Substances Included Synonyms

Therapeutic Toxic Class

A)

B)

Specific Substances

1) Vinyl Chloride Monomer (VCM)
2) Polyvinyl chloride (PVC)
3) Chloroethylene
4) Chloroethene
5) Chlorethene
6) Ethylene monochloride
7) Monochloroethene
8) Monochloroethylene
9) Chlorethylene
10) Chlorure de vinyle (French)
11) Cloruro di vinile (Italian)
12) VC
13) Winylu chlorek (Polish)
14) CAS 75-01-4
15) CHLORURE DE VINYL (FRENCH)
16) MONOCHLOROETHENE VINILE (CLORURO DI) (ITALIAN)
17) SP 60
18) VINILE (CHLORURO DI) (ITALIAN)

1.2.1) MOLECULAR FORMULA
1) C2-H3-Cl CH2CHCl

Available Forms Sources

A)

1) The technical grade of vinyl chloride is of 99.9 mole percent purity in the liquid phase (CGA, 1999a; Lewis, 1997) or 99.9 percent by weight since the 1960s (IPCS, 1999a).
2) The commercial grade contains 1 to 2 percent of impurities (HSDB, 2001).
3) IMPURITIES:

a) Water (at maximum of 120 mg/kg), hydrochloric acid (at maximum of 1 mg/kg), and acetylene (1-10 mg/kg) can be present as impurities (CGA, 1999a; IPCS, 1999a).
b) Dioxins can be formed as contaminants (IPCS, 1999a).
c) Other impurities include (HSDB, 2001; IPCS, 1999a):

1) acetaldehyde
2) 1,3-butadiene
3) butane
4) butene
5) 1-butyne-3-ene (vinyl acetylene)
6) chloroethane
7) chlorophene
8) chloromethane
9) diacetylene
10) 1,2-dichloroethane ethene (ethylene)
11) hydrogen peroxide
12) methyl chloride
13) propadiene (allene)
14) propene
15) propine
16) vinyl acetylene

4) ADDITIVES, sometimes added as stablizers (HSDB, 2001):

1) Hydroquinone
2) butyl catechol
3) phenol

B)

1) Vinyl chloride is produced by the dehydrochloronation of ethylene dichloride with alcoholic potassium, by the halogenation of ethylene, and by the addition reaction of acetylene and anhydrous hydrogen chloride (Ashford, 1994; Budavari, 2000a; CGA, 1999; Lewis, 1997).
2) Vinyl chloride is one component of cigarette smoke (ACGIH, 1992).
3) Although job-related exposure is usually through inhalation and dermal contact, non-occupational exposure is through drinking water and consumer products (Lewis, 1998).

C)

1) Vinyl chloride is used to make plastics, adhesives, as a raw material, mainly (98%) in the manufacture of polyvinyl chloride (PVC) resins, and in the production of vinyl chloride and vinyl acetate copolymers. Because PVC is one of the most energy-efficient materials, it is used to make a wide variety of end-use products such as automotive parts and accessories, furniture, packaging materials, pipes, wall coverings, and wire coatings. Vinyl chloride has also been used as an aerosol propellant (AAR, 1998; ACGIH, 1992; ATSDR, 1997; Baselt, 2000; Baxter et al, 2000; Bingham et al, 2001; Budavari, 2000a; CGA, 1999a; IPCS, 1999b; Lewis, 1997; Lewis, 1998).
2) "The use of vinyl chloride as an aerosol propellant, refrigerant, or a component of pharmaceuticals or cosmetics was banned in the US in 1974" (ACGIH, 1992).
3) PVC is found in a variety of hospital products including:

1) intravenous (IV) bags and tubing
2) umbilical artery catheters
3) blood bags and infusion tubing
4) enteral nutrition feeding bags
5) nasogastric tubes
6) peritoneal dialysis bags and tubing
7) tubing used in cardiopulmonary bypass (CPB) procedures
8) tubing used in extracorporeal membrane oxygenation
9) tubing used during hemodialysis

Overview

Life Support

A)

Clinical Effects

0.2.1)

A) SUMMARY: In acute exposure, deaths are most often due to CNS and respiratory depression. The primary toxic hazard is exposure to vinyl chloride monomer (VCM) gas rather than to poly vinyl chloride (PVC) products (except during pyrolysis). There may be a long latent period between exposure and symptom onset.
B) ACUTE: The nervous system is the primary target of acute vinyl chloride exposure. Signs and symptoms following ingestion include weakness; ataxia; inebriation; headache; fatigue; numbness; tingling and pallor or cyanosis of the extremities; nausea; abdominal pain; GI bleeding; visual disturbances; cardiac dysrhythmias; narcosis and death. Vinyl chloride is a severe irritant of the eyes, skin, and mucous membranes.
C) CHRONIC: Enhanced collagen deposition and thickening of the subepidermal layer of the skin, Raynaud's phenomenon, hepatomegaly, hepatic fibrosis, splenomegaly, thrombocytopenia, sensory-motor polyneuropathy, trigeminal sensory neuropathy, minor pyramidal signs, cerebellar and extrapyramidal motor disorders, degenerative bone changes, and acro-osteolysis may occur with chronic exposure to vinyl chloride. Vinyl chloride is a known human carcinogen and has caused angiosarcoma of the liver in heavily exposed workers.
D) DERMAL: Direct contact with liquid vinyl chloride or escaping gas can cause frostbite injury.
E) INHALATION: Inhalation may cause CNS and respiratory depression and seizures.

0.2.4)

A) Contact with escaping, compressed gas may cause mechanical injury and frostbite. The vapor is irritating to the eyes.

0.2.5)

A) VCM sensitizes animal hearts to epinephrine-induced dysrhythmias. Ventricular fibrillation may be a cause of sudden death.

0.2.6)

A) Various pulmonary abnormalities have occurred including dyspnea, asthma and pneumoconiosis.
B) A chronic interstitial pulmonary change is thought to be caused by vinyl chloride monomer; this change is distinct from a pneumoconiosis.

0.2.7)

A) VCM may cause CNS depression characterized by fatigue, headache, vertigo, ataxia, euphoria, visual disturbances, numbness and tingling in the extremities, narcosis, loss of consciousness, and death from respiratory failure.
B) Seizures may occur following inhalational exposure of VCM.

0.2.8)

A) Nausea, vomiting, diarrhea, and severe epigastric pain can result from ingestion of the liquid.

0.2.9)

A) In chronic/subacute exposures, the target organ is the liver. Direct hepatotoxicity, hepatomegaly, and hepatic cancers, including angiosarcoma, have been reported.
B) Portal hypertension can result from liver injury.

0.2.10)

A) Decreased libido and sperm count have occurred following chronic exposures in men.

0.2.13)

A) Thrombocytopenia, porphyrinuria, and capillary abnormalities have also been reported.

0.2.14)

A) Scleroderma, frostbite, irritation and cyanosis have been reported. Vinyl chloride may be absorbed through the skin.
B) Contact dermatitis has been associated with VCM or its plasticizers or additives.

0.2.15)

A) Acro-osteolysis, arthralgias, and cold extremities have been reported in workers exposed to VCM.

0.2.20)

A) Fetotoxicity and congenital malformations have been seen in animals. Human birth defects have not been substantiated.

0.2.21)

A) Vinyl chloride is a HUMAN CARCINOGEN inducing hepatic angiosarcoma, a rare form of liver cancer. Cancers of the brain, lungs, blood and digestive systems, and melanoma have also been associated with vinyl chloride monomer (VCM) exposure.

Laboratory Monitoring

A)

Treatment Overview

0.4.3)

A) Monitor for CNS and respiratory depression after acute exposure. Treatment should focus on good supportive care such as appropriate airway management and aggressive treatment of neurologic symptoms.
B) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).

1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.

C) VCM and PVC dust may cause various respiratory abnormalities and respiratory cancers. Workers exposed to dust should have periodic chest x-rays.
D) There is no specific test to detect VCM hepatic toxicity. Periodic monitoring of liver function tests in exposed workers is recommended, although there is disagreement about its utility.

0.4.4)

A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.

0.4.5)

A) OVERVIEW

1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

A)

Clinical Effects

Summary Of Exposure

A)

B)

C)

D)

E)

Heent

3.4.1)

A) Contact with escaping, compressed gas may cause mechanical injury and frostbite. The vapor is irritating to the eyes.

3.4.3)

A) BURNS: Conjunctivitis and corneal burns may result from exposure (ITI, 1995). Contact with escaping, compressed gas may cause mechanical injury and frostbite (ACGIH, 1991b).
B) IRRITATION: Vapors of VCM are moderately irritating to the eyes (CCOHS, 1988).
C) CORNEAL DAMAGE: A single case of human corneal injury was reported, which healed completely in 48 hours (Grant & Schuman, 1993).
D) WITH POISONING/EXPOSURE

1) CASE SERIES/FIRST RESPONDERS: In 2012, a survey was conducted by the New Jersey Department of Health with the assistance of the CDC and ATSDR to assess the health effects associated with acute exposure of vinyl chloride by emergency responders (n=93) following a release from a train derailment. Of the self-reported symptoms, irritation, pain, or burning of the eyes (11%) were frequently reported. Twenty-three percent of responders reported that they did not wear any type of personal protective equipment. Of note, air monitoring was not conducted following the release (Brinker et al, 2015).

