| 4. | Vinyl bromide | |
| 4.1 | Identification of the substance | |
| 4.1.1 | CAS No. | 593-60-2 |
| 4.1.2 | EINECS No. | 209-800-6 |
| 4.1.3 | EINECS Name | Bromoethylene |
| 4.1.4 | Synonyms | Bromoethene |
| 4.1.5 | Molecular Formula | C2H3Br |
| 4.1.6 | Structural Formula |  |
| 4.1.7 | Known uses | Intermediate in organic
synthesis and in the manufacture of polymers, copolymers, flame
retardant, pharmaceuti-cals and fumigants (9).
Purity: 99.8% min (9)Impurities: Water, 100 mg/kg; non-volatile matter (in-cluding inhibitor), 500 mg/kg max. inhibitor (hydro-quinone methyl ether), 175-225 mg/kg (9) |
| 4.1.8 | EU Classification | Carc 2;R45 Fx;R12 (Index No. 602-024-00-2 in Annex 1, Council Directive 67/548/EEC) |
| 4.2 | Physico-chemical Characteristics | |
| 4.2.1 | Physical Form | Gas, colourless liquid under pressure, characteristic pungent odour (9) |
| 4.2.2 | Molecular Weight | 106.96 |
| 4.2.3 | Melting Point/range (°C) | -139.5 (9) |
| 4.2.4 | Boiling Point/range (°C) | 15.8 (9) |
| 4.2.5 | Decomposition Temperature (°C) | When heated to decomposition it emits toxic fumes of Br- (11) |
| 4.2.6 | Vapour Pressure (Pa (°C)) | 119.32 x 103 at 20°C (9) |
| 4.2.7 | Relative Density (D420) | 1.4933 (9) |
| 4.2.8 | Vapour Density (air=1) | 3.7 (9) |
| 4.2.9 | Conversion Factor (1011 hPa at 25 °C) | 1 ppm = 0.00437 mg/l
1 mg/l = 228.833 ppm (9) |
| 4.2.10 | Solubility | Water: Insoluble
Ethanol: soluble Ether: soluble Acetone: soluble (12) |
| 4.2.11 | Partition Coefficient (log P ow) | 1.38 (1) |
| 4.2.12 | Flammability | Vinyl bromide has no flash point by standard tests in air (15). It is a very dangerous fire hazard when exposed to heat of flame, and it can reacts with violently with oxidizing materials (11) |
| 4.2.13 | Explosivity | With a high-energy ignition source the explosive limits are 9 to 15% by volume in air (15) |
| 4.2.14 | Oxidising properties | No data available |
| 4.3 | Toxicological Data | |
| 4.3.1 | Observations in humans | There have been no reported cases of cancer in humans associated with exposure to vinyl bromide. However, vinyl bromide has only been in commercial production since 1971. Due to the long latency period of cancer, no cases would have been expected (3). |
| 4.3.2 | Acute Toxicity | |
| 4.3.2.1 | Oral | Oral LD50, rats: approx. 500 mg/kg, when chilled 50% solution in corn oil was fed to male rats (15) |
| 4.3.2.2 | Dermal | No data available |
| 4.3.2.3 | Inhalation | 7 mmol/l (1,700 ppm) was
the highest tolerable concentration for mice exposed for 10 minutes.
Half that concentration produced pronounced anaesthesia (15).
Exposure of rats to a nominal concentration of 100,000 ppm (438 mg/l) resulted in deep anaesthesia and death within 15 min. Exposure of rats to a nominal concentration of 50,000 ppm (219 mg/l) resulted in unconsciousness within 25 min. All animals survived 1½-hour exposure, but not a 7-hour exposure. Exposure of rats to a nominal concentration of 25,000 ppm (109 mg/l) resulted in unconsciousness but no death within 7 hours of exposure. Necropsy of survivors of the 50,000 ppm group 2 weeks after the exposure revealed macroscopic liver and kidney damage. These effects were not seen in the 25,000 ppm group (15). |
| 4.3.2.4 | Other Routes | No data available |
| 4.3.2.5 | Skin Irritation | Nonirritating to the intact skin of rabbits, and produce no frostbite from evaporation of the liquid (15) |
| 4.3.2.6 | Eye Irritation | Slightly to moderately irritating to the eyes (15) |
| 4.3.2 7 | Irritation of Respiratory Tract | No data available |
| 4.3.2.8 | Skin Sensitisation | No data available |
| 4.3.2.9 | Sensitisation by Inhalation | No data available |
| 4.3.3 | Subchronic Toxicity | |
| 4.3.3.1 | Oral | No data available |
| 4.3.3.2 | Inhalation | Male and female rats, rabbits, and monkeys were exposed to 250 ppm or 500 ppm, 6 hours/day, for 6 months. Except for an increase in blood bromine ion concentration no apparent effect was observed (15) |
| 4.3.3.3 | Dermal | 30 mice received topical applications of vinyl bromide (15 mg/animal in 0.1 ml acetone, three times/week). No skin tumours were observed after 60 weeks. When test-ing for initiating action of vinyl bromide, applying phorbol myristate acetate (PMA) as a promoter, 1 mouse of 30 developed skin papilloma at day 412, whereas no skin tumours occurred in the 160 control animals (16) and (9). |
| 4.3.4 | Chronic Toxicity and Carcinogenicity | In a study, 120 Sprague-Dawley
rats/sex/group (144 in the control) were in whole-body exposure
chambers exposed to target concentrations of 0, 10, 50, 250, and
1250 ppm [actual concentrations were 0, 9.7, 52, 247, or 1235 ppm
(0, 0.043, 0.230, 1.095, or 5.474 mg/l), respectively] vinyl bromide
vapour for 6 hours/day, 5 days/week for 6, 12, 18, or 24 months.
