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SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 233
CCOHS Chemical Name: Chlorodifluoromethane

Synonyms:
CFC 22
Difluorochloromethane
FC-22
Fluorocarbon 22
HCFC 22
Monochlorodifluoromethane
Propellant 22
R 22
Refrigerant 22

Chemical Name French: Chlorodifluorométhane
Chemical Name Spanish: Clorodifluorometano

Trade Name(s):
Freon 22
Genetron 22

CAS Registry Number: 75-45-6
UN/NA Number(s): 1018
RTECS Number(s): PA6390000
Chemical Family: Halogenated aliphatic hydrocarbon / haloalkane / halomethane / fluorocarbon / chlorofluorocarbon / CFC
Molecular Formula: CH-Cl-F2
Structural Formula: Cl-CH-F2

SECTION 2. DESCRIPTION

Appearance and Odour:
Colourless gas or liquefied compressed gas. Odourless at concentrations up to 20% by volume; mild, ethereal odour at higher concentrations.(24,25)

Odour Threshold:
Information not available.

Warning Properties:
Insufficient information for evaluation.

Composition/Purity:
Chlorodifluoromethane is typically available as a liquefied gas with a minimum purity of 99.9%. It is shipped in steel cylinders under its own vapour pressure of 850 kPa (123 psig; 8.4 atm) at 21.1 deg C.(25) It is also available in an azeotropic mixture of 48.8% chlorodifluoromethane with 51.2% chloropentafluoroethane (R 115) (Fluorocarbon-502). Impurities present in commercial chlorodifluoromethane include dichlorofluoromethane.(5)

Uses and Occurrences:
Chlorodifluoromethane is used as a low-temperature refrigerant in air-conditioning units; as an aerosol propellant; and as an intermediate in the production of the fluorocarbon monomer tetrafluoroethylene (used to make Teflon). A mixture with chloropentafluoroethane (R115) is used as a refrigerant in food display cases, icemakers, home freezers, and heat pumps. It is no longer used to any significant extent as an industrial solvent.(4,5,25)
Chlorodifluoromethane is not known to occur as a natural product.(4)
Chlorodifluoromethane is included as a controlled substance in the Montreal Protocol on Substances that Deplete the Ozone Layer. Under these provisions, the production and imports of this substance will be phased out completely with a target date of 2030.


SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
Colourless gas or liquefied compressed gas. Odourless at concentrations up to 20% by volume; mild, ethereal odour at higher concentrations. Will not burn. Can decompose at high temperatures forming corrosive/toxic gases such as hydrogen fluoride, hydrogen chloride, carbonyl fluoride, carbonyl chloride, chlorine and phosgene. Cylinders or tanks may rupture and explode if heated. COMPRESSED GAS. Generally has low short-term toxicity, but can cause death during severe exposures, such as may occur during a major leak. Extremely high concentrations may cause light-headedness, giddiness, shortness of breath and irregular heart beat. Confined space hazard.



POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
Chlorodifluoromethane is generally considered to be low in short-term toxicity, but can cause death during severe exposures, such as may occur during a major leak. It is not clear whether death is due to oxygen deficiency (since chlorodifluoromethane displaces oxygen) or effects on the heart (irregular heart beat). High concentrations (above 5% (50000 ppm)) may cause lightheadedness, giddiness, and shortness of breath. Due to the risk of sudden death, and absence of warning properties for chlorodifluoromethane, symptoms of exposure (lightheadedness and/or irregular heart beat) must be responded to immediately.
There are several case reports of deaths due to oxygen deficiency. Air normally contains 20.9% oxygen. The available oxygen should be a minimum of 18% or harmful effects will result. Effects of oxygen deficiency are: 12-16% - breathing and pulse rate are increased, with slight muscular incoordination; 10-14% - emotional upsets, abnormal fatigue from exertion, disturbed respiration; 6-10% - nausea and vomiting, inability to move freely, collapse, possible lack of consciousness; below 6% - convulsive movements, gasping, possible respiratory collapse and death. Since exercise increases the body's need for oxygen, symptoms will occur more quickly during exertion in an oxygen-deficient environment.(17,18) Symptoms such as these, as well as heart effects (chest pain and racing heart beat) have been reported by victims of major chlorodifluoromethane leaks.(4,15,16)
Survivors of oxygen deprivation may experience damage to some or all organs including the central nervous system and the brain. These effects may or may not be reversible with time, depending on the degree and duration of the low oxygen and the amount of tissue injury.(17)
Chlorodifluoromethane decomposes upon heating to form very toxic gases, such as carbonyl fluoride, phosgene, hydrogen fluoride and hydrogen chloride. In one case, an employee experienced significant health effects following exposure to thermal decomposition products (assumed to be phosgene) after heating chlorodifluoromethane while cutting through a refrigeration pipe.(20)

