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VINYL TOLUENE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Vinyl toluene is an aromatic hydrocarbon.

Specific Substances

    A) No Synonyms were found in group or single elements
    1.2.1) MOLECULAR FORMULA
    1) C9-H10

Available Forms Sources

    A) USES
    1) Vinyl toluene's commercial use is primarily as a monomer in the plastics and surface-coating industries and as a component in the production of insecticides (ACGIH, 1991).
    2) It is used as a solvent and as a chemical intermediate (Lewis, 1993).
    3) Vinyl toluene is used in resin production and as a block-packaging component for radioactive waste (Clayton & Clayton, 1994).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Commercial vinyl toluene, also called METHYL STYRENE, is usually a mixture of the meta- and para- isomers in approximately a 60:40 ratio, but often the toxicological literature does not distinguish between the various possible forms. Ratios are identified here where deemed appropriate.
    B) Vinyl toluene is an irritant of the eyes and mucous membranes. At high concentrations, it causes narcosis in animals and it is expected that severe exposure will produce the same effect in humans.
    1) Human subjects exposed to 200 ppm detected a strong odor, but did not experience excessive discomfort. Exposure at 400 ppm produced strong eye and nasal irritation.
    C) Vinyl toluene has been shown in laboratory experiments to be a teratogen. In experimental situations it has exhibited reproductive effects. Experiments have shown mutations.
    D) According to the 1983 National Occupational Exposure Survey, as many as 25,353 employees in 2,028 plants are potentially exposed to vinyl toluene in the US.
    E) The toxicologic properties of vinyl toluene appear to be similar to those of styrene. The following clinical effects information is for STYRENE, although NOT ALL OF THESE have been noted in patients with vinyl toluene exposure:
    1) Styrene is irritating to eyes, mucous membranes of the respiratory and gastrointestinal tracts, and skin. Central nervous system depression may occur.
    a) Peripheral neuropathies have been reported following some, but not all styrene exposures. "Styrene sickness" with nausea, vomiting, appetite loss, and a sensation of drunkenness is common in exposed workers. Permanent neuropsychological abnormalities have been observed in chronically-exposed styrene workers.
    b) A variety of subclinical effects of questionable clinical significance on liver and renal functions, various blood components, and hormone levels have been reported. Changes in psychoneurological functioning have been described in chronically exposed workers. Styrene is questionably mutagenic and teratogenic.
    0.2.4) HEENT
    A) Vapors are irritating to the eyes and nose at 400 ppm.
    0.2.6) RESPIRATORY
    A) Respiratory irritant; potential for chemical pneumonitis by aspiration.
    0.2.7) NEUROLOGIC
    A) Vinyl toluene causes narcosis similar to styrene. Subchronic inhalation exposure caused reduced sensory and motor nerve conduction velocity and evoked motor action potential in rats, but this has not been shown to occur in humans following vinyl toluene exposure.
    0.2.14) DERMATOLOGIC
    A) Vinyl toluene is a skin irritant.
    0.2.20) REPRODUCTIVE
    A) In a study of women exposed to chemicals in the petrochemical production industry, methyl styrene was identified as a possible cause of disturbance in reproductive function and teratogenic effects. Evidence was found at concentrations not exceeding allowable levels (Ogleznev & Demchenko, 1993).
    B) ANIMAL STUDIES - Reported to be teratogenic in guinea pigs and fetotoxic in rats.
    0.2.21) CARCINOGENICITY
    A) No studies were found on possible carcinogenicity of vinyl toluene in humans.
    0.2.22) OTHER
    A) The main route of exposure is by inhalation.

Laboratory Monitoring

    A) Patients with acute exposure should have baseline liver and renal function tests, urinalysis, complete blood count, and amylase and lipase levels. Assess pulmonary function and respiratory gas exchange and chest x-ray if significant respiratory tract irritation occurs.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Avoid induced emesis.
    B) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting.
    C) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) Administer 100% humidified oxygen and airway protection as required.
    C) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    D) Neuropsychiatric examination may be helpful in significant or chronic exposures.
    0.4.4) EYE EXPOSURE
    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) DERMAL EXPOSURE
    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).
    2) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.

