii. The maximum seasonal mean mixing ratios of CFC-11 and CFC-12 at Kosan, Korea, were 270 +/- 4 pptv in the spring and 538 +/- 9 pptv in the winter, and the corresponding seasonal minima were 267 +/- 7 and 529 +/- 12 pptv. This occurred in the summer and was due to southeasterly winds from the northwestern Pacific Ocean. By performing a three-day isentropic backward trajectory analysis, it was shown that air masses at Kosan, and with the exception of summer, mainly originated from central and northern China. In particular, the mixing ratios of these two contaminant species are closely related with their air mass trajectories.

PMID: 11516020 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10914338&dopt=Abstract

J Occup Environ Med. 2000 Jul;42(7):693-703.

Use of a job-exposure matrix to assess occupational exposures in relation to birth defects.

Louik C, Frumkin H, Ellenbecker MJ, Goldman RH, Werler MM, Mitchell AA.

Slone Epidemiology Unit, School of Public Health, Boston University School of Medicine, Brookline, Mass., USA. clouik@slone.bu.edu

Accurate exposure assessment remains a challenge in occupational epidemiology. We evaluated one approach, use of a job-exposure matrix (JEM), by applying the National Institute for Occupational Safety and Health (NIOSH) JEM to a large case-control birth defects study that included parental occupation information. We investigated the JEM exposure predictions in several ways and found that for a substantial proportion of the parents in the birth defects study, the JEM yielded either no exposure data or nonsense predictions. Among exposure predictions that were plausible, most were of low probability. The high probability exposure predictions were statistically unstable, and neither low nor high probability exposure predictions were reliable. There was considerable discrepancy between the JEM predictions and expert assessments for five exposures of interest. Application of the NIOSH JEM to the birth defects study database (and probably other databases as well) does not provide a useful means of assessing occupational exposures.

PMID: 10914338 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8638181&dopt=Abstract

South Med J. 1996 May;89(5):516-8.

Secondary arterial hypertension linked to Freon exposure.

Voge VM.

Naval School of Health Sciences Bethesda Detachment, Fort Sam Houston, Tex., USA.

Freons are generally considered to be minimally toxic. There are no reports in the literature of Freons causing secondary arterial hypertension. We report two cases of acute, massive Freon exposure that preceded secondary arterial hypertension. We hypothesize that the arterial hypertension was precipitated by renal proximal tubular damage, although several other mechanisms are possible.

PMID: 8638181 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7924293&dopt=Abstract

Contact Dermatitis. 1994 Jul;31(1):41-4.

Allergic contact dermatitis from ethyl chloride and sensitization to dichlorodifluoromethane (CFC 12).

Bircher AJ, Hampl K, Hirsbrunner P, Buechner SA, Schneider M.

Department of Dermatology, University Hospital, Basel, Switzerland.

Despite the widespread use of ethyl chloride as a local anesthetic and chlorofluorocarbons as propellants in medical and cosmetic aerosols, contact allergy to these 2 gases is rare. In a 30-year-old woman, an unusual itchy dermatitis appeared at all skin sites where a medical aerosol containing ethyl chloride had been briefly applied. Subsequent re-exposure to the spray and patch tests revealed contact sensitization to ethyl chloride and dichlorodifluoromethane (CFC 12). Histologic and immunohistochemical examinations of the test reaction were consistent with a T-cell-mediated allergic reaction. The low incidence of contact allergy to ethyl chloride and chlorofluorocarbons may be due to the rapid evaporation of these volatile gases, thus preventing intense and prolonged contact with the skin and consequently contact sensitization. A modified patch test procedure using perforated plastic chambers to allow gas evaporation is necessary to test volatile agents.

PMID: 7924293 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8349485&dopt=Abstract

J Am Osteopath Assoc. 1993 Jun;93(6):714-8.

Unexpected adverse effects of Freon 11 and Freon 12 as medication propellants.

Oenbrink RJ.

Metered-dose inhalers are frequently used in treating pulmonary diseases associated with bronchoconstriction, chiefly asthma and chronic bronchitis. These aerosolized medications are not without the potential for adverse effects. The author describes two patients who likely had adverse reactions to the Freon propellants used in the inhalers. These reactions are reported in order to alert physicians to their possible occurrence and to suggest a rational treatment approach.