Skin Contact:
Direct contact with liquefied chlorodifluoromethane escaping from its cylinder can cause frostbite.(14) Symptoms of mild frostbite include numbness, prickling and itching of the affected area. Symptoms of more severe frostbite include a burning sensation and stiffness of the affected area. The skin may become waxy white or yellow. Blistering, necrosis (dead skin) and gangrene have developed in several cases. There may be no pain experienced at first, but there is intense pain when the frozen tissue thaws.
The gas is not irritating.

Eye Contact:
Direct contact with liquefied chlorodifluoromethane can cause frostbite of the eyes. Permanent eye damage or blindness can result. There are no reports of accidental injury from splash contact of liquid chlorodifluoromethane with the eyes.
The gas is considered non-irritating.

Ingestion:
Ingestion is not an applicable route of exposure for gases.

Effects of Long-Term (Chronic) Exposure

Heart/Blood Vessels:
Several studies have examined whether there is a relationship between chlorodifluoromethane exposure and effects on the heart. There have been limitations to each of the studies, e.g. mixed exposures, small numbers of subjects involved, inadequate control of variables, and bias in selection. While no consistent associations have been shown and no firm conclusions can be drawn, there is a persistent increase in reporting of lightheadedness and racing heartbeat (palpitations) among those repeatedly exposed to chlorodifluoromethane. It is possible that the long-term exposure levels studied are too low to produce measurable cardiac effects. Some other chlorofluorocarbons have shown greater potential for cardiac effects.
Following reports of hospital employees experiencing repeated episodes of palpitations, a study compared questionnaire responses of the employees with chlorodifluoromethane exposure to a control group. Representative sampling during use indicated an average exposure of 300 ppm chlorodifluoromethane for two minutes, with expectation that peaks would be higher. There was a 3.5-fold increase in the incidence of palpitations (rapid throbbing or fluttering of the heart) reported by the exposed group and evidence of arrhythmia (irregular heartbeat) on electrocardiograms.(21) This study has several limitations and the small numbers involved do not allow firm conclusions to be drawn.
In another study, 89 employees with intermittent exposures to a mixture of chlorofluorocarbons were assessed for cardiac effects. Highest exposures were reported to be a 1-minute peak of 1.4% (14000 ppm) and an 8-hour time-weighted average of 280 ppm. No significant or dose-related cardiac arrhythmias or central nervous system effects were observed. However, there was a somewhat higher prevalence of arrhythmias than observed in the general population.(22) There were many limitations to this study and exposures were mixed.
No clear association of heart rhythm abnormalities to chlorodifluoromethane exposure was observed in a small number (less than 6) of male refrigeration repair workers when compared to unexposed plumbers. The exposed group was occasionally exposed to chlorodifluoromethane at peak levels of 1300-10000 ppm (cited as 1300-10000 cm3/m3). One individual appeared to be more sensitive to the effects of exposure, but he experienced irregular heart rhythm at other times as well.(46)

Carcinogenicity:

No conclusions can be drawn from a study of employees exposed to a mixture of chlorofluorocarbons because employees were exposed to mixtures of chemicals and only a small number of employees were studied. The International Agency for Research on Cancer (IARC) has concluded that there is inadequate evidence for the carcinogenicity of chlorodifluoromethane to humans.(6)

The International Agency for Research on Cancer (IARC) has concluded that this chemical is not classifiable as to its carcinogenicity to humans (Group 3).