Cardiovascular

3.5.1)

A) VCM sensitizes animal hearts to epinephrine-induced dysrhythmias. Ventricular fibrillation may be a cause of sudden death.

3.5.2)

A) VENTRICULAR FIBRILLATION

1) WITH POISONING/EXPOSURE

a) Cardiac dysrhythmia is a sign of vinyl chloride poisoning (Lewis, 1998). Ventricular fibrillation may be a cause of sudden death after acute exposure (HSDB , 1989).

B) HYPERTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) OCCUPATIONAL EXPOSURE: Occupational exposure to vinyl chloride was associated with an increased incidence of hypertension (RR 2.28 95%CI 1.67 to 3.11 for the entire exposed group; RR 4.17 95%CI 2.46 to 7.04 in the group with the highest exposure to vinyl chloride) (Kotseva, 1996).

3.5.3)

A) ANIMAL STUDIES

1) DYSRHYTHMIA

a) VCM sensitized the DOG heart to epinephrine-induced dysrhythmias (Jucker, 1974).

2) CARDIAC FAILURE

a) Decreased myocardial contractility is associated with anesthetic doses in animals (Belej et al, 1974).

Respiratory

3.6.1)

A) Various pulmonary abnormalities have occurred including dyspnea, asthma and pneumoconiosis.
B) A chronic interstitial pulmonary change is thought to be caused by vinyl chloride monomer; this change is distinct from a pneumoconiosis.

3.6.2)

A) PNEUMONITIS

1) WITH POISONING/EXPOSURE

a) Various pulmonary abnormalities have occurred, including breathlessness, possibly resulting from impaired diffusion capacity.

1) Occupational exposure to high concentrations of VCM has been loosely associated with impaired pulmonary function, as measured by single breath total lung carbon monoxide (TLCO) diffusion (Lloyd et al, 1984).

b) Both mild obstructive and restrictive ventilatory defects have been associated with PVC dust exposure (Lee et al, 1991).
c) Fibrosis of the lungs may occur (Zenz, 1994).

B) BRONCHOSPASM

1) WITH POISONING/EXPOSURE

a) MEAT-WRAPPERS ASTHMA: Respiratory difficulties may arise in supermarket workers who use a hot wire to cut PVC wrap used in wrapping meat. This liberates VCM and HCL (Anderson Jr, 1974) (Stevens, 1974).

1) Meat wrappers asthma occurs following exposure to PVC pyrolysis products and possibly to plasticizers (Falk & Portnoy, 1976). Asthma caused by heat-cutting PVC wrap may be due to release of phthalic anhydrides, not PVC. The actual cause is uncertain.

b) In one study, workers in a polyvinyl chloride fabrication plant had pulmonary function tests suggesting acute and chronic airway obstruction (decreased FEV1/FVC ratio, increased incidence of cross shift falls in Vmax75 of 15% or more). In addition there was a relationship between longer duration of of employment and a reduction in FVC, suggesting a component of restrictive lung disease after chronic exposure (Ernst et al, 1988).

C) UPPER RESPIRATORY TRACT STRUCTURE

1) WITH POISONING/EXPOSURE

a) CASE SERIES/FIRST RESPONDERS: In 2012, a survey was conducted by the New Jersey Department of Health with the assistance of the CDC and ATSDR to assess the health effects associated with acute exposure of vinyl chloride by emergency responders (n=93) following a release from a train derailment. Of the self-reported symptoms, upper respiratory symptoms (26%) (eg, runny nose, burning nose or throat and hoarseness) and lower respiratory symptoms ( 22%) (eg, shortness of breath, chest tightness, wheezing, and burning of chest) were frequently reported. Twenty-three percent of responders reported that they did not wear any type of personal protective equipment. Of note, air monitoring was not conducted following the release (Brinker et al, 2015).

D) LOWER RESPIRATORY TRACT STRUCTURE

1) WITH POISONING/EXPOSURE

a) CASE SERIES/FIRST RESPONDERS: In 2012, a survey was conducted by the New Jersey Department of Health with the assistance of the CDC and ATSDR to assess the health effects associated with acute exposure of vinyl chloride by emergency responders (n=93) following a release from a train derailment. Of the self-reported symptoms, upper respiratory symptoms (26%) (eg, runny nose, burning nose or throat and hoarseness) and lower respiratory symptoms (22%) (eg, shortness of breath, chest tightness, wheezing, and burning of chest) were frequently reported. Twenty-three percent of responders reported that they did not wear any type of personal protective equipment. Of note, air monitoring was not conducted following the release (Brinker et al, 2015).

E) PNEUMOCONIOSIS

1) WITH POISONING/EXPOSURE

a) OCCUPATIONAL EXPOSURE: Pneumoconiosis has been reported in workers exposed to PVC powder or dust (Wagoner, 1983).

F) INTERSTITIAL PNEUMONIA

1) WITH POISONING/EXPOSURE

a) Vinyl chloride is thought to cause a chronic interstitial pulmonary change distinct from pneumoconiosis. PVC polymer dust may also be involved (Wagoner, 1983; Cordasco et al, 1980; Soutar, 1980; Mastrangelo, 1981).

G) PRIMARY MALIGNANT NEOPLASM OF RESPIRATORY TRACT

1) "Cancer of the respiratory system" has been reported in vinyl chloride workers, but no dose-response figures were given (ACGIH, 1991).

Neurologic

3.7.1)

A) VCM may cause CNS depression characterized by fatigue, headache, vertigo, ataxia, euphoria, visual disturbances, numbness and tingling in the extremities, narcosis, loss of consciousness, and death from respiratory failure.
B) Seizures may occur following inhalational exposure of VCM.

3.7.2)

A) DEPRESSIVE DISORDER

1) WITH POISONING/EXPOSURE

a) The nervous system is the main target of acute exposure to vinyl chloride, producing central nervous system depression (Bingham et al, 2001a).
b) Central nervous system depression begins at 8,000 to 10,000 ppm (Bingham et al, 2001a). Signs and symptoms of CNS depression include headache, dizziness, light-headedness, ataxia and inebriation, euphoria, dulling of the senses, visual disturbances, headache, numbness and tingling of the extremities and drowsiness (ATSDR, 1997; HSDB , 2001).
c) Exposure to 1,000 ppm for more than 5 minutes results in drowsiness, faltering gait, visual changes, and numbness and tingling of the extremities (Hathaway et al, 1996).
d) Exposure to 4,000 ppm for 5 minutes may have no effect; however, 8,000 ppm for 5 minutes results in dizziness, and 20,000 ppm for 5 minutes causes light-headedness, nausea, and diminished vision and hearing (Hathaway et al, 1996).
e) VCM has narcotic properties and may cause unconsciousness in concentrations of 10,000 to 20,000 ppm (Walker, 1981; Proctor & Hughes, 1978).

B) SEIZURE

1) WITH POISONING/EXPOSURE

a) Seizures may occur in deep anesthesia induced with VCM (Danziger, 1960).

C) HEADACHE

1) WITH POISONING/EXPOSURE

a) CASE SERIES/FIRST RESPONDERS: In 2012, a survey was conducted by the New Jersey Department of Health with the assistance of the CDC and ATSDR to assess the health effects associated with acute exposure of vinyl chloride by emergency responders (n=93) following a release from a train derailment. Of the self-reported symptoms, headache (26%) was one of the most common adverse events (Brinker et al, 2015).

D) FATIGUE

1) WITH POISONING/EXPOSURE

a) OCCUPATIONAL EXPOSURE: Fatigue has been a symptom reported after chronic exposure, as have paresthesias (Barlow & Sullivan, 1982).

E) NEUROPATHY

1) WITH POISONING/EXPOSURE

a) OCCUPATIONAL EXPOSURE: Workers chronically exposed to concentrations less than 50 ppm have shown axonal neuropathy (ATSDR, 1989). Peripheral nerve damage has been reported after occupational exposure (ATSDR, 1997).

F) ELECTROENCEPHALOGRAM ABNORMAL

1) WITH POISONING/EXPOSURE

a) EEG changes were seen in VCM workers (ATSDR, 1989; HSDB , 2001).

Gastrointestinal

3.8.1)

A) Nausea, vomiting, diarrhea, and severe epigastric pain can result from ingestion of the liquid.

3.8.2)

A) ABDOMINAL PAIN

1) WITH POISONING/EXPOSURE

a) Abdominal pain and gastrointestinal bleeding are signs and symptoms of overexposure (Budavari, 2000). Nausea, vomiting, diarrhea, and abdominal pain, sometimes intense enough to mimic acute surgical complication, may follow ingestion of the liquid (HSDB , 1989).

