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FLUOROCARBON 21

BACKGROUND INFORMATION

PHYSICAL AND CHEMICAL PROPERTIES

Chemical formula:

CHCl2F

Molecular weight:

102.92

Chemical name:

Dichlorofluoromethane

Synonyms:

FC-21, fluorocarbon 21, Freon 21

CAS number:

75–43–4

Melting point:

−135°C

Boiling point:

8.9°C

Specific gravity:

1.405 (9°C)

Solubility:

Insoluble in water; soluble in alcohol and ether

General characteristics:

Colorless, nearly odorless, nonflammable, heavy gas

Conversion factors:

1 ppm=4.2 mg/m3

1 mg/m3 =0.24 ppm

OCCURRENCE AND USE

Dichlorofluoromethane (FC-21) is used primarily as a solvent, as a refrigerant, in aerosol propellants, and in fire extinguishers. Recently, it has found use as a heat-transfer liquid in the space-shuttle program.

SUMMARY OF TOXICITY INFORMATION

EFFECTS ON HUMANS

The Committee is aware of no data on human exposure to FC-21.

EFFECTS ON ANIMALS

The lethal concentration of FC-21 for rats in a 4-h exposure was 49,900 ppm (Tappan and Waritz, 1964). A 2-h exposure of guinea pigs at 50,000–52,000 ppm was not fatal, but exposure produced loss of coordination in 3 min and unconsciousness within 30 min (Nuckolls, 1935). Exposure at 100,000 ppm killed rats and guinea pigs within 1 h (Weigand, 1971). Central nervous system effects (loss of coordination, tremors, and narcosis) were observed in both exposed species.

Contact of propylene glycol solutions of FC-21 with the skin of guinea pigs produced mild irritation at FC-21 concentrations of 25–40% (Goodman, 1976; Hood, 1964a). No irritation was seen at 2.5%. No evidence of sensitization potential was observed.



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Emergency and Continuous Exposure Limits for Selected Airborne Contaminants: Volume 2 FLUOROCARBON 21 BACKGROUND INFORMATION PHYSICAL AND CHEMICAL PROPERTIES Chemical formula: CHCl2F Molecular weight: 102.92 Chemical name: Dichlorofluoromethane Synonyms: FC-21, fluorocarbon 21, Freon 21 CAS number: 75–43–4 Melting point: −135°C Boiling point: 8.9°C Specific gravity: 1.405 (9°C) Solubility: Insoluble in water; soluble in alcohol and ether General characteristics: Colorless, nearly odorless, nonflammable, heavy gas Conversion factors: 1 ppm=4.2 mg/m3 1 mg/m3 =0.24 ppm OCCURRENCE AND USE Dichlorofluoromethane (FC-21) is used primarily as a solvent, as a refrigerant, in aerosol propellants, and in fire extinguishers. Recently, it has found use as a heat-transfer liquid in the space-shuttle program. SUMMARY OF TOXICITY INFORMATION EFFECTS ON HUMANS The Committee is aware of no data on human exposure to FC-21. EFFECTS ON ANIMALS The lethal concentration of FC-21 for rats in a 4-h exposure was 49,900 ppm (Tappan and Waritz, 1964). A 2-h exposure of guinea pigs at 50,000–52,000 ppm was not fatal, but exposure produced loss of coordination in 3 min and unconsciousness within 30 min (Nuckolls, 1935). Exposure at 100,000 ppm killed rats and guinea pigs within 1 h (Weigand, 1971). Central nervous system effects (loss of coordination, tremors, and narcosis) were observed in both exposed species. Contact of propylene glycol solutions of FC-21 with the skin of guinea pigs produced mild irritation at FC-21 concentrations of 25–40% (Goodman, 1976; Hood, 1964a). No irritation was seen at 2.5%. No evidence of sensitization potential was observed.

