Vinyl chloride
VINYL CHLORIDE
International Programme on Chemical Safety
Poisons Information Monograph 558
Chemical
1. NAME
1.1 Substance
Vinyl chloride
1.2 Group
Halogenated aliphatic hydrocarbon.
1.3 Synonyms
Chlorethene; chloroethene; chloroethylene;
chlorethylene; ethylene monochloride; monochloroethene;
monochloroethylene; VC; VCM; vinyl c monomer;
vinyl chloride inhibited; vinyl-chloride monomer;
chlorure de vinyle (French); cloruro di vinile (Italian); Vinylchlorid
(German); winylu chlorek (Polish)
1.4 Identification numbers
1.4.1 CAS number
75-01-4
1.4.2 Other numbers
RTECS NUMBER: KU9625000
SIC Code: 2813
PIN (UN NUMBER): 1086
(Sax, 1986; Budavari, 1989, Sax, 1989)
2. SUMMARY
2.1 Main risks and target organs
Acute exposures to vinyl chloride induce central nervous
system depression and cardiac arrhythmias. High
concentrations also cause irritation of the eyes and of the
respiratory tract. Hepatic changes have been observed
following massive exposure in animals.
Vinyl chloride is stored under pressure; exposure to the
escaping gas may cause frostbite.
Repeated exposure to vinyl chloride may cause vinyl chloride
disease, i.e. Raynaud's phenomenon, scleroderma-like changes,
acro-osteolysis and hepatic fibrosis. There is a causal
association between vinyl chloride exposure and angiosarcomas
of the liver. Vinyl chloride is also responsible for an
excess of other hepatic cancers, of brain tumours, lung
tumours and of malignancies of the lymphatic and
haemotopoietic system, in exposed workers.
2.2 Summary of clinical effects
Exposure to concentrations of 8,000 to 20,000 ppm caused
headache, nausea, dizziness and drowsiness. Coma was
observed above 70,000 ppm and cardiac arrhythmias at 120,000
ppm. Hepatic damage was observed in animals at more than
10,000 ppm.
Repeated exposure may induce Raynaud's phenomenon which
persists after termination of exposure to vinyl chloride.
Scleroderma-like lesions of the fingers and osteolysis of the
terminal phalanges are often associated with Raynaud's
syndrome but these usually improve after cessation of
exposure.
Repeated exposure to vinyl chloride may be responsible for
non-cirrhotic portal fibrosis which leads to portal
hypertension. Vinyl chloride induced angiosarcomas of the
liver; these generally result from prolonged exposure (>10
years) to high concentrations (>50 ppm). The latent period
between the first exposure and the discovery of the tumours
varies between 15 and 30 years. These tumours have a very
poor prognosis.
2.3 Diagnosis
There are no specific tests for the diagnosis of vinyl
chloride poisoning and/or the monitoring of exposure.
Standard liver enzyme and liver function tests are indicated
to confirm liver involvement, but are of little value in
detecting early stage of liver injury.
2.4 First aid measures and management principles
Remove from the area of exposure to fresh air. Maintain
clear airway. Monitor consciousness level and ECG.
Artificial ventilation may be needed. If frostbite has
occurred, wash the contaminated area with warm water until
circulation is restored.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Vinyl chloride is a synthetic chemical obtained either
by hydrochlorination of acetylene or by halogenation of
ethylene (ILO, 1983; Budavari, 1989).
3.2 Chemical structure
Molecular weight: 62.50
Molecular formula: C2H3C1
Structural formula: ClCH = CH2
3.3 Physical properties
3.3.1 Colour
Colourless
3.3.2 State/form
Gas
3.3.3 Description
Under normal conditions of temperature and
pressure, vinyl chloride is a colourless gas with mild
ethereal odour. It is usually handled under pressure
as a colourless liquid.