B) NAUSEA AND VOMITING

1) WITH POISONING/EXPOSURE

a) CASE SERIES/FIRST RESPONDERS: In 2012, a survey was conducted by the New Jersey Department of Health with the assistance of the CDC and ATSDR to assess the health effects associated with acute exposure of vinyl chloride by emergency responders (n=93) following a release from a train derailment. Of the self-reported symptoms, nausea and vomiting (14%) were frequently reported. Twenty-three percent of responders reported that they did not wear any type of personal protective equipment. Of note, air monitoring was not conducted following the release (Brinker et al, 2015).

C) HEMATEMESIS

1) WITH POISONING/EXPOSURE

a) Hematemesis may occur after ingestion (HSDB , 1989).

Hepatic

3.9.1)

A) In chronic/subacute exposures, the target organ is the liver. Direct hepatotoxicity, hepatomegaly, and hepatic cancers, including angiosarcoma, have been reported.
B) Portal hypertension can result from liver injury.

3.9.2)

A) ANGIOSARCOMA OF LIVER

1) WITH POISONING/EXPOSURE

a) OCCUPATIONAL EXPOSURE

1) Angiosarcoma of the liver, an otherwise rare cancer, has been associated with chronic occupational exposure to vinyl chloride (Baxter et al, 2000a).
2) INCIDENCE: Through 1986 a total of 120 cases of angiosarcoma in vinyl chloride workers had been reported to a worldwide registry (ATSDR, 1989).
3) LATENCY: The latent period between first exposure and diagnosis ranged from 15 to 29 years, with an average length of exposure of 18.3 years (ATSDR, 1989).
4) It has been reported in individuals exposed when cleaning PVC reaction chambers (Walker, 1981). The workers with highest risk for developing angiosarcoma have been reactor cleaners who scraped the solid, caked polymer from the inside of reaction vessels (ATSDR, 1989). This process of cleaning vessels by hand is now obsolete in industrialized nations, but still may be prevalent in developing countries.
5) No cases of angiosarcoma have been detected in workers exposed only to post-1974-permissible levels of 5 ppm or less (ATSDR, 1989).
6) DOSE-RESPONSE: No cases of angiosarcoma have been reported in individuals who have been exposed only to low levels of VCM (ATSDR, 1989).

a) Angiosarcoma may be preceded by liver cell hyperplasia and hypertrophy followed by fibrosis and nodular capsular fibrosis leading to prehepatic sclerosis; these changes and subsequent angiosarcoma occur after chronic exposure to concentrations of 50 to 100 ppm or higher (ATSDR, 1997; ATSDR, 1989; CCOHS, 1988).
b) These pathological changes are nearly unique to VCM exposure. Only thorium dioxide and arsenicals have been shown to produce a similar pattern. Chronic high doses (over 500 ppm) are thought to cause hepatic injury; lower doses (over 100 ppm) are more likely to lead to angiosarcoma (ATSDR, 1990).

B) HEPATIC FIBROSIS

1) WITH POISONING/EXPOSURE

a) OCCUPATIONAL EXPOSURE

1) Hepatomegaly as well as splenomegaly have been reported (Baselt, 2000a; Walker, 1981). Hepatic damage ranges from proliferation of hepatocytes and sinusoidal cells (may be associated with sinusoidal dilatation) to angiosarcoma. Cirrhosis is generally not observed (Popper et al, 1981).
2) Hepatotoxicity is generally seen after several months or years of exposure to higher concentrations of VCM, in the range of 500 to 1,000 ppm (ATSDR, 1989).
3) Hepatic and splenic fibrosis may occur (Baselt, 2000a; Zenz, 1994). Indeed, non-cirrhotic hepatic fibrosis and portal hypertension can result from exposure to vinyl chloride monomer. The latter may be a precursor to angiosarcoma (Baxter et al, 2000a; ILO , 1998). Hepatoportal sclerosis may be related to vinyl chloride exposure (Rempel, 1990).
4) One study found that workers exposed to 200 ppm vinyl chloride monomer for at least one year had a fourfold increased risk of developing periportal liver fibrosis (Maroni et al, 2003).
5) Another study reported that workers with a history of high exposure to vinyl chloride monomer had a significantly increased risk of developing liver fibrosis (odds ratio 5.5, 95% confidence interval 1.7 to 25.4) when compared with workers with lower exposure (Hsiao et al, 2004).

3.9.3)

A) ANIMAL STUDIES

1) ALCOHOL INTOLERANCE

a) Some preliminary animal studies indicate that concurrent chronic ethanol consumption and VCM exposure increase risk of hepatic cancers over VCM alone (Tamburro, 1978).

Genitourinary

3.10.1)

A) Decreased libido and sperm count have occurred following chronic exposures in men.

3.10.2)

A) LACK OF LIBIDO

1) WITH POISONING/EXPOSURE

a) Libido loss was reported in a series of 37 workers (Barlow & Sullivan, 1982).

B) SEMEN EXAM: ABNORMAL

1) WITH POISONING/EXPOSURE

a) Men exposed to levels of VCM as low as 30 mg/m(3) 5 years previously showed effects on spermatogenesis (RTECS , 2001).

3.10.3)

A) ANIMAL STUDIES

1) FERTILITY DECREASED MALE

a) Male rats given 1000 ppm for 6 hours 55 days prior to mating had lowered fertility (RTECS, 1989).

Hematologic

3.13.1)

A) Thrombocytopenia, porphyrinuria, and capillary abnormalities have also been reported.

3.13.2)

A) THROMBOCYTOPENIC DISORDER

1) WITH POISONING/EXPOSURE

a) OCCUPATIONAL EXPOSURE: Thrombocytopenia may be seen in workers exposed to VCM gas (Baselt, 2000a; Walker, 1981).

B) INCREASED CAPILLARY FRAGILITY

1) WITH POISONING/EXPOSURE

a) OCCUPATIONAL EXPOSURE: Wide-field capillary microscopy of the hands detected abnormalities in 48 of 152 (31.6 percent) of VCM workers hands and only 3 of 50 (6 percent) of the hands of non-exposed manual workers (Maricq et al, 1976).

C) PORPHYRIA DUE TO TOXIC EFFECT OF SUBSTANCE

1) WITH POISONING/EXPOSURE

a) CHRONIC: Pathologic porphyrinuria, especially secondary to coproporphyrinuria, is a consistent pathological finding, following chronic exposure, for the recognition of VCM-induced hepatocellular toxicity (Doss et al, 1984).

Dermatologic

3.14.1)

A) Scleroderma, frostbite, irritation and cyanosis have been reported. Vinyl chloride may be absorbed through the skin.
B) Contact dermatitis has been associated with VCM or its plasticizers or additives.

3.14.2)

A) SYSTEMIC SCLEROSIS

1) WITH POISONING/EXPOSURE

a) VCM-induced sclerodermic skin changes with new collagen formation and capillary abnormalities of the nail folds have been seen as part of acro-osteolysis (Walker, 1981).
b) Papular cutaneous sclerosis may occur (Zenz, 1994).

B) FROSTBITE

1) WITH POISONING/EXPOSURE

a) VCM is stored under pressure, and exposure to the escaping gas may cause frostbite (AAR, 1998; ACGIH, 1991). Contact with the liquid may also cause frostbite (Sittig, 1991).

C) CONTACT DERMATITIS

1) WITH POISONING/EXPOSURE

a) Contact dermatitis has been associated with exposure to vinyl chloride, but may be due to plasticizers and other additives (Schwartz et al, 1957).

D) SKIN IRRITATION

1) VCM is a skin irritant that can cause a rash (Schwartz et al, 1957; Sittig, 1991).

E) CYANOSIS

1) WITH POISONING/EXPOSURE

a) Cyanosis may result from exposure (Lewis, 1998).

F) POISONING

1) WITH POISONING/EXPOSURE

a) Percutaneous absorption is possible (Sittig, 1991).

Immunologic

3.19.2)

A) DISORDER OF CONNECTIVE TISSUE

1) WITH POISONING/EXPOSURE

a) Mixed connective tissue disease with characteristics of Raynaud's phenomenon, finger swelling, arthritis, and polymyositis, with anti-RNP antibodies has been reported in several patients exposed to polyvinyl chloride (Kahn et al, 1989).

Reproductive

3.20.1)

A) Fetotoxicity and congenital malformations have been seen in animals. Human birth defects have not been substantiated.

