Chlorodifluoromethane (Freon 22)
CAS No. 75-45-6
For more abstracts search PubMed or Toxnet

Return to Index Page
Adverse Effects
NTIS Reports

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


Note: See the long list of health studies and other reports concerning ozone and greenhouse effects from chlorodifluoromethane that are available from the National Technical Information Service (NTIS).



Chlorodifluoromethane (FC-22) was evaluated for embyotoxicity and teratogenicity in groups of 40 pregnant Charles River rats exposed to the test substance by inhalation at concentrations of 0, 0.05, 0.10, and 2.00% on days 6-15 of gestation. No clinical signs of toxicity were observed in maternal animals. The number of implantations, early and late resorptions, and number of live fetuses per litter were unaffected. There was a sporadic appearance of major malformations of the eye in all test groups. The increased incidence of eye defects was not statistically significant. Authors believe that the test substance may have interacted with the genetic make-up of affected fetuses and caused the increased expressivity of a mutant gene. The authors considered the test substance to be a mutagen under the conditions of this study.

Report Nos.
EPA/OTS; Doc #88-920004258


Teratogenicity was evaluated in 4 groups of 19 pregnant CD female rats receiving Arcton 22 via inhalation at concentration levels of 0, 100, 1,000 and 50,000 ppm for 6 hours per day on gestation days 6 through 15. There were no treatment-related effects in appearance, behavior, mortality, or pregnancy rate. At 50,000 ppm maternal weight gain was slightly lower than the control. There were no effects on body weight at 100 or 1,000 ppm. In all test groups litter size, post-implantation loss, litter wight, and mean fetal weight were similar to the control. At 50,000, there was an increased incidence of anophthalmic fetuses.

• Anophthalmic definition: Absence of an eye(s).  It can be a congenital (born without) or an acquired condition (surgically removed).

Report Nos.
EPA/OTS; Doc #87-890000011

Atmospheric Environment ; Volume 31, Issue 6 , March 1997, Pages 809-811

Estimated national releases to the atmosphere of chlorodifluoromethane (HCFC-22) during 1990

Pauline M. Midgley (a) and Archie McCulloch (b)

M&D Consulting, Ludwig str. 49, Leinfelden Musberg, D-70771, Germany
ICI Chemicals & Polymers Ltd, Runcorn, WA7 4QF, U.K.

Chlorodifluoromethane (HCFC-22), the most widely used substitute for chlorofluorocarbons, is currently emitted into the atmosphere at a global rate of about 220,000 tyr-1. In this work, national emissions of HCFC-22 for the year 1990 are estimated using the calculated emissions of CFC-12 as a surrogate distribution function. The releases so calculated match the sp arse published data in most cases.



Scand J Work Environ Health 2002 Jun;28(3):205-7

Inhalation of decomposed chlorodifluoromethane (freon-22) and myocardial infarction.

Sjogren B, Gunnare S, Sandler H.

Work Environment Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Bengt.Sjogren@niwl.se

After exposure to decomposed chlorodifluoromethane (freon-22), a 65-year-old man developed respiratory symptoms such as cough, blood-stained sputum, and increasing dyspnea. Three weeks later, his family doctor diagnosed infectious bronchitis. Another week later he died due to myocardial infarction. The discussion focuses on an inflammatory process caused by the inhalation of decomposed freon and its possible association with myocardial infarction.

PMID: 12109561 [PubMed - indexed for MEDLINE]

[Note from FAN:
Definition of dyspnea - shortness of breath, a subjective difficulty or distress in breathing, usually associated with disease of the heart or lungs; occurs normally during intense physical exertion or at a high altitude. Ref: Stedman's Concise Medical Distionary for the Health Professions. Illustrated 4th edition. 2001.]


AIHAJ 2000 Jul-Aug;61(4):539-43

Formation of phosgene during welding activities in an atmosphere containing chlorinated hydrocarbons.

Nieuwenhuizen MS, Groeneveld FR.

TNO Prins Maurits Laboratory, Rijswijk, The Netherlands.

