Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 75-45-6 Toxicity Effects

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Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Names (NTP)

  • FREON 22
  • DIFLUOROCHLOROMETHANE
  • MONOCHLORODIFLUOROMETHANE
  • REFRIGERANT R22
  • FLUOROCARBON 22
  • Chlorodifluoromethane

Human Toxicity Excerpts

  • IN EPIDEMIOLOGICAL STUDY OF HOSPITAL PERSONNEL, A 3.5-FOLD EXCESS OF PALPITATION WAS NOTED IN THOSE EXPOSED TO MONOCHLORODIFLUOROMETHANE. [SPEIZER FE ET AL; N ENGL J MED 292 (12): 624-6 (1975)]**PEER REVIEWED**
  • EARLY ... HUMAN EXPERIENCE INDICATED THAT HIGH VAPOR CONCN (EG, 20%) MAY CAUSE CONFUSION, PULMONARY IRRITATION, TREMORS & RARELY COMA, BUT THAT THESE EFFECTS WERE GENERALLY TRANSIENT & WITHOUT LATE SEQUELAE. ... CAUSE OF DEATH /FROM ABUSE OF FLUOROCARBONS/ IS IN CONSIDERABLE DOUBT ... FREEZING OF AIRWAY SOFT TISSUES CAN PROBABLY BE ELIMINATED AS A CAUSE OF DEATH EXCEPT IN CASES WHERE THE PRODUCT WAS SPRAYED DIRECTLY INTO THE MOUTH FROM ITS CONTAINER OR FROM A BALLOON CONTAINING SOME LIQUID. LARYNGEAL SPASM OR EDEMA, OXYGEN DISPLACEMENT, OR SENSITIZATION OF MYOCARDIUM TO ENDOGENOUS CATECHOLAMINES WITH SUBSEQUENT VENTRICULAR FIBRILLATION APPEAR TO BE REASONABLE POSSIBILITIES. /FLUOROCARBON REFRIGERANTS & PROPELLANTS/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-159]**PEER REVIEWED**
  • EXCESSIVE SKIN CONTACT WITH LIQUID FLUOROCARBONS SHOULD BE MINIMIZED TO PREVENT DEFATTING OF SKIN ... /FLUOROCARBONS/ [International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 897]**PEER REVIEWED**
  • Chlorodifluoromethane did not induce unscheduled DNA synthesis in human heteroploid EUE cells treated with a 20 mM soln generated at 500 ml/min (1:1 air) in presence or absence of S10. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V41 245 (1986)]**PEER REVIEWED**
  • An epidemiological study was made of 539 refrigeration workers exposed to a combination of chlorofluorocarbons, including chlorodifluoromethane, for at least 6 mo between 1950 to 1980 and followed up until 1980. There were 6 deaths due to cancer versus 5.7 expected, with 2 deaths from lung cancer versus 1.0 expected. (The Working Group noted that the study was small and there were few deaths from cancer.) [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V41 246 (1986)]**PEER REVIEWED**
  • A GAS OF LOW TOXICITY, BUT VERY HIGH CONCENTRATIONS ARE NOT ENTIRELY INERT. POSSIBLE LUNG INJURY. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-160]**PEER REVIEWED**
  • A SPECIAL CLASS OF CHEMICALS SUBJECT TO ABUSE BY INHALATION ARE THE FLUOROHYDROCARBONS, SUCH AS ... CHLORODIFLUOROMETHANE ... THE "SNIFFING" OF SUCH AEROSOL SPRAYS IS HAZARDOUS PRACTICE. ... 110 "SUDDEN SNIFFING DEATHS" /HAVE BEEN IDENTIFIED/ ... IN EACH CASE THE VICTIM SPRAYED THE AEROSOL INTO A PLASTIC BAG, INHALED THE CONTENTS, BECAME EXCITED, RAN 90 M OR SO, COLLAPSED, & DIED. NECROPSY FINDINGS WERE LARGELY NEGATIVE ... ALTHOUGH AMOUNT OF PROPELLANT ABSORBED INTO BLOOD FROM USE OF HAIRSPRAY, COSMETIC, HOUSEHOLD, & MEDICATED AEROSOLS MUST VARY WITH CIRCUMSTANCES, PHYSICIAN IS ADVISED TO COUNSEL ... PATIENT ON POTENTIAL DANGERS, PARTICULARLY FROM THEIR USE IN POORLY VENTILATED CONFINED AREAS. /FLUOROHYDROCARBONS/ [Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 910]**PEER REVIEWED**
  • Liquid may cause frostbite. [U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5., p. ]**PEER REVIEWED**
  • ... LOWER IN TOXICITY THAN CORRESPONDING CHLORINATED OR BROMINATED HYDROCARBONS. ... ASSOC WITH GREATER STABILITY OF C-F BOND; & PERHAPS ALSO WITH LOWER LIPOID SOLUBILITY ... TOXIC EFFECTS FROM REPEATED EXPOSURE, SUCH AS LIVER OR KIDNEY DAMAGE, HAVE NOT BEEN PRODUCED BY FLUOROMETHANES ... /FLUOROCARBONS/ [International Labour Office. Encyclopaedia of Occupational Health and Safety. 4th edition, Volumes 1-4 1998. Geneva, Switzerland: International Labour Office, 1998., p. 104.184]**PEER REVIEWED**
