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Vinyl Chloride
438 Vinyl Chloride
Vinyl Chloride
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Robert Kapp
Toxicokinetics
& 2005 Elsevier Inc. All rights reserved.
Vinyl chloride is readily absorbed via all routes of exposure and rapidly distributed throughout the body. Following oral administration in male rats, peak blood concentrations are noted in less than 10 min. Approximately 40% of inhaled vinyl chloride is absorbed while as much as 95% is absorbed upon ingestion. Highest concentrations are found in the liver and kidneys. Storage of vinyl chloride is limited by the rapid metabolism and subsequent excretion. Vinyl chloride is biotransformed by cytochrome P450-mixed function oxidase systems (CYP 2E1), with the two primary metabolites being chloroethylene oxide and chloroacetaldehyde. These materials are further converted to chloroethanol and monochloroacetic acid. Metabolites are primarily excreted in urine. When rats were exposed to vinyl chloride at 100 ppm for 5 h, B70% of the absorbed dose was excreted as urinary metabolites within 24 h. The half-life for urinary excretion in rats was B4 h. With an increase in dose via either inhalation or ingestion, the proportion exhaled increased and urinary and fecal elimination decreased.
CHEMICAL ABSTRACTS SERVICE REGISTRY NUMBER: CAS 75-01-4 SYNONYMS: Chlorethene; Chlorethylene; Chloroethene; Chloroethylene; Ethene, chloro-; Ethylene monochloride; Ethylene, chloro-; Monochloroethene; Monochloroethylene; Monovinyl chloride; Trovidur; VC; VCM; Vinyl C monomer; Vinyl chloride monomer; Vinyl chlorine RELATED COMPOUNDS: Vinyl bromide (CAS 593-602); Vinyl fluoride (CAS 72-02-5); Vinylidene chloride (CAS 75-35-4); 1,2-Dichloroethene (CAS 540-59-0); Hexachlorobutadiene (CAS 8768-3) CHEMICAL/PHARMACEUTICAL/OTHER CLASS: Vinyl monomers; Halogenated hydrocarbons CHEMICAL FORMULA: C2H3Cl CHEMICAL STRUCTURE: H 2C
Cl
Uses Vinyl chloride is produced in the following industrial reactions: (1) the thermal cracking of 1,2-dichloroethane, which is produced by the chlorination and/ or oxychlorination of ethylene; and (2) the hydrochlorination of acetylene. The vast majority of vinyl chloride is used for the production of polyvinyl chloride (PVC) and the manufacture of copolymers with monomers such as vinyl acetate or vinylidene chloride. A much smaller proportion of vinyl chloride is used in the production of chlorinated solvents – primarily trichloroethanes.
Exposure Routes and Pathways The main route of occupational exposure to vinyl chloride is by inhalation that can occur in plastics manufacturing plants. Inhalation exposure to the general public is generally quite limited and probably restricted to accidental releases from hazardous waste sites and landfills. Vinyl chloride has been detected in surface and well waters, sediment and soil samples near manufacturing facilities. Some dietary exposure can occur from leaching from certain PVC materials into packaged foodstuffs.
Mechanism of Toxicity The mechanism of noncancer toxicity have not been extensively studied. Some immunological changes have been noted suggesting that one of the reactive metabolites binds to IgG, thus initiating immune responses depositing precipitates that can cause blockage in capillaries. It is also suggested that peripheral nervous system symptoms such as paresthesia, numbness, and pain in the extremities may be a direct result of vinyl chloride exposure or may be due to tissue anoxia because of vascular blockage. Vinyl chloride is also a human and animal carcinogen associated with an increased incidence of hepatic angiosarcoma. Chloroethylene oxide, chloroacetaldehyde, and monochloroacetic acid all react covalently with DNA and RNA. This alkylation results in highly effective base-pair substitutions that can lead to neoplastic transformation. These reactive metabolites might also interact with chromosomes causing clastogenic effects.