-Boiling point: -14°C (7°F)
-Melting point: -154°C (-245°F)
-Autoignition temperature 472°C (882°F)
-Flash point: -78°C (-112°F) (open cup)
-Specific gravity: 0.9121 (20/4°C)
-Vapour pressure: 2530 mm Hg (20°C)
-Vapour density: 2.15 (air = 1)
-Solubility: slightly soluble in water (2.4 g/l at
25°C)
soluble in ethanol, ether, carbon tetrachloride and
benzene
-Conversion factor: 1 ppm = 2.56 mg/m3 = 0.391 ppm
(25°C; 760 mm Hg)
3.4 Hazardous characteristics
-Explosive limits: 3.6 to 33%
Vinyl chloride (vinyl chloride) is highly flammable and forms
explosive mixtures with air (see above). Peroxides may form
from long-term exposure to air; these can initiate explosive
polymerization of vinyl chloride.
Vinyl chloride reacts vigorously with oxidizers. It may
attach iron and steel in the presence of moisture. It is
also incompatible with aluminium and copper. It can liberate
hydrogen chloride upon treatment with strong alkalis.
It undergoes exothermic polymerization in the presence of
light, or air and heat, or a catalyst.
Thermal degradation of polyvinyl chloride (PVC) releases
hydrogen chloride (HCI) and many other compounds. The main
toxic products found in smoke or fumes are HCI, chlorine gas,
phosgene, and carbon monoxide.
Small fires may be extinguished with dry chemical, carbon
dioxide or halon.
Vinyl chloride should be kept out of water sources and
sewers. Appropriate local health and pollution control
authorities should be notified of releases.
4. USES/CIRCUMSTANCES OF POISONING
4.1 Uses
4.1.1 Uses
4.1.2 Description
Vinyl chloride is used for the production of
vinyl chloride homo-polymer and co-polymer resins;
these have many applications. It was formerly
considered for use as an anaesthetic agent, but was
finally abandoned for this purpose because of cardiac
arrhythmias during anaesthesia. It has also been used
as a refrigerant, an extraction solvent, a propellant,
and for the production of methyl chloroform (ECETOC,
1988).
4.2 High risk circumstances of poisoning
Vinyl chloride is a gas at room temperature, therefore,
the most likely circumstance of poisoning is inhalation. As
all processus using vinyl chloride are generally enclosed,
inhalation results from accidental leak of liquid or vapour.
This may result in systemic poisoning; escaping compressed
gas may also cause frostbite; vinyl chloride vapours can
cause asphyxia by displacement of oxygen from the breathing
atmosphere in cases of massive leaks (ECETOC, 1988).
4.3 Occupationally exposed populations
Only workers engaged in the production of vinyl chloride
or of vinyl chloride polymers can be exposed to the toxic
monomer. Today all processes using vinyl chloride are
generally enclosed and exposure of workers is unlikely. In
the past, the highest air concentrations of vinyl chloride
were found in polymerization plants. Those workers who
charged, discharged and cleaned the autoclaves were so highly
exposed that subacute poisoning was not uncommon. In
developed countries, vinyl chloride atmospheric concentration
at the workplace is now generally less than 1 ppm (ECETOC,
1988).
The general public may be exposed to only very small amounts
of vinyl chloride: from inhalation of air in the vicinity of
plants, by ingestion on foods or drinks with PVC-based
packaging (from which vinyl chloride can migrate), and by
inhalation of tobacco smoke (ECETOC, 1988). Calculation of
daily inhalation rates indicates the amount inhaled ranges
from 4 µg/person/day to more than 100 µg/person/day for
populations living in the immediate vicinity of some vinyl
chloride plants. Exposure from food sources is less than 0.1
µg/day (ECETOC, 1988).
5. ROUTES OF EXPOSURE
5.1 Oral
Ingestion is unlikely and has not been reported. Vinyl
chloride may be absorbed through the digestive system.
5.2 Inhalation
Vinyl chloride is a gas at room temperature, therefore,
inhalation is the major route of entry. It has been
responsible for most cases of poisoning.
5.3 Dermal
Vinyl chloride may be absorbed through the skin.
Escaping compressed gas may also cause frostbite.
5.4 Eye
Vinyl chloride vapours are moderately irritating to the
eyes. Contact with escaping compressed gas may cause
mechanical injury and frostbite.
5.5 Parenteral
Not described.
5.6 Others
Not described.
6. KINETICS
6.1 Absorption by route of exposure
Vinyl chloride is absorbed via inhalation, ingestion, or
through the skin. However, since this substance is a gas at
room temperature, inhalation is the major route of entry.