3.20.2)

A) HUMANS

1) Vinyl chloride monomer is considered a 'reproductive toxicant', although a causal association with birth defects remains to be shown (Schardein, 2000). Data on the potential human teratogenicity of VCM are inconclusive (Barlow & Sullivan, 1982; Theriault et al, 1983; Uzych, 1988). Some sources have concluded there is insufficient evidence to claim that VCM is a human teratogen (Hemminki & Vineis, 1985).
2) Increased fetal loss and congenital malformations have been reported in communities with vinyl chloride facilities, without correlation to proximity or parental occupational exposure (Harbison, 1998; (Schardein, 2000).

a) An excess of birth defects, including nervous system defects, deformities of the genital and upper alimentary tracts, and clubfoot, were reported in a group of still- and live-born children in three Ohio towns in proximity to vinyl chloride plants (HSDB , 2001).
b) In subsequent studies, malformations were seen, but there was no relationship with parental occupation or residential distance from the source of vinyl chloride (Edmonds, 1975; Edmonds et al, 1978; Theriault et al, 1983).
c) A study of birth defects in New Jersey concluded that the increase in central nervous system defects found was probably associated with vinyl chloride emissions (HSDB , 2001).
d) However, a study of birth defects in Shawinigan, Canada, found that excesses in birth defects could not be accounted for by atmospheric vinyl chloride levels (HSDB , 2001).

B) ANIMAL STUDIES

1) NEGATIVE RESULTS - Teratogenicity studies produced negative results in mouse, rat and rabbit (Schardein, 2000).
2) FETOTOXICITY - VCM was fetotoxic in rats at 500 ppm and caused increased post-implantation mortality in fetal rats at 1500 ppm. Musculoskeletal abnormalities were seen at 500 ppm in mice and rats (RTECS , 2001).
3) VCM was not teratogenic in rodents or rabbits exposed to airborne concentrations as high as 2,500 ppm (John et al, 1977).

3.20.3)

A) HUMANS

1) An increased incidence of pre-eclampsia has been reported in pregnant workers, compared with that of unexposed controls (Harbison, 1998).
2) There have been anecdotal reports of increased fetal mortality in the offspring of male VCM workers, and birth defects in communities near VCM plants (Barlow & Sullivan, 1982; Baxter et al, 2000a; Clemmenson, 1982; Sever & Hessol, 1985).
3) Increased risk for fetal loss was reported among wives of VCM workers (Infante et al, 1976), but this study has been criticized because its methods of data collection and reporting were indirect (Paddle, 1976). Two independent studies failed to find increased spontaneous abortions among wives of vinyl chloride workers (Sanotsky et al, 1980; Mur et al, 1992). No significant increase of spontaneous abortions was seen in a group of 44 female workers exposed to vinyl chloride and other plastics (Lindbohm et al, 1985).
4) A review of the literature on effects of human paternal exposure to VCM on the unborn was inconclusive (Uzych, 1988).

B) ANIMAL STUDIES

1) PLACENTAL TRANSFER - Rats exposed to various levels during pregnancy demonstrated via measurements of fetal blood levels and amniotic fluid considerable transfer of VCM to the fetus (Barlow & Sullivan, 1982; Zenz, 1994).
2) VCM was fetotoxic in rats at 500 ppm and caused increased post-implantation mortality in fetal rats at 1500 ppm (RTECS , 2001).
3) Increased pre-implantation mortality was seen in embryonic mice when the MALES had been exposed to a very high level of 30,000 ppm 5 days before mating (RTECS , 2001).

3.20.5)

A) ANIMAL STUDIES

1) Decreased female fertility was seen in rats exposed to 250 ppm 55 days prior to mating (RTECS , 2001).

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS75-01-4 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) IARC Classification

a) Listed as: Vinyl chloride
b) Carcinogen Rating: 1

1) The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. This category is used when there is sufficient evidence of carcinogenicity in humans. Exceptionally, an agent (mixture) may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent (mixture) acts through a relevant mechanism of carcinogenicity.

3.21.2)

A) Vinyl chloride is a HUMAN CARCINOGEN inducing hepatic angiosarcoma, a rare form of liver cancer. Cancers of the brain, lungs, blood and digestive systems, and melanoma have also been associated with vinyl chloride monomer (VCM) exposure.

3.21.3)

A) HEPATIC CARCINOMA

1) Angiosarcoma of the liver (an otherwise rare cancer), hemangiosarcoma, and hepatocellular carcinoma have been associated with chronic occupational exposure to vinyl chloride (Baxter et al, 2000a; Hozo et al, 2000; Weihrauch et al, 2000; Saurin et al, 1997; Forman et al, 1985; ILO , 1998; Riordan et al, 1991; Walker, 1981). Primary liver cancer is also seen (Baxter et al, 2000a; Du CL & Wang, 1998).
2) SIGNS AND SYMPTOMS - Symptoms at clinical onset of angiosarcoma are nonspecific and include fatigue, anorexia and weight loss, nausea, abdominal pain, vomiting, indigestion, diarrhea, and chest pain. There is no specific diagnostic test other than liver biopsy (CCOHS, 1988; ATSDR, 1989).
3) LATENCY - 5 to 30 years (Dietz et al, 1985; Michot et al, 1987). Average 22 years (Kielhorn et al, 2000).
4) MORTALITY - Vinyl chloride causes cancer directly (Dietz et al, 1985). Workers chronically exposed to vinyl chloride experience significantly higher mortality due to cancer of the liver and biliary tract than does the general population (Jones et al, 1988; Wong et al, 1991).
5) DOSE-RELATED - An updated mortality study on workers exposed to VCM found liver cancer was related to cumulative dose of VCM (Wu et al, 1989).
6) The eventual total number of expected occupationally-related cases of angiosarcoma may range from approximately 250 to 1500, depending on which predictive model is used (Forman et al, 1985).

a) An update on a mortality study of persons exposed to VCM at Dow Chemical Company has shown fewer than expected deaths from total cancers (Dahar et al, 1988). This result is consistent with a model predicting a decrease in cancer deaths from VCM over time.
b) In a contemporary cohort from the US, of various cancers (liver, lung, brain), only liver cancer met dose-response criteria (Wu, 1988).

7) A mortality study of British VCM workers and a follow-up of European workers found excess deaths only from liver cancer (Jones et al, 1988; Ward et al, 2001), and in a contemporary US cohort from only liver, lung and brain cancer. Of these, only liver cancer met dose-response criteria (Wu et al, 1989).
8) A recent meta-analysis of 6 studies addressing occupational exposure to vinyl chloride and its relation to cancer mortality found a weak, but statistically significant increase in primary liver cancers other than angiosarcoma of the liver. This analysis also found that vinyl chloride may cause an increase of soft tissue sarcomas. Lung and brain cancer, lymphatic and hematopoietic neoplasm could not be excluded. Mortality from other neoplasms did not appear to be increased(Boffetta et al, 2003).
9) In one study, 2 pooled analyses of worker cohorts from 37 vinyl chloride plants in North America and 19 plants in Europe (22,000 workers with a total of 640,000 person-years of observation, followed-up for up to 50 years) were used to evaluate cancer risk among workers exposed to vinyl chloride. Overall, 1778 cancer deaths were noted versus 1829.46 expected (corresponding to a standardized mortality ratio (SMR) of 0.97; 95% CI = 0.93-1.02). There were 71 deaths from liver angiosarcomas; 60 deaths from liver cancer (other than angiosarcomas) versus 44.35 expected (SMR =1.35, 95% CI = 1.03-1.74). A slight excess risk for liver cancer other than angiosarcomas was observed. This could be due to residual misclassification of angiosarcomas as unspecified liver cancers. This study found no evidence of any excess mortality from lung, laryngeal, soft tissue sarcoma, brain, lymphoid and hematopoietic neoplasms following vinyl chloride exposure (Bosetti et al, 2003).
10) HEMANGIOSARCOMA - A case of hemangiosarcoma of the liver and spleen with metastases in the periportal and epipancreatic lymph nodes in a vinyl chloride worker has been described (Michot et al, 1987):

a) This tumor was first diagnosed more than 30 years after discontinuance of chronic occupational vinyl chloride exposure. The presenting complaints were weight loss, nausea, anorexia, aching in the shoulders and spontaneous bleeding.
b) The patient was found to have microangiopathic hemolysis, anemia, thrombocytopenia, hypoprothrombinemia, hypoproteinemia, and enlargement of the spleen and liver. The patient died two days after the onset of the microangiopathic hemolysis.