Acute and Short-Term Toxicity (or Exposure) Animal
Vinyl chloride appears to have a low toxicity when administered by inhalation, with LC50 values
Vinyl Chloride 439
reported to be in the 130 000–500 000 mg l 1 range. The oral LD50, on the other hand, is reported to be 500 mg kg 1. Vinyl chloride is reported to be slightly irritating to the eyes and respiratory tract at high concentrations. Inhalation can cause headache, nausea, central nervous system (CNS) depression, lung and kidney irritation, inhibition of blood clotting, and cardiac arrhythmias in animals. Human
Vinyl chloride is a CNS depressant; loss of consciousness can occur following exposure to high concentrations (25 000 mg m 3). Acute exposure to high ambient concentrations can lead to dizziness, light-headedness, nausea, headache, irritability, cognitive problems, paresthesia, and irritation of the eyes and respiratory tract.
Chronic Toxicity (or Exposure) Animal
Chronic animal studies report increased mortality and weight loss, as well as effects on the liver, kidney, and CNS at levels as low as 1.3 mg kg 1 day 1. Animal studies have shown increased testicular damage as well as decreased male fertility in rats exposed to low levels of vinyl chloride for 12 months. In addition, some animal studies have shown decreased fetal weights and increased terata at maternally toxic inhalation exposure levels of vinyl chloride. Animal studies have also reported that inhaled vinyl chloride increases the incidence of angiosarcoma of the liver. Human
Chronic inhalation or oral exposure to low levels of vinyl chloride may cause liver damage in humans. Some individuals occupationally exposed to high levels of vinyl chloride develop a specific syndrome termed ‘vinyl chloride disease’. This is characterized by dizziness, numbness, earache, headache, blurred vision, fatigue, nausea, shortness of breath, Raynaud’s phenomenon, loss of weight, changes in bone structure at the ends of the fingers, joint, and muscle pain, and scleroderma-type changes in the skin. Several unsubstantiated case reports have reported reduced male sexual performance upon occupational exposure to vinyl chloride. There have been mixed epidemiological results with respect to teratogenic effects in human exposure. Epidemiological studies conducted on humans exposed to inhaled vinyl chloride have shown increases in angiosarcoma of the liver. Hepatocellular carcinoma of the liver as well as some brain tumors
have been reported; however, the data are not considered definitive. Vinyl chloride has been reported to be mutagenic and clastogenic in human studies. US Environmental Protection Agency (EPA) has classified vinyl chloride as group A, human carcinogen, and group K – known human carcinogen. International Agency for Research on Cancer classifies vinyl chloride as group 1 – carcinogenic to humans. National Institute for Occupational Safety and Health and Occupational Safety and Health Administration (OSHA) both categorize vinyl chloride as Ca – potential occupational carcinogen. US National Toxicology Program categorizes vinyl chloride as K – known to be a human carcinogen. American Conference of Governmental Industrial Hygienists (ACGIH) categorizes vinyl chloride as threshold limit value (TLV)-A1 – confirmed human carcinogen.
Clinical Management Upon massive exposure, the primary risks are CNS effects and cardiac arrhythmias; therefore, the evaluation of vital functions and life-support measures should be taken and the victim should be decontaminated and removed from the area to minimize further exposure. Vinyl chloride exposure can irritate the skin, eyes, and mucous membranes, and the liquid can cause frostbite. The affected area should be washed with copious amounts of lukewarm or cold water. Hot water should not be used. Oral ingestion of vinyl chloride is unlikely; however, should that occur, it is suggested that water or milk be administered and, in addition, gastric lavage and administration of activated charcoal can be used as a means to reduce absorption. Upon ocular exposure, the eye should be generously washed with tap water. Refer for medical attention. In case of dermal exposure, contaminated clothing should be removed and the skin should be rinsed with tap water. Titanium tetrachloride ingestion should be referred for medical attention. Vomiting should NOT be induced. Upon inhalation, the victim should be moved to fresh air and given artificial respiration if indicated. The body should be placed in a half-upright position. Refer for medical attention.