Range Of Toxicity

    A) Odor may be tolerable up to 200 ppm, objectionable at 300 ppm, and irritating at 400 ppm.

Clinical Effects

Summary Of Exposure

    A) Commercial vinyl toluene, also called METHYL STYRENE, is usually a mixture of the meta- and para- isomers in approximately a 60:40 ratio, but often the toxicological literature does not distinguish between the various possible forms. Ratios are identified here where deemed appropriate.
    B) Vinyl toluene is an irritant of the eyes and mucous membranes. At high concentrations, it causes narcosis in animals and it is expected that severe exposure will produce the same effect in humans.
    1) Human subjects exposed to 200 ppm detected a strong odor, but did not experience excessive discomfort. Exposure at 400 ppm produced strong eye and nasal irritation.
    C) Vinyl toluene has been shown in laboratory experiments to be a teratogen. In experimental situations it has exhibited reproductive effects. Experiments have shown mutations.
    D) According to the 1983 National Occupational Exposure Survey, as many as 25,353 employees in 2,028 plants are potentially exposed to vinyl toluene in the US.
    E) The toxicologic properties of vinyl toluene appear to be similar to those of styrene. The following clinical effects information is for STYRENE, although NOT ALL OF THESE have been noted in patients with vinyl toluene exposure:
    1) Styrene is irritating to eyes, mucous membranes of the respiratory and gastrointestinal tracts, and skin. Central nervous system depression may occur.
    a) Peripheral neuropathies have been reported following some, but not all styrene exposures. "Styrene sickness" with nausea, vomiting, appetite loss, and a sensation of drunkenness is common in exposed workers. Permanent neuropsychological abnormalities have been observed in chronically-exposed styrene workers.
    b) A variety of subclinical effects of questionable clinical significance on liver and renal functions, various blood components, and hormone levels have been reported. Changes in psychoneurological functioning have been described in chronically exposed workers. Styrene is questionably mutagenic and teratogenic.

Heent

    3.4.1) SUMMARY
    A) Vapors are irritating to the eyes and nose at 400 ppm.
    3.4.3) EYES
    A) IRRITATION - Vinyl toluene vapors caused eye irritation in humans at 400 ppm (Hathaway et al, 1991; ACGIH, 1991).
    1) It was a mild eye irritant in rabbits at a dose of 90 mg using the standard Draize test; no corneal injury was evident (Hathaway et al, 1991; Grant, 1986; RTECS , 1995)
    3.4.5) NOSE
    A) IRRITATION - Vapors are irritating to the mucous membranes at 400 ppm (HSDB, 1995).
    B) METAPLASIA - Non-neoplastic proliferation of the nasal mucosa occurred in rats exposed to 100 or 300 ppm and in mice exposed to 10 or 25 ppm for 2 years (ACGIH, 1991).

Respiratory

    3.6.1) SUMMARY
    A) Respiratory irritant; potential for chemical pneumonitis by aspiration.
    3.6.2) CLINICAL EFFECTS
    A) IRRITATION SYMPTOM
    1) Vinyl toluene caused respiratory irritation in humans at 400 ppm (ACGIH, 1991).
    B) PNEUMONITIS
    1) Although no cases have been reported, ingested vinyl toluene has the potential to cause chemical pneumonitis from aspiration into the lungs.
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) Pulmonary edema has been seen in mice exposed to vinyl toluene for 4 hours in an LD50 study (RTECS , 1995).
    2) RESPIRATORY DISORDER
    a) DYSPLASIA of the bronchial epithelial lining and lymphoid hyperplasia of the lung were seen in rats exposed to 1300 ppm for 6 hours per day for 10 intermittent days (HSDB, 1995).
    b) PULMONARY INFLAMMATION - Mice exposed to 160 ppm for 6 hours/day, 5 days/week for 13 weeks showed pulmonary inflammation (ACGIH, 1991).
    c) Chronic inflammation of the bronchioles was seen in mice exposed to 10 or 25 ppm for 6 hours/day, 5 days/week for 102 weeks (ACGIH, 1991).