11) Liver tumors were found in a man exposed by intermittent inhalation to 200 ppm for 14 years (RTECS , 2001). Angiosarcoma of the liver has been reported in individuals exposed to PVC when cleaning reaction chambers (Walker, 1981). Up to 1986, a total of 120 cases of angiosarcoma in vinyl chloride workers had been reported to a worldwide registry (ATSDR, 1989). The eventual total number of expected occupation-related cases of angiosarcoma ranges from approximately 250 to 1500, depending on which predictive model is used (Forman et al, 1985).
12) Hepatic angiosarcoma may be preceded by liver cell hyperplasia and hypertrophy, followed by fibrosis and nodular capsular fibrosis leading to prehepatic sclerosis; these changes and subsequent angiosarcoma occur after chronic exposure to concentrations of 50 to 100 ppm or higher (ATSDR, 1989; CCOHS, 1988).
13) These pathological changes are virtually unique to VCM exposure. Only thorium dioxide and certain arsenicals have been shown to produce a similar pattern. Exposure to chronic high airborne levels of VCM (greater than 500 ppm) are thought to cause hepatic injury; exposure to lower levels (greater than 100 ppm) is more likely to lead to hepatic angiosarcoma (ATSDR, 1990).
14) An updated mortality study of workers exposed to VCM found that liver cancer was related to cumulative dose of VCM (Wu et al, 1989). A mortality study of British VCM workers found excess deaths only from liver cancer (Jones et al, 1988). In a contemporary USA cohort with only liver, lung, and brain cancer noted; of these, only liver cancer met dose-response criteria (Wu et al, 1989).
15) The latent period between first exposure and diagnosis was between 5 to 30 years, with an average length of exposure of 18.3 years (Dietz et al, 1985; Michot et al, 1987; ATSDR, 1989).
16) Workers with highest risk for developing angiosarcoma were reactor cleaners, who scraped the solid, caked polymer from the inside of reaction vessels (ATSDR, 1989). This process of hand cleaning is now obsolete in industrialized nations. The absence of newer cases may be due to an insufficient latent period. The latent period for cancers may be 15 years or more.
17) A case of hemangiosarcoma of the liver and spleen with metastases in the periportal and epipancreatic lymph nodes in a vinyl chloride worker has been described (Michot et al, 1987). This tumor was first diagnosed more than 30 years after discontinuance of chronic occupational vinyl chloride exposure (Michot et al, 1987).
18) The presenting complaints were weight loss, nausea, anorexia, aching in the shoulders, and spontaneous bleeding (Michot et al, 1987). The patient was found to have microangiopathic hemolysis, anemia, thrombocytopenia, hypoprothrombinemia, hypoproteinemia, and enlargement of the spleen and liver (Michot et al, 1987). Definitive diagnosis of hemangiosarcoma, as distinct from angiosarcoma, should be determined by an experienced liver pathologist.

B) LEUKEMIA

1) A study of Russian workers exposed to VCM found excess deaths from leukemias and lymphomas, especially in women, but not angiosarcomas (Smulevich et al, 1988).

a) The reason for this difference in distribution of cancers in contrast with Western studies is not readily apparent. It may reflect a sex difference, because the study cohort for this study was approximately one-third women.

2) BLOOD SYSTEM - One report associated exposure to VCM with an unspecified cancer of the blood (RTECS , 2001), but this has not been confirmed in other studies.
3) In one study, 2 pooled analyses of worker cohorts from 37 vinyl chloride plants in North America and 19 plants in Europe (22,000 workers with a total of 640,000 person-years of observation, followed-up for up to 50 years) were used to evaluate cancer risk among workers exposed to vinyl chloride. Overall, 1778 cancer deaths were noted versus 1829.46 expected (corresponding to a standardized mortality ratio (SMR) of 0.97; 95% CI = 0.93-1.02). This study found no evidence of any excess mortality from lung, laryngeal, soft tissue sarcoma, brain, lymphoid and hematopoietic neoplasms following vinyl chloride exposure (Bosetti et al, 2003).

C) BRAIN CARCINOMA

1) In one study, 9 of 10 cases of brain cancer had a histologic diagnosis of glioblastoma multiforme, related to occupational exposure to vinyl chloride (HSDB , 2001).
2) In a study of 10,173 men, malignancies of the brain and other parts of the nervous system were the only types in significant excess (HSDB , 2001).
3) Nine retrospective mortality studies consistently found an increased risk for brain cancer as well as liver cancer (HSDB , 2001).
4) In one study, 2 pooled analyses of worker cohorts from 37 vinyl chloride plants in North America and 19 plants in Europe (22,000 workers with a total of 640,000 person-years of observation, followed-up for up to 50 years) were used to evaluate cancer risk among workers exposed to vinyl chloride. Overall, 1778 cancer deaths were noted versus 1829.46 expected (corresponding to a standardized mortality ratio (SMR) of 0.97; 95% CI = 0.93-1.02). This study found no evidence of any excess mortality from lung, laryngeal, soft tissue sarcoma, brain, lymphoid and hematopoietic neoplasms following vinyl chloride exposure (Bosetti et al, 2003).

D) PULMONARY CARCINOMA

1) Vinyl chloride monomer (polyvinyl chloride production) is a suspected cause of lung cancer (Raffle et al, 1994).
2) A prospective cohort study in France of 1,100 VCM workers and matched controls found no excess deaths from cancer in the exposed group, but there was increased incidence of angiosarcoma and lung cancers (Laplanche et al, 1987).
3) An ongoing study of all the VCM workers in Italy has reported excess deaths from cancers of the esophagus, liver and respiratory system for three of the nine plants (Belli et al, 1987).
4) In one study, 2 pooled analyses of worker cohorts from 37 vinyl chloride plants in North America and 19 plants in Europe (22,000 workers with a total of 640,000 person-years of observation, followed-up for up to 50 years) were used to evaluate cancer risk among workers exposed to vinyl chloride. Overall, 1778 cancer deaths were noted versus 1829.46 expected (corresponding to a standardized mortality ratio (SMR) of 0.97; 95% CI = 0.93-1.02). This study found no evidence of any excess mortality from lung, laryngeal, soft tissue sarcoma, brain, lymphoid and hematopoietic neoplasms following vinyl chloride exposure (Bosetti et al, 2003).

E) GASTRIC CARCINOMA

1) DIGESTIVE SYSTEM - Excess deaths from digestive cancers were found in one study of 451 occupationally exposed persons (HSDB , 2001).

F) MELANOMA MALIGNANT

1) An ongoing study of Norwegian workers exposed to VCM and polyvinyl chloride found a significant increase in incidence of malignant melanoma (6 cases vs. 1.1 expected) (Heldaas et al, 1987). On further follow up of this cohort, there were 7 cases of melanoma vs 2.07 expected (Langard et al, 2000).

G) RISK FACTORS

1) COMMUNITY RISK - There are some preliminary data that suggest that living near (less than 2 miles) a PVC plant may increase the risk of neoplasms (Wagoner, 1983). A recent review has concluded that the current risk to the general public from environmental contamination by VCM is negligible (Doll, 1988).

H) OTHER NON-SPECIFIC

1) Buccal cavity, pharyngeal, digestive tract, lung, brain and lymphatic cancers have been reported after 1 year of occupational exposure (Bingham et al, 2001a).
2) Cancers of the thyroid and breast have also been associated with exposure to VCM, but most studies have not noted these effects (ECETOC, 1988). Of the various reported cancer sites, only that for the liver is certain (Salmon, 1985).

I) ANIMAL STUDIES

1) VCM is historically interesting, because it is one of the few human carcinogens whose human toxicity was predicted first in an animal model. It causes zymbal gland and other tumors in rats (Viola, 1970; Maltoni et al, 1974; RTECS , 2001).
2) Vinyl chloride is considered carcinogenic by RTECS criteria (RTECS , 2001):

a) Increased liver and kidney tumors were seen in rats exposed to 3,463 mg/kg VCM by the oral route for 52 weeks.
b) Tumors of the skin and appendages were seen in rats inhaling 1 to 5 ppm, 4 hours daily for 52 weeks. It also produced vascular and skin/appendage tumors at 50 ppm, 7 hours daily for 26 weeks or 50 ppm, 6 hours daily for 43 weeks, and liver and skin/appendage tumors at 100 ppm.
c) VCM was an equivocal tumor agent in rats for skin/appendage and gastrointestinal tumors when administered IP at 21 mg/kg for 65 weeks or injected subcutaneously at 21 mg/kg for 67 weeks.
d) VCM was carcinogenic in rats by the oral route for liver angiosarcoma and kidney tumors at 34 gm/kg over 3 years. It was carcinogenic in rats at 250 ppm for 2 years for tumors of the ears and angiosarcoma.
e) Transplacental endocrine tumors were found when pregnant rats were exposed to 10,000 ppm for 4 hours.
f) VCM was carcinogenic in mice at 50 ppm for 30 weeks for vascular and/or skin/appendage tumors. It was carcinogenic in mice by inhalation at 50 ppm, 6 hours daily over 4 weeks for tumors of the respiratory system and skin/appendages; 30 weeks of exposure at this dose produced tumors of the liver and skin/appendages.
g) VCM was carcinogenic in mice for tumors of the respiratory system and liver at 50 ppm for 47 weeks.
h) VCM was carcinogenic in hamsters at 50 ppm, 4 hours daily for 30 weeks for lymphomas and skin/appendage tumors.

