MOBILE VIEW  | 

BENZAL CHLORIDE

Classification   |    Detailed evidence-based information

Therapeutic Toxic Class

    A) Benzal chloride is a dichlorinated toluene derivative, prepared by chlorination of toluene (Budavari, 1989; Sax & Lewis, 1987).

Specific Substances

    A) No Synonyms were found in group or single elements
    1.2.1) MOLECULAR FORMULA
    1) C7-H6-Cl2

Available Forms Sources

    A) FORMS
    1) It is stabilized by additives such as propylene oxide (Sittig, 1991a).
    2) It is a very refractive liquid (Budavari, 1996).
    3) It has been described as colorless to brown oily liquid with faint aromatic to pungent odor (HSDB , 2000; Lewis, 1997).
    4) Impurities of benzal chloride include: benzyl chloride, benzaldehyde, benzoic acid, and benzotrichloride. The technical grade has a minimal purity of 95% (HSDB , 2000).
    5) Benzal chloride can occur as a contaminant in other commercial products. Levels of 0.15 mg/m(3) benzal chloride have been measured in the air of a vinyl floor tile manufacturing plant; the source was traced to benzal chloride contamination of butyl benzyl phthalate, a plasticizer (Rittfeldt et al, 1983).
    B) SOURCES
    1) It is produced by side-chain chlorination of toluene in the presence of light, with the coproduction of benzyl chloride/benzotrichloride (Ashford, 1994a; Lewis, 1997).
    a) The yield is 70% when 2.0 to 2.2 moles of chlorine is present in the reaction per mole of toluene (HSDB , 2000).
    2) It can also be formed by reaction of dichlorocarbene with benzene (HSDB , 2000).
    C) USES
    1) Benzal chloride is used in dyes and in the manufacture of benzaldehdye (by hydrolysis of benzal chloride), benzoyl chloride, and cinnamic acid (by heating with sodium acetate) (Budavari, 1996; IARC, 1982; Sittig, 1991a).

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Benzal chloride is absorbed after oral, inhalation and ingestion exposure, and may be fatal after absorption. Like all of the chlorinated toluenes, benzal chloride has strong irritant properties. Exposure may cause central nervous system depression. It is irritating to the eyes, skin and respiratory tract, and may cause burns to the eyes and skin. Skin exposure causes redness and pain. Eye exposure causes redness, irritant pain and strong lacrimation.
    B) Inhalation produces coughing, labored breathing, nausea and a sore throat. Ingestion causes a burning sensation and vomiting; irritation of the esophagus or the gastrointestinal tract may be expected.
    C) CNS excitation or depression is possible. Degenerative changes in the myocardium, liver, and kidneys have been seen in experimental animals administered lethal doses. Limited evidence exists that benzal chloride is carcinogenic in experimental animals and humans.
    0.2.4) HEENT
    A) Conjunctivitis and mucosal irritation of the nose and throat may be seen.
    0.2.5) CARDIOVASCULAR
    A) Degenerative changes in the myocardium have been noted in fatally poisoned experimental animals.
    0.2.6) RESPIRATORY
    A) Respiratory irritation and pulmonary edema may occur.
    0.2.7) NEUROLOGIC
    A) Central nervous system excitation and depression have been seen in animals.
    0.2.8) GASTROINTESTINAL
    A) Irritation of the esophagus or gastrointestinal tract could occur following ingestion.
    0.2.9) HEPATIC
    A) Degenerative changes in the liver have occurred in experimental animals.
    0.2.10) GENITOURINARY
    A) Degenerative changes in the kidneys were produced in experimental animals.
    0.2.14) DERMATOLOGIC
    A) Dermal irritation may be noted.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the potential reproductive hazard of this agent.
    0.2.21) CARCINOGENICITY
    A) Increased deaths from respiratory tract cancers and Hodgkin's disease have been reported in workers exposed to benzal chloride and benzoyl chloride.
    B) IARC CLASSIFICATION - HUMAN - Inadequate Evidence (IARC, 1982)

Laboratory Monitoring

    A) Monitor liver and renal function tests in serious exposures. Monitor arterial blood gases and chest x-ray in patients with inhalation exposure.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) 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.
    B) 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) Carefully observe patients with ingestion for signs of esophageal or GI tract irritation.
    F) If signs of esophageal irritation are present, esophagoscopy may be considered.
    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 supplemental oxygen with assisted ventilation as required. If CNS depression or severe upper airway irritation occur, assure airway patency and oxygenation. Endotracheal intubation could be necessary.
    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.