  • Two groups of three male volunteers were exposed by inhalation to chlorodifluoromethane at either 327 or 1833 mg/cu m for 4 hr. The average maximal blood concentrations were 0.25 and 1.36 ug/ml, respectively, and were achieved within 1 hr of the beginning of exposure. The average blood/air partition coefficients for chlorodifluoromethane towards the end of the exposure period were 0.82 and 0.76, respectively, and the fat/air partition coefficients were 7.7 and 8.1. Thus, the fat/blood partition coefficient was estimated to be approximately 10. Three phases for the elimination of chlorodifluoromethane in breath were identified, with estimated half-lives of 0.005, 0.2 and 2.6 hr. An average of 2.1% of the inhaled chlorodifluoromethane was recovered from the exhaled air over 26 hr and minimal amounts were found in urine. Minimal changes in the fluoride concentration in urine were observed, which is consistent with a low degree of metabolism. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 1340 (1999)]**PEER REVIEWED**
  • Two simultaneous accidental, lethal exposures to chlorodifluoromethane alone were associated with concentrations (in ul/ml) of the chemical in body fluid samples taken 16 hr after death of: blood, 37.1 and 26.0; urine, 1.7 and 0.9; vitreous humor, 1.0 and 0.7. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 1341 (1999)]**PEER REVIEWED**
  • The effects of occupational exposure to chlorodifluoromethane (FC 22) & dichlorodifluoromethane (FC 12) on cardiac rhythm were examined. The subjects were 6 men who repaired refrigerators (age 31-56, mean 46 yr) & a control group of six plumbers (age 29-54, mean 45 yr). Ambulatory electrocardiograms (ECG) were recorded for 24 hr on the day of exposure & on a control day. The ECG tapes were automatically analysed with a Reynolds pathfinder 3 apparatus & 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 & the control day & with the tape of the control. In addn, the number of ventricular ectopic beats during exposure was compared with the number occurring during the rest of the day. The concns of fluorocarbons were measured in 4 instances. High peak concns of fluorocarbons (1300-10,000 cm3/m3) were measured during refrigerator repair work. No clear connection between fluorocarbons & cardiac arrhythmia was found, although one subject had several ventricular ectopic beats which may have been connected with exposure. [Antti-Poika M et al; Br J Ind Med 47 (2): 138-140 (1990)]**PEER REVIEWED**
  • The prevalence of cardiac arrhythmia in refrigerator repairmen exposed to fluorocarbons (FCs) was assessed in a field study of 89 repairmen. The exposure concns of FCs in the breathing zone were measured by experienced industrial hygienists using a direct recording infrared spectrometer. The recording of heart activity was carried out at the same time as the measurement of FCs. Most cooling systems contained FC-12 (75718) or FC-22 (75456). The highest FC level recorded in 1 min was 14,000 ppm & the highest time weighted exposure during 8 hr was 280ppm. Two types of arrhythmia were detected, ectopic beats & sudden bradycardias. In a within subject comparison, no significant differences between arrhythmia frequencies during exposed & unexposed periods & no consistent dose effect relations were observed. The frequencies of arrhythmia when unexposed were somewhat higher than previously reported. Misclassification of exposure & the possible confounding effect of physical workload & psychological strain may have obscured any causal relation. The authors conclude that the results do not support the notion that FCs induce cardiac arrhythmia in occupationally exposed refrigerator repairmen. [Edling C et al; British Journal of Industrial Medicine 47 (3): 207-212 (1990)]**PEER REVIEWED**