The American Conference of Governmental Industrial Hygienists (ACGIH) has designated this chemical as not classifiable as a human carcinogen (A4).

The US National Toxicology Program (NTP) has not listed this chemical in its report on carcinogens.

Teratogenicity and Embryotoxicity:
There is no human information available. In animal studies, developmental effects were not observed in the absence of maternal toxicity. Fetotoxicity and eye defects were observed in the presence of maternal toxicity.

Reproductive Toxicity:
There is no human information available. A small number of animal studies indicate that chlorodifluoromethane is not harmful to the male reproductive system.

Mutagenicity:
There is insufficient information available to conclude that chlorodifluoromethane is mutagenic. There is no human information available. Some positive results (bone marrow chromosome damage) were obtained in tests using rats, but the effects were not dose- or time-related and, in some cases, were not reproducible. Negative results were obtained in one dominant lethality study and inconclusive results in another.

Toxicologically Synergistic Materials:
There is no information available.

Potential for Accumulation:
Studies with male volunteers have shown poor absorption and rapid elimination following inhalation exposure. The half-life (the time it take to eliminate 50% of the dose) of the longest elimination phase was 2.6 hours.(23) Animal studies have shown that chlorodifluoromethane is rapidly absorbed into the bloodstream by all routes of administration, is not metabolized to any significant extent and is eliminated unchanged in the expired air. Studies with rabbits exposed to very high concentrations (30% and 40% chlorodifluoromethane) showed a rapid increase in the concentration in blood with saturation reached in about 5 minutes. After exposure stopped, blood concentrations dropped quickly (up to 50% drop in 1 minute) with none detectable after 1 hour.(3)


SECTION 4. FIRST AID MEASURES

Inhalation:
If symptoms are experienced, remove source of contamination or move victim to fresh air. If breathing is difficult, oxygen may be beneficial if administered by trained personnel, preferably on a doctor's advice. Obtain medical attention immediately.

Skin Contact:
LIQUID: Quickly remove victim from source of contamination and briefly flush with lukewarm, gently flowing water until the chemical is removed. DO NOT attempt to rewarm the affected area on site. DO NOT rub area or apply dry heat. Gently remove clothing or jewelry that may restrict circulation. Carefully cut around clothing that sticks to the skin and remove the rest of the garment. Loosely cover the affected area with a sterile dressing. DO NOT allow victim to drink alcohol or smoke. Quickly transport victim to an emergency care facility. GAS: No effects expected.

Eye Contact:
LIQUID: Quickly remove victim from source of contamination. Immediately and briefly flush with lukewarm, gently flowing water until the chemical is removed. DO NOT attempt to rewarm. Cover both eyes with a sterile dressing. DO NOT allow victim to drink alcohol or smoke. Quickly transport victim to an emergency care facility. GAS: No effects expected.

Ingestion:
Not an applicable route of exposure for gases.

First Aid Comments:
Provide general supportive measures (comfort, warmth, rest).
Consult a doctor and/or the nearest Poison Control Centre for all exposures except minor instances of inhalation or skin contact.
All first aid procedures should be periodically reviewed by a doctor familiar with the material and its conditions of use in the workplace.



SECTION 5. FIRE FIGHTING MEASURES

Flash Point:
Not combustible (does not burn)

Lower Flammable (Explosive) Limit (LFL/LEL):
Not applicable

Upper Flammable (Explosive) Limit (UFL/UEL):
Not applicable

Autoignition (Ignition) Temperature:
Not applicable

Sensitivity to Mechanical Impact:
Not sensitive. Stable material.

Sensitivity to Static Charge:
Insufficient information is available to determine whether liquefied chlorodifluoromethane can accumulate static charge. Since it does not burn, it will not be ignited by a static discharge.