The formation of phosgene During welding activities in an atmosphere containing chlorinated hydrocarbons was investigated. Four different chlorinated hydrocarbons were studied under laboratory conditions. Results are presented as time-averaged phosgene concentration in a total volume of 250 L of air being purged through a 52-L reaction vessel during 20 min. It was found that the formation of phosgene was in the order dichloromethane < Freon-22 < carbon tetrachloride << trichoroethylene. Local concentrations may be higher depending on dispersion phenomena. The interpretation in terms of occupational health was rather difficult because of the interaction with smoke particles and because of possible nonhomogeneous dispersion of phosgene around the workers. In the case of dichloromethane and carbon tetrachloride the short-term maximum allowable concentration (MAC) of phosgene was not attained at the respective MAC values of the chlorinated hydrocarbons themselves. In the case of trichloroethylene and Freon-22, however, the short-term MAC-value of phosgene was attained even when the concentration was still much below the respective MAC-values.

PMID: 10976684 [PubMed - indexed for MEDLINE]


IARC Monogr Eval Carcinog Risks Hum 1999;71 Pt 3:1339-43


PMID: 10476408 [PubMed - indexed for MEDLINE]


IARC Monogr Eval Carcinog Risk Chem Hum 1986;41:237-52


PMID: 3473028 [PubMed - indexed for MEDLINE]


J Emerg Med 1998 Mar-Apr;16(2):167-9

Facial injury and airway threat from inhalant abuse: a case report.

Kurbat RS, Pollack CV Jr.

Department of Emergency Medicine, Maricopa Medical Center, Phoenix, Arizona, USA.

Fluorinated hydrocarbons cause toxicity in humans via their dysrhythmogenic potential and their local physical effects on the skin and mucous membranes. The former is generally the more life-threatening toxic consequence. We present a case of fluorinated hydrocarbon injury resulting from an intentional inhalation exposure that created facial frostbite, which threatened the patient's airway. The clinical range and management of these tissue-toxic effects are reviewed.

PMID: 9543396 [PubMed - indexed for MEDLINE]


Forensic Sci Int 1996 Sep 30;82(2):171-5

Headspace GC/MS testing for chlorodifluoromethane in two fatal cases.

Kintz P, Baccino E, Tracqui A, Mangin P.

Institut de Medecine, Legale, Strasbourg, France.

Two cases of lethal poisoning due to chlorodifluoromethane (Freon 22) inhalation are described. The fluorocarbon was determined in biological tissues by headspace gas chromatography/mass spectrometry. Ions monitored were m/z 67, 86 and 51, the latter being used for quantification. Blood concentrations were 26.0 and 37.1 microliters/ml. In both cases, the drug was also identified in urine, vitreous humor and bile, but in much lower concentrations.

PMID: 8885375
[PubMed - indexed for MEDLINE]


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]


J Accid Emerg Med 1995 Sep;12(3):212-3

Occupational phosgene poisoning: a case report and review.

Wyatt JP, Allister CA.

Department of Accident and Emergency, Royal Alexandra Hospital, Paisley, Strathclyde, UK.

Phosgene is a highly toxic gas to which some workers may be occupationally exposed. This case report demonstrates the possibility of refrigeration workers suffering phosgene poisoning after heating certain chlorinated fluorocarbons ('freons'). The need to suspect phosgene exposure and observe such patients is emphasized, especially in view of the delay in clinical deterioration observed in some patients who subsequently develop adult respiratory distress syndrome.

Publication Types:

  • Review
  • Review Literature

PMID: 8581252 [PubMed - indexed for MEDLINE]


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]


Med Lav 1992 Jul-Aug;83(4):361-4

[Sudden death caused by freon 22?]

[Article in Italian]

Dal Grande M, Zanderigo C, Coato F, Menegolli S, Cipriani E, Pancheri V, Malesani F, Perbellini L.

ULSS 26 della Regione Veneto, Servizio di Prevenzione Igiene e Sicurezza negli Ambienti di Lavoro (S.P.I.S.A.L.), Bussolengo.