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Emergency and Continuous Exposure Limits for Selected Airborne Contaminants: Volume 2 Transient eye irritation was seen after instillation of liquid FC-21 chilled to the temperature of dry ice or of a 40% solution in propylene glycol into the eyes of rabbits (Brittelli, 1976; Hood, 1964b). Mild lacrimation, but no corneal or iritic effect, was seen after FC-21 was sprayed directly into the eyes of rabbits (Hood, 1964b). A group of 10 rats exposed at 10,000 ppm, 6 h/d, 5 d/wk, for 2 wk all survived, but pathologic examination revealed liver damage (Trochimowicz et al., 1977b). In a later 90-d study, groups of 54 rats and 4 dogs were similarly exposed at 1,000 and 5,000 ppm (Trochimowicz et al., 1977a). Excessive mortality and bilateral hair loss were seen in both groups of rats. The dogs lost weight at both concentrations. Histopathologic examination revealed cirrhosis in all rats, but only minimal changes in the livers of dogs exposed at 5,000 ppm. No compound-related effects were seen in dogs exposed at 1,000 ppm. Another incomplete 90-d study reported gross pathologic changes in the livers of rats exposed at 500 ppm, probable changes at 200 ppm, but no gross effects at 50 ppm (Allied Chemical, unpublished report to TLV Committee, 1978). FC-21, like other chlorofluorocarbons and hydrocarbons, is capable of sensitizing the beagle heart to exogenous epinephrine in 5-min cardiac-sensitization screening studies (Mullin, 1975). A concentration of 10,000 ppm produced a marked response in 2 of 12 exposed dogs. No response was seen at 5,000 ppm; at this concentration, FC-21 is considered slightly less cardiotoxic than FC-11, which produced sensitization at 5,000 ppm. In the monkey, respiratory depression and tachycardia were seen after 5 min at 25,000 ppm (Aviado and Smith, 1975). Kelly et al. (1978) exposed 25 pregnant rats to FC-21 at 10,000 ppm 6 h/d on days 6–15 of gestation. There was an unspecified adverse effect on maternal weight and a preimplantation loss of fertilized ova in 15 of the 25 rats. No teratogenic effects were observed. INHALATION EXPOSURE LIMITS The ACGIH (1980, 1983) established a TLV-TWA for FC-21 of 10 ppm (40 mg/m3). This represented a downward revision from the previous TLV-TWA of 1,000 ppm and was recommended because data had suggested that FC-21 was considerably more hepatotoxic than closely related fluorinated compounds and was similar in that respect to chloroform (ACGIH, 1980). OSHA (1983) recommended a permissible exposure level (PEL) of 1,000 ppm. COMMITTEE RECOMMENDATIONS On the basis of 5-min cardiac-sensitization screening findings in dogs, which were positive at 10,000 ppm and negative at 5,000 ppm; hepatotoxic effects in rats exposed at 10,000 ppm over a 2-wk period; and reproductive changes with exposure at 10,000 ppm at a critical period in gestation, the Committee recommends a 60-min EEL of 100 ppm.

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Emergency and Continuous Exposure Limits for Selected Airborne Contaminants: Volume 2 For 24-h and 90-d exposures, the most relevant data are those from the two 90-d studies in rats and dogs. In rats, 50 ppm was a no-observed-adverse-effect concentration; 1,000 ppm was the minimal-effect concentration in dogs, causing weight loss. On the basis of the subchronic data in animals, which suggest that the toxicity of FC-21 is greater than that of other fluorocarbons and similar to that of chloroform, the Committee has applied an uncertainty factor of 1,000 to the minimal-effect concentration in dogs and recommends a 90-d CEL of 1 ppm. For a single 24-h exposure, a somewhat higher concentration would be expected not to have adverse effects, and a 24-h EEL of 3 ppm is recommended. The Committee’s recommended EELs and CEL for FC-21 are shown below.     1984 60-min EEL 100 ppm 24-h EEL 3 ppm 90-d CEL 1 ppm