3.21.4)

A) CARCINOGENICITY RISK

1) VCM is one of the few human carcinogens whose human toxicity was predicted first in an animal model. It causes zymbal gland and other tumors in rats (Viola, 1970; Maltoni et al, 1974; RTECS , 1996). Increased liver and kidney tumors were seen in rats exposed to 3463 mg/kg of VCM by the oral route for 52 weeks. Tumors of the skin and appendages were seen in rats inhaling airborne concentrations of 1 to 5 ppm, 4 hours daily for 52 weeks. Transplacental endocrine tumors were found when pregnant rats were exposed to an airborne concentration of 10,000 ppm for 4 hours. It was an equivocal tumor agent in rats for skin/appendage and gastrointestinal tumors when given intraperitoneally a dose of 21 mg/kg for 65 weeks or subcutaneously at a dose of 21 mg/kg for 67 weeks.
2) It was carcinogenic in mice exposed to 50 ppm for 30 or 43 weeks, causing vascular and/or skin/appendage tumors. It was carcinogenic in hamsters at 50 ppm, 4 hours daily for 30 weeks for lymphomas and skin/appendage tumors. It was carcinogenic in rats, producing vascular and skin/appendage tumors at 50 ppm, 7 hours daily for 26 weeks, and liver and skin/appendage tumors at 100 ppm. It was carcinogenic in mice for tumors of the respiratory tract and liver at 50 ppm for 47 weeks. It was carcinogenic in rats exposed by the oral route, causing angiosarcoma and kidney tumors at a dose of 34 gm/kg over 3 years.
3) It was carcinogenic in mice exposed by inhalation to an airborne concentration of 50 ppm, 6 hours daily over 4 weeks, causing tumors of the respiratory tract and skin/appendages; 30 week exposure at this dose produced tumors of the liver and skin/appendages. It was carcinogenic in rats exposed to an airborne concentration of 250 ppm for 2 years, causing tumors of the ears and angiosarcoma.
4) Vinyl chloride has induced angiosarcoma of the liver in all species tested. The rate of tumors in exposed humans is similar to that in experimental animals (Whysner et al, 1996).
5) Local hyperplasia and cell proliferation appear to play a role in the development of VCM-induced angiosarcoma (ACGIH, 1992).

Genotoxicity

A)

B)

Musculoskeletal

3.15.1)

A) Acro-osteolysis, arthralgias, and cold extremities have been reported in workers exposed to VCM.

3.15.2)

A) DISORDER OF BONE

1) WITH POISONING/EXPOSURE

a) ACRO-OSTEOLYSIS: This is a condition combining lytic lesions of the bones, usually the terminal phalanges, Raynaud syndrome and sclerodermatous skin changes. There is an incidence of 3% to 5% of this condition in workers who clean PVC reaction chambers (Walker, 1981). Other authors have found a prevalence rate of 2 to 3 percent (Kemp et al, 1986). This acro-osteolysis results in "pseudo clubbing" (Raffle et al, 1994).
b) Degenerative bone changes occur with chronic exposure (Baselt, 2000a).

B) PERIPHERAL ISCHEMIA

1) WITH POISONING/EXPOSURE

a) Cold hands and feet were reported in a group of 37 workers studied (Barlow & Sullivan, 1982).

C) JOINT PAIN

1) WITH POISONING/EXPOSURE

a) Arthralgia as well as myalgia were reported in this same group of 37 workers (Barlow & Sullivan, 1982). Joint pain reportedly occurs after exposure to 8,000 ppm for 5 minutes (Sittig, 1991).

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) No toxic serum or blood level has been established.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) Standard liver enzymes and liver function tests and serum creatinine assays are indicated to confirm liver involvement, but are of little value in detecting early stages of liver injury or associating exposure to low levels of VCM (ATSDR, 1989; Sugita et al, 1986).
2) Fasting serum bile acid level and indocyanine green clearance rate may be sensitive monitors for latent chemical liver injury (ATSDR, 1989).
3) Pre-placement and periodic medical examinations including liver function tests should be performed on individuals with potential for exposure to VCM.

B) HEMATOLOGIC

1) Complete blood count with peripheral smear is indicated to assess liver damage.

4.1.3)

A) URINARY LEVELS

1) Clinical tests on urine that may be indicated include coproporphyrin and total urinary porphyrins, bilirubin, BUN and creatinine, and urinalysis (ATSDR, 1989).

a) Porphyrinuria, especially secondary coproporphyrinuria with subclinical chronic hepatic porphyria, has been consistently found in the presence of hepatotocellular damage induced by VCM (HSDB , 2001).

2) Thiodiglycolic acid in the urine indicates recent exposure. (ATSDR, 1997). Values found for persons occupationally exposed to 0.14 to 7 ppm ranged from 0.3 to 4 mg/L (HSDB , 2001).

a) Urinary thiodiglycolic acid levels are unreliable in persons exposed to less than 5 ppm vinyl chloride (in air) on several days following exposure (ATSDR, 1989). Levels peak at approximately 20 hours after vinyl chloride exposure (ATSDR, 1989).

4.1.4)

A) OTHER

1) OTHER

a) DIFFERENTIAL DIAGNOSIS - Exclude ethanol, carbon tetrachloride, iron overload, vitamin A overdose, and viral infection as possible causes of liver abnormalities. Consider biliary obstruction and metastatic colorectal cancer in differential diagnosis of liver injury (ATSDR, 1989).
b) An absence of anti-nuclear antibodies in patients with vinyl chloride disease can be used to rule out systemic sclerosis (ATSDR, 1997).
c) Wide-field capillary microscopy of the hands may be a useful method to detect early stages of vinyl chloride disease (HSDB , 2001).
d) A specific mutant p21 serum protein (Asp 13 c-Ki-ras) may be useful for detecting presence of vinyl chloride-induced angiosarcoma at pre-clinical stages. It was present in 89 percent of VC-exposed workers with liver angiomas and in 49 percent of exposed workers with no frank cancer (Devivo et al, 1994).

Radiographic Studies

A)

1) Morphological liver structure change (periportal fibrosis) was the primary ultrasonography finding associated with workers with a vinyl chloride monomer (VCM) exposure history. Workers with a minimum VCM exposure history of 200 ppm annually had a risk of periportal fibrosis four times that of non-exposed workers . The authors suggest that liver ultrasonography may be of diagnostic value and may be useful to include in medical surveillance protocols for VCM workers (Maroni et al, 2003).

Methods

A)

1) Flame-ionization gas chromatography is satisfactory for blood and breath VCM concentrations as low as 0.01 ppm, but is most accurate with recent exposures (Baselt, 2000a; Harrison & Hathaway, 1990).

a) HEPATIC INJURY - Only liver biopsy can distinguish between vinyl chloride and other etiologies of hepatic damage (Harrison & Hathaway, 1990).
b) NIOSH analytical method 1007 for measuring vinyl chloride in ambient air involves adsorbing air samples of 0.7 to 5 liters onto charcoal, eluting with carbon disulfide, followed by gas chromatography with flame ionization detection. The detectable range is 1 to 64 mg/m(3) (HSDB , 2001) RTECS, 1989).

2) DIFFERENTIAL DIAGNOSIS - Exclude ethanol, carbon tetrachloride, iron overload, vitamin A overdose, and viral infection as possible causes of liver abnormalities. Consider biliary obstruction and metastatic colorectal cancer in differential diagnosis of liver injury (ATSDR, 1989).
3) An absence of anti-nuclear antibodies in patients with vinyl chloride disease can be used to rule out systemic sclerosis (ATSDR, 1997).
4) Wide-field capillary microscopy of the hands may be a useful method to detect early stages of vinyl chloride disease (HSDB , 2001).
5) A specific mutant p21 serum protein (Asp 13 c-Ki-ras) may be useful for detecting presence of vinyl chloride-induced angiosarcoma at pre-clinical stages. It was present in 89 percent of VC-exposed workers with liver angiomas and in 49 percent of exposed workers with no frank cancer (Devivo et al, 1994).

Treatment

Life Support

A)

Monitoring

A)

Oral Exposure

6.5.3)

A) MONITORING OF PATIENT

1) Monitor for CNS and respiratory depression.

B) SURGICAL PROCEDURE

1) ANGIOSARCOMA - The most successful treatment for angiosarcoma with respect to long-term survival is surgical resection, when this is clinically feasible (ATSDR, 1989).

Inhalation Exposure

6.7.1)

A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

6.7.2)

A) MONITORING OF PATIENT

1) PULMONARY -

a) VCM and PVC dust may cause various respiratory abnormalities, and possibly, respiratory cancers.
b) Workers exposed to dusts should have periodic chest x-rays.

2) HEPATIC -

a) Exposures to VCM vapors may cause hepatic cancers, including angiosarcoma.
b) There is no specific test to detect VCM toxicity. Authors disagree concerning the usefulness of normal liver enzyme profile testing. Suggestions from one study is included below.
c) This study recommends a comprehensive liver study program for workers involved with VCM.