Neurologic

    3.7.1) SUMMARY
    A) Vinyl toluene causes narcosis similar to styrene. Subchronic inhalation exposure caused reduced sensory and motor nerve conduction velocity and evoked motor action potential in rats, but this has not been shown to occur in humans following vinyl toluene exposure.
    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) Vinyl toluene can cause drowsiness (Sittig, 1985). The anesthetic effects are similar to those of styrene (Clayton & Clayton, 1994).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) Vinyl toluene causes narcosis in mice, rats, rabbits and guinea pigs exposed by the oral, inhalation, and dermal routes (HSDB, 1995; (Hathaway et al, 1991).
    2) NEUROPATHY
    a) NERVE CONDUCTION VELOCITY - Rats exposed to 100 to 300 ppm, 6 hours/day, 5 days/week for up to 15 weeks showed reduced sensory and motor nerve conduction velocity characteristic of axonal degeneration. The NOAEL was 50 ppm (Seppalainen & Savolainen, 1982a).
    1) Rats also showed decreased amplitude of evoked motor action potentials (Seppalainen & Savolainen, 1982b).
    2) No effects were seen from exposures for less than 12 weeks (Seppalainen & Savolainen, 1982).
    b) In another study, decreased motor and sensory nerve conduction velocities were seen in rats exposed to 300 ppm for 6 hours/day, 5 days/week for up to 21 weeks. Magnitude of effects was related to duration of exposure. No effects were seen at 100 ppm (Gagnaire et al, 1986).
    1) No overt signs of neurotoxicity were seen in rats exposed to 300 ppm (Gagnaire et al, 1986).
    c) In a 2-year inhalation study, there was no evidence of neurotoxicity in mice or rats exposed to vinyl toluene at concentrations up to 300 ppm (ACGIH, 1991).
    d) CONCLUSION - Vinyl toluene appears to be a weak peripheral neurotoxin in rats; to date, similar effects have not been reported in exposed humans.

Hepatic

    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) Hepatocellular necrosis was produced in mice with inhalation exposure to 200 ppm, 6 hours per day for 15 days (RTECS , 1995).
    2) LIVER FATTY
    a) Rats, guinea pigs, rabbits, and monkeys showed increased hepatic weight and fatty degeneration of the liver when exposed to 1250 ppm for 92 to 100 7- to 8-hour exposures (ACGIH, 1991).

Genitourinary

    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) FATTY DEGENERATION - Rats, guinea pigs, rabbits, and monkeys exposed to 1250 ppm in 92 to 100 7- to 8-hour exposures had increased kidney weights; NOAEL was 600 ppm (ACGIH, 1991) HSDB, 1995).
    2) NEPHROPATHY TOXIC
    a) Nephropathy was evident in male, but not female, rats exposed to 160 to 1000 ppm for 6 hours/day, 5 days/week for 13 weeks (ACGIH, 1991).

Dermatologic

    3.14.1) SUMMARY
    A) Vinyl toluene is a skin irritant.
    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) Vinyl toluene is a skin irritant (Sittig, 1985) HSDB, 1995).
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) Erythema, edema, and superficial necrosis were produced at the site of application on rabbit skin (Hathaway et al, 1991). Vinyl toluene is a moderate skin irritant in rabbits using the standard Draize test (RTECS , 1995).
    2) DERMATITIS
    a) Although it has been reported to elicit a positive patch test in an individual known to be sensitized to styrene, vinyl toluene was inactive in a guinea pig maximization test (Sjoberg et al, 1982).

Immunologic

    3.19.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) Although it has been reported to elicit a positive patch test in an individual known to be sensitized to styrene, vinyl toluene was inactive in a guinea pig maximization test (Sjoborg et al, 1982).