PMID: 8349485 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8455004&dopt=Abstract

J Forensic Sci. 1993 Mar;38(2):477-83.

Fatality due to recreational use of chlorodifluoromethane and chloropentafluoroethane.

Fitzgerald RL, Fishel CE, Bush LL.

Mass Spectrometry Laboratory, VA Hospital, San Diego, CA.

Reports on fatalities of chlorofluorocarbons usually involve chlorotrifluoroethane, trichlorofluoromethane, dichlorodifluoromethane or chlorodifluoromethane, where analysis was done using packed column gas chromatography. In this case a death was caused by an azeotropic mixture of chlorodifluoromethane and chloropentafluoroethane, a combination that has not previously been reported in the forensic literature. This report details the analysis using mass selective detection employing capillary gas chromatography columns currently used in many toxicology laboratories. Postmortem toxicology revealed blood concentrations of chlorodifluoromethane and chloropentafluoroethane of 71 mg/L and 0.30 mg/L, respectively. Brain, liver, and lung concentrations of chlorodifluoromethane were (mg/kg) 2.8, 4.4, and 1.6, respectively. Brain, liver, and lung concentrations of chloropentafluoroethane were (mg/kg) 0.80, 0.80, and 0.11, respectively. The victim's blood contained 5.5 mg/L caffeine. Lidocaine, used in resuscitation attempts, was also present in the victim's blood. No other alkali-extractable drugs or volatile alcohols were detected in the victim's blood. The cause of death was acute respiratory arrest due to chlorofluorocarbon inhalation.

PMID: 8455004 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1510059&dopt=Abstract

Am J Forensic Med Pathol. 1992 Jun;13(2):115-9.

Atypical autoerotic deaths.

Gowitt GT, Hanzlick RL.

Fulton County Medical Examiner's Office, Atlanta, GA 30303.

So-called "typical" autoerotic fatalities are the result of asphyxia due to mechanical compression of the neck, chest, or abdomen, whereas "atypical" autoeroticism involves sexual self-stimulation by other means. We present five atypical autoerotic fatalities that involved the use of dichlorodifluoromethane, nitrous oxide, isobutyl nitrite, cocaine, or compounds containing 1-1-1-trichloroethane. Mechanisms of death are discussed in each case and the pertinent literature is reviewed.

PMID: 1510059 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3389660&dopt=Abstract

Ann N Y Acad Sci. 1988;534:261-82.

Long-term carcinogenicity bioassays on three chlorofluorocarbons (trichlorofluoromethane, FC11; dichlorodifluoromethane, FC12; chlorodifluoromethane, FC22) administered by inhalation to Sprague-Dawley rats and Swiss mice.

Maltoni C, Lefemine G, Tovoli D, Perino G.

Institute of Oncology F. Addarii, Bologna, Italy.

Three propellant chlorofluorocarbons, namely trichlorofluoromethane (FC11), dichlorodifluoromethane (FC12), and chlorodifluoromethane (FC22) were administered by inhalation at a concentration of 5000, 1000 and 0 ppm, 4 hours daily, 5 days weekly, for 104 and 78 weeks, to rats and mice, respectively. The animals were kept under observation until spontaneous death. Under the experimental conditions, all three compounds failed to show any carcinogenic effects.

PMID: 3389660 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3339298&dopt=Abstract

J Fam Pract. 1988 Jan;26(1):18.

No Abstract available

Freon 12 and verruca lesions.

McDow RA.

Publication Types: Letter

PMID: 3339298 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3427952&dopt=Abstract

Contact Dermatitis. 1987 Oct;17(4):243-5.

No Abstract available

Contact allergic dermatitis caused by freon 12 in deodorants.

Valdivieso R, Pola J, Zapata C, Cuesta J, Puyana J, Martin C, Losada E.

Servicio de Alergia, Hospital Ramon y Cajal, Madrid, Spain.

PMID: 3427952 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3569997&dopt=Abstract

Gig Sanit. 1987 Mar;(3):73-4.

No Abstract available

[Hygienic evaluation of freon-12 and its allowable level in the water of bodies of water]

[Article in Russian]

Antonova VI, Salmina ZA, Petrova NA.