  • 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 & 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 concns of chlorodifluoromethane & chloropentafluoroethane of 71 mg/L & 0.30 mg/L, respectively. Brain, liver, & lung concns of chlorodifluoromethane were (mg/kg) 2.8, 4.4, and 1.6, respectively. Brain, liver, & lung concns of chloropentafluoroethane were (mg/kg) 0.80, 0.80, & 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. [Fitzgerald RL et al; J Forensic Sci 38 (2): 477-483 (1993)]**PEER REVIEWED**
  • 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 & 51, the latter being used for quantification. Blood concentrations were 26.0 & 37.1 mul/ml. In both cases, the drug was also identified in urine, vitreous humor and bile, but in much lower concentrations. [KINTZ P et al; FORENSIC SCIENCE INTERNATIONAL 82 (2): 171-175 (1996)]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • Since FC 22 is a high pressure fluorocarbon, it is more appropriate to make a comparison with another high pressure compound, for example FC 12. Both fluorocarbons cause early respiratory depression, bronchoconstriction, tachycardia, myocardial depression, & hypotension in approximately equivalent concn (5 to 10%) in dogs & monkeys. The difference between the two high pressure fluorocarbons is that FC 22 does not induce cardiac arrhythmia in the monkey, although it sensitizes the heart to epinephrine in the mouse, & that FC 22 does not decrease pulmonary compliance in the monkey. [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 1181]**PEER REVIEWED**
  • ... CARDIAC SENSITIZATION DID NOT OCCUR IN DOGS EXPOSED TO FC-22 AT 25,000 PPM ALTHOUGH POSITIVE RESPONSE COULD BE EVOKED EXPERIMENTALLY AT 50,000 PPM. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 282]**PEER REVIEWED**
  • IN RHESUS MONKEYS (M MULATTA), INHALATION OF 10-20% CONCN OF FREON 22 INCREASED THE PULMONARY RESISTANCE OR BRONCHOCONSTRICTION. [AVIADO DM, SMITH DG; TOXICOLOGY 3 (2): 241-52 (1975)]**PEER REVIEWED**
  • ... GUINEA PIGS SHOWED DEFINITE NERVOUS SYSTEM RESPONSE TO CONCN OF 16% BY VOL IN AIR, OVER PERIOD OF 55 MIN. THEY SHOWED TREMORS & CONVULSIVE MOVEMENTS BUT RECOVERED ON REMOVAL. AT 40%, THEY SHOWED TREMORS & WERE HELPLESS OVER A PERIOD OF 2.5 HR BUT RECOVERED ... AT CONCN OF 58%, DEATH OCCURRED IN 8 MIN. [Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963., p. 1324]**PEER REVIEWED**
  • IN ACUTE, 2 HR EXPOSURES ... CONCN OF 75,000 TO 100,000 PPM PRODUCED EXCITATION AND/OR CHANGES IN EQUILIBRIUM IN BOTH RATS AND GUINEA PIGS. /CNS DEPRESSION/ ... OCCURRED AT 200,000 PPM AND MORTALITY RESULTED AT 300,000 AND 400,000 PPM. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 282]**PEER REVIEWED**
  • ... MICE /EXPOSED/ FOR 2-HR PERIODS ... TOLERATED ... /A MAXIMUM/ CONCN ... /OF/ 1120 MG/L OF AIR (320,000 PPM), WHILE THE MINIMUM FATAL LEVEL WAS 1300 MG/L (370,000 PPM). THE MINIMUM CONCN CAPABLE OF ALTERING REFLEX RESPONSE IN RABBITS VARIED BETWEEN 40-70 MG/L (11,000-20,000 PPM). /IN GUINEA PIGS/ ... 2-HR EXPOSURES AT APPROXIMATELY 200,000 PPM, THE HIGHEST LEVEL TESTED, DID NOT CAUSE DEATH; HOWEVER, 50,000 PPM PRODUCED MILD CLINICAL CHANGES & MINIMAL EFFECTS WERE NOTED AT 25,000 PPM. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 282]**PEER REVIEWED**
  • In a 10-month experiment ... rats, mice, and rabbits /were exposed/ for 6 hours daily except Sunday at a concentration of 50 mg/L FC-22 (14,000 ppm); rats and mice also inhaled 7 mg/L (2000 ppm) daily for 10 months. The 50-mg/L exposures produced alterations in body weight, physiological endurance, and hematological characteristics; pathological changes were noted in the lungs, CNS, heart, liver, kidneys, and spleen. No effects were noted in animals exposed at the 7-mg/L concentration. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 282]**PEER REVIEWED**