Environmental Fate Anthropogenic sources are responsible for all of the vinyl chloride found in the environment. Vinyl chloride has been identified in at least 493 of the 1416 hazardous waste sites that have been included on the EPA National Priorities List. Of these sites,
440 Vinylidene Chloride
491 are located in the United States and two are located in the commonwealth of Puerto Rico. Most of the vinyl chloride released into the environment is eventually transported to the atmosphere, whereas lesser amounts are transported to the groundwater. Vinyl chloride has been detected in the ambient air in the vicinity of vinyl chloride and PVC manufacturing plants and hazardous waste sites. The compound has also leached into groundwater from spills, landfills, and industrial sources. In the atmosphere, vinyl chloride is eliminated by reaction with photochemically generated hydroxyl radicals (half-life ¼ 1–2 days): products include hydrochloric acid, formaldehyde, formyl chloride, acetylene, chloroacetaldehyde, chloroacetylchloranial, and chloroethylene epoxide. Dry deposition is not an important elimination pathway. In photochemical smog, the half-life is reduced to a few hours. In water, volatilization is the primary elimination process. Half-lives for volatilization from a typical pond, river, and lake have been estimated at 43, 9, and 35 h, respectively. In soil, vinyl chloride can volatilize from soil surfaces or leach into groundwater.
Ecotoxicology Vinyl chloride can bioconcentrate to a limited extent in aquatic organisms. Biomagnification of vinyl chloride in terrestrial and aquatic food chains does not appear to be important because of its high volatility and the fact that it is readily metabolized by
higher-trophic-level organisms. Little is known regarding biomagnification in terrestrial food chains.
Exposure Standards and Guidelines The reference dose for vinyl chloride is 0.003 mg kg 1 day 1, the reference concentration is 0.01 mg m 3. The ACGIH TLV, time-weighted average, is 13 mg m 3 and the OSHA permissible exposure level is 2.6 mg m 3. See also: Carcinogenesis; Liver; Occupational Toxicology; Polymers; Respiratory Tract.
Further Reading Albertini R, Clewell H, Himmelstein MW, et al. (2003) The use of non-tumor data in cancer risk assessment: Reflections on butadiene, vinyl chloride, and benzene. Regulatory Toxicology and Pharmacology 37: 105–132. Lemen RA (2001) Unsaturated Halogenated Hydrocarbons. In: Bingham E, Cohrssen B, and Powell CH (eds.) Patty’s Toxicology, 5th edn., vol. 2, pp. 247–255. New York: Wiley.
Relevant Websites http://www.epa.gov – Vinyl Chloride (from the US Environmental Protection Agency’s Technology Transfer Network Air Toxics Website). http://risk.lsd.ornl.gov – Toxicity summary for Vinyl Chloride (from the Risk Assessment Information System (RAIS)).
Vinylidene Chloride Anna M Fan Published by Elsevier Inc.
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CHEMICAL ABSTRACTS SERVICE REGISTRY NUMBER: CAS 75-35-4 SYNONYMS: 1,1-Dichloroethylene; 1,1-Dichloroethene; Vinylidene dichloride; Sconatex CHEMICAL/PHARMACEUTICAL/OTHER CLASS: Vinylidene chloride is an unsaturated halogenated hydrocarbon. CHEMICAL FORMULA: C2H2Cl2
Uses The principal use of vinylidene chloride is in the production of polyvinylidene chloride polymers (PVDC). PVDC is used in the food packing industry
for making flexible films such as in Saran and Velon wraps and as a barrier coating for paper, cellulose, polypropylene, and other plastics. These polymers are also used in the textile industry for drapery fabric, furniture and automobile upholstery; as flame retardant coatings for fiber and carpet backing; and in piping, coating for steel pipes, and adhesive applications.
Exposure Routes and Pathways The principal sources of exposure to vinylidene chloride in the environment are ambient air especially near industrial sources and contaminated drinking water. Exposure can occur through inhalation, ingestion, and eye or skin contact. Air releases account for 99% of the total environmental releases. Ambient levels are primarily from emissions from polymer synthesis and fabrication industries, mostly
Vinyl Chloride
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Robert Kapp
Toxicokinetics
& 2005 Elsevier Inc. All rights reserved.