Combustion and Thermal Decomposition Products:
Chlorofluorocarbons, like chlorodifluoromethane, decompose in a fire or on exposure to extreme heat (e.g. a welding torch), or hot surfaces above 290 deg C (554 deg F) to form hydrogen chloride, hydrogen fluoride, chlorine, carbonyl chloride, carbonyl fluoride, phosgene, carbon monoxide, and carbon dioxide.(20,47,48)

Fire Hazard Summary:
Chlorodifluoromethane does not burn. At high temperatures or in contact with hot surfaces or red-hot metal, chlorodifluoromethane decomposes to form toxic and/or corrosive hydrogen fluoride, hydrogen chloride, carbonyl fluoride, carbonyl chloride, chlorine and phosgene. Closed containers may explode if exposed to excess heat for a sufficient period of time, releasing large quantities of toxic gases or vapours.

Extinguishing Media:
Chlorodifluoromethane is not combustible. Use extinguishing media suitable for the surrounding fire.

Fire Fighting Instructions:
If a fire occurs in an area where chlorodifluoromethane cylinders are used or stored, move cylinder(s) or container(s) from fire area, if this can be done without risk. Explosive decomposition may occur under fire conditions. Use extreme caution since heat may rupture containers, which may rocket.
If the chlorodifluoromethane containers cannot be moved, cool fire-exposed cylinders, containers or equipment by application of hose streams. Cooling should begin as soon as possible (within the first several minutes) and should concentrate on any unwetted portions of the container. Apply water from as far a distance as possible, until well after the fire is out. No part of a cylinder should be subjected to a temperature higher than 52 deg C (approximately 125 deg F).
Most cylinders or containers are provided with a pressure relief valve designed to vent contents when they are exposed to elevated temperatures. Take care not to block pressure relief valves. If possible, avoid spraying cold areas of equipment.
Stay away from ends of tanks, but be aware that flying material from ruptured tanks may travel in any direction. Personnel should withdraw immediately in case of rising sounds from venting safety device or any discolouration of tanks due to fire.
For a massive fire, use unmanned hose holder or monitor nozzles and evacuate the area.

Protection of Fire Fighters:
The decomposition products of chlorodifluoromethane are corrosive and very toxic (skin absorption and inhalation hazards). Do not enter without wearing specialized protective equipment suitable for the situation. Firefighter's normal protective clothing (Bunker Gear) will not provide adequate protection. A full-body encapsulating chemical protective suit with positive pressure self-contained breathing apparatus (NIOSH approved or equivalent) may be necessary.



NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD IDENTIFICATION

NFPA - Comments:
NFPA has no listing for this chemical in Codes 49 or 325.


SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 86.47

Conversion Factor:
1 ppm = 3.54 mg/m3; 1 mg/m3 = 0.28 ppm at 25 deg C (calculated)

Physical State: Gas
Melting Point: -160.0 deg C (-256 deg F) (19,28,29,30)
Boiling Point: -40.8 deg C (-41.44 deg F) at 103.3 kPa (1 atm) (4,19,29,30)
Relative Density (Specific Gravity): Not applicable (gas)
Solubility in Water: Slightly soluble (0.3% w/w at 101.3 kPa and 25 deg C) (19,25,30)
Solubility in Other Liquids: Soluble in acetone, chloroform and diethyl ether.(5,49)
Coefficient of Oil/Water Distribution (Partition Coefficient): Log P(oct) = 1.08 (31)
pH Value: Not available Not available
Vapour Density: 3.07 at 21.1 deg C (air = 1) (19)
Vapour Pressure: 939-949 kPa, absolute (9.27-9.37 atm, abs) at 21.1 deg C (19,25)
Vapour Pressure at 50 deg C: Approximately 2000 kPa, absolute (19.70 atm, abs) (19,25)
Saturation Vapour Concentration: Not applicable. Gas at room temperature.
Evaporation Rate: Not applicable. Gas at room temperature.
Henry's Law Constant: 2979 Pa.m3/mol (cited as log H = 0.08 (dimensionless)) at 25 deg C (experimental) (35)
Critical Temperature: 96.0 deg C (204.8 deg F; 369.2 K) (25,28,29,30)
Critical Pressure: 4988 kPa, absolute (49.2 atm, abs) (19)