  • COMMERCIAL PREPARATIONS OF FREON 22 WERE MUTAGENIC TO SALMONELLA TYPHIMURIUM IN AMES ASSAY & EFFECT WAS NOT DEPENDENT ON PRESENCE OF RAT LIVER HOMOGENATE. SIMILAR MUTAGENIC ACTIVITY OF A PURIFIED SAMPLE OF MONOCHLORODIFLUOROMETHANE INDICATED THAT THE EFFECT OF COMMERCIAL FREON 22 WAS NOT DUE TO THE PRESENCE OF IMPURITIES. [LONGSTAFF E, MCGREGOR DB; TOXICOL LETT 2 (1): 1-4 (1978)]**PEER REVIEWED**
  • BASED ON EXPERIMENTS WITH RATS, MICE, DOGS, & MONKEYS, MONOCHLORODIFLUOROMETHANE WAS CLASSIFIED AS PROPELLANT WITH INTERMEDIATE TOXICITY, CLASS 3. [AVIADO DM; TOXICOLOGY 3 (3): 321-32 (1975)]**PEER REVIEWED**
  • EARLY ANIMAL ... EXPERIENCE INDICATED THAT HIGH VAPOR CONCN (EG, 20%) MAY CAUSE CONFUSION, PULMONARY IRRITATION, TREMORS & RARELY COMA, BUT THAT THESE EFFECTS WERE GENERALLY TRANSIENT & WITHOUT LATE SEQUELAE. /FLUOROCARBON REFRIGERANTS & PROPELLANTS/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-159]**PEER REVIEWED**
  • On the basis of early inhalation experiments in guinea pigs & rats, FC 22 was shown to be two to three times less toxic than FC 11. More recent comparative studies indicate an eight- to ten-fold difference in cardiotoxicity in mice & dogs. [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 3094]**PEER REVIEWED**
  • ... A 4 wk study /was conducted/ in which rats, guinea pigs, dogs, & cats were exposed at 50,000 ppm FC-22. Twenty exposures of 3.5 hr each produced no clinical, biochemical, or pathological effects. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 282]**PEER REVIEWED**
  • The toxicological effect of fluorocarbon-22 was studied using mice and rabbits. The following symptoms were observed during continuous inhalation in sequence as time proceeded: reeling, weakness of forelegs, falling down, flow of mucous fluid from mouth and nose, mydriasis and lacrimation, violent movement of body and extremities and cyanosis. The lethal concn (LC50) for 30 min exposure in mice was 27.7% and the threshold concn for death in rabbits was about 30%. Blood concn was in direct proportion to inhaled concn. The cause of death was thought to be respiratory insufficiency. [Sakata M et al; Toxicol Appl Pharmacol 59 (1): 64-70 (1981)]**PEER REVIEWED**
  • Adult male Sprague-Dawley rats (nine weeks old) were exposed to 50,000 ppm Freon 22, five hr/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. [Lee IP, Suzuki K; Fundam Appl Toxicol 1 (3): 266-70 (1981)]**PEER REVIEWED**
  • Two short-term in vitro tests for mutagenicity (Salmonella reverse mutation and BHK21 cell transformation) were conducted on a series of fluorocarbons. Chlorodifluoromethane was positive in one or both of the tests and could be considered potentially carcinogenic to animals. Rats were dosed for 1 yr by gavage 5 days a week with chlorodifluoromethane in corn oil at a single dosage of 300 mg/kg. The animals were observed until week 125 with detailed necropsy at termination. Chlorodifluoromethane did not induce tumors. [Longstaff E et al; Toxicol Appl Pharmacol 72 (1): 15-31 (1984)]**PEER REVIEWED**
  • The relative potency of effect of a wide range of halogenated and unsubstituted hydrocarbons /including chlorodifluoromethane/ on the central nervous system (CNS) and heart of experimental animals was determined. The chemicals used caused stimulation or depression of the rat CNS after 10 min inhalation at 0.24-80% (vol/vol), and cardiac sensitization in dogs after 5 min inhalation at 0.12-80% (vol/vol). [Clark DG, Tinston DJ; Hum Toxicol 1 (3): 239-47 (1982)]**PEER REVIEWED**
  • Ninety-day studies, conducted with 6 fluorocarbons including chlorodifluoromethane, showed that the lowest toxic concn were greater than 5,000 ppm when admin to beagle dogs. With rats, the lowest toxic concn were greater than 10,000 ppm. Admin took place on 90 consecutive days for 6 hr/day. [Leuschner F et al; Arzneim-Forsch 33 (10): 1475-6 (1983)]**PEER REVIEWED**