In studies on human volunteers exposed to 2.5 to 23 ppm,
retention of inhaled vinyl chloride in the lung was estimated
to be 27 to 42% (ECETOC, 1988).
6.2 Distribution by route of exposure
Vinyl chloride is distributed throughout the body. The
highest concentrations are in the liver and kidneys, followed
by the lungs and spleen (ATSDR, 1989).
6.3 Biological half-life by route of exposure
Not determined.
6.4 Metabolism
Vinyl chloride is mainly transformed in the liver. The
mixed function oxidase system is the major metabolic route.
The cytochrome P450 isozyme implicated in the metabolism
of FCM is inducible by ethanol, phenobarbitone and
polychlorobiphenyls. The alcohol dehydrogenase system and
the catalase system may also be involved. vinyl chloride is
first metabolised to chloroethylene oxide. This unstable
epoxide is then transformed into chloroacetaldehyde which is
further converted to chloroethanol or monochloroacetic acid.
Chloroethylene oxide, chloroacetaldehyde and monochloroacetic
acid are the main toxic metabolites of vinyl chloride.
Conjugation with glutathione is the main detoxification
mechanism for these three compounds. It is responsible for
the production of the two main urinary metabolites of vinyl
chloride: N-acetyl-S-(hydroxy-2-ethyl)-cysteine and
thiodiglycolic acid (ECETOC, 1988):
-a fast one with a half-life of 1.5 minutes;
-a second one with a half-life of 1000 minutes;
-a slow one with a half-life of about 4000 minutes.
In humans, the main urinary metabolite of vinyl chloride is
thiodiglycolic acid. Its excretion increases with exposure
to the parent compound. The measurement of thiodiglycolic
acid concentration in urine should, however, not be used to
evaluate exposure to vinyl chloride because its sensitivity
is low, and also because at usual levels of exposure, the
results fluctuate widely (ECETOC, 1988).
7. TOXICOLOGY
7.1 Mode of action
Like many other chlorinated hydrocarbons, vinyl chloride
itself may cause central nervous system depression and
cardiac arrhythmias in cases of massive poisoning.
Chloroethylene oxide is a highly reactive metabolite; it is
probably responsible for most of the mutagenic and
carcinogenic effects of vinyl chloride (ECETOC, 1988).
Chloroacetaldehyde is also a metabolite of high cytoxicity
and some mutagenic potential (ECETOC, 1988).
The epoxidation of vinyl chloride to chloroethylene oxide is
the key step in the metabolism of vinyl chloride; it is
readily saturable; nevertheless covalent binding to DNA
occurs at levels well below the saturation limit (Watanabe et
al., 1978); this may explain the induction of tumours even at
low exposure levels (Maltoni and Lefemine, 1975).
The main detoxification pathway for all three toxic
metabolites of vinyl chloride is conjugation with
glutathione.
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
Exposure to more than 120,000 ppm
may be fatal (ILO, 1983).
Early inhalational experiments on human
subjects found vinyl chloride to be narcotic
at 70,000 to 100,000 ppm and to cause
arrhythmias at 120,000 ppm (Oster et al.,
1947).
Concentrations of 8,999 to 20,000 ppm caused
dizziness, nausea and headache (Baselt, 1982;
ILO, 1983).
Acute exposures in the range of 8,000 to
13,000 ppm for five minutes may be tolerated
with no apparent symptoms (ATSDR, 1989).
7.2.1.2 Children
No data.
7.2.2 Relevant animal data
LD50 (oral, rat) = 500 mg/kg (RTECS, 1994)
LC 50 (mice) = 130,000 ppm x 2 hours (RTECS, 1994)
When mice and rats were exposed to vinyl chloride at
concentrations of 10,000 to 30,000 ppm for 30 minutes,
the principal effect was narcosis; congestion, oedema
and haemorrhages of the lungs and congestion of the
liver and kidneys were also observed (Prodam et al.,
1975).