Other Physical Properties:
DIELECTRIC CONSTANT; 6.11 at 24 deg C (liquefied gas) (25,30); 1.004 at 25.4 deg C and 51 kPa (vapour) (25,29)
RELATIVE DIELECTRIC STRENGTH: 1.3 (nitrogen = 1) (25)


SECTION 10. STABILITY AND REACTIVITY

Stability:
Normally stable. Chlorodifluoromethane will decompose if heated above 290 deg C (554 deg F).(28)

Hazardous Polymerization:
Does not occur.

Incompatibility - Materials to Avoid:

NOTE: Chemical reactions that could result in a hazardous situation (e.g. generation of flammable or toxic chemicals, fire or detonation) are listed here. Many of these reactions can be done safely if specific control measures (e.g. cooling of the reaction) are in place. Although not intended to be complete, an overview of important reactions involving common chemicals is provided to assist in the development of safe work practices.


REACTIVE METALS (e.g. sodium, potassium, lithium, barium, calcium, and powdered aluminum, magnesium and zinc) - can react violently or explosively.(26,27,47)
ALUMINUM METAL- can react with fresh metal surfaces, particularly when heated, giving off a great amount of heat (exothermic reaction), which can melt the metal.(26)
LIQUEFIED CHLORODIFLUOMETHANE and WATER - may produce explosions when the liquid-water differential is greater than 92 deg C.(26)

Hazardous Decomposition Products:
None reported.

Conditions to Avoid:
Open flames, high temperatures, hot surfaces including hot metal surfaces

Corrosivity to Metals:
Pure, dry chlorodifluoromethane is not corrosive at normal temperatures to the common construction metals, such as cast iron, steel, stainless steels (e.g. types 304/347, 316 and 400 series), aluminum, copper, brass, bronze, nickel and its alloys, Hastelloy, Inconel, Monel, lead, tantalum, titanium and zirconium.(25,32,33)

Corrosivity to Non-Metals:
Chlorodifluoromethane can attack some plastics (e.g. nylon, polysulfone and polyvinyl chloride), and elastomers (e.g. Butyl GR-1, cellulose acetate butyrate, Viton A, hard rubber, isoprene, natural rubber, nitrile Buna-N, polyurethane and SBR styrene).(32,34)


SECTION 11. TOXICOLOGICAL INFORMATION

LC50 (rat): approximately 22% (220000 ppm) (4-hour exposure) (1, citing personal communication)
LC50 (rat): 35% (350000 ppm) (15-minute exposure; oxygen concentration maintained at 20%) (2)
LC50 (mouse): approximately 27.7% (277000 ppm) (30-minute exposure; oxygen concentration maintained at 20%) (3)

Eye Irritation:

Slight irritation was reported in rabbits following exposure to an unspecified concentration of the gas for 5 or 30 seconds.(4, citing an unpublished report) No further details are available.

Skin Irritation:

Skin irritation was observed when 0.5 mL of the liquefied material was applied, under cover, to intact or broken rabbit skin.(4, citing an unpublished report) There are no further details available.

Effects of Short-Term (Acute) Exposure:

Inhalation toxicity is low, requiring exposures of greater than 20% (200000 ppm) to cause death from depression of the central nervous system. Signs of toxicity in rats were tremor of the limbs and head, convulsions, unconsciousness, shallow respiration and death from respiratory depression. Death always occurs during exposure, not after. Recovery from non-lethal exposure was rapid - within 10 minutes animals appeared normal with no delayed effects. Extremely high exposures have also been shown to cause cardiac toxicity such as decreased heart rate, myocardial depression, decreased blood pressure and irregular heart beat.(1,4,5)