Purity: 99.9%. Impurities: 197 ppm (0.02%) hydroquinone methyl ether
(CAS No. 150-76-5) as stabiliser, 282 ppm (0.03%) ethylene oxide
(CAS No. 75-21-8), 7 ppm (0.0007%) acetylene (CAS No. 74-86-2), and
80 ppm (0.008%) aldehydes and ketones. Dose-related decrease in body
weight and an increase in mortality. The 5.4625 mg/l group was
terminated at 18 month due to excessive mortality. Some blood
parameters were changed. Angiosarcoma, primarily of the liver, was
induced in both male and female in all four exposure groups. Also a
significant increase in the number of Zymbal's gland neoplasms was
seen as well as increased incidence of hepatocellular neoplasms (4,
9, and 2).
Newborn Wistar rats were exposed from their first day of life to an atmospheric concentration of 8.74 mg/l 8 hours/day, 5 days/week, for up to 15 weeks. Two weeks after cessation of exposure, the animals were sacrificed and the liver taken for histochemical evaluation of ATPase deficient foci as a measure of pre-neoplastic foci. An obvious oncogenic potential approx. 0.1 of that of vinyl chloride was seen (6). |
| 4.3.5 | Mutagenicity | |
| 4.3.5.1 | Gene Mutation | Salmonella typhimurium
strains TA-1530 and TA-100 were exposed to vinyl bromide in air for
various time periods. Vinyl bromide was mutagenic both in the
absence and presence of a metabolic system from the liver of Aroclor-induced
rats or phenobarbital-induced mice or humans (9).
Vinyl bromide was strongly positive in three test strains of Drosophila and weakly positive in three test strains (w/w+ eye mosaic assay) (13) The in vivo genotoxicity of vinyl bromide was tested in the alkaline single cell gel electrophoresis (comet) assay in mouse organs (stomach, liver, kidney, bladder, lung, brain, and bone marrow). Vinyl bromide resulted in DNA damage in all organs investigated except for the bone marrow. The DNA damage was apparently not attributed to cytotoxicity (14). |
| 4.3.5.2 | Chromosome Abnormalities | No data available |
| 4.3.5.3 | Other Genotoxic Effects | No data available |
| 4.3.6 | Reproductive Toxicity, Embryotoxicity, and Teratogenicity | |
| 4.3.6.1 | Reproductive Toxicity | No data available |
| 4.3.6.2 | Teratogenicity | No data available |
| 4.3.7 | Other Toxicity Studies | Vinyl bromide can act as a direct alkylating agent. Following exposure of rats to vinyl bromide by inhalation, protein and nucleic acid adducts were found in various tissues (5). |
| 4.3.8 | Toxicokinetics | Vinyl bromide is readily absorbed by the lungs in rats and is rapidly metabolised. Metabolism was saturable at exposure concentration > 55 ppm and was associated with release of bromine in to the plasma. In vitro experiments indicate that the primary metabolite of vinyl bromide is the epoxide, 2-bromoethylene oxide (CAS No. unknown), which rearranges to 2-bromoacetaldehyde (CAS No. 17157-48-1). Both metabolites are alkylating agents (5) and (7). |
| 4.4 | Ecotoxicity | As no ecotoxicity data were
available, the data for the analogous substance vinyl chloride (CAS:
75-01-4) were used.
For vinyl chloride the LC50 (fish) was 356-406 mg/l (Leuciscus idus melanotus). The bioconcentration factor in fish was 7, LogPow 1.38 (1) |
| 4.5 | Environmental Fate | As no environmental fate data were available, the data for the analogous substance vinyl chloride (CAS: 75-01-4) were used. Vinyl chloride (75-01-4) is not readily biodegradable (1) |
| 4.6 | Environmental Concentrations | No data were available. |
| 4.7 | Conclusion | |
| 4.7.1 | Health Assessment | Sufficient toxicological
data were identified for a health assessment of Vinyl bromide. Most
of the data were cited from recognized scientific toxicological
reviews. No data on sensitisation or reproductive toxicity were
identified. No chromosome aberration tests or any other mutagenicity
tests except the gene mutation tests were found. No relevant data on
humans were identified.
