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ETHYL BENZENE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Ethyl benzene is a substituted aromatic compound.

Specific Substances

    A) No Synonyms were found in group or single elements
    1.2.1) MOLECULAR FORMULA
    1) C8-H10

Available Forms Sources

    A) FORMS
    1) Ethylbenzene is available in the following grades of purity: "research grade: 99.98%; pure grade: 99.5%; technical grade: 99.0%" (CHRIS, 2001).
    B) SOURCES
    1) Ethylbenzene can be prepared from acetophenone; by dehydrogenation of naphthenes; by catalytic cyclization and aromatization or alkylation of benzene (using a phosphoric acid, alumina-silica, aluminum trichloride, or boron trifluoride catalyst); by the superfractionation of mixed xylene; reaction of ethylmagnesium bromide and chlorobenzene; extraction from coal oil; recovery from benzene-toluene-xylene (BTX) processing; or by reaction of ethylmagnesium bromide with chlorobenzene in the presence of dichloro(1,2-bis(diphenylphosphino)ethane nickel(II)) (Ashford, 1994a; ATSDR, 1999; Bingham et al, 2001a; HSDB, 2001; Lewis, 1993).
    2) Ethylbenzene is a natural component of soil (Dragun, 1988a).
    3) Ethylbenzene has been detected in atmospheric air, is present in the gaseous phase of cigarette smoke, and is a constituent of urban air pollution (Clayton & Clayton, 1982).
    4) INDUSTRIAL GRADE XYLENE: Industrial grade xylene contains approximately 20 percent ethylbenzene as a contaminant (ACGIH, 1991a).
    C) USES
    1) Ethylbenzene is a petrochemical used in synthetic rubber and plastic production; as a solvent and diluent; in automotive and aviation fuels; in the production of cellulose acetate; as a chemical precursor for styrene; as a resin solvent; in alkyl surface coatings; as a chemical intermediate in the production of diethylbenzene, acetophenone, ethyl anthraquinone, ethylbenzene sulfonic acids, propylene oxide, and alpha-methylbenzyl alcohol; it is also an unrecovered component of gasoline (ACGIH, 1991a; Budavari, 1996a; Bingham et al, 2001a; Hathaway et al, 1996a; HSDB, 2001).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Ethylbenzene is an eye, skin, and mucous membrane irritant.
    B) Exposure to ethylbenzene at significant concentrations may cause profuse lacrimation, conjunctivitis, nasal and respiratory tract irritation, chest constriction, vertigo, ataxia, headache, irritability, and functional nervous system disturbances. Narcosis may also occur.
    C) Chronic exposure in humans may cause fatigue, sleepiness, headache, and irritation of the eyes and respiratory tract.
    D) In experimental animals, exposure to ethylbenzene has caused eye, skin, and mucous membrane irritation; changes in liver and kidney weights; CNS depression; pulmonary edema; respiratory failure; leukocytosis; and increased platelet counts.
    0.2.4) HEENT
    A) Ethylbenzene can be an eye irritant.
    0.2.6) RESPIRATORY
    A) Ethyl benzene is a respiratory tract irritant and is a pulmonary aspiration hazard following large ingestions. In fatal cases, pulmonary edema had developed; death occurs in respiratory failure. However, human studies demonstrated no signs or symptoms of respiratory tract irritation at 85 and 100 ppm.
    0.2.7) NEUROLOGIC
    A) Ethyl benzene has CNS depressant (narcotic) properties at high concentrations.
    B) CNS symptoms may include headache, nausea, weakness, incoordination, dizziness, sleepiness, loss of coordination, judgement, and consciousness, and coma or death may occur with significant exposure. Cerebral edema may occur in fatal poisonings.
    0.2.8) GASTROINTESTINAL
    A) Ethyl benzene is a pulmonary aspiration hazard following ingestion, and is toxic with ingestion exposure. Ingestion would be predicted to cause GI tract irritation or burns.
    0.2.9) HEPATIC
    A) Slight changes in the liver occurred in rats exposed to 600 ppm for up to 16 weeks.
    0.2.10) GENITOURINARY
    A) Slight changes in the kidneys occurred in rats exposed to 600 ppm for up to 16 weeks.
    0.2.13) HEMATOLOGIC
    A) Ethyl benzene has been shown NOT to have the myelotoxic activity associated with BENZENE.
    0.2.14) DERMATOLOGIC
    A) Dermal contact causes inflammation and erythema. Ethyl benzene can be absorbed through intact skin.
    0.2.20) REPRODUCTIVE
    A) Ethyl benzene is teratogenic and fetotoxic in experimental animals, and has been detected in umbilical cord blood.