Reproductive

    3.20.1) SUMMARY
    A) In a study of women exposed to chemicals in the petrochemical production industry, methyl styrene was identified as a possible cause of disturbance in reproductive function and teratogenic effects. Evidence was found at concentrations not exceeding allowable levels (Ogleznev & Demchenko, 1993).
    B) ANIMAL STUDIES - Reported to be teratogenic in guinea pigs and fetotoxic in rats.
    3.20.2) TERATOGENICITY
    A) OCCUPATIONAL EXPOSURE
    1) In a study of women exposed to chemicals in the petrochemical production industry, methyl styrene was identified as a possible cause of disturbance in reproductive function and teratogenic effects. Evidence was found at concentrations not exceeding allowable levels (Ogleznev & Demchenko, 1993).
    B) ANIMAL STUDIES
    1) CONGENITAL ANOMALY
    a) Teratogenic in guinea pigs at a dose of 6 ppm for 4 months or 6200 ppm for 1 month (ACGIH, 1991) HSDB, 1995).
    2) LACK OF EFFECT
    a) Not teratogenic in rats (Schardein, 1993).
    3.20.3) EFFECTS IN PREGNANCY
    A) ANIMAL STUDIES
    1) FETOTOXICITY
    a) Fetotoxicity and increases in post-implantation mortality were seen in rats when given IP at a total dose of 3750 mg/kg on days 1 to 15 of gestation (ACGIH, 1991; RTECS , 1995).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS25013-15-4 (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 toluene
    b) Carcinogen Rating: 3
    1) The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    3.21.2) SUMMARY/HUMAN
    A) No studies were found on possible carcinogenicity of vinyl toluene in humans.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) No studies were found on possible carcinogenicity of vinyl toluene in humans.
    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) No evidence of carcinogenicity was seen in rats exposed to 100 or 300 ppm, or in mice exposed to 10 or 25 ppm for 6 hours/day, 5 days/week for 103 weeks (Boorman G, 1990; ACGIH, 1991).
    2) Rats and mice were given para- vinyl toluene (97 percent para- isomer, 3 percent meta- isomer) by gavage at doses up to 500 mg/kg for 104 weeks for rats and 250 mg/kg for 78 weeks in mice. No evidence of carcinogenicity was seen (Conti et al, 1988).

Genotoxicity

    A) Vinyl toluene has been active for inducing mutations, chromosome aberrations, and sister chromatid exchanges in mammalian cells. The genetically active form(s) is (are) presumably the analogous styrene oxide metabolite(s). Negative results have also been seen, presumably due to lack of formation or stability of the active intermediate(s).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Patients with acute exposure should have baseline liver and renal function tests, urinalysis, complete blood count, and amylase and lipase levels. Assess pulmonary function and respiratory gas exchange and chest x-ray if significant respiratory tract irritation occurs.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Blood levels of vinyl toluene and/or metabolites might be useful only to confirm exposure and diagnosis.
    2) Monitor liver and renal function tests and amylase and lipase levels in patients with significant acute exposure.
    B) ACID/BASE
    1) Patients with significant respiratory tract irritation should have pulmonary function and gas exchange assessed.
    C) HEMATOLOGIC
    1) Monitor complete blood count in significant exposures.
    4.1.3) URINE
    A) URINALYSIS
    1) Monitor urinalysis in significant exposures.
    B) URINARY LEVELS
    1) Quantitation of urinary metabolites may be a useful indicator of exposure, as for styrene, but this has not been validated for vinyl toluene in human studies.
    4.1.4) OTHER
    A) OTHER
    1) PULMONARY FUNCTION TESTS
    a) If respiratory tract irritation is present, it may be useful to monitor pulmonary function tests.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) If respiratory tract irritation is present, monitor chest x-ray.