1) The testing starts with a 12 or 18 channel screen and if abnormally high values are found, progresses through liver scans and biopsies, depending upon the test results.
2) Of all the liver function tests, GGTP determination seems to be the most useful (Makk et al, 1974).

d) PATHOLOGIC PORPHYRINURIA, especially secondary to coproporphyrinuria with a transition to subclinical chronic hepatic porphyria is a consistent pathobiologic marker and may aid in the diagnosis of incipient

B) SURGICAL PROCEDURE

1) The most successful treatment for angiosarcoma with respect to long-term survival is surgical resection, when clinically feasible (ATSDR, 1989).

C) SEIZURE

1) SUMMARY

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

2) DIAZEPAM

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

3) NO INTRAVENOUS ACCESS

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

4) LORAZEPAM

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2010; Chin et al, 2008).

5) PHENOBARBITAL

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

6) OTHER AGENTS

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

D) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

6.8.1)

A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

6.8.2)

A) INJURY OF CORNEA

1) There have been very few cases of eye toxicity from vinyl chloride. Corneal damage, healing within 48 hours occurred in only one case report.
2) Such cases should be managed by, or in consultation with, an ophthalmologist.

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

6.9.1)

A) DERMAL DECONTAMINATION

1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

6.9.2)

A) FROSTBITE

1) PREHOSPITAL

a) Rewarming of a localized area should only be considered if the risk of refreezing is unlikely. Avoid rubbing the frozen area which may cause further damage to the area (Grieve et al, 2011; Hallam et al, 2010).

2) REWARMING

a) Do not institute rewarming unless complete rewarming can be assured; refreezing thawed tissue increases tissue damage. Place affected area in a water bath with a temperature of 40 to 42 degrees Celsius for 15 to 30 minutes until thawing is complete. The bath should be large enough to permit complete immersion of the injured part, avoiding contact with the sides of the bath. A whirlpool bath would be ideal. Some authors suggest a mild antibacterial (ie, chlorhexidine, hexachlorophene or povidone-iodine) be added to the bath water. Tissues should be thoroughly rewarmed and pliable; the skin will appear a red-purple color (Grieve et al, 2011; Hallam et al, 2010; Murphy et al, 2000).
b) Correct systemic hypothermia which can cause cold diuresis due to suppression of antidiuretic hormone; consider IV fluids (Grieve et al, 2011).
c) Rewarming may be associated with increasing acute pain, requiring narcotic analgesics.
d) For severe frostbite, clinical trials have shown that pentoxifylline, a phosphodiesterase inhibitor, can enhance tissue viability by increasing blood flow and reducing platelet activity (Hallam et al, 2010).

3) WOUND CARE

a) Digits should be separated by sterile absorbent cotton; no constrictive dressings should be used. Protective dressings should be changed twice per day.
b) Perform twice daily hydrotherapy for 30 to 45 minutes in warm water at 40 degrees Celsius. This helps debride devitalized tissue and maintain range of motion. Keep the area warm and dry between treatments (Hallam et al, 2010; Murphy et al, 2000).
c) The injured extremities should be elevated and should not be allowed to bear weight.
d) In patients at risk for infection of necrotic tissue, prophylactic antibiotics and tetanus toxoid have been recommended by some authors (Hallam et al, 2010; Murphy et al, 2000).
e) Non-tense clear blisters should be left intact due to the risk of infection; tense or hemorrhagic blisters may be carefully aspirated in a setting where aseptic technique is provided (Hallam et al, 2010).
f) Further surgical debridement should be delayed until mummification demarcation has occurred (60 to 90 days). Spontaneous amputation may occur.
g) Analgesics may be required during the rewarming phase; however, patients with severe pain should be evaluated for vasospasm.
h) IMAGING: Arteriography and noninvasive vascular techniques (e.g., plain radiography, laser Doppler studies, digital plethysmography, infrared thermography, isotope scanning), have been useful in evaluating the extent of vasospasm after thawing and assessing whether debridement is needed (Hallam et al, 2010). In cases of severe frostbite, Technetium 99 (triple phase scanning) and MRI angiography have been shown to be the most useful to assess injury and determine the extent or need for surgical debridement (Hallam et al, 2010).
i) TOPICAL THERAPY: Topical aloe vera may decrease tissue destruction and should be applied every 6 hours (Murphy et al, 2000).
j) IBUPROFEN THERAPY: Ibuprofen, a thromboxane inhibitor, may help limit inflammatory damage and reduce tissue loss (Grieve et al, 2011; Murphy et al, 2000). DOSE: 400 mg orally every 12 hours is recommended (Hallam et al, 2010).
k) THROMBOLYTIC THERAPY: Thrombolysis (intra-arterial or intravenous thrombolytic agents) may be beneficial in those patients at risk to lose a digit or a limb, if done within the first 24 hours of exposure. The use of tissue plasminogen activator (t-PA) to clear microvascular thromboses can restore arterial blood flow, but should be accompanied by close monitoring including angiography or technetium scanning to evaluate the injury and to evaluate the effects of t-PA administration. Potential risk of the procedure includes significant tissue edema that can lead to a rise in interstitial pressures resulting in compartment syndrome (Grieve et al, 2011).
l) CONTROVERSIAL: Adjunct pharmacological agents (ie, heparin, vasodilators, prostacyclins, prostaglandin synthetase inhibitors, dextran) are controversial and not routinely recommended. The role of hyperbaric oxygen therapy, sympathectomy remains unclear (Grieve et al, 2011).
m) CHRONIC PAIN: Vasomotor dysfunction can produce chronic pain. Amitriptyline has been used in some patients; some patients may need a referral for pain management. Inability to tolerate the cold (in the affected area) has been observed following a single episode of frostbite (Hallam et al, 2010).
n) MORBIDITIES: Frostbite can produce localized osteoporosis and possible bone loss following a severe case. These events may take a year or more to develop. Children may be at greater risk to develop more severe events (ie, early arthritis) (Hallam et al, 2010).

B) SYSTEMIC SCLEROSIS DUE TO CHEMICAL

1) Scleroderma has been seen after chronic exposure to these agents.

C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Abstracts

Case Reports

A)

1) Two fatal cases of acute exposure to VCM occurred in Ontario in 1958 and 1959. Exposures were in excess of 100,000 ppm, and deaths were from respiratory failure (CCOHS, 1988).

Range Of Toxicity

Summary

A)

Minimum Lethal Exposure

A)

1) Exposure to more than 120,000 ppm may be fatal in humans (ILO, 1983).
2) Two vinyl chloride workers died by asphyxiation due to breathing very high levels; concentration levels were not reported (ATSDR, 1997; Baselt, 2000a).

B)

1) In animal studies, brief exposure to 100,000 to 400,000 ppm was fatal in rats (ATSDR, 1997).

Maximum Tolerated Exposure

A)

1) ROUTE OF EXPOSURE

a) Because vinyl chloride is a gas, the most typical route of exposure is inhalation. Occupational exposure to vinyl chloride has been associated with an increased incidence of angiosarcoma of the liver and other malignant tumors, acro-osteolysis, Raynaud syndrome, scleroderma, thrombocytopenia, circulatory disturbances and impaired liver function; very high concentrations cause central nervous system depression. It appears that metabolism of vinyl chloride is necessary before many of its toxic effects occur (Bingham et al, 2001a; Hathaway et al, 1996).
b) "The main route of occupational exposure is via inhalation, and occurs primarily in vinyl chloride or polyvinyl chloride plants" (IPCS, 1999b).
c) Inhalation studies in male human volunteers indicate that absorption was rapid; approximately 42 percent was absorbed. The percentage of VCM retained was independent of its concentration in inspired air (Zenz, 1994).
d) Absorption is rapid by oral exposure (Zenz, 1994).
e) Skin absorption is possible (Sittig, 1991).

2) CONCENTRATION LEVEL

a) Occupational exposure to vinyl chloride amounted to several thousands of mg/m(3) in the 1940s and 1950s, several hundreds of mg/m(3) in the 1960s and early 1970s, and 13 to 26 mg/m(3) in most countries in the late 1970s (IPCS, 1999b).
b) The reported effects of vinyl chloride have largely been due to the high exposure of workers prior to 1974 (IPCS, 1999a).
c) Early inhalational experiments on human subjects found vinyl chloride to cause CNS depression at 7% to 10% and to cause dangerous arrhythmias at 12 percent (Oster et al, 1947).
d) Humans exposed to 4000 ppm for 5 minutes reported no effects; 8000 ppm for 5 minutes reported some dizziness; and 20,000 ppm for 5 minutes reported dizziness, light-headedness, nausea, and dulling of vision and auditory cues (Hathaway et al, 1996).
e) One 3-minute inhalation exposure at 25,000 ppm was reported to cause confusion, headache, and dizziness (ACGIH, 1992).