Range Of Toxicity

    A) Inhalation exposure to 12 to 160 ppm/2 hours was fatal in some experimental animals. A 2-hour inhalation exposure to 100 mg/m(3) (15.2 ppm) caused central nervous system excitation, dermal irritation, and eye and respiratory tract irritation in mice and rats.

Summary Of Exposure

    A) Benzal chloride is absorbed after oral, inhalation and ingestion exposure, and may be fatal after absorption. Like all of the chlorinated toluenes, benzal chloride has strong irritant properties. Exposure may cause central nervous system depression. It is irritating to the eyes, skin and respiratory tract, and may cause burns to the eyes and skin. Skin exposure causes redness and pain. Eye exposure causes redness, irritant pain and strong lacrimation.
    B) Inhalation produces coughing, labored breathing, nausea and a sore throat. Ingestion causes a burning sensation and vomiting; irritation of the esophagus or the gastrointestinal tract may be expected.
    C) CNS excitation or depression is possible. Degenerative changes in the myocardium, liver, and kidneys have been seen in experimental animals administered lethal doses. Limited evidence exists that benzal chloride is carcinogenic in experimental animals and humans.

Heent

    3.4.1) SUMMARY
    A) Conjunctivitis and mucosal irritation of the nose and throat may be seen.
    3.4.3) EYES
    A) CONJUNCTIVITIS - Eye irritation and lacrimation may be seen following vapor exposure (Grant, 1986; Lewis, 1992).
    3.4.5) NOSE
    A) MUCOSAL IRRITATION - Benzal chloride vapors are irritating to the mucosa of the nose and throat (IARC, 1982; Mikhailova, 1965).
    3.4.6) THROAT
    A) MUCOSAL IRRITATION - Benzal chloride vapors are irritating to the mucosa of the nose and throat (IARC, 1982; Mikhailova, 1965).

Cardiovascular

    3.5.1) SUMMARY
    A) Degenerative changes in the myocardium have been noted in fatally poisoned experimental animals.
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) Degenerative changes in the myocardium have been noted in fatally poisoned experimental animals (Mikhailova, 1965). This effect has not been reported in exposed humans.

Respiratory

    3.6.1) SUMMARY
    A) Respiratory irritation and pulmonary edema may occur.
    3.6.2) CLINICAL EFFECTS
    A) IRRITATION SYMPTOM
    1) Irritation of the respiratory tract may be seen with inhalation exposure (IARC, 1982; Mikhailova, 1965). The similar chlorinated toluene compound, benzyl chloride, has produced pulmonary edema (CHRIS, 1995).

Neurologic

    3.7.1) SUMMARY
    A) Central nervous system excitation and depression have been seen in animals.
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) CNS EXCITATION/DEPRESSION - Fatally poisoned experimental animals have demonstrated excitation and depression of the central nervous system (Mikhailova, 1965). These effects have not been reported in exposed humans.

Gastrointestinal

    3.8.1) SUMMARY
    A) Irritation of the esophagus or gastrointestinal tract could occur following ingestion.
    3.8.2) CLINICAL EFFECTS
    A) GASTRITIS
    1) Human ingestions have not been reported. Irritation of the esophagus or gastrointestinal tract might be predicted based on the other irritant properties of benzal chloride.

Hepatic

    3.9.1) SUMMARY
    A) Degenerative changes in the liver have occurred in experimental animals.
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) Degenerative changes in the liver have been noted in fatally poisoned experimental animals (Mikhailova, 1965). This effect has not been reported in exposed humans.

Genitourinary

    3.10.1) SUMMARY
    A) Degenerative changes in the kidneys were produced in experimental animals.
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) Degenerative changes in the kidneys have been noted in fatally poisoned experimental animals (Mikhailova, 1965). This effect has not been reported in exposed humans.