Methods

    A) CHROMATOGRAPHY
    1) Vinyl toluene was determined in breathing zone air samples using gas chromatography after collection on charcoal tubes and desorption with carbon disulfide (Samimi & Falbo, 1982).
    2) Urinary metabolites were extracted in ethyl acetate after acidification and converted to the methoxyamine-hydrochlorides or methyl esters for separation using gas chromatography (Bergemalm-Rynell & Steen, 1982).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Symptomatic patients should probably be admitted to the hospital until all symptoms are improving.
    6.3.3) DISPOSITION/INHALATION EXPOSURE
    6.3.3.1) ADMISSION CRITERIA/INHALATION
    A) Patients with respiratory tract irritation or central nervous system depression should be admitted until all symptomatology is improving.
    6.3.5) DISPOSITION/DERMAL EXPOSURE
    6.3.5.1) ADMISSION CRITERIA/DERMAL
    A) Symptomatic patients should be carefully assessed for the presence of other manifestations of toxicity. Patients with systemic abnormalities or severe dermal abnormalities should be admitted for further care until all symptomatology is improving. Patients with isolated dermal abnormalities should be followed carefully, but may not need inpatient care, depending on the severity and extent of their dermal findings.

Monitoring

    A) Patients with acute exposure should have baseline liver and renal function tests, urinalysis, complete blood count, and amylase and lipase levels. Assess pulmonary function and respiratory gas exchange and chest x-ray if significant respiratory tract irritation occurs.

Oral Exposure

    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) Induction of emesis is not recommended because of the potential for CNS depression and esophageal irritation.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) DILUTION
    1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    B) IRRITATION SYMPTOM
    1) Although not reported in humans, significant gastric and esophageal irritation could occur with ingestion of large amounts. Observe carefully for signs of serious complications such as perforation, bleeding, or mediastinitis.
    2) If signs of serious esophageal irritation are present, endoscopy may be considered for evaluation and monitoring. Possible late sequelae of serious esophageal irritation could be stricture formation, requiring consultation and evaluation.
    C) MONITORING OF PATIENT
    1) Monitor EKG, liver and renal function tests, urinalysis, complete blood count, and amylase and lipase in serious ingestions.
    D) AIRWAY MANAGEMENT
    1) If central nervous system depression occurs, airway patency and oxygenation must be carefully evaluated and airway protective measures including endotracheal intubation undertaken if indicated.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    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) TREATMENT
    A) OXYGEN
    1) Administer 100% humidified supplemental oxygen with assisted ventilation as required.
    B) AIRWAY MANAGEMENT
    1) If central nervous system depression occurs, airway patency and oxygenation must be carefully evaluated and airway protective measures including endotracheal intubation undertaken if indicated.
    C) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    D) NEUROLOGICAL EXAMINATION
    1) NEUROPSYCHIATRIC EXAMINATION - Neuropsychiatric testing may be useful as a measurement of psycho-organic impairment in patients with significant (especially chronic) exposure.
    E) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    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) TREATMENT
    A) GENERAL TREATMENT
    1) A thorough ophthalmic examination including funduscopy should be done in any patient with complaints involving the eyes.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

    6.9.1) DECONTAMINATION
    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) TREATMENT
    A) IRRITATION SYMPTOM
    1) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) EFFICACY
    1) No studies have addressed the use of extracorporeal elimination procedures in vinyl toluene poisoning.

Range Of Toxicity

Summary

    A) Odor may be tolerable up to 200 ppm, objectionable at 300 ppm, and irritating at 400 ppm.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.
    B) ANIMAL DATA
    1) Exposure of rats and guinea pigs to 1350 ppm for 7 hours/day for 100 days caused the death of some of the rats and slight liver damage in guinea pigs. There were no effects in female monkeys at this concentration (Hathaway et al, 1991).