Laboratory Monitoring

    A) Urinary levels of mandelic acid can be used as an indicator of exposure to ethylbenzene.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Because of the potential for CNS depression or gastrointestinal tract irritation, Do NOT induce emesis.
    B) Weigh the potential toxicity of the amount of ethylbenzene ingested against the substantial risk of aspiration. Ethylbenzene may "wick" up around a lavage tube, allowing pulmonary aspiration.
    1) Significant esophageal or gastrointestinal tract irritation or burns may occur following ingestion. The possible benefit of early removal of some ingested material by cautious gastric lavage must be weighed against potential complications of bleeding or perforation.
    C) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    D) 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.
    E) Observe patients with ingestion carefully for the possible development of esophageal or gastrointestinal tract irritation or burns. If signs or symptoms of esophageal irritation or burns are present, consider endoscopy to determine the extent of injury.
    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) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
    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.
    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.
    3) Some chemicals can produce systemic poisoning by absorption through intact skin. Carefully observe patients with dermal exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.

Range Of Toxicity

    A) At the time of this review, the minimum lethal human dose and the maximum tolerated human exposure to this agent have not been delineated.

Clinical Effects

Summary Of Exposure

    A) Ethylbenzene is an eye, skin, and mucous membrane irritant.
    B) Exposure to ethylbenzene at significant concentrations may cause profuse lacrimation, conjunctivitis, nasal and respiratory tract irritation, chest constriction, vertigo, ataxia, headache, irritability, and functional nervous system disturbances. Narcosis may also occur.
    C) Chronic exposure in humans may cause fatigue, sleepiness, headache, and irritation of the eyes and respiratory tract.
    D) In experimental animals, exposure to ethylbenzene has caused eye, skin, and mucous membrane irritation; changes in liver and kidney weights; CNS depression; pulmonary edema; respiratory failure; leukocytosis; and increased platelet counts.

Heent

    3.4.1) SUMMARY
    A) Ethylbenzene can be an eye irritant.
    3.4.3) EYES
    A) Ethylbenzene can be an eye irritant (Clayton & Clayton, 1994; Budavari, 1996; Lewis, 1997; Lewis, 2000) Hathaway, 1996).
    3.4.5) NOSE
    A) Ethylbenzene can be a mucous membrane irritant (Budavari, 1996; Lewis, 2000) Hathaway, 1996; (Clayton & Clayton, 1994).
    3.4.6) THROAT
    A) Ethylbenzene is a mucous membrane irritant (Budavari, 1996; Lewis, 2000) Hathaway, 1996; (Clayton & Clayton, 1994).

Respiratory

    3.6.1) SUMMARY
    A) Ethyl benzene is a respiratory tract irritant and is a pulmonary aspiration hazard following large ingestions. In fatal cases, pulmonary edema had developed; death occurs in respiratory failure. However, human studies demonstrated no signs or symptoms of respiratory tract irritation at 85 and 100 ppm.
    3.6.2) CLINICAL EFFECTS
    A) IRRITATION SYMPTOM
    1) Ethylbenzene is toxic with inhalation of significant amounts, and may cause irritation of the mucous membranes (Budavari, 1996; Lewis, 1997; Lewis, 2000) Hathaway, 1996; (ACGIH, 1991; Clayton & Clayton, 1994).
    2) Human studies demonstrated no signs or symptoms of respiratory tract irritation at 85 and 100 ppm (Bardodej & Bardodejova, 1961) 1970).
    B) APNEA
    1) Death may occur through respiratory failure (Lewis, 2000).
    C) ACUTE LUNG INJURY
    1) Pulmonary edema has been seen in fatal cases (Lewis, 2000).
    D) SUFFOCATING
    1) Ethyl benzene can be a pulmonary aspiration hazard (HSDB , 2000).

Neurologic

    3.7.1) SUMMARY
    A) Ethyl benzene has CNS depressant (narcotic) properties at high concentrations.
    B) CNS symptoms may include headache, nausea, weakness, incoordination, dizziness, sleepiness, loss of coordination, judgement, and consciousness, and coma or death may occur with significant exposure. Cerebral edema may occur in fatal poisonings.
    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) Ethyl benzene has narcotic properties at high concentrations (Budavari, 1996) Hathaway, 1996).
    B) DIZZINESS
    1) Dizziness may occur at high concentrations (Lewis, 2000).
    C) CEREBRAL EDEMA
    1) Cerebral edema may be seen in fatal cases (Lewis, 2000).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) Ataxia, loss of consciousness, and tremor have been seen in experimental animals (Lewis, 2000).