  • Groups of 80 male & 80 female Alderley Park Swiss-derived mice (age unspecified) were exposed by inhalation to 0 (2 groups), 1000, 10,000 or 50,000 ppm (0, 3540, 35,400 or 177,000 mg/cu m) chlorodifluoromethane (CFC 22; purity, > 99.8%) for 5 hr/day on 5 days/wk for up to 83 (males) or 94 (females) weeks, by which time approx 80% of animals had died. There was no significant increase in the overall incidence of benign or malignant tumors in treated animals compared to concurrent controls. A small but statistically significant dose-related increase (p= 0.006) in the incidence of hepatocellular carcinomas was observed in males (control, 0/74 & 1/77; low-dose, 0/78; mid-dose, 3/80; high-dose, 4/80). The tumor incidences in treated groups were all within the range of those in historical controls (2-10%) for this strain of mouse. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V41 242 (1986)]**PEER REVIEWED**
  • Groups of 80 male and 80 female Alderley Park Wistar-derived rats (age unspecified) were exposed by inhalation to 0 (2 groups), 1000, 10,000 or 50,000 ppm (0, 3540, 35,400 or 177,000 mg/cu m) chlorodifluoromethane (CFC 22; purity >99.8%) for 5 hr/day, on 5 days/wk for up to 118 (females) or 131 (males) wk, by which time approx 80% of animals had died. Body-wt gain was reduced in high-dose males up to wk 80. Treatment did not affect number of animals with benign tumors. Among males, the proportions of animals with malignant tumors were higher in treated groups (controls, 16/80 & 18/80; low-dose, 27/80; mid-dose, 22/80; high-dose, 33/80), due primarily to increases in incidences of fibrosarcomas (controls, 5/80 & 7/80; low-dose, 8/80; mid-dose, 5/80; high-dose, 18/80). The numbers of animals in which such tumors involved the salivary glands were, 1, 0, 1, 0 & 7, respectively. The increase in the overall incidence of fibrosarcomas occurred between weeks 105 & 130. In addition, 4 high-dose males had Zymbal-gland tumors, whereas no such tumor was found in males of the other groups. No increased incidence of malignant tumors was observed in treated females. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V41 242 (1986)]**PEER REVIEWED**
  • ... Mild liver changes were observed in rabbits exposed to 6% (212 g/cu m) ... for 5 hr/day on 5 days/wk for 8-12 wk; one of 14 rabbits developed supraventricular arrhythmia. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V41 243 (1986)]**PEER REVIEWED**
  • CD rats were exposed to 0, 100, 1000 or 50,000 ppm (0, 0.354, 3.54 or 177 g/cu m) ... for 6 hr/day on days 6-15 of gestation. About 1/2 of the fetuses were selected for detailed histological observations of the eye and related structures. There were 646 rats (> 6000 fetuses) in the control group & 418 (> 4000 fetuses) in each exposure group. The highest dose level induced maternal (decreased body-weight gain) and fetal (slightly reduced body weight) toxicity and elevated the incidence of anophthalmia. The incidence of litters containing a fetus with anophthalmia increased from 1.65 per thousand litters in the control group to 15.67 per thousand at 50,000 ppm (177 g/cu m). [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V41 244 (1986)]**PEER REVIEWED**
  • In a ... study in rabbits ... groups of 14-16 New Zealand rabbits were exposed by inhalation to 0, 100, 1000 or 50,000 ppm (0, 0.354, 3.54 or 177 g/cu m) chlorodifluoromethane for 6 hr/day during days 6-18 of pregnancy. The high-dose level exerted maternal toxicity (lowered weight gain) during the first 4 days of treatment, but no other effect was noted in the does or fetuses. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V41 244 (1986)]**PEER REVIEWED**
  • Chlorodifluoromethane (20 mM soln generated 500 ml/min; 1:1 air) was tested in assays for forward mutation in Schizosaccharmoyces pombe & for mitotic gene conversion in Saccharomyces cerevisiae, in the presence & absence of mouse-liver S10; no activity was shown in either test system. Chlorodifluoromethane also gave negative results in host-mediated assay in CD-1 mice administered a single dose of 816 mg/kg body weight in oil by gavage, in which S pombe or S cerevisiae were injected into the venous orbital sinus & incubated for 5 or 15 hr before harvesting and scoring. (The Working Group noted that the site of recovery of the cells was not indicated.) [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V41 245 (1986)]**PEER REVIEWED**