Exposure of rats to 50,000 or 10,000 ppm for 6 hours
(Jaeger et al., 1974; Reynolds et al., 1975) produced
centrilobular hepatocellular vacuolisation at both
levels with pretreatment with phenobarbitone, and at
the highest level only without pretreatment. More
subtle hepatic injury has been observed at lower doses
(15,000 ppm × 2 - 8 hr/d × 5 d/wk × 1 to 6 weeks).
7.2.3 Relevant in vitro data
The relevant in vitro data concern the
genotoxicity of vinyl chloride (see 7.5).
7.2.4 Workplace standards
Vinyl chloride is a demonstrated carcinogen,
and OSHA's recommended PEL (Permissible Exposure
Limit) is one ppm for an eight-hour TWA (Time Weighted
Average concentration), with a five ppm ceiling at 15
minutes. The TLV (Threshold Limit value) recommended
by ACGIH is 5 ppm, with a short-term limit, averaged
over 15 minutes of 10 ppm (ACGIH, 1992).
In France, the TWA is 1 ppm for plants built after
1980, and 3 ppm for those built before.
In Germany, the TWA is 3 ppm for plants producing
polyvinyl chloride; it is only 2 ppm for other
plants.
7.2.5 Acceptable daily intake
Vinyl chloride is a carcinogen in experimental
animals and man. As a no-effect level has not been
established, there is no acceptable daily intake.
The EPA emission standards for chemicals released to
the atmosphere set a limit of 10 ppm for vinyl
chloride, measured at the source.
EPA has issued a maximum contaminant level of 2 ppb
for vinyl chloride in drinking water.
The residual vinyl chloride content in polymers in
contact with food should be limited to:
-5 ppb in vinyl chloride mono- or co-polymer films and
coatings, and plasticised polyvinyl chloride (PVC)
bottles;
-10 ppb in rigid PVC;
-50 ppb in water-pipes and vinyl chloride-vinylidene
chloride copolymer films.
7.3 Carcinogenicity
According to IARC, vinyl chloride is carcinogenic to
humans (Group 1). It has been associated with tumours of the
liver, brain, lung, lymphatic and haematopoietic system. A
large number of studies have substantiated the causal
associations between vinyl chloride and angiosarcoma of the
liver. vinyl chloride also causes other forms of hepatic
cancer and other localization of angiosarcomas as well as
brain tumours, lung tumours, and malignancies of the
lymphatic and haematopoietic system (IARC, 1979, IARC,
1987).
Vinyl chloride administered orally, or by inhalation, to
hamsters, mice and rats also produced tumours in the mammary
gland, lung, Zymbal gland and skin and angiosarcomas of the
liver. Pretreatment with ethanol increased the incidence of
liver tumours induced by vinyl chloride in rats (IARC, 1979;
IARC, 1987).
7.4 Teratogenicity
Vinyl chloride is not a teratogen in rodents (IARC,
1979; IARC, 1987). Although one pape reported increased
rates of malformations and fetal loss in cities where vinyl
chloride plants were located (Infante et al., 1976),
subsequent studies did not substantiate an association
between vinyl chloride exposure and birth defects in humans
(IARC, 1979; IARC 1987).
7.5 Mutagenicity
Vinyl chloride is bound covalently to isolated DNA in
the presence of a metabolic system. It alkylated DNA in
several tissues of mice and rats exposed in vivo. It was
mutagenic to bacteria, plants and to Schizosaccharomyces
pombe but not to other fungi; it induced gene conversion in
yeast. It was responsible for sex-linked recessive lethal
mutations in Drosophila. It induced mutation and unscheduled
DNA synthesis in different systems of mammalian cells in
vitro. In vivo, it also induced chromosomal aberrations,
sister chromatid exchanges and micronuclei in rodents
(ECETOC, 1988). Vinyl chloride induced sister chromatid
exchanges in human lymphocytes in vitro (ECETOC, 1988). An
excess of chromosomal aberrations was observed in peripheral
blood lymphocytes of workers (ECETOC, 1988) exposed to vinyl
chloride 85 to 500 ppm).
7.6 Interactions
As the main metabolic pathway of vinyl chloride depends
on microsomal cytochrome P450, pretreatment with inducers
such as phenobarbitone, ethanol or PCB will increase the
production of toxic metabolites (mainly of chloroethylene
oxide) and the toxic effects of vinyl chloride (ECETOC,
1988).
