VINYL HALIDES - CARCINOGENICITY
Vinyl Bromide, Vinyl Chloride, and Vinylidene Chloride
Vinyl Bromide, Vinyl Chloride, and Vinylidene Chloride
September 21, 1978
Vinyl chloride is known to cause angiosarcoma of the liver and cancers of other sites in laboratory animals and in humans. At this time, adequate carcinogenicity studies of vinyl bromide and vinylidene chloride have been conducted only in laboratory animals. In view of the present state of knowledge in carcinogenesis, substances that cause cancer in laboratory animals are considered a potential cancer risk to humans.
Vinyl chloride is the only vinyl halide for which an OSHA exposure standard currently exists. In light of the recent laboratory animal studies demonstrating carcinogenicity of vinyl bromide and vinylidene chloride, NIOSH and OSHA have jointly prepared this Current Intelligence Bulletin. Its purpose is to advise the occupational health community of the pertinent data and implications for exposed workers. NIOSH and OSHA request that producers, distributors professional associations, and unions transmit the information in this Bulletin to their customers, employees, associates, and members.
Laboratory studies have demonstrated that exposure by inhalation to vinyl chloride,1-2 vinyl bromide,3 and vinylidene chloride1,4 all caused angiosarcoma of the liver and other cancers in animals. Angiosarcoma of the liver was induced in rats exposed to 25 ppm vinyl chloride, in rats exposed to 50 ppm vinyl bromide, and in mice exposed to 55 ppm vinylidene chloride.
At lower levels, exposure to vinyl chloride (1 ppm) has induced mammary carcinomas,5 exposure to vinyl bromide (10 ppm) has induced lymph node angiosarcoma,3 and exposure to vinylidene chloride (25 ppm) has induced adenocarcinomas of the kidney.4 Table 1 presents a summary of tumors in animals exposed to these vinyl halides.
| vinyl bromide
| rat
| liver
| angiosarcoma
|
|
| zymbal gland
| squamous cell carcinoma
|
|
| lung
| metastatic angiosarcoma,
bronchioalveolar carcinoma,
bronchioalveolar adenoma
|
|
| breast
| adenocarcinoma
|
|
| mesenteric lymph node
| angiosarcoma
|
|
| lymphatic
| lymphosarcoma
| vinyl chloride
| rat
| mammary gland
| carcinoma
|
|
| skin
| squamous cell carcinoma
|
|
| liver
| angiosarcoma
|
|
| lung
| adenocarcinoma, angiosarcoma
|
|
| zymbal gland
| carcinoma
|
|
| kidney
| nephroblastoma
|
| mouse
| liver
| angiosarcoma
|
|
| mammary gland
| anaplastic and squamous metaplasia
|
|
| lung
| bronchioaveolar adenoma
|
|
| liver
| hepatic cell carcinoma
|
|
| kidney
| renal adenoma
|
|
| skin
| keratoacanthoma
|
| rabbit
| skin
| acanthoma
|
|
| lung
| adenocarcinoma
|
| hamster
| liver
| angiosarcoma
|
|
| skin
| trichoepithelioma, basalioma
|
|
| lymphatic
| lymphoma
| vinylidene chloride
| mouse
| liver
| angiosarcoma |
|
| lung
| bronchioalveolar adenoma
|
|
| kidney
| adenocarcinoma
|
| rat
| mesenteric lymph node
| angiosarcoma
|
|
| breast
| mammary tumor
|
|
| zymbal gland
| carcinoma
|
|
Several investigators have reported that vinyl chloride is mutagenic in Salmonella typhimurium and pombe6-11 and in Escherichia coli.12-14 Vinyl chloride also has been shown to be mutagenic in the yeast mutation assay,11 in the Drosophila recessive lethal test,15-16 and in the host-mediated assay.11 Studies also have shown vinyl chloride to be mutagenic in Tradescantia.17 Three reports bearing on the mutagenicity of vinyl bromide have been noted to date. Bartsch et al.,18 and Simmons19 have independently reported that vinyl bromide induced mutations in the bacterium, Salmonella typhimurium. In addition, Sparrow17 has demonstrated a significant increase in mutants in Tradescantia exposed to vinyl bromide vapors. Vinylidene chloride has been shown to induce mutations in Salmonella typhimurium,10, 20-22 in Escherichia coli,12 and in Tradescantia.17
Other adverse health effects in animals attributed to exposure to vinyl halides include central nervous system (CNS) effects, cardiovascular effects, respiratory effects, skin effects, skeletal effects, and liver or spleen abnormalities.1
Studies of workers exposed to vinyl chloride have demonstrated an excessive risk of death from cancer of the lung, brain, lymphatic system, and angiosarcoma of the liver.1, 23 Cancers of the same sites were previously induced in animals following exposure to vinyl chloride.2
Liver angiosarcoma in humans is a very rare malignant tumor of the blood vessels. Though no clinical signs or symptoms, or laboratory examinations have been found to be specific for the early diagnosis of this cancer, affected individuals may complain of fatigue, abdominal pain, weight loss, anorexia, nausea, vomiting, melena, indigestion, jaundice, hematemesis, or diarrhea. Other manifestations may include liver enlargement and liver function abnormalities. In adults, untreated angiosarcoma of the liver usually is fatal within 8 months. Even with treatment, death usually occurs within 16 months.