  • ... /There was an/ increase in mutation frequency in Salmonella typhimurium TA 100 exposed to a concn of 50% in air for 24 hr (details not given) .... Chlorodifluoromethane was tested in 2 studies of dominant lethal mutations in mice, in which male mice were exposed to various concn (10 to 100,000 ppm; 35.4 to 354,000 mg/cu m) for 6 hr/day for 5 consecutive days. No consistent time- or treatment-related effect was observed. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V41 245 (1986)]**PEER REVIEWED**
  • Groups of 60 male and 60 female Swiss mice, nine weeks of age, were exposed by inhalation to 0, 1000 or 5000 ppm (0, 3540 or 17700 mg/cu m) chlorodifluoromethane (FC 22; purity, 99.98%) for 4 hr per day on five days per week for 78 weeks. The animals were kept under observation until spontaneous death (survival unspecified). Full necropsy was performed on all animals. No effects were found on survival or body weight. No difference related to treatment was found in the incidence of benign or malignant tumors. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 1340 (1999)]**PEER REVIEWED**
  • Groups of 60 male and 60 female Sprague Dawley rats, eight weeks of age, were exposed by inhalation to 0, 1000 or 5000 ppm (0, 3540 or 17700 mg/cu m) chlorodifluoromethane (FC 22; purity, 99.98%) for 4 hr per day on five days per week for 104 weeks. Full necropsy was performed on all animals. No effects were found on survival or body weight. No difference related to treatment was found in the incidence of benign or malignant tumors. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 1340 (1999)]**PEER REVIEWED**
  • Chlorodifluoromethane causes malformations of the eyes of fetal rats, but has no reproductive effects in male rats and does not cause prenatal toxicity in rabbits following exposure by inhalation. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V711342 (1999)]**PEER REVIEWED**
  • Chlorodifluoromethane is mutagenic to Salmonella typhimurium but it did not induce either mutation or gene conversion in Saccharomyces cerevisiae. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 1342 (1999)]**PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LC50 Mouse 30 min 27.7% [Sakata M et al; Toxicol Appl Pharmacol 59 (1): 64-70 (1981)]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • ... MAIN FACTOR AFFECTING FATE OF FLUOROCARBONS IS BODY FAT, WHERE THEY ARE CONCENTRATED & SLOWLY RELEASED INTO BLOOD AT CONCN THAT SHOULD NOT CAUSE ANY RISK OF CARDIAC SENSITIZATION. /FLUOROCARBONS/ [National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 781]**PEER REVIEWED**
  • Fluorocarbon-22 was studied in mice and rabbits. Blood concn was in direct proportion to inhaled concn. The concn in fat was greater than in other tissues after prolonged inhalation. When inhalation was short, the concn in fat was less than in other tissues. [Sakata M et al; Toxicol Appl Pharmacol 59 (1): 64-70 (1981)]**PEER REVIEWED**
  • THERE IS A SIGNIFICANT ACCUMULATION OF FLUOROCARBONS IN BRAIN, LIVER & LUNG COMPARED TO BLOOD LEVELS, SIGNIFYING A TISSUE DISTRIBUTION OF FLUOROCARBONS SIMILAR TO THAT OF CHLOROFORM. /FLUOROCARBONS/ [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 1203]**PEER REVIEWED**
  • Absorption of fluorocarbons is much lower after oral ingestion (35-48 times) than after inhalation. ... The lung generally have the highest fluorocarbon concn on autopsy. /Fluorocarbons/ [Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 884]**PEER REVIEWED**