PMID: 3569997 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3781256&dopt=Abstract

Gig Sanit. 1986 Sep;(9):19-22.

No Abstract available

[Hygienic evaluation of the meat of birds frozen in a refrigerant medium (freon-12)]

[Article in Russian]

Bronnikova IA, Petrova GA, Venger KP, Mazurenko NP.

PMID: 3781256 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=4026874&dopt=Abstract

Biochem Pharmacol. 1985 Aug 15;34(16):2839-46.

Effects of anesthetics and dichlorodifluoromethane on the activities of glyceraldehyde-phosphate dehydrogenase and pectin methylesterase.

Laverty DM, Fennema O.

Solutions of glucose-3-phosphate dehydrogenase (GPD) and pectin methylesterase (PME) were exposed to various anesthetics and dichlorodifluoromethane (F-12) to determine the abilities of these chemicals to inhibit enzyme activity. An aqueous solution of PME was exposed to saturation levels of the test chemicals for 30 min at 21 degrees. All test chemicals were inhibitory (measured after release of the test chemical) with propane being most inhibitory followed in order by F-12, cyclopropane, Ethrane (F2HCOF2CCHClF) and halothane (CF3CHClBr). GPD was exposed to various concentrations of F-12 and halothane for various times at 0 degrees and 33 degrees. Halothane at 33 degrees and a saturation concentration reduced the initial reaction velocity of GPD to zero after a 10-min exposure period. F-12 was somewhat less inhibitory than halothane, but inhibition in all instances was irreversible. Halothane was found to affect the circular dichroism and optical rotary dispersion spectra of GPD, with the magnitude of the changes generally increasing with treatment time. The observed changes were believed to arise from side-chain transitions of GPD.

PMID: 4026874 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6449983&dopt=Abstract

C R Seances Soc Biol Fil. 1980;174(1):52-7.

[Effect of difluorodichloromethane (FC 12) on the cardiac cellular electric activity of mammals]

[Article in French]

Lessard Y, Callec JJ, Paulet G.

The cardiotoxicity of high concentrations of inhaled difluorodichloromethane (FC 12) has now been acknowledged. In the present study, the effects of FC 12 on the electrical activity of cells in the atrial and ventricular myocardium of anesthetized rats were recorded with "flexibly mounted" intracellular microelectrodes. The major phenomena observed in both types of cells were: a distinct decrease in the diastolic potential, a decrease inthe amplitude of the action potential, modifications in the shape of the action potential. Analysis of the simultaneously obtained electrocardiogram specifies the rhythm abnormalities which consist of an important decrease in the atrio-ventricular conduction and changes in the myocardial excitability. The cardiotoxicity of FC 12 is assumed to affect passive or active transmembrane ionic movements. Possible mechanisms are suggested here.

PMID: 6449983 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=150924&dopt=Abstract

C R Seances Soc Biol Fil. 1978;172(2):337-47.

[Role of endogenous adrenaline in cardiac arrhythmia induced by dichlorodifluoromethane (FC 12) in mammals]

[Article in French]

Lessard Y, Desbrousses S, Paulet G.

During the inhalation of normally oxygenated gas mixtures containing light or middle concentrations of FC 12, the presence of perfused epinephrine is necessary to induce cardiac arrhythmia in rabbits and dogs. The only inhalation of normally oxygenated gas mixtures containing a very high concentration of FC 12 produces in rabbits and dogs an important decrease in arterial pressure, tachycardia, a fall in respiratory amplitude, an acceleration reflex of respiratory frequency and cardiac arrhythmia. The same experiments in baro and chemodenervated animals show that : respiratory depression due to FC 12 still occurs, but not through the arterial chemoreceptors ; tachycardia has a reflex origin : barodenervation reveals the negative chromotropic effect of FC 12 and increases the fall in arterial pressure, mainly due to the negative inotropic effect of FC 12 ; adrenaline is necessary for FC 12-induced arrhythmia : barodenervation suppresses tachycardia due to the release of endogenous epinephrine and abolishes any arrhythmia.

PMID: 150924 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=263946&dopt=Abstract

J Forensic Sci. 1977 Jan;22(1):34-9.