Gastrointestinal

    3.8.1) SUMMARY
    A) Ethyl benzene is a pulmonary aspiration hazard following ingestion, and is toxic with ingestion exposure. Ingestion would be predicted to cause GI tract irritation or burns.
    3.8.2) CLINICAL EFFECTS
    A) INTESTINAL ABSORPTION
    1) Ethyl benzene is toxic with ingestion exposure (Lewis, 1997).
    B) GASTRITIS
    1) Based on its other irritant properties, ethyl benzene would be predicted to cause GI tract irritation or burns if ingested.

Hepatic

    3.9.1) SUMMARY
    A) Slight changes in the liver occurred in rats exposed to 600 ppm for up to 16 weeks.
    3.9.2) CLINICAL EFFECTS
    A) LIVER DAMAGE
    1) Slight changes in the liver occurred in rats exposed to 600 ppm for up to 16 weeks (Elovarra et al, 1985; (pp 29-31; Clayton & Clayton, 1994; ACGIH, 1991). This effect has not been reported in exposed humans.
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) Slight changes in the liver occurred in rats exposed to 600 ppm for up to 16 weeks (Elovarra et al, 1985; (pp 29-31).

Genitourinary

    3.10.1) SUMMARY
    A) Slight changes in the kidneys occurred in rats exposed to 600 ppm for up to 16 weeks.
    3.10.2) CLINICAL EFFECTS
    A) TOXIC NEPHROPATHY
    1) Slight changes in the kidneys occurred in rats exposed to 600 ppm for up to 16 weeks (Elovarra et al, 1985; (pp 29-31; ACGIH, 1991). This effect has not been reported in exposed humans.
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) Slight changes in the kidneys occurred in rats exposed to 600 ppm for up to 16 weeks (Elovarra et al, 1985; (pp 29-31).

Hematologic

    3.13.1) SUMMARY
    A) Ethyl benzene has been shown NOT to have the myelotoxic activity associated with BENZENE.
    3.13.2) CLINICAL EFFECTS
    A) HEMATOLOGY FINDING
    1) LACK OF EFFECT
    a) Despite its chemical similarity to BENZENE, ethyl benzene DOES NOT have myelotoxic properties (ACGIH, 1991).
    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) Despite its chemical similarity to BENZENE, ethyl benzene DOES NOT have myelotoxic properties (ACGIH, 1991).

Dermatologic

    3.14.1) SUMMARY
    A) Dermal contact causes inflammation and erythema. Ethyl benzene can be absorbed through intact skin.
    3.14.2) CLINICAL EFFECTS
    A) DERMATITIS
    1) Skin irritation, inflammation, and erythema may result from direct dermal exposure to ethylbenzene (Clayton & Clayton, 1994; Budavari, 1996; Lewis, 1997) Hathaway, 1996).
    B) SKIN ABSORPTION
    1) Ethyl benzene can be absorbed through intact skin (Hathaway, 1996).

