Absorption, Distribution and Excretion
Vinyl chloride dissolved in either oil or water when administered to rats by gavage, was absorbed extremely rapidly. Peak blood serum concentrations of vinyl chloride were observed within 10 minutes of dosing.
Pulmonary absorption of vinyl chloride in humans appeared to be rapid and the percentage absorbed was independent of the concentration inhaled. ... Adult male volunteers exposed for 6 hr to 2.9, 5.8, 11.6 or 23.1 ppm (7.5, 15, 30 or 60 mg/cu m) by gas mask retained on average approximately 42% of inhaled vinyl chloride. Pulmonary uptake is determined in part by the blood:air partition coefficient, which is 1.16 for vinyl chloride.
Animal data have demonstrated that pulmonary and gastrointestinal absorption of vinyl chloride occurs readily and rapidly. On the contrary, dermal absorption of airborne vinyl chloride is probably not significant. In monkeys, ... only 0.023-0.031% of the total available vinyl chloride was absorbed by the dermal route, whereas absorption in rats was virtually complete following single oral doses (44-92 mg/kg bw) of vinyl chloride in aqueous solution. When rats were exposed to initial concentrations of < 260 mg/cu m (100 ppm), about 40% of inhaled (14)C-vinyl chloride was absorbed by the lung.
The main routes of elimination of vinyl chloride and its metabolites are exhalation and urinary excretion, respectively. Accordingly, thiodiglycolic acid has been reported to be the major metabolite of vinyl chloride detected in the urine of exposed workers. Urinary levels of thiodiglycolic acid were correlated with levels of vinyl chloride in the air at concentrations of > 5 ppm.
For more Absorption, Distribution and Excretion (Complete) data for Vinyl chloride (18 total), please visit the HSDB record page.

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Metabolism / Metabolites
Vinyl chloride is primarily and rapidly metabolized in the liver, and this metabolism is saturable. ...The first step in the metabolism of vinyl chloride is oxidation, which is predominantly mediated by human cytochrome P450 (CYP) 2E1, to form the highly reactive chloroethylene oxide, which can spontaneously rearrange to chloroacetaldehyde. ... Conjugation of chloroethylene oxide and chloroacetaldehyde with glutathione (GSH) eventually leads to the major urinary metabolites N-acetyl-S-(2-hydroxyethyl)cysteine and thiodiglycolic acid. Chloroethylene oxide and chloroacetaldehyde can also be detoxified to glycolaldehyde by microsomal epoxide hydrolase (mEH) and to the urinary metabolite chloroacetic acid by aldehyde dehydrogenase 2 (ALDH2), respectively.
Following oral administration of (14)C-vinyl chloride, (14)C-carbon dioxide, (14)C-labelled urea and glutamic acid were identified as minor metabolites.
After inhalation of (14)C vinyl chloride by rats ... three urinary metabolites have been detected: N-acetyl-S-(2-hydroxyethyl)cysteine, thiodiglycolic acid, and an unidentified substance.
The principal (14)C urinary metabolites of orally administered (14)C-vinyl chloride, in the male rat, are N-acetyl-S-(2 hydroxyethyl)cysteine, N-acetyl-S-vinylcysteine and thiodiglycollic acid and lesser amounts of urea, glutamic acid, chloracetic acid and traces of methione and serine. The proportions of the three major urinary metabolites in the rat appear to be unaffected by either the dose, or the route of administration.
For more Metabolism/Metabolites (Complete) data for Vinyl chloride (10 total), please visit the HSDB record page.
VINYL CHLORIDE has known human metabolites that include 2-Chlorooxirane.
Vinyl chloride absorbed primarily via inhalation or ingestion is rapidly distributed throughout the body. It is metabolized mainly in the liver by cytochrome P-450 monooxygenases, first into chloroethylene oxide, then into chloroacetaldehyde, which are the main toxic metabolites. Chloroacetaldehyde is further converted into chloroethanol and monochloroacetic acid. Detoxification occurs in conjunction with glutathione, producing mainly thiodiglycolic acid, which is excreted in the urine. At high doses vinyl chloride may also be excreted by exhalation. (L3, T5)

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Biological Half-Life
Based on limited data: fairly rapid; [TDR, p. 1224]
The pattern of pulmonary elimination of 10 and 1000 ppm vinyl chloride was described by apparently similar first-order kinetics, with half-lives of 20.4 and 22.4 minutes respectively. The half lives for the initial phase of excretion of (14)C radioactivity in urine were 4.6 and 4.1 hours, respectively.