To date there have been no reported cases of cancer in humans associated with exposure to vinyl bromide or vinylidene chloride. However, vinyl bromide has been in commercial production in the U.S. only since 1971. Due to the long latent period characteristic of occupationally-induced cancers, typically 15-40 years, no unusual risk of cancer among exposed workers would be expected to be be detected at this time. Vinylidene chloride has been in commercial production and use since the early 1940's. The only study24 reported to date showed no excessive cancer risk among workers occupationally exposed to vinylidene chloride, but methodologic limitations of this study do not permit an adequate evaluation of the carcinogenic risk of vinylidene chloride to humans.
Mutagenicity and Reproductive Effects
Cytogenetic studies have demonstrated a significant increase in the frequency of chromosomal aberrations in the lymphocytes of workers exposed to vinyl chloride.25-31 Further evidence for the mutagenicity of vinyl chloride has been provided by investigations showing an increase in fetal wastage among wives of male workers following occupational exposure to vinyl chloride.32-33 No studies addressing mutagenic or reproductive hazards among vinyl bromide or vinylidene chloride exposed populations have been reported.
Numerous other adverse health effects have been observed in humans exposed to vinyl chloride, as detailed in Table 2. Reports of effects on workers exposed to vinylidene chloride in combination with other vinyl compounds include liver function abnormalities, headache, vision problems, dizziness, fatigue, weakness, and neurological sensory disturbances. No similar reports for vinyl bromide exposure were found.1
neurologic
| dizziness, lightheartedness, dulling vision and
hearing, drowsiness, headache, loss of memory, euphoria
nervousness, numbness or tingling in fingers
or toes
| gastrointestinal
| nausea, loss of appetite abdominal distress,
varices of esophagus or stomach, black stools,
bloody vomitus
| cardiovascular
| increased blood pressure Raynaud's Syndrome
| hepatic
| liver enlargement, liver function abnormalities,
increased sulphbromophthalein retention liver
damage, serum enzyme abnormalities
| respiratory
| coughing and sneezing bronchial rales, emphyzema,
pulmonary fibrosis, decreased respiratory function
lung function disturbances
| hematologic
| anemia, reticulocytosis, leukopenia, thrombocytopenia, splenomegaly
| dermatologic
| contact dermatitis, scleroderma-like skin changes
| musculoskeletal
| calf and joint pain, acroosteolysis
| other
| increased perspiration cold sensation in fingers
and hands, fatigue, weight loss, weakness, impotency
|
|
There is a lack of information regarding the carcinogenicity of vinyl fluoride and vinylidene fluoride. However, both have been shown to be mutagenic in bacterial systems.1 This evidence of mutagenicity is cause for concern.
vinyl chloride
| chemicals and allied products
electrical equipment and supplies
furniture and fixtures
| vinyl bromide
| chemicals and allied products
rubber and plastics products
leather and leather products fabricated metal products
wholesale trade
| vinylidene chloride
| chemicals and allied products
special trade contractors
fabricated metal products
general building contractors
wholesale trade
leather and leather products
| vinylidene fluoride
| chemicals and allied products
machinery, except electrical
electrical equipment and supplies
food and kindred products
medical and other health services
|
|
*No NOHS information available for vinyl fluoride [return to table]
From 1972-1974, NIOSH conducted the NIOSH National Occupational Hazards Survey (NOHS), on a sample of about 900,000 employees at 4,636 facilities, in order to determine the potential for worker exposure to chemicals and physical agents.
NOHS algorithms used Bureau of the Census 1970 population counts to permit extrapolation from the sample to the United States worker population of 1970. Table 4 presents a summary of NOHS estimates of worker exposure to vinyl halides.34
The exposure estimates include two categories. Definite estimates are extrapolated from actual observations of the use of the specific chemical or the use of a trade name product, known to contain the chemical. Probable estimates include additional extrapolations from observations of trade name products suspected of containing the chemical because of generic formulations.
| vinyl chloride
| vinyl bromide
| vinylidene chloride
| vinylidene fluoride
| vinyl fluoride
| |
Summaries of the current Department of Labor - Occupational Safety and Health Administration (OSHA) exposure standards and NIOSH recommended exposure standards for the vinyl halide compounds are given in Table 5.
vinyl chloride
| vinyl bromide
| vinylidene chloride
| vinylidene fluoride
| vinyl fluoride
| |
Detailed NIOSH recommendations for the control of exposure to these substances in the workplace are contained in the Vinyl Halides Criteria Document.1
[signature] Eula Bingham, Ph.D. Assistant Secretary of Labor Occupational Safety and Health Administration | [signature] J. Michael Lane, M.D. Acting Director National Institute for Occupational Safety and Health |
Chlorethene | Monochloroethylene |
Chlorethylene | Trovidur |
Chloroethene | VC |
Chloroethylene | VCM |
Ethene, Chloro- | Vinyl Chloride |
Ethylene, Chloro- | Vinyl Chloride Monomer |
Ethylene Monochloride | Vinyl C Monomer |
Monochloroethene |
Bromoethene | Ethylenep Brom- |
Bromoethylene | NCI-C50373 |
Ethene, Bromo- | Vinyl Bromide |
1,1,-DCE | NCI-C54262 |
1,1,-Dichloroethene | Sconatex |
1,1,-Dichloroethylene | Vinylidene Chloride |
Ethene, l,l,-Dichloro- | Vinylidene Chloride (II) |
Ethylene, 1,1,-Dichloro |
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This page was last updated: 11, 1997
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