As the three main toxic metabolites are detoxified
through conjugation with glutathione, administration of
N-acetylcysteine might have a protective effect; however,
this hypothesis has never been tested.
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative Confirmation Test(s)
8.2.1.3 Simple Quantitative Method(s)
8.2.1.4 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and their
interpretation
8.5 Overall interpretation of all toxicological analyses and
toxicological investigations.
Biomedical analysis
Standard liver enzymes and liver function tests are indicated
to confirm liver involvement, but are of little value in
detecting early stages of liver injury. The increase of
coproporphyrinuria - which is a consistent finding in the
presence of vinyl chloride-induced hepatic damage - also
lacks specificity.
Urinary thiodiglycolic acid levels are unreliable in persons
exposed to less than 5 ppm vinyl chloride.
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
Not reported.
9.1.2 Inhalation
Massive exposure (see 7.2.1.1) to vinyl
chloride may induce headache, nausea, central nervous
system depression (dizziness, drowsiness, then coma)
and cardiac arrhythmias. High concentrations also
cause irritation of the eyes and of the respiratory
tract. Hepatic changes increased by ethanol or
phenobarbitone pretreatment have been observed
following massive exposure in animals (ECETOC, 1988);
such effects have not been reported in humans.
9.1.3 Skin exposure
Vinyl chloride is stored under pressure;
exposure to the escaping gas may cause
frostbite.
9.1.4 Eye contact
Contact with escaping compressed gas may cause
mechanical injury and frostbite.
Vapours of vinyl chloride are moderately irritating to
the eyes.
9.1.5 Parenteral exposure
Not reported.
9.1.6 Other
Not reported.
9.2 Chronic poisoning
9.2.1 Ingestion
Not reported.
9.2.2 Inhalation
Repeated exposure to vinyl chloride may induce
vinyl chloride disease which is characterized by
scleroderma-like changes of the fingers, Raynaud's
phenomenon and acro-osteolysis. Hepatic damage is
initially an enlargement and a proliferation of
hepatocytes and sinusoïdal cells. Hepatic fibrosis
and peliosis may result after several years. Portal
hypertension is a usual complication of hepatic
fibrosis. There is a causal association between
exposure to vinyl chloride and the incidence of
angiosarcomas of the liver. Vinyl chloride also
causes other forms of hepatic cancers as well as brain
tumours, lung tumours and malignancies of the
lymphatic and haematopoietic system.
9.2.3 Skin exposure
No data available.
9.2.4 Eye contact
Vapours of vinyl chloride are moderately
irritating to the eyes.
9.2.5 Parenteral exposure
No data available.
9.2.6 Other
Not reported.
9.3 Course, prognosis, cause of death
In acute poisoning, death may result from central
nervous system depression and/or cardiac arrhythmias.
There is an increased incidence of deaths from malignant
neoplasms in vinyl chloride exposed workers. Angiosarcomas
of the liver have a very poor prognosis. They generally
result from prolonged exposure (>10 years) to high
concentrations (>50 ppm) of vinyl chloride; the latent
period between first exposure and diagnosis varies from 15 to
30 years (IARC, 1979; IARC, 1987; ECETOC, 1988).
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Vinyl chloride sensitized the hearts of dogs to
epinephrine-induced arrhythmias. Cardiac arrhythmias
may be a complication of massive exposure to vinyl
chloride (Oster et al., 1947).
Repeated exposure to vinyl chloride may induce
Raynaud's syndrome; all the fingers may be involved or
only a few of them; this phenomenon generally persists
when exposure is terminated (Carpentier et al., 1984).
Portal hypertension may be a result of hepatic
fibrosis (Smith et al., 1976).
An excess of angiosarcomas of the liver has been
observed in workers exposed to vinyl chloride;
angiosarcomas of other localizations have also been
reported (IARC, 1979; IARC 1987).
9.4.2 Respiratory
Massive exposure to vinyl chloride may be
responsible for irritation of the respiratory tract;
congestion, oedema and haemorrhages of the lungs have
been observed in experimental animals (Prodan et al.,
1975).