Toxicity Summary
IDENTIFICATION AND USE: Vinyl chloride is a colorless gas or liquid (below 77 degrees F). It is used in the plastics industry to manufacture polyvinyl chloride, and in organic syntheses. It has been used as refrigerant and spray can propellant. HUMAN STUDIES: Vinyl chloride causes angiosarcoma of the liver, and hepatocellular carcinoma. Past occupational exposure to several hundred ppm of vinyl chloride for periods ranging from one month to 3 years has been associated with development of "vinyl chloride disease". Vinyl chloride disease is characterized by acroosteolysis, a condition characterized by lytic lesions of bones (primarily of fingers), scleroderma of the connective tissue in the fingers with dermal thickening, and a Raynaud-like condition with reversible arteriole constriction causing numbness, pallor and cyanosis of the fingers. The attribution of acroosteolysis to vinyl chloride exposure is based almost entirely on case reports and has been estimated to affect <3% of workers involved in the polymerization of vinyl chloride. In patients with chronic occupational exposure, neurological disturbances include sensory-motor polyneuropathy, trigeminal sensory neuropathy, slight pyramidal signs and cerebellar and extrapyramidal motor disorders. Psychiatric disturbances included neurasthenic or depressive syndromes. Sleeplessness and loss of sexual functions were frequently encountered. Pathological EEG alterations were found in a high proportion of patients. A chronic hepatic disorder of porphyrin metabolism was found in 36 workers with vinyl chloride-induced hepatic injury following long-time industrial exposure. Pathologic porphyrinuria, especially secondary coproporphyrinuria with transition to subclinical chronic hepatic porphyria, is a consistent pathobiochemical parameter for the recognition of vinyl chloride hepatic lesions. The major immunological abnormalities reported in vinyl chloride disease patients include hyperimmunoglobulinemia with a polyclonal increase in IgG, cryoglobulinemia, cryofibrinogenemia, and in vivo activation of complement. Vinyl chloride is an occupational carcinogen which caused micronuclei in human cells. There was significant increase in chromosomal abnormalities in cultured peripheral lymphocytes from 57 male workers when compared with controls. Sister chromatid exchange was the more sensitive endpoint for indicating a biological response. ANIMAL STUDIES: Brief (30 minutes) exposures to concentrations of vinyl chloride ranging from 100,000 to 400,000 ppm have been shown to be fatal in rats, guinea pigs and mice. Symptoms of intoxication in rats and mice include muscular incoordination and twitching, CNS depression and respiratory failure. Intense salivation and lacrimation have been noted in rats, guinea pigs and rabbits exposed acutely to high concentrations (375-700 mg/L) of vinyl chloride gas. When placed on skin or in eyes, liquid vinyl chloride may freeze tissue and produce a chemical burn as it evaporates, causing damage to the underlying tissue. Profound CNS depression was reported in guinea-pigs exposed to vinyl chloride at 65,000 mg/cu m for 90 min. Ataxia was observed at this dose level after 5 min of exposure. The anesthetic action of vinyl chloride was also observed in dogs and mice. Investigators reported deep CNS depression in rats and mice exposed to 260,000 mg/cu m for 30 min. The CNS depressant effect was preceded by increased motor activity after 5 min of exposure, twitching of extremities (after 10 min), ataxia (after 15 min) and tremor (after 15 min). Rats exposed to 130,000 mg/cu m for 60 min showed ataxia preceded by hyperactivity but no /CNS depressant/ effect. Forty rabbits were exposed for 4 hours/day on 5 days/week for 12 months to air containing (10,000 ppm) vinyl chloride. Between 9 and 15 months exposure, 12 skin acanthomas and 6 lung adenocarcinomas were seen. No similar tumors occurred in 20 controls after 15 months observation. Rats were exposed to 10,000 ppm vinyl chloride in air for 4 hours/day on 5 days/week for 5 weeks, starting at the age of 13 weeks (120 rats per group) or 1 day (43 and 46 rats). Animals were observed for 135 weeks. One hepatoma was reported in the older rats in newborn rats, 10 angiosarcomas and 15 hepatomas were found. No liver tumors were reported in 249 controls. Vinyl chloride was administered for 7 hr/day on days 6-18 of gestation in mice, rats, and rabbits. It was concluded that although maternal toxicity observed, vinyl chloride alone did not cause significant embryonal or fetal toxicity and was not teratogenic in any of the species at concentrations tested. Vinyl chloride produced a significant increase in the frequency of recessive lethal mutations in male Drosophila melangaster. Mutagenic activity of vinyl chloride was reported in yeast (S. pombe and S. cerevisiae) in the presence of metabolic activation. Vinyl chloride was mutagenic to S. pombe in the "host mediated" assay when mice were treated with an oral dose of 700 mg/kg of vinyl chloride. Using Salmonella tester strains, direct mutagenicity of vinyl chloride was reported at 20% (v/v) in air (200,000 ppm) in the absence of metabolic activation. Mutagenic response was increased by metabolic activation. However, 20% vinyl chloride (v/v in air) was inactive in systems employing S. typhimurium strains TA1536, TA1537 and TA1538. ECOTOXICITY STUDIES: In Daphnia magna exposure, results indicated impacts of vinyl chloride on the regulation of genes related to glutathione-S-transferase (GST), juvenile hormone esterase (JHE), and the vitelline outer layer membrane protein (VMO1).
Vinyl chloride poisoning exhibits many of the characteristics of autoimmune diseases. This is believed to be the result of a reactive vinyl chloride intermediate metabolite binding to an immunoglobulin, altering the protein and initiating an immune response. The metabolites of vinyl chloride, especially choloroethylene oxide, are mutagenic and act by covalently binding to DNA. This produces cyclic etheno-adducts, which cause base-pair transitions during transcription and DNA crosslinks. Metabolites also may cause oxidative stress and affecting tumor supressor genes, as vinyl chloride has been known to produce specific mutations in the p53 and Ki-ras genes. Vinyl chloride metabolites are also believed to exert toxic effects in the liver by covalently binding to liver proteins, resulting in cellular toxicity. (L3, A65)