Dermatologic

    3.14.1) SUMMARY
    A) Dermal irritation may be noted.
    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) Benzal chloride is irritating to the skin (IARC, 1982).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the potential reproductive hazard of this agent.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of benzal chloride.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of benzal chloride exposure during pregnancy or lactation.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS98-87-3 (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: benzal chloride
    b) Carcinogen Rating: 2A
    1) The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans. This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent (mixture) may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals and strong evidence that the carcinogenesis is mediated by a mechanism that also operates in humans. Exceptionally, an agent, mixture or exposure circumstance may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans.
    3.21.2) SUMMARY/HUMAN
    A) Increased deaths from respiratory tract cancers and Hodgkin's disease have been reported in workers exposed to benzal chloride and benzoyl chloride.
    B) IARC CLASSIFICATION - HUMAN - Inadequate Evidence (IARC, 1982)
    3.21.3) HUMAN STUDIES
    A) PULMONARY CARCINOMA
    1) Six cases of respiratory tract cancers have been reported in benzoyl chloride production workers who also had exposure to benzal chloride. All of these workers were relatively young and three were non-smokers (IARC, 1982).
    2) In a follow-up study on 951 workers, excess deaths were found from lung cancer (SMR = 180) and Hodgkin's disease (SMR = 714). The deaths were not clearly due to occupational exposure to benzal chloride, however (Sorahan & Cathcart, 1989).
    3.21.4) ANIMAL STUDIES
    A) SKIN CARCINOMA
    1) ANIMAL STUDIES
    a) MOUSE SKIN PAINTING STUDIES - Skin tumors were induced in female ICR mice treated with ten microliters applied 3 times/week for 4 weeks, followed by twice a week until 9.8 months (Fukuda et al, 1981).
    b) In another experiment, 58 percent of animals treated with 2.3 microliters 2 times/week for 50 weeks developed squamous cell carcinomas and/or fibrosarcomas (Fukuda et al, 1981).
    c) The authors concluded that benzal chloride was a stronger carcinogen than its analogues, benzyl chloride, or benzotrichloride (Fukuda et al, 1981).

Genotoxicity

    A) DNA repair and mutations were seen in several microorganisms.

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor liver and renal function tests in serious exposures. Monitor arterial blood gases and chest x-ray in patients with inhalation exposure.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor liver and renal function tests in patients with significant exposure.
    2) Monitor arterial blood gases in patients with significant inhalation exposure or respiratory tract irritation.

Radiographic Studies

    A) OTHER
    1) Monitor chest x-ray in patients with significant inhalation exposure or respiratory tract irritation.

Methods

    A) CHROMATOGRAPHY
    1) Workplace air can be assayed for benzal chloride content by a gas chromatographic method with adsorption on a polymeric adsorbant and carbon tetrachloride desorption (IARC, 1982). This method has a lower limit of detection of about 10 parts per billion (70 micrograms per cubic meter) (IARC, 1982).

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) All patients who are symptomatic following benzal chloride ingestion should be admitted to the hospital and closely monitored until all symptoms have resolved.
    6.3.3) DISPOSITION/INHALATION EXPOSURE
    6.3.3.1) ADMISSION CRITERIA/INHALATION
    A) All patients with respiratory tract irritation following benzal chloride inhalation exposure should be admitted to the hospital and carefully monitored for the possible development of severe irritation or pulmonary edema.

Monitoring

    A) Monitor liver and renal function tests in serious exposures. Monitor arterial blood gases and chest x-ray in patients with inhalation exposure.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) INHALATION EXPOSURE -
    1) 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.
    2) If central nervous system depression or severe upper airway irritation occurs, assure airway patency and oxygenation. Endotracheal intubation may be necessary.
    3) 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.
    B) DERMAL EXPOSURE -
    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.
    C) EYE EXPOSURE -
    1) 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.
    D) ORAL EXPOSURE -
    1) Do not induce emesis
    2) 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.
    3) 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.
    4) 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.
    a) 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.
    5) 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.
    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) INDUCED EMESIS SHOULD be AVOIDED -
    B) GASTRIC LAVAGE/PRECAUTIONS
    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
    1) 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.
    2) 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.
    3) 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.
    4) 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).
    5) 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.
    D) 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) 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) Observe patients carefully for signs of esophageal or gastrointestinal tract irritation (including nausea, vomiting, diarrhea, abdominal pain, bleeding, perforation).
    2) If signs of esophageal irritation are present, esophagoscopy may be considered to determine the extent of injury.
    C) MONITORING OF PATIENT
    1) Monitor liver and renal function tests in patients with significant exposure.
    D) AIRWAY MANAGEMENT
    1) If central nervous system depression or severe upper airway irritation occur, assure airway patency and oxygenation. Endotracheal intubation could be necessary. .
    E) HOSPITAL ADMISSION
    1) All patients who are symptomatic following benzal chloride ingestion should be admitted to the hospital and closely monitored until all symptoms have resolved.