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Emergency and Continuous Exposure Limits for Selected Airborne Contaminants: Volume 2 REFERENCES American Conference of Governmental Industrial Hygienists. 1980. Dichlorofluoromethane. Documentation of the Threshold Limit Values. 4th ed. Concinnati, Ohio: American Conference of Governmental Industrial Hygienists p. 132. American Conference of Governmental Industrial Hygienists. 1983. TLVs(R): Threshold Limit Values for Chemical Substances and Physical Agents in the Work Environment with Intended Changes for 1983–1984. Cincinnati, Ohio: American Conference of Governmental Industrial Hygienists. 93 p. Aviado, D.M., and Smith, D.G. 1975. Toxicity of aerosol propellants in the respiratory and circulatory systems. VIII. Respiration and circulation in primates. Toxicology 3:241–252. Brittelli, M.R. 1976. Eye irritation tests in rabbits with dichlorofluoromethane. Report No. 751–75. Newark, Delaware: E.I.du Pont de Nemours and Co., Haskell Laboratory for Toxicology and Industrial Medicine. 2 p. [Unpublished] Goodman, N.C. 1976. Primary skin irritation and sensitization tests on guinea pig with methane, dichlorofluoro. Report No. 750–75. Newark, Delaware: E.I.du Pont de Nemours and Co., Haskell Laboratory for Toxicology and Industrial Medicine. 2 p. [Unpublished] Hood, D.B. 1964a. Freon-21: Eye irritation, skin irritation and sensitization tests. Report No. 105–64. Newark, Delaware: E.I.du Pont de Nemours and Co., Haskell Laboratory for Toxicology and Industrial Medicine. 3 p. [Unpublished] Hood, D.B. 1964b. Eye irritation tests with Freon-21. Report No. 107–64. Newark, Delaware: E.I.du Pont de Nemours and Co., Haskell Laboratory for Toxicology and Industrial Medicine. 2 p. [Unpublished] Kelly, D.P., Culik, R., Trochimowicz, H.J., and Fayerweather, W.E. 1978. Inhalation teratology studies on three fluorocarbons. Toxicol. Appl. Pharmacol. 45:293, abstr. no. 170. Mullin, L.S. 1975. Cardiac sensitization with Freon-21R. Report No. 707–75. Newark, Delaware: E.I. du Pont de Nemours and Co., Haskell Laboratory for Toxicology and Industrial Medicine. 2 p. [Unpublished] Nuckolls, A.H. 1935. Underwriters’ Laboratories Report on the comparative life, fire, and explosion hazards of dichloromonofluoromethane (FC-21). Miscellaneous Hazard No. 2630. Chicago: Underwriters’ Laboratories. [15] p. Occupational Safety and Health Administration. 1983. Toxic and Hazardous Substances. Air contaminants. 29 CFR 1910.1000.

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Emergency and Continuous Exposure Limits for Selected Airborne Contaminants: Volume 2 Tappan, C.H., and Waritz, R.S. 1964. Acute inhalation toxicity of Freon-21R (fluorodichloromethane). Report No. 128–64. Newark, Delaware: E.I. du Pont de Nemours and Co., Haskell Laboratory for Toxicology and Industrial Medicine. 2 p. [Unpublished] Trochimowicz, H.J., Lyon, J.P., Kelly, D.P., and Chiu, T. 1977a. Ninety-day inhalation toxicity studies on two fluorocarbons. Toxicol. Appl. Pharmacol. 41:200, abstr. no. 164. Trochimowicz, H.J., Moore, B.L., and Chiu, T. 1977b. Subacute inhalation toxicity studies on eight fluorocarbons. Toxicol. Appl. Pharmacol. 41:198–199, abstr. no. 161. Weigand, W. 1971. [Studies on inhalation toxicity of fluorine derivatives of methane, ethane, and cyclobutane.] Zentralbl. Arbeitsmed. 21:149–156 (in German).