Inhalation:
In a 2-hour study with rats and guinea pigs, concentrations above 7.5% (75000 ppm) produced excitation and/or changes in equilibrium. Unconsciousness occurred at 20% (200000 ppm) after 45 minutes and death resulted at 30-40% (300000-400000 ppm).(7) Autopsy has shown lung injury (emphysema, congestion and bleeding) following lethal exposures.(3) Rats, guinea pigs, dogs and cats exposed at 5% (50000 ppm) for 3.5 hours/day for 4 weeks showed no clinical, biochemical or pathological effects.(7) Effects on the heart have been reported in rats during exposure to concentrations of 15-60% (150000-600000 ppm) for 2 minutes.(1) In mice, exposure to 40% (400000 ppm) did not cause irregular heart beat (arrhythmia), but did sensitize the heart to epinephrine-induced arrhythmia. This effect also occurred at 5% (50000 ppm) in dogs.(8) In dogs, cardiac effects were not evident following a 5-minute exposure to 2.5% (25000 ppm), but did occur in 2/12 animals exposed to 5% (50000 ppm) for 5 minutes (9) and in 50% of dogs exposed for 5 minutes to 14% (140000 ppm) (2). Autopsy findings of the heart after sudden death were normal, indicating that the dogs did not have a heart condition predisposing to sudden death.(2) In a limited study, dogs showed twitching movements and partial unconsciousness (anesthesia) after 10 minutes of exposure to 25%, 40%, 50% or 70% (250000, 400000, 500000 or 700000 ppm). At 70%, respiratory depression occurred, requiring assisted ventilation to prevent suffocation.(36)

Effects of Long-Term (Chronic) Exposure:

Lifetime studies of mice and rats with exposures up to 5% (50000 ppm) did not show any significant treatment-related effects.

Inhalation:
Rats and mice were exposed for their lifetimes by inhalation to up to 5% (50000 ppm) with no effect on mortality, blood or chemistry studies. Changes in body and organ weights in rats and increased activity in mice were noted at 5%.(4,10,11,37,38) Rats and dogs exposed to 1% (10000 ppm) for 13 weeks showed no effects on behaviour, weight gain or any biochemical or tissue studies. There was no effect on cardiac function in dogs.(1,4,5 - original not available in English) Rats and mice exposed to 0.2% or 1.4% (2000 or 14000 ppm) for 10 months showed no effects at 0.2%. At 1.4%, depressed body weight gain, depressed oxygen consumption and central nervous system (CNS) changes were observed. Rabbits exposed to 1.4% showed reduced hemoglobin levels.(1,4-citing a Russian study) Male rats exposed to 0 or 5% (50000 ppm) for 8 weeks showed no effects in blood or tissue studies, except a slight decrease in prostate weight and minor changes in blood triglycerides, glucose and cholesterol.(12)

Skin Contact:
Repeated application on shaved skin for 6 weeks (10 second spray, 2 times/day, 5 days/week) caused redness, slight swelling and delayed hair regrowth in rats.(4-original not in English)

Skin Sensitization:
Negative results were obtained in guinea pigs tested with liquefied chlorodifluoromethane in a modified maximization test.(4, citing an unpublished report)

Carcinogenicity:
The International Agency for Research on Cancer (IARC) has evaluated the available studies and concluded that there is limited evidence for the carcinogenicity of chlorodifluoromethane in experimental animals.(5,6)
An increase in overall tumour incidence was not observed in male rats after inhalation exposure to 0-5% (50000 ppm) for 131 weeks (5 hr/d; 5 d/wk). However, the incidence of multiple malignant tumours (salivary gland or skin fibrosarcomas) was increased with exposure to 5% (statistical significance not stated). This effect was attributed to a weak, non-specific carcinogenic or promoting effect of chlorodifluoromethane. Similar effects were not observed in female rats exposed to the same concentration for 118 weeks, nor in mice exposed to up to 50000 ppm for 83-94 weeks (5 hr/d; 5 d/wk).(11,37,38)