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 or severe upper airway irritation occur, assure airway patency and oxygenation. Endotracheal intubation may be necessary.
    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) 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) CONSULTATION - Prolonged flushing and early ophthalmic consultation may be required.
    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) EXTRACORPOREAL ELIMINATION
    1) No studies have addressed the utilization of extracorporeal elimination techniques in benzal chloride poisoning.

Summary

    A) Inhalation exposure to 12 to 160 ppm/2 hours was fatal in some experimental animals. A 2-hour inhalation exposure to 100 mg/m(3) (15.2 ppm) caused central nervous system excitation, dermal irritation, and eye and respiratory tract irritation in mice and rats.

Minimum Lethal Exposure

    A) ADULT
    1) The minimum lethal human dose to this agent has not been delineated.

Maximum Tolerated Exposure

    A) ADULT
    1) The maximum tolerated human exposure to this agent has not been delineated.
    2) Editor's Note: Combined exposures to alpha-chlorinated toluenes (which benzal chloride is one) and benzene carbonyl chloride are classified as "probably carcinogenic to humans (Group 2A)" by IARC (IARC , 2000).
    B) ANIMAL DATA
    1) A 2-hour inhalation exposure to 100 mg/m(3) (15.2 ppm) caused central nervous system excitation, dermal irritation, and eye and respiratory tract irritation in mice and rats (IARC, 1982).
    2) "There is limited evidence in experimental animals for the carcinogenicity of benzal chloride" (IARC , 2000).

Workplace Standards

    A) ACGIH TLV Values for CAS98-87-3 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS98-87-3 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS98-87-3 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    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): 2A ; Listed as: benzal chloride
    a) 2A : The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans. This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent (mixture) may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals and strong evidence that the carcinogenesis is mediated by a mechanism that also operates in humans. Exceptionally, an agent, mixture or exposure circumstance may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Category 1 ; Listed as: alpha-Chlorinated toluenes: benzyl dichloride
    a) Category 1 : Substances that cause cancer in man and can be assumed to make a significant contribution to cancer risk. Epidemiological studies provide adequate evidence of a positive correlation between the exposure of humans and the occurence of cancer. Limited epidemiological data can be substantiated by evidence that the substance causes cancer by a mode of action that is relevant to man.
    6) MAK (DFG, 2002): Category 2 ; Listed as: Benzyl dichloride
    a) Category 2 : Substances that are considered to be carcinogenic for man because sufficient data from long-term animal studies or limited evidence from animal studies substantiated by evidence from epidemiological studies indicate that they can make a significant contribution to cancer risk. Limited data from animal studies can be supported by evidence that the substance causes cancer by a mode of action that is relevant to man and by results of in vitro tests and short-term animal studies.
    7) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS98-87-3 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: RTECS, 2000
    1) LD50- (ORAL)MOUSE:
    a) 2462 mg/kg
    2) LD50- (ORAL)RAT:
    a) 3249 mg/kg

Toxicologic Mechanism

    A) Benzal chloride is a direct irritant of eyes, skin, and mucous membranes (Grant, 1986; IARC, 1982).
    B) Benzal chloride is mutagenic in bacterial assays and there is limited evidence that it has carcinogenic properties (IARC, 1982).

Physical Characteristics

    A) It is a very refractive liquid (Budavari, 2000).
    B) It has been described as colorless to brown oily liquid with faint aromatic to pungent odor (HSDB , 2000; Lewis, 1997).

Molecular Weight

    A) 161.03

Other

    A) ODOR THRESHOLD
    1) Data not available (CHRIS , 2000).

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