Case report of a plumber's fatal work accident. Investigations on the causes of death made at post mortem showed that the worker had absorbed a large quantity of freon 22 (chlorodifluoromethane) which is known to be a narcotic agent and capable of inducing cardiac arrhythmia. It is believed freon inhalation was the cause of loss of consciousness with consequent death from drowning in the water issuing from the pipes. It is concluded that preventive measures need to be reinforced by adequate information to the workforce on the risks connected to this type of gas.

PMID: 1461194 [PubMed - indexed for MEDLINE]


Int Arch Occup Environ Health 1992;64(5):383-7

Human inhalation pharmacokinetics of chlorodifluoromethane (HCFC22).

Woollen BH, Marsh JR, Mahler JD, Auton TR, Makepeace D, Cocker J, Blain PG.

Human Toxicology Team, ICI Central Toxicology Laboratory, Macclesfield, Cheshire, UK.

Two groups of three male volunteers were exposed to atmospheric concentrations of either 327 or 1833 mg m-3 chlorodifluoromethane (HCFC22) for 4 h. Blood, urine and expired air samples were taken during and after the exposure period and analysed for HCFC22. Urine samples were also analysed for fluoride ion. During the exposure period, blood concentrations of HCFC22 approached a plateau, and the average peak blood concentrations of 0.25 and 1.36 micrograms cm-3 were proportional to dose. HCFC22 concentrations in expired air were similar to the exposure concentration during the exposure period. The ratio between venous blood and breath concentrations of HCFC22 towards the end of the exposure period was on average 0.77, which is consistent with in vitro estimates of the partition coefficient. In the post-exposure period, three phases for the elimination of HCFC22 were identified, with estimated half-lives of 0.005, 0.2 and 2.6h. HCFC22 was detected in urine samples taken in the post-exposure period, and the rate of decline was consistent with the terminal rate of elimination estimated from blood and breath measurements. On average 2.1% of the inhaled HCFC22 was recovered in breath within 26 h of exposure. This is consistent with the low solubility in blood and fat. Minimal changes in fluoride ion concentrations in urine following exposure indicate that HCFC22 is unlikely to be metabolised to a significant extent. Following inhalational exposure HCFC22 is poorly absorbed and is rapidly eliminated from the body. Possible biological monitoring strategies could be based on measurements of HCFC22 in urine or breath samples collected after the end of an exposure period.

PMID: 1487335 [PubMed - indexed for MEDLINE]


Environ Health Perspect 1991 Dec;96:185-91

Metabolism and toxicity of hydrochlorofluorocarbons: current knowledge and needs for the future.

Anders MW.

Department of Pharmacology, University of Rochester, NY 14642.

Hydrochlorofluorocarbons (HCFCs) are being developed as replacements for chlorofluorocarbons (CFCs) that deplete stratospheric ozone. The depletion of stratospheric ozone may increase the intensity of ultraviolet radiation at the earth's surface, which may be associated with global, adverse human health effects. The greater tropospheric lability of HCFCs, which is due to the presence of C-H bonds, reduces HCFC migration to the stratosphere; HCFCs should, therefore, cause less depletion of stratospheric ozone than CFCs. HCFCs under development include HCFC-22 (chlorodifluoromethane), HCFC-123 (2,2-dichloro-1,1,1-trifluoroethane), HCFC-132b (1,2-dichloro-1,1-difluoroethane), HCFC-134a (1,1,1,2-tetrafluoroethane), HCFC-141b (1,1-dichloro-1-fluoroethane, and HCFC-142b (1-chloro-1,1-difluoroethane). With the exception of HCFC-22, which is already in use, the metabolism and toxicity of HCFCs have not been studied in detail. By analogy to chlorinated ethanes, predictions can be made about the possible metabolism of HCFCs, but there are insufficient data available to predict rates of metabolism. Although most HCFCs appear to show low acute toxicity, some HCFCs are mutagenic in the Ames test. Hence, future research on HCFCs should include studies on the in vivo and in vitro metabolism of HCFCs as well as on their toxicity in in vivo and in vitro systems.

Publication Types:

  • Review
  • Review, Tutorial

PMID: 1820265 [PubMed - indexed for MEDLINE]


Br J Ind Med 1990 Mar;47(3):207-12

Cardiac arrhythmia in refrigerator repairmen exposed to fluorocarbons.