Teratogenicity, Embryotoxicity and/or Fetotoxicity:
Developmental effects have not been observed in the absence of maternal toxicity. Fetotoxicity and eye defects have been observed in the presence of maternal toxicity.
Rats exposed to 0, 100 or 1000 ppm on days 6-15 (6 hr/d) of pregnancy showed no effects on the offspring and no maternal toxicity. Exposure to 50000 ppm was associated with maternal toxicity (decreased body weight gain). Also at 50000 ppm, the offspring showed a significant reduction in mean fetal weight and an increase in the incidence of eye defects. Malfunction of a fan resulted in the animals being exposed to much higher concentrations for 5-10 minutes. Signs of maternal toxicity (distress, hunched posture) were observed following this accidental exposure, which was estimated to be a maximum of 166667 ppm.(39) Rabbits were exposed to 0, 100, 1000 or 50000 ppm on days 6-18 (6 hr/d) of pregnancy. No significant effects were observed in the offspring. Maternal toxicity (slight weight loss during the first 4 days of exposure) was observed.(40) Rats were exposed by inhalation from days 4-13 or days 6-15 (6 hr/d) of pregnancy to 0, 0.1 or 1.0% (0, 100 or 1000 ppm). In a second experiment, rats were exposed by inhalation from days 6-15 (6 hr/d) of pregnancy to 0, 0.05, 0.10, or 2.0% (0, 500, 1000, or 20000 ppm). There were no signs of maternal toxicity. A non-significant increase in eye defects was observed. Pregnancy outcomes and other measures of fetal development were not significantly affected.(41)

Reproductive Toxicity:
The available evidence suggests that chlorodifluoromethane is not toxic to male reproduction.
Male rats exposed to 0 or 5% (50000 ppm) for 8 weeks had no changes in testes or sperm. Serial mating for 10 weeks (each male rat housed with different virgin female each week) showed no effects on live implants, reabsorption sites and the number of dead implants. Growth and development of embryos resulting from breeding of treated males was normal.(12) No effects on male fertility nor sperm damage were observed in two dominant lethal assays using up to 10% (100000 ppm).(44,45)

Mutagenicity:
There is insufficient information available to conclude that chlorodifluoromethane is mutagenic. Some positive results (bone marrow chromosome damage) were obtained in tests using rats, but the effects were not dose- or time-related and, in some cases, were not reproducible. Negative results were obtained in one dominant lethality study and inconclusive results in another.
There were no dominant lethal mutations in male rats exposed by inhalation to 5% (50000 ppm) for 8 weeks, then mated serially for 10 weeks.(12) Weak evidence of a dominant lethal effect was reported for male mice exposed by inhalation for 5 consecutive days (6 hr/d) at concentrations up to 100000 ppm. No dose- or time-related trends were firmly established.(11,44,45) Rats were exposed by inhalation to 1000, 10000, or 150000 ppm for single 2-hour exposures (sampled at 6 hrs (experiment 1) or 24 hrs after exposure (experiment 2)) or for 5 days (6 hr/d; sampled at 6 hrs after exposure (experiment 3)). Some positive results (bone marrow chromosome damage) were observed, but the effects were generally not dose-related and not statistically significant, particularly when gaps were excluded. The authors indicate that cytotoxicity may have been occurring at the higher exposure concentrations.(42) In a related experiment, male rats were exposed to 10, 100, 500 or 1000 ppm for 5 days (6 hr/d). Positive results (bone marrow chromosome damage) were obtained, but the results were not dose-related. In addition, the low exposure concentration was poorly controlled and ranged between 23 and 80 ppm.(43) Negative results (mouse micronucleus assay) were obtained following the administration of 816 mg/kg in corn oil.(4-unconfirmed)
Negative results were obtained in studies using cultured mammalian cells.(1,4,5,6,11) Positive results were obtained in some test with bacteria, but negative results were obtained in yeast.(1,4,11)