Vinyl chloride is readily absorbed via all routes of exposure and rapidly distributed throughout the body. Following oral administration in male rats, peak blood concentrations are noted in less than 10 min. Approximately 40% of inhaled vinyl chloride is absorbed while as much as 95% is absorbed upon ingestion. Highest concentrations are found in the liver and kidneys. Storage of vinyl chloride is limited by the rapid metabolism and subsequent excretion. Vinyl chloride is biotransformed by cytochrome P450-mixed function oxidase systems (CYP 2E1), with the two primary metabolites being chloroethylene oxide and chloroacetaldehyde. These materials are further converted to chloroethanol and monochloroacetic acid. Metabolites are primarily excreted in urine. When rats were exposed to vinyl chloride at 100 ppm for 5 h, B70% of the absorbed dose was excreted as urinary metabolites within 24 h. The half-life for urinary excretion in rats was B4 h. With an increase in dose via either inhalation or ingestion, the proportion exhaled increased and urinary and fecal elimination decreased.
CHEMICAL ABSTRACTS SERVICE REGISTRY NUMBER: CAS 75-01-4 SYNONYMS: Chlorethene; Chlorethylene; Chloroethene; Chloroethylene; Ethene, chloro-; Ethylene monochloride; Ethylene, chloro-; Monochloroethene; Monochloroethylene; Monovinyl chloride; Trovidur; VC; VCM; Vinyl C monomer; Vinyl chloride monomer; Vinyl chlorine RELATED COMPOUNDS: Vinyl bromide (CAS 593-602); Vinyl fluoride (CAS 72-02-5); Vinylidene chloride (CAS 75-35-4); 1,2-Dichloroethene (CAS 540-59-0); Hexachlorobutadiene (CAS 8768-3) CHEMICAL/PHARMACEUTICAL/OTHER CLASS: Vinyl monomers; Halogenated hydrocarbons CHEMICAL FORMULA: C2H3Cl CHEMICAL STRUCTURE: H 2C
Cl
Uses Vinyl chloride is produced in the following industrial reactions: (1) the thermal cracking of 1,2-dichloroethane, which is produced by the chlorination and/ or oxychlorination of ethylene; and (2) the hydrochlorination of acetylene. The vast majority of vinyl chloride is used for the production of polyvinyl chloride (PVC) and the manufacture of copolymers with monomers such as vinyl acetate or vinylidene chloride. A much smaller proportion of vinyl chloride is used in the production of chlorinated solvents – primarily trichloroethanes.
Exposure Routes and Pathways The main route of occupational exposure to vinyl chloride is by inhalation that can occur in plastics manufacturing plants. Inhalation exposure to the general public is generally quite limited and probably restricted to accidental releases from hazardous waste sites and landfills. Vinyl chloride has been detected in surface and well waters, sediment and soil samples near manufacturing facilities. Some dietary exposure can occur from leaching from certain PVC materials into packaged foodstuffs.
Mechanism of Toxicity The mechanism of noncancer toxicity have not been extensively studied. Some immunological changes have been noted suggesting that one of the reactive metabolites binds to IgG, thus initiating immune responses depositing precipitates that can cause blockage in capillaries. It is also suggested that peripheral nervous system symptoms such as paresthesia, numbness, and pain in the extremities may be a direct result of vinyl chloride exposure or may be due to tissue anoxia because of vascular blockage. Vinyl chloride is also a human and animal carcinogen associated with an increased incidence of hepatic angiosarcoma. Chloroethylene oxide, chloroacetaldehyde, and monochloroacetic acid all react covalently with DNA and RNA. This alkylation results in highly effective base-pair substitutions that can lead to neoplastic transformation. These reactive metabolites might also interact with chromosomes causing clastogenic effects.