Edling C, Ohlson CG, Ljungkvist G, Oliv A, Soderholm B.

Department of Occupational Medicine, University Hospital, Uppsala, Sweden.

A field study of 89 refrigerator repairmen was carried out to ascertain whether occupational exposure to fluorocarbons induces cardiac arrhythmia. The concentrations of fluorocarbons in the breathing zones and the heart activity were recorded simultaneously. Most cooling systems contained FC 12 or FC 22. The highest level recorded in one minute was 14,000 ppm and the highest time weighted level during eight hours was 280 ppm. Two types of arrhythmia were recorded, ectopic beats and sudden bradycardia. A within subject comparison design was applied and the main parameter was the difference in arrhythmia frequencies between exposed and unexposed periods. No appreciable differences between exposed and unexposed periods and no consistent dose effect relations were observed, although subjects in the medium exposure category showed a difference of borderline significance (Wilcoxon's test: p = 0.05, one tailed). The frequencies of arrhythmia when unexposed were somewhat higher than previously reported. Misclassification of the exposure and the possible confounding effect of physical workload and psychological strain may have obscured a causal relation and therefore a minor effect cannot be ruled out. The results do not support the notion that fluorocarbons induce cardiac arrhythmia in occupationally exposed refrigerator repairmen.

PMID: 2328227 [PubMed - indexed for MEDLINE]


Br J Ind Med 1990 Feb;47(2):138-40

Cardiac arrhythmias during occupational exposure to fluorinated hydrocarbons.

Antti-Poika M, Heikkila J, Saarinen L.

Institute of Occupational Health, Helsinki, Finland.

The effects of occupational exposure to chlorodifluoromethane (FC 22) and dichlorodifluoromethane (FC 12) on cardiac rhythm were examined. The subjects were six men who repaired refrigerators (age 31-56, mean 46 years) and a control group of six plumbers (age 29-54, mean 45 years). Ambulatory electrocardiograms (ECG) were recorded for 24 hours on the day of exposure and on a control day. The ECG tapes were automatically analysed with a Reynolds pathfinder 3 apparatus and all aberrant complexes recorded by the machine were checked. One person read all the tapes without knowing whether or not they were recorded during exposure. The number of ventricular ectopic beats were compared between the day of exposure and the control day and with the tape of the control. In addition, the number of ventricular ectopic beats during exposure was compared with the number occurring during the rest of the day. The concentrations of fluorocarbons were measured in four instances. High peak concentrations of fluorocarbons (1300-10,000 cm3/m3) were measured during refrigerator repair work. No clear connection between fluorocarbons and cardiac arrhythmia was found, although one subject had several ventricular ectopic beats which may have been connected with exposure.

PMID: 2310718 [PubMed - indexed for MEDLINE]


J Appl Physiol 1989 May;66(5):2468-71

Solubility of Freon 22 in human blood and lung tissue.

Varene N, Choukroun ML, Marthan R, Varene P.

Laboratoire d'Exploration Fonctionnelle Respiratoire Centre Hospitalier Regional de Bordeaux, Universite de Bordeaux II, France.

The solubility of Freon 22 in human blood and lung tissue was determined using the chromatographic method of Wagner et al. (J. Appl. Physiol. 36: 600-605, 1974). In normal human blood, the mean Bunsen coefficient of solubility (alpha B) was 0.804 cm3 STPD.cm-3.ATA-1 at 37 degrees C. It increased with hematocrit (Hct) according to the equation alpha B = 0.274 Hct + 0.691. Tissue homogenates were prepared from macroscopically normal lung pieces obtained at thoracotomy from eight patients undergoing resection for lung carcinoma. The Bunsen solubility coefficients were 0.537 +/- 0.068 and 0.635 +/- 0.091 in washed and unwashed lung, respectively. These values can be used in the determination of both cardiac output and pulmonary tissue volume in humans by use of the rebreathing technique.

PMID: 2745307 [PubMed - indexed for MEDLINE]


Br J Anaesth 1989 Apr;62(4):425-8

Solubility of freon-22 in blood and lung tissue.