Reproductive

    3.20.1) SUMMARY
    A) Ethyl benzene is teratogenic and fetotoxic in experimental animals, and has been detected in umbilical cord blood.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) MALFORMATIONS MULTIPLE
    a) Ethyl benzene caused retarded skeletal development, extra ribs, tail misplacement and decreased weight gain in fetal rats exposed to a high dose of 2,400 mg/m(3), which was also toxic to the mothers (Tatrai et al, 1982). However, lower doses of less than 100 ppm produced skeletal abnormalities, affected female fertility, were fetotoxic and caused smaller litter sizes in rats (RTECS , 2001).
    b) Increased malformations (extra ribs and urinary tract defects) were seen in mice and rats (but not in rabbits) exposed to 600 to 2,400 mg/m(3) ethyl benzene during gestation (Ungvary & Tatrai, 1985). In another study, ethyl benzene apparently was not teratogenic (Hardin et al, 1981).
    3.20.3) EFFECTS IN PREGNANCY
    A) PLACENTAL BARRIER
    1) It has been detected in human umbilical cord (fetal) blood, and would thus be available to the fetus (Clayton & Clayton, 1994).
    B) ANIMAL STUDIES
    1) ABORTION - Rabbits exposed during gestation had fewer live pups per litter and/or increased abortions (IARC, 2000).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) PRIOR EXPOSURE/FERTILITY - Prior inhalation exposure of female rats to ethylbenzene at 2 concentrations (100 or 1000 ppm for 6 hours/day, for 3 weeks) may have lowered fertility, but NOT in a dose-dependent fashion (ACGIH, 1991).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS100-41-4 (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: Ethylbenzene
    b) Carcinogen Rating: 2B
    1) The agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans. This category is used for agents, mixtures and exposure circumstances for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent, mixture or exposure circumstance for which there is inadequate evidence of carcinogenicity in humans but limited evidence of carcinogenicity in experimental animals together with supporting evidence from other relevant data may be placed in this group.
    3.21.3) HUMAN STUDIES
    A) LACK OF EFFECT
    1) Ethyl benzene was not carcinogenic in humans in two limited studies reviewed by IARC. No increase in cancer incidence was found in workers exposed to ethyl benzene, but the description of the methods in this study was inadequate to permit evaluation. In the second study, no excess mortality from cancer was found during a 15-year follow-up period. Latent periods for the development of cancer may be longer than 15 years. The question of whether or not ethyl benzene is a human carcinogen requires further study (IARC, 2000).
    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) Ethyl benzene was carcinogenic in rats and mice in a 2-year inhalation study at a dose of 750 ppm. There was clear evidence of renal tubule adenomas in male rats and increased testicular adenomas. There was some evidence of increased renal tubule adenomas in female rats. There was also some evidence of alveolar/bronchiolar tumors in male mice, and some evidence of liver tumors in female mice (NTP, 1999).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Urinary levels of mandelic acid can be used as an indicator of exposure to ethylbenzene.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) This agent may cause hepatotoxicity. Monitor liver function tests in patients with significant exposure.
    2) This agent may cause nephrotoxicity. Monitor renal function tests and urinalysis in patients with significant exposure.
    4.1.3) URINE
    A) URINARY LEVELS
    1) Urinary levels of mandelic acid can be used as an indicator of exposure to ethylbenzene (Bardodej & Bardidejova, 1970; (Gromiec & Piotrowski, 1984).
    a) In humans, the major urinary metabolite of ethylbenzene is R-mandelic acid, with a 19:1 ratio with S-mandelic acid (Korn et al, 1992).
    4.1.4) OTHER
    A) OTHER
    1) TISSUE
    a) Ethylbenzene has been detected in the subcutaneous adipose tissues of workers manufacturing rubber components following 3 days of exposure (Clayton & Clayton, 1994).

Methods

    A) OTHER
    1) Obtain chest X-ray in patients with symptoms of aspiration pneumonitis. Early chest X-rays prior to symptom development were not predictive of aspiration pneumonitis in one study (Wason & Katona, 1987).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Urinary levels of mandelic acid can be used as an indicator of exposure to ethylbenzene.

Oral Exposure

    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) Because of the potential for CNS depression or gastrointestinal tract irritation, do NOT induce emesis.
    B) GASTRIC LAVAGE
    1) Weigh the potential toxicity of the amount of ethylbenzene ingested against the substantial risk of aspiration. Ethylbenzene may "wick" up around a lavage tube, allowing pulmonary aspiration.
    2) Significant esophageal or gastrointestinal tract irritation or burns may occur following ingestion. The possible benefit of early removal of some ingested material by cautious gastric lavage must be weighed against potential complications of bleeding or perforation.
    3) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    4) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    5) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    6) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    7) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    C) ACTIVATED CHARCOAL/CATHARTIC
    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) 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).
    B) IRRITATION SYMPTOM
    1) Observe patients with ingestion carefully for the possible development of esophageal or gastrointestinal tract irritation or burns. If signs or symptoms of esophageal irritation or burns are present, consider endoscopy to determine the extent of injury.
    C) AIRWAY MANAGEMENT
    1) If CNS depression occurs, ensure airway patency and administer supplemental oxygen with assisted ventilation if required.

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) BRONCHOSPASM
    1) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
    B) 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).
    C) AIRWAY MANAGEMENT
    1) If CNS depression occurs, ensure airway patency and administer supplemental oxygen with assisted ventilation if required.
    D) 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).