Impaired pulmonary function with decreased alveolo-
capillary permeability, as measured by single breath
transfer for carbon monoxide (TLCO), was observed in
workers exposed both to vinyl chloride and polyvinyl
chloride dust (Lloyd et al., 1984).
The incidence of lung cancers is increased in workers
exposed to vinyl chloride (IARC, 1979; IARC 1987;
ECETOC, 1988).
9.4.3 Neurologic
9.4.3.1 Central Nervous System (CNS)
Vinyl chloride may cause central
nervous system depression. Concentrations of
8,000 to 20,000 ppm induced headache, nausea,
dizziness and drowsiness. At higher
concentrations, vinyl chloride is narcotic.
Seizures may occur in deep coma induced by
vinyl chloride (Oster et al., 1947; Danziger,
1960; ECETOC 1988).
Symptoms similar to those observed in workers
with solvent-induced organic psychosyndromes
have been reported after repeated exposure to
vinyl chloride (Langhauer-Lewowicka et al.,
1983).
An excess of brain tumours has been observed
in workers exposed to vinyl chloride (IARC,
1979; IARC, 1987; ECETOC, 1988).
9.4.3.2 Peripheral nervous system
Distal axonal peripheral neuropathy
has been reported in exposed workers
(Perticoni et al., 1986).
9.4.4 Gastrointestinal
Nausea, vomiting, diarrhea and abdominal pain
may be observed in cases of acute vinyl chloride
poisoning (Oster et al., 1947; Danziger, 1960; ECETOC,
1988).
9.4.5 Hepatic
Massive vinyl chloride poisoning may produce
centrilobular hepatocellular vacuolisation and
necrosis (Jaeger et al., 1974; Prodan et al., 1975;
Reynolds et al., 1975).
Repeated exposures to vinyl chloride also induce
hepatic damage. This is clinically and biologically
asymptomatic during years or decades. the initial
lesion is a hyperplasia of sinusoïdal cells and of
hepatocytes. Then perisinusoïdal fibrosis, portal
fibrosis and subcapsular fibrosis occur. Finally,
non-cirrhotic portal fibrosis leads to portal
hypertension with hepatomegaly, splenomegaly, and
oesophageal varices (Lee et al., 1977; Suciu et al.,
1975).
There is a causal association between exposure to
vinyl chloride and the incidence of angiosarcomas of
the liver. The latent period between the first
exposure and the discovery of the tumour various
between 15 and 30 years. Angiosarcomas generally
result from prolonged exposure (>10 years) to high
concentrations (>50 ppm) of the monomer. This tumour
has a very poor prognosis. vinyl chloride also causes
other types of hepatic cancer (IARC, 1979; IARC, 1987;
ECETOC, 1988).
9.4.6 Urinary
Not reported.
9.4.7 Endocrine and reproductive systems
Vinyl chloride has no demonstrated effects on
endocrine and reproductive systems.
9.4.8 Dermatological
Vinyl chloride is stored under pressure;
exposure to the escaping gas may cause frostbite.
Repeated exposure to vinyl chloride may induce
scleroderma-like changes of the hands. These skin
lesions are generally thought to be the consequence of
the Raynaud's phenomenon. The reality might be more
complex as scleroderma-like lesions usually disappear
after termination of exposure to vinyl chloride, when
Raynaud's phenomenon persists (Suciu et al., 1975).
Some authors have suggested that vinyl chloride
disease (i.e. Raynaud's phenomenon, scleroderma-like
changes, acro-osteolysys, protal fibrosis) might be an
immune complex disorder (Ward et al., 1976).
9.4.9 Eyes, ears, nose, throat: local effects
Vapours of vinyl chloride are moderately
irritating to the eyes and the respiratory tract.
Exposure to escaping compressed gas may cause
frostbite.
9.4.10 Haematological
Thrombocytopenia may be seen in workers
exposed to vinyl chloride. It is probably a
consequence of splenomegaly which results from hepatic
fibrosis and portal hypertension (Smith et al., 1976).
The incidence of malignancies of the lymphatic and
haematopoietic system is increased in workers exposed
to vinyl chloride (IARC, 1979; IARC 1987; ECETOC,
1988).