Vinyl bromide is a very dangerous fire hazard when exposed to heat of flame, and it can react violently with oxidizing materials. The Commission of the European Communities has classified it: "Extremely flammable" (Fx; R12) (Annex 1, Council Directive 67/548/EEC). Vinyl bromide possesses a moderate acute toxicity. Because of the high vapour pressure inhalation is the most relevant route of exposure. Direct contact of undiluted vinyl bromide to the eye may result in a slightly to moderately irritation, whereas it is apparently not skin irritating. Some evidence mutagenic activities in vitro and in vivo have been found. The carcinogenicity of vinyl bromide was considered by IARC last time in 1987. They concluded that there is sufficient evidence for the carcinogenicity of vinyl bromide in experimental animals, and that vinyl bromide is probably carcinogenic to humans (Group 2A) (8, 9, 10). The Commission of the European Communities with has recently adjusted the classification of vinyl bromide: "May cause cancer" (Carc2; R45) (Annex 1, Council Directive 67/548/EEC). |
| 4.7.2 | Environmental Assessment | No ecotoxicity or
environmental fate data for vinyl bromide were available for
environmental assessment.
Vinyl chloride is officially classified with Carc1; R45 Fx;R12 (1). The available data indicate no environmental classification of the substance. |
| 4.8 | References | 1. NOVA 2003 Database.
Datasheets on substances, which are included in the national
monitoring of the aquatic environment 1998-2003. Draft edition.
Denmark.
2. Integrated Risk Information System (IRIS). Vinyl bromide. Update Code: 9410. U.S. Environmental Protection Agency (U.S. EPA); 1998. IRIS accession number: 671. SilverPlatter Information. CHEM-BANK (November 1998). SP-018-047. 3. Bahlman LJ, Alexander V, Infante PF, Wagoner JK, Lane JM, Bingham E. Vinyl halides: Carcinogenicity. American Industrial Hygiene Association Journal 1979; 40(4):A30-A40. 4. Benya TJ, Busey WM, Dorato MA, Berteau PE. Inhalation carcinogenicity bioassay of vinyl bromide in rats. Toxicology and Applied Pharmacology 1982; 64(3):367-79. 5. Berlin A, Draper MH, Duffus JH, van der Venne MT Editors. The toxicology of chemicals - 1. Carcinogenicity, Volume III - Summary reviews of the scientific evidence. Commission of the European Communities: 2985 Luxembourg, Grand Duchy of Luxembourg: Office for Official Publications of the European Communities, 1991: 159-62. 6. Bolt HM, Laib RJ, Stockle G. Formation of pre-neoplastic hepatocellular foci by vinyl bromide in newborn rats. Archives of Toxicology 1979; 43(1):83-4. 7. Gargas ML, Andersen ME. Metabolism of inhaled brominated hydrocarbons: validation of gas uptake results by determination of a stable metabolite. Toxicology and Applied Pharmacology 1982; 66(1);55-68. 8. IARC Working Group on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Monomers, Plastics and Synthetic Elastomers, and Acrolein. Switzerland: International Agency for Research on Cancer, World Health Organisation, 1979: 367-75. (IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans; 19). 9. IARC Working Group on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Chemicals Used in Plastics and Elastomers. Switzerland: International Agency for Research on Cancer, World Health Organisation, 1986: 133-45. (IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans; 39). 10. IARC Working Group on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42. Switzerland: International Agency for Research on Cancer, World Health Organisation, 1987: 73. (IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans; Supplement 7). 11. Lewis RJ Editor. Sax's Dangerous Properties of Industrial Materials. 9th edition. New York: Van Nostrand Reinhold, 1996. 12. Lide DR, Frederikse HPR Editors. CRC Handbook of Chemistry and Physics. 78th edition. Boca Raton, New York: CRC Press, Inc., 1997: 3-58. 13. Rodriguez-Arnaiz R, Vogel EW, Szakmary A. Strong intra-species variability in the metabolic conversion of six procarcinogens to somatic cell recombinagens in Drosophila. Mutagenesis 1993; 8(6):543-51. 14. Sasaki YF, Saga A, Akasaka M et al. Detection of in vivo genotoxicity of haloalkanes and haloalkenes carcinogenic to rodents by the alkaline single cell gel electrophoresis (comet) assay in multiple mouse organs. Mutation Research - Genetic Toxicology and Environmental Mutagenesis 1998; 419(1 -3):13-20. 15. Torkelson TR. Halogenated Aliphatic Hydrocarbons Containing Chlorine, Bromine, and Iodine. Chapter 38: Clayton GD, Clayton FE, Editors. Patty's Industrial Hygiene and Toxicology. 4th edition. Vol. 2. New York: John Wiley & Sons, Inc., 1994: 4178-81. 16. Van Duuren BL. Chemical structure, reactivity, and carcinogenicity of halohydrocarbons. Environmental Health Perspectives 1977; 21:17-23. |