Maximum Tolerated Exposure

    A) ACUTE
    1) The lowest published toxic concentration for a human (inhalation route) is 400 ppm (RTECS , 1995).
    2) Human subjects noted ocular and upper respiratory tract irritation at a 400 ppm vinyl toluene concentration; strong, objectionable odor at 300 ppm; and strong, tolerable odor at 200 ppm. At 50 ppm, the odor was detectable, but there was no irritation of mucous membranes. The odor was reported to be undetectable at less than 10 ppm (ACGIH, 1991).
    3) Another study concluded that the disagreeable odor became irritating at 50 ppm (ACGIH, 1991).
    B) CONCENTRATION LEVEL
    1) One investigator determined that adverse effects would not be expected in healthy workers exposed at concentrations of vinyl toluene not exceeding 100 ppm (ACGIH, 1991).
    C) ANIMAL DATA
    1) Exposure to 580 ppm is well tolerated by most laboratory animals (Clayton & Clayton, 1994).
    2) Exposure of guinea pigs to 1350 ppm for 7 hours/day for 100 days caused slight liver damage. There were no effects in female monkeys at this concentration (Hathaway et al, 1991).
    3) Rats tolerated exposure to 300 ppm for 60 hours without clinical symptoms, although they appeared relatively inactive (Hathaway et al, 1991).
    a) At this concentration, vinyl toluene was found to accumulate in perirenal fat and was more effective than styrene, xylene, or toluene in producing neurochemical effects as determined by enzyme assays.
    4) The liquid dropped in the eyes of rabbits caused slight conjunctival irritation (Hathaway et al, 1991).
    5) Applied to rabbit skin, vinyl toluene produced erythema with the development of edema and superficial necrosis (Hathaway et al, 1991).
    6) In two-year toxicology and carcinogenesis studies, there was no evidence of carcinogenic activity for male or female rats exposed to 100 or 300 ppm by inhalation (6 hours/day, 5 days/week for 103 weeks), and no evidence of carcinogenic activity for male or female mice exposed to 10 or 25 ppm on the same schedule (Boorman G, 1990).

Workplace Standards

    A) ACGIH TLV Values for CAS25013-15-4 (American Conference of Governmental Industrial Hygienists, 2010):
    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 toluene
    a) TLV:
    1) TLV-TWA: 50 ppm
    2) TLV-STEL: 100 ppm
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A4
    2) Codes: Not Listed
    3) Definitions:
    a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    c) TLV Basis - Critical Effect(s): URT and eye irr
    d) Molecular Weight: 118.18
    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 CAS25013-15-4 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Vinyl toluene
    2) REL:
    a) TWA: 100 ppm (480 mg/m(3))
    b) STEL:
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s):
    3) IDLH:
    a) IDLH: 400 ppm
    b) Note(s): Not Listed

    C) Carcinogenicity Ratings for CAS25013-15-4 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Vinyl toluene
    a) A4 :Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) 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): 3 ; Listed as: Vinyl toluene
    a) 3 : The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Vinyl toluene
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS25013-15-4 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Vinyl toluene
    2) Table Z-1 for Vinyl toluene:
    a) 8-hour TWA:
    1) ppm: 100
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 480
    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) TOXICITY VALUES
    A) LD50- (ORAL)MOUSE:
    1) 3.16 g/kg (Clayton & Clayton, 1994; RTECS, 1995)
    B) LD50- (INTRAPERITONEAL)RAT:
    1) 2324 mg/kg (RTECS, 1995)
    C) LD50- (ORAL)RAT:
    1) 2255 mg/kg (RTECS, 1995)
    2) 4 g/kg (ACGIH, 1991)
    3) 4.0-5.7 g/kg (Clayton & Clayton, 1994)
    D) TCLo- (INHALATION)HUMAN:
    1) 400 ppm (RTECS, 1995)

Pharmacology Toxicology

Toxicologic Mechanism

    A) Vinyl toluene is apparently converted to styrene oxide intermediates by cytochrome P-450 (Heinonen, 1984).

Physicochemical

Physical Characteristics

    A) Vinyl toluene is a colorless liquid with what has been described as an aromatic, strong, or disagreeable odor (AAR, 1992; ACGIH, 1991; Lewis, 1993).
    B) No information on the taste of vinyl toluene was found at the time of this review.
    C) It occurs commercially as a mixture primarily of the meta- (50% to 70%) and para- (30% to 45%) isomers (ACGIH, 1991).
    D) Vinyl toluene is produced by the dehydrogenation of meta- and para-ethyl toluene or by catalytic reforming (ACGIH, 1991).

Ph

    1) No information found at the time of this review.

Molecular Weight

    A) 118.19 (RTECS , 1995)

References

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