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) SKIN ABSORPTION
    1) Some chemicals can produce systemic poisoning by absorption through intact skin. Carefully observe patients with dermal exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) GENERAL TREATMENT
    1) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.
    D) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Range Of Toxicity

Summary

    A) At the time of this review, the minimum lethal human dose and the maximum tolerated human exposure to this agent have not been delineated.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.
    B) ANIMAL DATA
    1) Exposure to 10,000 ppm for 2 to 3 hours produced immediate and intense eye and nose irritation, ataxia, narcosis, and death in guinea pigs; exposure to 5000 ppm was lethal within or after 8 hours (Hathaway et al, 1996).
    2) When exposed to a 1 percent concentration of ethylbenzene vapor in air, guinea pigs undergo ataxia, tremor of the extremities, loss of consciousness, and death from respiratory failure. Edematous congestion of the brains and lungs were pathological findings (Lewis, 2000).

Maximum Tolerated Exposure

    A) ROUTE OF EXPOSURE
    1) A 0.1% concentration of ethylene vapor in air is irritating to human eyes, while a concentration of 0.2% is extremely irritating to the nose and throat, resulting in dizziness and a sense of constriction in the chest (Lewis, 2000).
    2) Six human subjects exposed to 200 ppm ethylbenzene experienced transient eye irritation; at 1000 ppm, there was eye irritation with profuse lacrimation, but tolerance developed rapidly.
    a) With exposure to 2000 ppm, eye irritation and lacrimation were immediate and severe and were accompanied by moderate nasal irritation, chest constriction, and vertigo; 5000 ppm produced intolerable irritation to the eyes and nose (ACGIH, 1991).
    3) With human chronic exposures to airborne concentrations exceeding 100 ppm, complaints included fatigue, headache, sleepiness, and mild irritation to the eyes and respiratory tract (Hathaway et al, 1996).
    4) In human subjects, 22 to 33 mg/cm(2) per hour was the rate of ethylbenzene absorption through the skin of the hand and forearm (Hathaway et al, 1996).
    B) ANIMAL DATA
    1) Repeated oral administration of ethylbenzene to female rats, 5 days/week for a period of 6 months at doses of 13.6 or 136 mg/kg/day, produced no apparent effects in these animals (ACGIH, 1991).
    2) Repeated inhalation exposure to an airborne concentrations of 400 ppm ethylbenzene had no apparent effect on guinea pigs, rabbits, and rhesus monkeys, but a slight increase in liver and kidney weights in both sexes of rats was noted (ACGIH, 1991).
    3) Slight conjuctival irritation, but no corneal injury resulted when two drops of ethylbenzene liquid were placed in the eyes of a rabbit. Dermal application of liquid ethylbenzene to rabbits produced erythema, exfoliation, and vesiculation (Hathaway et al, 1996).

Workplace Standards

    A) ACGIH TLV Values for CAS100-41-4 (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) Ethyl benzene
    a) TLV:
    1) TLV-TWA: (100 ppm)
    2) TLV-STEL: (125 ppm)
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A3
    2) Codes: BEI
    3) Definitions:
    a) A3: Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.
    b) BEI: The BEI notation is listed when a BEI is also recommended for the substance listed. Biological monitoring should be instituted for such substances to evaluate the total exposure from all sources, including dermal, ingestion, or non-occupational.
    c) TLV Basis - Critical Effect(s): (URT and eye irr; CNS impair)
    d) Molecular Weight: 106.16
    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:
    1) See Notice of Intended Changes; Adopted values enclosed in parentheses are those for which changes are proposed in the Notice of Intended Changes.
    b) Notice of Intended Changes
    1) Ethyl benzene
    a) TLV:
    1) TLV-TWA: 20 ppm
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A3
    2) Codes: BEI
    3) Definitions:
    a) A3: Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.
    b) BEI: The BEI notation is listed when a BEI is also recommended for the substance listed. Biological monitoring should be instituted for such substances to evaluate the total exposure from all sources, including dermal, ingestion, or non-occupational.
    c) TLV Basis - Critical Effect(s): URT irr; kidney dam; cochlear impair
    d) Molecular Weight: 106.16
    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 CAS100-41-4 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Ethyl benzene
    2) REL:
    a) TWA: 100 ppm (435 mg/m(3))
    b) STEL: 125 ppm (545 mg/m(3))
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s):
    3) IDLH:
    a) IDLH: 800 ppm
    b) Note(s): [10%LEL]
    1) [10%LEL]: The 10%LEL designation is provided where the IDLH was based on 10% of the lower explosive limit. This is used for safety purposes in some cases even though toxicity is not indicative of irreversible health effects or impairment of escape exists only at higher concentrations.