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Toxicity Data
LC50 (rat) = 180,000/15m
LD50: 500 mg/kg (Oral, Rat) (T15)

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Interactions
Groups each of 25-35 bred Sprague Dawley rats were exposed to vinyl chloride (500 and 2,500 ppm) for 7 hrs daily on days 6-15 of gestation. Some of the mice in the high dose group were given ethanol (15%) in their drinking water on day 6-15 of gestation. The rats were sacrificed on day 21 of gestation and the fetuses examined for visceral and skeletal abnormalities. The dams were examined for corpora lutea, implantations and intrauterine deaths. At the highest dose levels there was significant increase in absolute and relative liver weight. The effect was more pronounced in the group also exposed to ethanol. There was no significant effect on litter size, the number of implantation sites/dam or incidence of absorption in any of the exposed animals. Fetal body weight and crown-rump length were significantly reduced in the 2,500 ppm group in combination with ethanol, but not in the 2500 ppm vinyl chloride alone group. However decreased fetal body weight was observed in rats exposed to 500 ppm vinyl chloride. Unilateral and bilateral dilated uterers were observed in litters of rats exposed to 2500 ppm vinyl chloride. No increase in the incidence of skeletal anomalies were observed in litters of rats exposed to 2500 ppm vinyl chloride. However, rats exposed to both 2500 ppm vinyl chloride and ethanol, showed a significant increase in incidence of spurs, and missing centra of the cervical vertebrae.
Groups each of 15 to 20 bred rabbits (New Zealand) were exposed to 500, or 2500 ppm vinyl chloride for 7 hrs daily on days 6-18 of gestation. Some of the rabbits in the higher dose groups were also exposed to 15% ethanol in their drinking water (days 6-18). On day 29 of gestation the pregnant rabbits were sacrificed, and the fetuses examined for visceral and skeletal abnormalities. The dams were examined for corpora lutea, implantations, and intrauterine deaths. There was no effect on maternal weight gain or liver weight or food consumption in rabbits exposed to 2500 ppm vinyl chloride alone, but those exposed to a combination of vinyl chloride and alcohol showed a significant decrease in weight gain and food consumption. Exposure to vinyl chloride alone did not cause any change in the incidence of reabsorptions, but exposure to vinyl chloride plus ethanol caused a marked increase in the number of resorption. There were no differences in fetal body weight or crown-rump length in the exposed group. Delayed ossification was observed at all dose levels.
Sprague-dawley male rats received either 5% ethanol in drinking water or drinking water only for 4 weeks prior to beginning inhalation of 600 ppm vinyl chloride for 4 hr/day on 5 days/wk for 12 mo. After 60 weeks from the first vinyl chloride exposure, liver tumors were found in 75% of the vinyl chloride-ethanol rats and in 38% of the vinyl chloride-only group.
Vinyl chloride exerts a protective effect on hepatotoxicity when admin with vinylidene chloride.
For more Interactions (Complete) data for Vinyl chloride (8 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat oral 500 mg/kg