  • Chlorodifluoromethane is very rapidly cleared from the blood of rats and rabbits exposed by inhalation. Little distribution to tissues or metabolism occurs in rats, with recoveries from expired air as CO2 in 15-24 hr and in the urine, being about 0.1% and 0.02% of the dose, respectively. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 1341 (1999)]**PEER REVIEWED**
  • Two groups of three male volunteers were exposed by inhalation to chlorodifluoromethane at either 327 or 1833 mg/cu m for 4 hr. The average maximal blood concentrations were 0.25 and 1.36 ug/ml, respectively, and were achieved within 1 hr of the beginning of exposure. The average blood/air partition coefficients for chlorodifluoromethane towards the end of the exposure period were 0.82 and 0.76, respectively, and the fat/air partition coefficients were 7.7 and 8.1. Thus, the fat/blood partition coefficient was estimated to be approximately 10. Three phases for the elimination of chlorodifluoromethane in breath were identified, with estimated half-lives of 0.005, 0.2 and 2.6 hr. An average of 2.1% of the inhaled chlorodifluoromethane was recovered from the exhaled air over 26 hr and minimal amounts were found in urine. Minimal changes in the fluoride concentration in urine were observed, which is consistent with a low degree of metabolism. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 1340 (1999)]**PEER REVIEWED**

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Metabolism/Metabolites

  • Approx 0.1 and 0.06% of an inhaled dose was recovered as (14)C-carbon dioxide after exposure of rats to 500 & 10,000 ppm (1.77 & 35.4 g/cu m) (14)C-chlorodifluoromethane, respectively, for 15-24 hr by inhalation. The amount of radioactivity excreted in the urine was approx 0.03 & 0.01% of the inhaled doses, respectively. Similar findings have been reported recently, indicating that there is little or no metabolism of chlorodifluoromethane in rats. After incubation of (36)Cl-chlorodifluoromethane with Aroclor-induced rat-liver homogenates, no release of chloride was detected. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V41 244 (1986)]**PEER REVIEWED**
  • Chlorodifluoromethane inhaled by male Wistar rats at a concentration of 160 ppm (566 mg/cu m) underwent no detectable metabolism and prior treatment of rats with either DDT or phenobarbital did not stimulate its metabolic transformation. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 1341 (1999)]**PEER REVIEWED**

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TSCA Test Submissions

  • Oncogenicity was evaluated in male and female Alderley Park rats (80/sex/group) exposed to chlorodifluoromethane via inhalation at 0 (2 groups), 1000, 10,000 and 50,000 ppm for 5 hrs/day, 5 days/week for 27-30 months. The only reported finding of significance was an increase in the incidence of malignant neoplasms, due mainly to fibrosarcoma of the salivary gland in both sexes at 50,000 ppm. The incidence of these tumors was significant only after 25 months. This preliminary report did not contain information concerning the histopathological results of the study.[ICI Americas, Inc.; Chlorofluorocarbon 22 (CFC 22 - chlorodifluoromethane). (1981), EPA Document No. FYI-OTS-0481-0111, Fiche No. 0111-0 ]**UNREVIEWED**
  • Oncogenicity was evaluated in male and female Alderley Park mice (80/sex/group) exposed to chlorodifluoromethane via inhalation at 0 (2 groups), 1000, 10,000 and 50,000 ppm for 5 hrs/day, 5 days/week for 27-30 months. There was no increase in overall tumor incidence or significant increase in neoplasms (benign or malignant) observed between exposed animals and controls. This preliminary report did not contain information concerning the histopathological results of the study.[ICI Americas, Inc.; Chlorofluorocarbon 22 (CFC 22 - chlorodifluoromethane). (1981), EPA Document No. FYI-OTS-0481-0111, Fiche No. 0111-0 ]**UNREVIEWED**

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.

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Web page last updated on May 14, 2008