    C) Carcinogenicity Ratings for CAS100-41-4 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A3 ; Listed as: Ethyl benzene
    a) A3 :Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.
    2) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A3 ; Listed as: Ethyl benzene
    a) A3 :Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.
    3) EPA (U.S. Environmental Protection Agency, 2011): D ; Listed as: Ethylbenzene
    a) D : Not classifiable as to human carcinogenicity.
    4) 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): 2B ; Listed as: Ethylbenzene
    a) 2B : The agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans. This category is used for agents, mixtures and exposure circumstances for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent, mixture or exposure circumstance for which there is inadequate evidence of carcinogenicity in humans but limited evidence of carcinogenicity in experimental animals together with supporting evidence from other relevant data may be placed in this group.
    5) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Ethyl benzene
    6) MAK (DFG, 2002): Category 3A ; Listed as: Ethylbenzene
    a) Category 3A : Substances for which the criteria for classification in Category 4 or 5 are fulfilled but for which the database is insufficient for the establishment of a MAK value.
    7) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS100-41-4 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Ethyl benzene
    2) Table Z-1 for Ethyl benzene:
    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: 435
    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) References: ATSDR, 1999 Bingham et al, 2001 Budavari, 1996 CHRIS, 2001 ) ITI, 1995 Lewis, 2000 OHM/TADS, 2001 RTECS, 2001
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 2272 mg/kg (Lewis, 2000)
    b) 2624 mcL/kg
    2) LD50- (ORAL)RAT:
    a) 3500 mg/kg -- liver, kidney, ureter, bladder effects
    b) 3.5-5.5 g/kg (Bingham et al, 2001)
    c) 0.5 to 5 g/kg (CHRIS, 2001)
    d) 3500 mg/kg (ITI, 1995)
    e) 5/46 mL/kg (Bingham et al, 2001)
    f) 5.46 g/kg (Budavari, 1996)
    g) male, 4769 ppm (ATSDR, 1999)
    h) 5231 mg/kg for 14D (OHM/TADS, 2001)
    3) LD50- (SKIN)RAT:
    a) 15.5-17.8 g/kg (Bingham et al, 2001)
    4) TCLo- (INHALATION)HUMAN:
    a) 100 ppm for 8H -- eye, central nervous system, and pulmonary effects
    5) TCLo- (SUBCUTANEOUS)HUMAN:
    a) 1000 ppm (OHM/TADS, 2001)
    6) TCLo- (INHALATION)MOUSE:
    a) 750 ppm for 6H/2Y-intermittent -- tumorigenic
    b) 782 ppm for 6H/4W-intermittent -- changes in liver weight
    c) 975 ppm for 6H/97D-intermittent -- changes in bladder and liver weight
    7) TCLo- (INHALATION)RAT:
    a) female, 600 mg/m(3) for 24H-at 7-15D of pregnancy -- post-implantation mortality; fetal death; developmental abnormalities of the musculoskeletal system
    b) female, 2400 mg/m(3) for 24H-at 7-15D of pregnancy -- fetotoxicity (except death)
    c) female, 97 ppm for 7H-15D prior to mating -- female fertility index
    d) female, 96 ppm for 7H-at 1-19D of pregnancy -- developmental abnormalities of the musculoskeletal system
    e) female, 985 ppm for 7H-at 1-19D of pregnancy -- fetotoxicity
    f) 750 ppm for 6H/2Y-intermittent -- tumorigenic
    g) 782 ppm for 6H/4W-intermittent -- changes in liver weight and blood
    h) 740 ppm for 6H/92D-intermittent -- changes in bladder, liver, and lung weight

Pharmacology Toxicology

Toxicologic Mechanism

    A) Ethylbenzene is a primary irritant of the eyes, skin, and mucous membranes, and has narcotic properties (Lewis, 2000) Hathaway, 1996; (ACGIH, 1991; Clayton & Clayton, 1994). It may cause minor liver and kidney toxicity (Hathaway, 1996; (ACGIH, 1991; Clayton & Clayton, 1994).

Physicochemical

Physical Characteristics

    A) Ethylbenzene is a colorless, flammable liquid with an odor that has been described as pungent, aromatic, sweet, and gasoline-like. Its vapors are heavier than air (Bingham et al, 2001; HSDB , 2001; ITI, 1995; Lewis, 2000).

Ph

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

Molecular Weight

    A) 106.17

References

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