Acute and Short-Term Toxicity (or Exposure) Animal
Vinyl chloride appears to have a low toxicity when administered by inhalation, with LC50 values
Vinyl Chloride 439
reported to be in the 130 000–500 000 mg l 1 range. The oral LD50, on the other hand, is reported to be 500 mg kg 1. Vinyl chloride is reported to be slightly irritating to the eyes and respiratory tract at high concentrations. Inhalation can cause headache, nausea, central nervous system (CNS) depression, lung and kidney irritation, inhibition of blood clotting, and cardiac arrhythmias in animals. Human
Vinyl chloride is a CNS depressant; loss of consciousness can occur following exposure to high concentrations (25 000 mg m 3). Acute exposure to high ambient concentrations can lead to dizziness, light-headedness, nausea, headache, irritability, cognitive problems, paresthesia, and irritation of the eyes and respiratory tract.
Chronic Toxicity (or Exposure) Animal
Chronic animal studies report increased mortality and weight loss, as well as effects on the liver, kidney, and CNS at levels as low as 1.3 mg kg 1 day 1. Animal studies have shown increased testicular damage as well as decreased male fertility in rats exposed to low levels of vinyl chloride for 12 months. In addition, some animal studies have shown decreased fetal weights and increased terata at maternally toxic inhalation exposure levels of vinyl chloride. Animal studies have also reported that inhaled vinyl chloride increases the incidence of angiosarcoma of the liver. Human
Chronic inhalation or oral exposure to low levels of vinyl chloride may cause liver damage in humans. Some individuals occupationally exposed to high levels of vinyl chloride develop a specific syndrome termed ‘vinyl chloride disease’. This is characterized by dizziness, numbness, earache, headache, blurred vision, fatigue, nausea, shortness of breath, Raynaud’s phenomenon, loss of weight, changes in bone structure at the ends of the fingers, joint, and muscle pain, and scleroderma-type changes in the skin. Several unsubstantiated case reports have reported reduced male sexual performance upon occupational exposure to vinyl chloride. There have been mixed epidemiological results with respect to teratogenic effects in human exposure. Epidemiological studies conducted on humans exposed to inhaled vinyl chloride have shown increases in angiosarcoma of the liver. Hepatocellular carcinoma of the liver as well as some brain tumors
have been reported; however, the data are not considered definitive. Vinyl chloride has been reported to be mutagenic and clastogenic in human studies. US Environmental Protection Agency (EPA) has classified vinyl chloride as group A, human carcinogen, and group K – known human carcinogen. International Agency for Research on Cancer classifies vinyl chloride as group 1 – carcinogenic to humans. National Institute for Occupational Safety and Health and Occupational Safety and Health Administration (OSHA) both categorize vinyl chloride as Ca – potential occupational carcinogen. US National Toxicology Program categorizes vinyl chloride as K – known to be a human carcinogen. American Conference of Governmental Industrial Hygienists (ACGIH) categorizes vinyl chloride as threshold limit value (TLV)-A1 – confirmed human carcinogen.
Clinical Management Upon massive exposure, the primary risks are CNS effects and cardiac arrhythmias; therefore, the evaluation of vital functions and life-support measures should be taken and the victim should be decontaminated and removed from the area to minimize further exposure. Vinyl chloride exposure can irritate the skin, eyes, and mucous membranes, and the liquid can cause frostbite. The affected area should be washed with copious amounts of lukewarm or cold water. Hot water should not be used. Oral ingestion of vinyl chloride is unlikely; however, should that occur, it is suggested that water or milk be administered and, in addition, gastric lavage and administration of activated charcoal can be used as a means to reduce absorption. Upon ocular exposure, the eye should be generously washed with tap water. Refer for medical attention. In case of dermal exposure, contaminated clothing should be removed and the skin should be rinsed with tap water. Titanium tetrachloride ingestion should be referred for medical attention. Vomiting should NOT be induced. Upon inhalation, the victim should be moved to fresh air and given artificial respiration if indicated. The body should be placed in a half-upright position. Refer for medical attention.