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) Litchfield, M.H., et al. The toxicological evaluation of chlorofluorocarbon 22 (CFC 22). Food and Chemical Toxicology. Vol. 22, no. 6 (1984). p. 465-475
(2) Clark, D.G., et al. Acute inhalation toxicity of some halogenated and non-halogenated hydrocarbons. Human Toxicology. Vol. 1, no. 3 (1982). p. 239-247
(3) Sakata, M., et al. Acute toxicity of fluorocarbon-22: toxic symptoms, lethal concentration, and its fate in rabbit and mouse. Toxicology and Applied Pharmacology. Vol. 59, no. 1 (1981). p. 64-70
(4) International Programme on Chemical Safety (IPCS). Partially halogenated chlorofluorocarbons (methane derivatives). Environmental Health Criteria; 126. World Health Organization, 1991
(5) International Agency for Research on Cancer (IARC). Chlorodifluoromethane. In: IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. Vol. 41. Some halogenated hydrocarbons and pesticide exposures. World Health Organization, 1986. p. 237- 252
(6) International Agency for Research on Cancer (IARC). Chlorodifluoromethane. In: IARC monographs on the evaluation of carcinogenic risks to humans. Vol. 71. Part 3. Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide. World Health Organization, 1999. p. 1339-1343
(7) Weigand, W. Studies on the inhalation toxicity of fluorine derivatives of methane, ethane, and cyclobutane. Zentralblatt fur Arbeitsmedizin und Arbeitsschutz. Vol. 5 (1971). p. 149-156 (English Translation: NIOSHTIC Control Number: 00069201)
(8) Aviado, D.M., et al. Toxicity of aerosol propellants on the respiratory and circulatory systems. I. Cardiac arrhythmia in the mouse. Toxicology. Vol. 2 (1974). p. 31-42
(9) Reinhardt, C.F., et al. Cardiac arrhythmias and aerosol "sniffing". Archives of Environmental Health. Vol. 22 (Feb. 1971). p. 265-279
(10) Maltoni, C., et al. Long-term carcinogenicity bioassays on three chlorofluorocarbons (trichlorofluoromethane, FC11; dichlorodifluoromethane, FC12; chlorodifluoromethane, FC22) administered by inhalation to Sprague-Dawley rats and Swiss mice. Annals of the New York Academy of Sciences. Vol. 534 (1988). p. 261-282
(11) Longstaff, E. Carcinogenic and mutagenic potential of several fluorocarbons. Annals of the New York Academy of Sciences. Vol. 534 (1988). p. 283-298
(12) Lee, I.P., et al. Studies on the male reproductive toxicity of Freon 22. Fundamental and Applied Toxicology. Vol. 1, no. 3 (May/June 1981). p. 266-270
(13) Maltoni, C., et al. Experimental contributions in identifying brain potential carcinogens in the petrochemical industry. Annals of the New York Academy of Sciences. Vol. 381 (1982). p. 216-249
(14) Kurbat R.S., et al. Facial injury and airway threat from inhalant abuse: a case report. The Journal of Emergency Medicine. Vol. 16, no. 2 (1998). p. 167-169
(15) Burt, S. NIOSH Health Hazard Evaluation Report. Dimond Ice Chalet, Anchorage, Alaska. HETA-91-0246-2354. National Institute for Occupational Safety and Health (NIOSH), 1993
(16) Gunter, B.J., et al. NIOSH Health Hazard Evaluation Report. Refrigeration Workers, Salt Lake City, Utah. HETA-81-043-1207. National Institute for Occupational Safety and Health (NIOSH), 1982
(17) Wilkenfeld, M. Simple asphyxiants. In: Environmental and Occupational Medicine. 3rd ed. Edited by W.N. Rom. Lippincott-Raven Publishers, 1998. p. 651-655
(18) Leikauf, G.D., et al. Inorganic compounds of carbon, nitrogen and oxygen. In: Patty's Industrial Hygiene and Toxicology. Vol. 3. Edited by G.D. Clayton, et al. 5th ed. John Wiley & Sons, 2001
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Information on chemicals reviewed in the CHEMINFO database is drawn from a number of publicly available sources. A list of general references used to compile CHEMINFO records is available in the database Help.


Review/Preparation Date: 2004-06-22



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