Franks PJ, Hooper RH, Jones PR.

Department of Human Sciences, Loughborough University of Technology.

Despite the frequent use of freon-22 (e.g. to measure pulmonary blood flow), there is no agreement on its solubility in water or body fluids. The values in the literature vary, often quoted without reference to measurement or identification as Ostwald or Bunsen coefficients. We used a Scholander apparatus and determined the Bunsen solubility coefficient (mlgas.(mlfluid.atmosphere)-1) at 37 degrees C as: 0.476 in water; 0.673 in human whole blood; 0.479 in human plasma; 0.662 in canine whole blood; 0.437 in canine plasma; and 1.077 in homogenized canine lung tissue. As pure freon was used, these solubilities may not be applicable if freon-22 does not obey Henry's law. In man, the Ostwald solubility coefficient is calculated as 0.76 ml/ml whole blood at BTPS. These results provide information for further studies involving freon-22, and clear the confusion which has arisen from poorly defined solubility coefficients.

PMID: 2706179 [PubMed - indexed for MEDLINE]


Nippon Hoigaku Zasshi 1988 Aug;42(4-5):372-80

[A toxicological study of the effects of freon 22 inhalation--the behavior of rats exposed to freon inhalation and an evaluation of freon concentrations in their tissue]

[Article in Japanese]

Komoriya H, Nakamura I, Ohya I.

PMID: 3204706 [PubMed - indexed for MEDLINE]


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]


Prog Clin Biol Res 1985;163B:301-5

The relevance for man of animal data on reproductive toxicity of industrial chemicals.

Sullivan FM, Barlow SM.

PMID: 3920665 [PubMed - indexed for MEDLINE]


Boll Soc Ital Biol Sper 1984 Sep 30;60(9):1811-7

[Effects of the use of FRIGEN (AG-Ffm-HOECST) on the determination of blood levels of some proteins (IgA, IgM, IgG, C3c, C4) in cord blood of healthy newborn infants at term by laser nephelometry]

[Article in Italian]

Costanzo A, Meninno V, Addeo L, Canzano G, Lombardi S.

The purpose of this paper is to establishes the FRIGEN effects on the determination of IgA, IgM, IgG, C3c, C4 cord-blood levels, by means of laser-nephelometry. The results show substantial interferences only in the IgA levels, whereas the other on almost all proteins are not affected, the found interference can be due to the amount of IgA bound to B-lipoprotein, that are precipitated by FRIGEN.

PMID: 6525301 [PubMed - indexed for MEDLINE]


Food Chem Toxicol 1984 Jun;22(6):465-75

The toxicological evaluation of chlorofluorocarbon 22 (CFC 22).

Litchfield MH, Longstaff E.

PMID: 6539738 [PubMed - indexed for MEDLINE]


Toxicol Appl Pharmacol 1981 Jun 15;59(1):64-70

Acute toxicity of fluorocarbon-22: toxic symptoms, lethal concentration, and its fate in rabbit and mouse.

Sakata M, Kazama H, Miki A, Yoshida A, Haga M, Morita M.

PMID: 7256758 [PubMed - indexed for MEDLINE]


Fundam Appl Toxicol 1981 May-Jun;1(3):266-70

Studies on the male reproductive toxicity of Freon 22.

Lee IP, Suzuki K.

Freons have been used extensively as refrigerants and as propellants in household products, and yet their possible effects on male reproduction have received little attention. In the present study, adult male Sprague-Dawley rats (nine weeks of age) were exposed to 50 000 ppm Freon 22, five hrs per day for eight weeks. The control group received filtered air at an identical flow rate. At the end of the eight week exposure period, body and organ weights, hematology, blood chemistry, plasma gonadotropins, and fertility parameters were not significantly different from controls, with the exception of serum cholesterol levels, which were slightly higher, and glucose and triglyceride levels which were lower. The weight of coagulating glands was also lower than those of controls, but did not interfere with fertility function.

PMID: 6820943 [PubMed - indexed for MEDLINE]

Return to Chlorodifluoromethane Index Page


Fluoride Action Network | Pesticide Project | 315-379-9200 | pesticides@fluoridealert.org