Electron impact mass spectrometric detection of Freon in biological specimens.

Urich RW, Wittenberg PH, Bowerman DL, Levisky JA, Pflug JL.

Freons from an aerosol spray can were detected in the blood, liver, brain, and lung of a 14-year-old girl who died after intentional inhalation. A headspace mass spectrometric analytical technique was employed to detect the fluorocarbons. The spectra from the specimens showed the presence of m/e peaks at 101, 103, and 105 from the ion (CFCL2)+ which arises from fragmentation of trichlorofluoromethane (Freon 11) and dichlorodifluoromethane (Freon 12), and peaks at 85 and 87 from the ion (CF2Cl)+ which arises from fragmentation of dichlorodifluoromethane (Freon 12). The technique presented here provides greater specificity than previously reported analytical procedures for the identification of these volatile toxic chemical compounds in biological specimens.

PMID: 263946 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1011368&dopt=Abstract

Jpn Heart J. 1976 Nov;17(6):753-9.

Electrocardiographic changes in rats after inhalation of dichlorotetrafluoroethane, Arcton 114, C2Cl2F4.

Durakovic Z, Stilinovic L, Bakran I Jr.

The effects of dichlorotetrafluoroethane, Arcton 114, on the heart of rats were examined in 17 white rats. The animals inhaled dichlorotetrafluoroethane for 1 or 1.5 min. Severe electrocardiographic changes including marked bardycardia, atrioventricular heart block of the second degree and complete heart block were registered. Cardiac standstill appearing 11 to 31 min after inhalation was a death cause in all rats. These results are similar to our previous results concerning the effects of dichlorodifluoromethane (Arcton 12) on the heart of rats.

PMID: 1011368 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7144&dopt=Abstract

Am J Physiol. 1976 Jun;230(6):1701-7.

Effects of hypoxia and Freon 12 on mechanics of cardiac contraction.

Kilen SM, Harris WS.

Data are presented which indicate that the mechanism of tension depression and subsequent recovery from dichlorodifluoromethane (Freon 12), an aerosol gas recently described as a potent cardiac depressant agent, differs from that of hypoxia. To analyze these differences, 22 rat papillary muscles, contracting isometrically in a myograph, were studied during and subsequent to 15-min interventions of of hypoxia. Freon 12 with adequate oxygenation, or Freon 12 combined with hypoxia. During each of the three interventions the developed force (F) was markedly depressed, while peak shortening velocity (Vpm) was selectively more depressed by Freon and Freon combined with hypoxia than by hypoxia alone. While hypoxia shortened the time to peak force (TTP) and one-half relaxation time (RT1/2) markedly, Freon 12 with adequate oxygenation slightly shortened RT1/2 (P is less than 0.001) but failed to shorten TTP significantly. In contrast, Freon 12 administered during hypoxia shortened TTP and RT1/2 significantly (P is less than 0.001), more than did hypoxia or Freon 12 alone. Posthypoxic prolongation of TTP and RT1/2 was not seen during recovery from Freon 12. This prolongation was depressed during recovery from Freon 12 given either during hypoxia or during recovery from hypoxia. The results indicate that Freon 12 and hypoxia act synergically, although the mechanisms through which they mediate their actions on myocardial tissue are not identical.

PMID: 7144 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1209645&dopt=Abstract

Toxicology. 1975 Nov;5(2):127-38.

Hemodynamic effects of aerosol propellants. I. Cardiac depression in the dog.

Simaan JA, Aviado DM.

The inhalation of fluorocarbons caused a depression of myocardial contractility, aortic hypotension, a decrease in cardiac output and an increase in pulmonary vascular resistance. The minimal concentrations that elicited these changes are as follows: 1% trichlorofluoromethane (FC11); 2.5% dichlorotetrafluoroethane (FC114); and 10% dichlorodifluoromethane (FC12). Inhalation of 20% octafluorocyclobutane (FC318) and difluoroethane (FC152a) did not influence these hemodynamic parameters. As in previous comparisons, the most widely used aerosol propellants are potentially cardiotoxic in the anesthetized dog.