B)

1) CASE SERIES/FIRST RESPONDERS: In 2012, a survey was conducted by the New Jersey Department of Health with the assistance of the CDC and ATSDR to assess the health effects associated with acute exposure of vinyl chloride by emergency responders (n=93) following a release from a train derailment. Of the self-reported symptoms, headache (26%) was a common adverse event. Upper respiratory symptoms (26%) (eg, runny nose, burning nose or throat and hoarseness) and lower respiratory symptoms (22%) (eg, shortness of breath, chest tightness, wheezing, and burning of chest) were also frequently reported. Other clinical events included coughing (15%), neurologic (14%) (ie, dizziness, weakness, and loss of balance), nausea and/or vomiting (14%), increased congestion (11%) and irritation, pain, or burning of the eyes (11%). Twenty-three percent of responders reported that they did not wear any type of personal protective equipment. Of note, air monitoring was not conducted following the release (Brinker et al, 2015).

C)

1) Reportedly, workers exposed to chronic low concentrations of vinyl chloride showed degenerative bone changes, circulatory disturbances, thrombocytopenia, splenomegaly, hepatomegaly, hepatic fibrosis, and angiosarcoma of the liver (Baselt, 2000a).
2) Vinyl chloride disease has been reported when workers were exposed to several hundred parts per million for periods ranging from months to years. The effects are: enhanced collagen deposition and thickening of the subepidermal layer of the skin; Raynaud's phenomenon (arteriole constriction causing whitening of the fingers and numbness); and, in some cases, acro-osteolysis (resorption of the terminal phalanges) (Hathaway et al, 1996).

a) No new cases of vinyl chloride disease have been reported in the US since 1974, when occupational exposure levels were reduced (Hathaway et al, 1996).
b) Occupational exposure to vinyl chloride has also been associated with an increased incidence of scleroderma and impaired liver function; very high concentrations can cause central nervous system (CNS) depression (Clayton & Clayton, 1994; Hathaway et al, 1996).

3) Vinyl chloride together with carbon disulfide have been associated with loss of libido and diminished potency in occupationally exposed man. Women 41 to 50 years of age employed in polyvinyl chloride and acrylic glass manufacturing for 21 years or longer showed exposure-associated declines in sexual function without increase in miscarriages or abortions. Higher incidence of preeclampsia in pregnant workers have also been reported (Harbison, 1998).

Workplace Standards

A)

1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.

a) Adopted Value

1) Vinyl chloride

a) TLV:

1) TLV-TWA: 1 ppm
2) TLV-STEL:
3) TLV-Ceiling:

b) Notations and Endnotes:

1) Carcinogenicity Category: A1
2) Codes: Not Listed
3) Definitions:

a) A1: Confirmed Human Carcinogen: The agent is carcinogenic to humans based on the weight of evidence from epidemiologic studies.

c) TLV Basis - Critical Effect(s): Lung cancer; liver dam
d) Molecular Weight: 62.5

1) For gases and vapors, to convert the TLV from ppm to mg/m(3):

a) [(TLV in ppm)(gram molecular weight of substance)]/24.45

2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:

a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance

e) Additional information:

B) NIOSH REL and IDLH Values for CAS75-01-4 (National Institute for Occupational Safety and Health, 2007):

1) Listed as: Vinyl chloride
2) REL:

a) TWA:
b) STEL:
c) Ceiling:
d) Carcinogen Listing: (Ca) NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).
e) Skin Designation: Not Listed
f) Note(s): See Appendix A

3) IDLH: Not Listed

C) Carcinogenicity Ratings for CAS75-01-4 :

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A1 ; Listed as: Vinyl chloride

a) A1 :Confirmed Human Carcinogen: The agent is carcinogenic to humans based on the weight of evidence from epidemiologic studies.

2) EPA (U.S. Environmental Protection Agency, 2011): A ; Listed as: Vinyl chloride

a) A : Human Carcinogen.

3) EPA (U.S. Environmental Protection Agency, 2011): A ; Listed as: Vinyl chloride

a) A : Human Carcinogen.

4) EPA (U.S. Environmental Protection Agency, 2011): A ; Listed as: Vinyl chloride

a) A : Human Carcinogen.

5) EPA (U.S. Environmental Protection Agency, 2011): A ; Listed as: Vinyl chloride

a) A : Human Carcinogen.

6) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 1 ; Listed as: Vinyl chloride

a) 1 : The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. This category is used when there is sufficient evidence of carcinogenicity in humans. Exceptionally, an agent (mixture) may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent (mixture) acts through a relevant mechanism of carcinogenicity.

7) NIOSH (National Institute for Occupational Safety and Health, 2007): Ca ; Listed as: Vinyl chloride

a) Ca : NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).

8) MAK (DFG, 2002): Category 1 ; Listed as: Vinyl chloride

a) Category 1 : Substances that cause cancer in man and can be assumed to make a significant contribution to cancer risk. Epidemiological studies provide adequate evidence of a positive correlation between the exposure of humans and the occurence of cancer. Limited epidemiological data can be substantiated by evidence that the substance causes cancer by a mode of action that is relevant to man.

9) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

D) OSHA PEL Values for CAS75-01-4 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) Listed as: Vinyl chloride; see 29 CFR 1910.1017
2) Table Z-1 for Vinyl chloride; see 29 CFR 1910.1017:

a) 8-hour TWA:

1) ppm:

a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.

2) mg/m3:

a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.

3) Ceiling Value:
4) Skin Designation: No
5) Notation(s): Not Listed

Toxicity Information

7.7.1)

A) Budavari, 2000 IPCS, 1999b NTP, 1997; OHM/TADS, 2001; RTECS, 2001

1) LD50- (ORAL)RAT:

a) 500 mg/kg

2) TCLo- (INHALATION)HUMAN:

a) Male, 30 mg/m(3) at 5Y prior to mating -- affected spermatogenesis
b) Male, 200 ppm for 14Y- intermittent -- caused tumors
c) 20 ppm (OHM/TADS, 2001)
d) 500 ppm for 4Y-Intermittent -- carcinogenic effects (NTP, 1997)

3) TCLo- (INHALATION)MOUSE:

a) Male, 30,000 ppm for 6H at 5D prior to mating -- caused pre-implantation mortality
b) Female, 500 ppm for 7H at 6-15D of pregnancy -- caused fetotoxicity and developmental abnormalities
c) 50 ppm for 30W-intermittent -- caused tumors

4) TCLo- (INHALATION)RAT:

a) 28,000 ppm for 7H/6W- intermittent -- affected weight gain, transferases, and hepatic microsomal mixed oxidase
b) Female, 10,000 ppm for 4H at 12-18D of pregnancy -- caused tumors
c) 5000 ppm for 7H/52W-intermittent -- affected liver weight, spleen weight, and bladder weight
d) 2000 ppm for 8H/92D-intermittent -- affected liver weight, spleen weight, and leukocyte count
e) 50 ppm for 52W-Intermittent (NTP, 1997)
f) Female, 1500 ppm for 24H at 1-9D of pregnancy -- caused post implantation mortality
g) Female, 500 ppm for 7H at 6-15D of pregnancy -- caused fetotoxicity and developmental abnormalities
h) Female, 250 ppm for 6H at 55D prior to mating -- affected female fertility index
i) Male, 100 ppm for 6H at 26W prior to mating -- affected testes, epididymis, and sperm duct
j) 1 ppm for 4H/52W-intermittent -- caused tumors
k) 400 mg/m(3) for 24H/14W -continuous -- affected muscle spasticity, serum composition, and liver weight

5) TCLo- (INTRAPERITONEAL)RAT:

a) 21 mg/kg for 65W-Intermittent (NTP, 1997)

Pharmacology Toxicology

Toxicologic Mechanism

A)

B)

C)

Physicochemical

Physical Characteristics

A)

1) If high temperature is expected at atmospheric pressure, 40-100 ppm of phenol is used as inhibitor of polymerization. It can polymerize in the presence of air sunlight, or heat (CHRIS , 2001).

B)

Molecular Weight

A)

Other

A)

1) "The actual vapor concentrations that can be detected have never been adequately determined and vary from one individual to another, in impurities in the sample, and probably in duration of exposure" (Bingham et al, 2001a).
2) "Although vinyl chloride has a faintly sweet odor at high concentrations, the odor is of no value in preventing excessive exposure" (Bingham et al, 2001a).
3) 3.4 ppm in water (ATSDR, 1993; Sittig, 1991)
4) 260 ppm in air (CHRIS , 2001; Sittig, 1991)
5) 3000 ppm in air (ATSDR, 1997; Sittig, 1991)
6) 4000 ppm in air (Sittig, 1991)

Animal Toxicology

References

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VINYL CHLORIDE

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

Hepatic

Genitourinary

Hematologic

Dermatologic

Immunologic

Reproductive

Carcinogenicity

Genotoxicity

Musculoskeletal

Monitoring Parameters Levels

Radiographic Studies

Methods

Life Support

Monitoring

Oral Exposure

Inhalation Exposure

Eye Exposure

Dermal Exposure

Case Reports

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Workplace Standards

Toxicity Information

Toxicologic Mechanism

Physical Characteristics

Molecular Weight

Other

General Bibliography