Vinyl chloride is a colorless gas. It burns easily and it is not stable at high temperatures. It has a mild, sweet odor. It is a manufactured substance that does not occur naturally. It can be formed when other substances such as trichloroethane, trichloroethylene, and tetrachloroethylene are broken down. Vinyl chloride is used to make polyvinyl chloride (PVC). PVC is used to make a variety of plastic products, including pipes, wire and cable coatings, and packaging materials. Vinyl chloride is also known as chloroethene, chloroethylene, and ethylene monochloride.
Vinyl chloride can cause cancer according to California Labor Code.
Vinyl chloride appears as a colorless gas with a sweet odor. Easily ignited. Shipped as a liquefied gas under own vapor pressure. Contact with the unconfined liquid may cause frostbite by evaporative cooling. Leaks may be liquid or vapor. Vapors are heavier than air. May asphyxiate by the displacement of air. Under prolonged exposure to fire or intense heat the containers may rupture violently and rocket. Suspected carcinogen. Used to make plastics, adhesives, and other chemicals.
Chloroethene is a monohaloethene that is ethene in which one of the hydrogens has been replaced by a chloro group. It has a role as a carcinogenic agent. It is a member of chloroethenes, a monohaloethene and a gas molecular entity.
Vinyl Chloride is a chlorinated hydrocarbon occurring as a colorless, highly flammable gas with a mild, sweet odor that may emit toxic fumes of carbon dioxide, carbon monoxide, hydrogen chloride and phosgene when heated to decomposition. Vinyl chloride is primarily used to make polyvinyl chloride to manufacture plastics. Exposure to this substance affects the central and peripheral nervous system and causes liver damage. Prolonged exposure to vinyl chloride can cause a set of symptoms that is characterized by Raynaud's phenomenon, joint and muscle pain and scleroderma-like skin changes. Vinyl chloride is a known human carcinogen and is associated with an increased risk of developing liver cancer, predominantly angiosarcoma of the liver, but is also linked to brain and lung cancer as well as cancer of the lymphatic and hematopoietic system. (NCI05)
Vinyl chloride is a man-made organic compound, formed when other substances such as trichloroethane, trichloroethylene, and tetrachloroethylene are broken down. In its monomer form it is acutely hazardous, thus it is primarily used for the production of polymers. At room temperature it is a flammable, colorless gas with a sweet odor, but it is easily condensed and usually stored as a liquid. It is one ingredient of cigarette.(L3)
A gas that has been used as an aerosol propellant and is the starting material for polyvinyl resins. Toxicity studies have shown various adverse effects, particularly the occurrence of liver neoplasms.
See also: Poly(vinyl chloride) (related).

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Mechanism of Action
Vinyl chloride carcinogenicity occurs via a genotoxic pathway and is understood in some detail. Vinyl chloride is metabolized to a reactive metabolite, probably chloroethylene oxide, which is believed to be the ultimate carcinogenic metabolite of vinyl chloride. The reactive metabolite then binds to DNA, forming DNA adducts that, if not repaired, ultimately lead to mutations and tumor formation.
There is a large body of data showing that VC acts as a genotoxic carcinogen. After metabolic activation to CEO /chloroethylene oxide/ by CYP2E1, VC exerts various genotoxic effects (including gene mutations and chromosomal aberrations) in different organisms, including bacteria, yeasts, mammalian cells in culture, Drosophila, rodents and humans. Among the mutagenic events induced by VC, base-pair substitutions appear, so far, to be the most frequent. VC in the presence of an activation system has a transforming activity on mammalian (rodent) cells in culture. Studies in vitro have demonstrated that metabolically activated VC and its electrophilic metabolites CEO and CAA /chloroacetaldehyde/ can alkylate nucleic acid bases. 7-OEG, the major DNA adduct formed by VC and CEO does not exhibit promutagenic properties. In contrast, four minor adducts, Epsilon A, Epsilon C, N2,3-Epsilon G and 1,N2-Epsilon G, show promutagenic properties, inducing mainly base-pair substitution mutations and a low level of frameshift mutations.

(C2-H3-CL)X-

62.4987

64.008

9002-86-2

26793-37-3;25037-47-2;9002-86-2

6338

Colorless gas or liquid (below 77 degrees F) [Note: Shipped as a liquefied compressed gas]

1.4 g/mL at 25 °C(lit.)

-245 °F (NTP, 1992)
-153.84 °C
-154 °C
-256 °F
-256 °F

1.245

0

0

0

3

10.3

0

ClC([H])=C([H])[H]

BZHJMEDXRYGGRV-UHFFFAOYSA-N

InChI=1S/C2H3Cl/c1-2-3/h2H,1H2

chloroethene

Chloroethylene homopolymerise; Polyvinyl chloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)