9.4.11 Immunological
Some authors have suggested that vinyl
chloride disease (i.e. Raynaud's phenomenon,
scleroderma-like changes, acroosteolysis, portal
fibrosis) might be an immune complex disorder.
Circulating immune complexes were detected in some
patients (Ward et al., 1976).
9.4.12 Metabolic
9.4.12.1 Acid base disturbances
Not reported.
9.4.12.2 Fluid and electrolyte disturbances
Not reported.
9.4.12.3 Other
Pathologic porphyrinuria,
especially increased coproporphyrinuria
appears to be a consistent finding in vinyl
chloride hepatic disease; however, the
specificity of this sign is very poor, as all
hepatic diseases and many other intoxications
may increase coproporphyrinuria.
9.4.13 Allergic
Not reported.
9.4.14 Other clinical effects
Acroosteolysis is the lysis of terminal
phalanges of some fingers of the hands and, sometimes,
of the feet. It is generally associated with
scleroderma-like lesions of the skin.
Remineralisation of the bone occurs after termination
of exposure to vinyl chloride; this process may be
long and persistent deformations of the fingers are
not infrequent (Carpentier et al., 1984; Suciu et al.,
1975).
9.4.15 Special risks
As the first step of vinyl chloride
metabolism, leading to its toxic metabolites, is
catalysed by cytochrome P450 isozyme(s), people with
increased cytochrome P450 activity may have an
increased risk of developing systemic toxic effects:
alcoholic patients, subjects treated with
barbiturates, or workers simultaneously exposed to
inducers (i.e. isopropanol, acetone, methyl ethyl
ketone) might be particularly sensitive to the toxic
effects of vinyl chloride.
9.5 Others
No data available.
9.6 Summary
10. MANAGEMENT
10.1 General principles
The evaluation of vital functions and life-supporting
measures are essential. rapid and effective decontamination
should be performed. In cases of massive exposure, the main
risks are central nervous system depression and the
occurrence of cardiac arrhythmias; therefore, close clinical
and ECG monitoring are needed. Hepatic damage should be
suspected. As the main toxic metabolites of vinyl chloride
are detoxified through conjugation with glutathione,
administration of N-acetylcysteine might have a protective
effect, though this has never been demonstrated.
The medical surveillance of chronically exposed workers
cannot be strictly defined: clinical and laboratory tests for
the monitoring of exposure to vinyl chloride and/or of its
toxic effects are poorly sensitive and non specific. The
main goal should be to minimize exposure and the monitoring
of atmospheric concentrations is certainly the most efficient
evaluation of worker's exposure.
10.2 Life supportive procedures and symptomatic treatment
Make a proper assessment of airway, breathing,
circulation and neurological status of the patient. Maintain
a clear airway. Administer oxygen if cyanosis is present.
Aspirate secretions from airway. Start artificial
respiration for respiratory failure. Open and maintain at
least one intravenous route.
If frostbite has occurred, wash frostbitten area with warm
water until circulation is restored. Do not rub or massage
the frozen area.
10.3 Decontamination
Inhalation: Take proper precautions to ensure safety of
rescuers before attempting rescue. Remove source of
contamination or move victim to fresh air. Begin artificial
respiration if required. Eye exposure: irrigate with flowing
lukewarm, gently flowing water or saline, immediately and
continuously for 15 minutes holding the eyelids open. All
patients should be evaluated by an ophthalmologist. Skin
contact: Remove all contaminated clothing and shoes. Flush
contaminated area with lukewarm, gently running water for at
least 15 minutes.
10.4 Enhanced elimination
A good urinary output and a good respiratory state are
mandatory. There are no references about other methods of
elimination.
10.5 Antidote treatment
10.5.1 Adults
As the main toxic metabolites of vinyl
chloride are detoxified through conjugation with
glutathione, administration of N-acetylcysteine might
have a protective effect. This hypothesis has, to our
knowledge, never been tested in humans or experimental
models.
10.5.2 Children
See 10.5.1
10.6 Management discussion
An overexposure to vinyl chloride vapours can produce
different degrees of central nervous system depression from
dizziness and light-headedness to unconsciousness and death.