PMID: 1209645 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1133731&dopt=Abstract

J Pharm Sci. 1975 Jun;64(6):1052-4.

Fluorocarbon aerosol propellants V: binding interaction with human albumin.

Chiou WL, Hsiao JH.

Binding of trichloromonofluoromethane, dichlorodifluoromethane, and dichlorotetrafluoroethane was studied in aqueous 5% human albumin solution, using the partition coefficient method in sealed serum bottles. The partition coefficient and the fraction of fluorocarbons bound were highly dependent on fluorocarbon concentrations. The average binding sites per molecule of albumin were 2.17, 0.30, and 0.42 and the binding association constants were 1.11 X10-3, 1.73 X10-3, and 5.06X10-3 M-minus 1, respectively. At the lowest concentration studied, 62.3, 25.5, and 65.6% were found bound to albumin, respectively. This appears to represent the first extensive study on any gas-albumin interaction.

PMID: 1133731 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1132863&dopt=Abstract

Forensic Sci. 1975 Feb;5(1):53-9.

Determination of fluorocarbon 11 and fluorocarbon 12 in post-mortem tissues: a case report.

Poklis A.

This report describes the death of a teenager due to inhalation of fluorocarbon aerosol propellants and presents a method for the determination of trichlorofluoromethane (fluorocarbon 11) and dichlorodifluoromethane (fluorocarbon 12) in post-mortem samples. The post-mortem blood and tissue levels of these fluorocarbons are also presented. The distribution of fluorocarbon 11 and fluorocarbon 12 is similar to that observed in chloroform deaths.

PMID: 1132863 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=235808&dopt=Abstract

Toxicology. 1975;3(2):213-24.

Toxicity of aerosol propellants in the respiratory and circulatory systems. VI. Influence of cardiac and pulmonary vascular lesions in the rat.

Doherty RE, Aviado DM.

Three propellants were selected for investigation in rats because of their non-uniform effect in mice and monkeys. Trichlorofluoromethane (FC 11) provoked arrhythmia in all three animal species, dichlorodifluoromethane (FC 12) in monkeys and rats but not in mice, and difluoroethane (FC 152a) only in rats. In rats the alterations in heart rate and electrocardiographic pattern during inhalation of these propellants are largely brought about by release of catecholamines from the adrenal gland, because adrenalectomy or prior injection of beta-adrenergic blocking drugs decreased the incidence of cardiac effects. Rats that have pulmonary vascular thrombosis or cardiac necrosis become more sensitive to proarrhythmic activity of these propellants.

PMID: 235808 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=5083543&dopt=Abstract

J Pharmacol Exp Ther. 1972 Nov;183(2):245-55.

No Abstract available

Direct depression of myocardial contractility by the aerosol propellant gas, dichlorodifluoromethane.

Kilen SM, Harris WS.

PMID: 5083543 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=5080672&dopt=Abstract

Am Ind Hyg Assoc J. 1972 Apr;33(4):207-16.

No Abstract available

Experimental human exposures to fluorocarbon 12 (dichlorodifluoromethane).

Azar A, Reinhardt CF, Maxfield ME, Smith PE Jr, Mullin LS.

PMID: 5080672 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=5727091&dopt=Abstract

Am Ind Hyg Assoc J. 1968 Sep-Oct;29(5):513-6.

No Abstract available

Community air quality guides. Dichlorodifluoromethane. (Difluorodichloromethane, Fluorocarbon No. 12). CCl-2F2.

[No authors listed]

PMID: 5727091 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=5743565&dopt=Abstract

J Forensic Sci. 1968 Jul;13(3):407-10.

No Abstract available

A fatal case involving trichloromonofluoromethane and dichlorodifluoromethane.

Baselt RC, Cravey RH.

PMID: 5743565 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=4962252&dopt=Abstract

Toxicol Appl Pharmacol. 1967 Mar;10(2):270-89.

No Abstract available

Effects on experimental animals of long-term inhalation of trichloroethylene, carbon tetrachloride, 1,1,1-trichloroethane, dichlorodifluoromethane, and 1,1-dichloroethylene.

Prendergast JA, Jones RA, Jenkins LJ Jr, Siegel J.

PMID: 4962252 [PubMed - indexed for MEDLINE]


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