Environmental Fate Anthropogenic sources are responsible for all of the vinyl chloride found in the environment. Vinyl chloride has been identified in at least 493 of the 1416 hazardous waste sites that have been included on the EPA National Priorities List. Of these sites,
440 Vinylidene Chloride
491 are located in the United States and two are located in the commonwealth of Puerto Rico. Most of the vinyl chloride released into the environment is eventually transported to the atmosphere, whereas lesser amounts are transported to the groundwater. Vinyl chloride has been detected in the ambient air in the vicinity of vinyl chloride and PVC manufacturing plants and hazardous waste sites. The compound has also leached into groundwater from spills, landfills, and industrial sources. In the atmosphere, vinyl chloride is eliminated by reaction with photochemically generated hydroxyl radicals (half-life ¼ 1–2 days): products include hydrochloric acid, formaldehyde, formyl chloride, acetylene, chloroacetaldehyde, chloroacetylchloranial, and chloroethylene epoxide. Dry deposition is not an important elimination pathway. In photochemical smog, the half-life is reduced to a few hours. In water, volatilization is the primary elimination process. Half-lives for volatilization from a typical pond, river, and lake have been estimated at 43, 9, and 35 h, respectively. In soil, vinyl chloride can volatilize from soil surfaces or leach into groundwater.
Ecotoxicology Vinyl chloride can bioconcentrate to a limited extent in aquatic organisms. Biomagnification of vinyl chloride in terrestrial and aquatic food chains does not appear to be important because of its high volatility and the fact that it is readily metabolized by
higher-trophic-level organisms. Little is known regarding biomagnification in terrestrial food chains.
Exposure Standards and Guidelines The reference dose for vinyl chloride is 0.003 mg kg 1 day 1, the reference concentration is 0.01 mg m 3. The ACGIH TLV, time-weighted average, is 13 mg m 3 and the OSHA permissible exposure level is 2.6 mg m 3. See also: Carcinogenesis; Liver; Occupational Toxicology; Polymers; Respiratory Tract.
Further Reading Albertini R, Clewell H, Himmelstein MW, et al. (2003) The use of non-tumor data in cancer risk assessment: Reflections on butadiene, vinyl chloride, and benzene. Regulatory Toxicology and Pharmacology 37: 105–132. Lemen RA (2001) Unsaturated Halogenated Hydrocarbons. In: Bingham E, Cohrssen B, and Powell CH (eds.) Patty’s Toxicology, 5th edn., vol. 2, pp. 247–255. New York: Wiley.
Relevant Websites http://www.epa.gov – Vinyl Chloride (from the US Environmental Protection Agency’s Technology Transfer Network Air Toxics Website). http://risk.lsd.ornl.gov – Toxicity summary for Vinyl Chloride (from the Risk Assessment Information System (RAIS)).
Vinylidene Chloride Anna M Fan Published by Elsevier Inc.
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CHEMICAL ABSTRACTS SERVICE REGISTRY NUMBER: CAS 75-35-4 SYNONYMS: 1,1-Dichloroethylene; 1,1-Dichloroethene; Vinylidene dichloride; Sconatex CHEMICAL/PHARMACEUTICAL/OTHER CLASS: Vinylidene chloride is an unsaturated halogenated hydrocarbon. CHEMICAL FORMULA: C2H2Cl2
Uses The principal use of vinylidene chloride is in the production of polyvinylidene chloride polymers (PVDC). PVDC is used in the food packing industry
for making flexible films such as in Saran and Velon wraps and as a barrier coating for paper, cellulose, polypropylene, and other plastics. These polymers are also used in the textile industry for drapery fabric, furniture and automobile upholstery; as flame retardant coatings for fiber and carpet backing; and in piping, coating for steel pipes, and adhesive applications.
Exposure Routes and Pathways The principal sources of exposure to vinylidene chloride in the environment are ambient air especially near industrial sources and contaminated drinking water. Exposure can occur through inhalation, ingestion, and eye or skin contact. Air releases account for 99% of the total environmental releases. Ambient levels are primarily from emissions from polymer synthesis and fabrication industries, mostly