Vapours are irritating to mucous membranes, but the liquid
product may cause frostbite. The main problem is chronic
occupational exposure due to potential effects of "vinyl
chloride disease" and oncogenic effects. For these special
situations, prevention is the key-word. A constant and
comprehensive medical control of workers is a fundamental
requirement, as biochemical or toxicological tests are not
specific for early diagnosis and consequent management.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Two fatalities occurred in workers exposed to vinyl
chloride vapours, while cleaning polymerization tanks
(Danziger, 1960).
In the first case, a 21 year old worker was found dead at the
bottom of a tank. Autopsy revealed congestion of the liver,
spleen and kidneys.
In the second one, the victim was a 39 year old man who was
found dead 20 minutes after he went alone in a pit. Autopsy
showed cyanotic nails, kerato-conjunctivitis, and congested
kidneys.
A 51 year old man was hospitalized with a 6 week history of
anorexia, fatigue, right sided abdominal pain, and
progressive abdominal distension. He had experienced a
weight loss of approximately 7 kilograms and recently
developed jaundice. He reported working as an autoclave
cleaner in a PVC production plant for 9 years until 15 years
before his hospitalization. Clinical examination revealed
jaundice and a massive hepatomegaly. Liver function test
showed increased bilirubin and gamma-glutamyltranspeptidase
and hypoalbuminaemia. An abdominal computed tomographic scan
showed diffuse enlargement of the liver with an abnormal
texture. The patient's condition deteriorated rapidly.
Ascites developed, then oliguric renal failure and
encephalopathy. Death occurred 21 days after
hospitalization. Autopsy revealed a hepatic angiosarcoma
(Riordan et al., 1991).
Two cases of vinyl chloride disease involving autoclave
cleaners at a PVC manufacturing factory were reported by Juhe
and Weltman (1967). Both workers had Raynaud syndromes and
subsequently developed acro-osteolysis. Symptoms presented
included diffuse swelling of the hands, thickening of the
finger end phalanges, and ivory coloured plate-like
infiltrations on the skin of hands and wrists. X-rays
revealed acro-osteolysis.
12. ADDITIONAL INFORMATION
12.1 Specific preventive measures
The exposure limits are fundamental points of reference
for correct prevention.
Warning properties: odour is inadequate warning of excessive
exposure.
Ventilation: control airborne concentrations below the
exposure guideline. Use only with adequate ventilation.
Local exhaust ventilation may be necessary for some
operations.
Ingestion: do not consume or store food in the work area.
Wash hands before smoking or eating.
Inhalation: when respiratory protection is required for
certain operations, use an approved air-purifying respirator.
When airborne exposure guideline may be exceeded, use an
approved positive-pressure self-contained breathing
apparatus.
Eyes: use safety glasses. If vapour exposure causes eye
discomfort, use a full-face supplied air respirator.
Skin: use protective clothing materials such as nitrile
butadiene, rubber chlorinated polyethylene (CPE) and
Viton(R). Selection of specific items such as gloves, boots
or full-body suit will depend on operation.
Storage: store in cool, dry, well-ventilated areas, out of
direct sunlight. Keep material away from sparks, flames and
other ignition sources.
Spills: in case of small spills, evacuate area and let
evaporate. Disposal by controlled incineration with a
scrubber attached to remove any hydrochloric acid formed.
Fires: extinguish the flame bay carbon dioxide or dry
chemical (ILO, 1983).
12.2 Other
13. REFERENCES
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14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESSES
Author: Alberto Furtado Rahde
Rua Riachuelo 677 Ap 201
90010-270 Porto Alegre
Brazil
Telephone: 55 51 227 54 19
Telefax: 55 51 224 65 63/229 90 67/339 15 64
Date: December 1992
Reviewer: Robert Garnier
Centre Anti-Poisons de Paris
Hôpital Fernand Widal
200, rue du Faubourg Saint-Denis
75475 Paris Cédex 10
France
Telephone: 33 1 40 05 43 29
Telefax: 33 1 40 05 41 93
Date: July 1993
Peer review: INTOX Meeting, September 1994 (Drs McKeown,
Garnier, Hartigan-Go, Wickstrom)
Editor: Dr M. Ruse (October, 1997)