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DIEPOXYBUTANE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Diepoxybutane is an epoxide compound used as a chemical intermediate, a cross-linking agent for textile fibers, in polymer curing, as an alkylating chemical in research, for preventing microbial spoilage, and in the preparation of various pharmaceutical agents and erythritol (Shaham et al, 1987; EPA, 1985; Clayton & Clayton, 1982; Windholz et al, 1983; IARC, 1976).

Specific Substances

    1) Diepoxybutane
    2) Butane, 1,2:3,4-diepoxy
    3) 1,1'-Bi(ethylene oxide)
    4) Bioxiran
    5) Bioxirane
    6) 2,2'-Bioxirane
    7) Butadiene diepoxide
    8) Butadiene dioxide
    9) Butanedione
    10) 1,2:3,4-Diepoxybutane
    11) 2,4-Diepoxybutane
    12) Dioxybutadiene
    13) ENT 26592
    14) Erythritol anhydride
    15) Threitol, 1,2:3,4-dianhydro-
    16) Molecular Formula: C4-H6-O2
    17) CAS 1464-53-5
    18) References: RTECS, 1983; EPA, 1985; Windholz et al, 1983; Grant, 1986; IARC, 1976
    1.2.1) MOLECULAR FORMULA
    1) C4-H6-O2

Available Forms Sources

    A) USES
    1) Diepoxybutane is an epoxide compound used as a chemical intermediate, a cross-linking agent for textile fibers, in polymer curing, as an alkylating chemical in research, for preventing microbial spoilage, and in the preparation of various pharmaceutical agents and erythritol (Shaham et al, 1987; EPA, 1985; Clayton & Clayton, 1982; Windholz et al, 1983; IARC, 1976).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Diepoxybutane, an alkaline corrosive, is an epoxide compound used as a chemical intermediate, a cross-linking agent for textile fibers, in polymer curing, as an alkylating chemical in research, for preventing microbial spoilage, and in the preparation of various pharmaceutical agents and erythritol.
    B) TOXICOLOGY: Diepoxybutane may cause liquefaction necrosis. It can saponify the fats in the cell membrane, destroying the cell and allowing deep penetration into mucosal tissue. In gastrointestinal tissue, an initial inflammatory phase may be followed by tissue necrosis (sometimes resulting in perforation), then granulation and finally stricture formation.
    C) EPIDEMIOLOGY: Diepoxybutane is generally available for industrial use only. Exposure is unusual.
    D) WITH POISONING/EXPOSURE
    1) Diepoxybutane is an alkaline corrosive. Although there is limited information regarding specific human toxicity following exposure, the following effects may occur, based on documented human exposures with other alkaline corrosives.
    2) MILD TO MODERATE ORAL TOXICITY: Patients with mild ingestions may only develop irritation or grade I (superficial hyperemia and edema) burns of the oropharynx, esophagus or stomach; acute or chronic complications are unlikely. Patients with moderate toxicity may develop grade II burns (superficial blisters, erosions and ulcerations) and are at risk for subsequent stricture formation, particularly esophageal. Some patients (particularly young children) may develop upper airway edema.
    a) Alkaline corrosive ingestion may produce burns to the oropharynx, upper airway, esophagus and occasionally stomach. Spontaneous vomiting may occur. The absence of visible oral burns does NOT reliably exclude the presence of esophageal burns. The presence of stridor, vomiting, drooling, and abdominal pain are associated with serious esophageal injury in most cases.
    b) PREDICTIVE: The grade of mucosal injury at endoscopy is the strongest predictive factor for the occurrence of systemic and GI complications and mortality.
    3) SEVERE ORAL TOXICITY: May develop deep burns and necrosis of the gastrointestinal mucosa. Complications often include perforation (esophageal, gastric, rarely duodenal), fistula formation (tracheoesophageal, aortoesophageal), and gastrointestinal bleeding. Hypotension, tachycardia, tachypnea and, rarely, fever may develop. Stricture formation (esophageal, less often oral or gastric) is likely to develop long term. Esophageal carcinoma is another long term complication. Upper airway edema is common and often life threatening. Severe toxicity is generally limited to deliberate ingestions in adults in the US, because alkaline products available in the home are generally of low concentration.
    4) INHALATION EXPOSURE: Mild exposure may cause cough and bronchospasm. Severe inhalation may cause upper airway edema and burns, stridor, and rarely acute lung injury.
    5) OCULAR EXPOSURE: Ocular exposure can produce severe conjunctival irritation and chemosis, corneal epithelial defects, limbal ischemia, permanent visual loss and in severe cases perforation.
    6) DERMAL EXPOSURE: Mild exposure causes irritation and partial thickness burns. Prolonged exposure or high concentration products can cause full thickness burns.
    0.2.4) HEENT
    A) Conjunctival irritation to severe eye injury may be observed. Irritation of the upper respiratory tract mucosa may be seen.
    0.2.6) RESPIRATORY
    A) Severe respiratory tract irritation and pulmonary edema may occur.
    0.2.8) GASTROINTESTINAL
    A) A potential exists for severe irritation or burns of the esophagus or gastrointestinal tract following ingestion.
    0.2.13) HEMATOLOGIC
    A) Bone marrow depression has been observed in rat studies.
    0.2.14) DERMATOLOGIC
    A) Severe dermal irritation or burns may occur.
    0.2.16) ENDOCRINE
    A) Thymic atrophy and splenic involution has been observed in experimental animals.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    0.2.21) CARCINOGENICITY
    A) Diepoxybutane is not regarded as a potential human carcinogen.

Laboratory Monitoring

    A) Obtain a complete blood count in symptomatic patients following an alkaline corrosive ingestion.
    B) In patients with signs and symptoms suggesting severe burns, perforation, or bleeding (or adults with deliberate, high volume or high concentration ingestions), obtain renal function tests, serum electrolytes, INR, PTT, type and crossmatch for blood, and monitor urine output. Serum lactate and base deficit may also be useful in these patients.
    C) Monitor pulse oximetry or arterial blood gases in patients with signs and symptoms suggestive of upper airway edema or burns.
    D) Obtain an upright chest x-ray in patients with signs and symptoms suggesting severe burns, perforation, or bleeding (or adults with deliberate, high volume or high concentration ingestions) to evaluate for pneumomediastinum or free air under the diaphragm. The absence of these findings DOES NOT rule out the possibility of necrosis or perforation of the esophagus or stomach. Obtain a chest radiograph in patients with pulmonary signs or symptoms.
    E) Several weeks after ingestion, barium contrast radiographs of the upper GI tract are useful in patients who sustained grade II or III burns, to evaluate for strictures.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) There is no information available about treatment of diepoxybutane-induced corrosive injury; the following data is derived from experience with other corrosive agents.
    B) MANAGEMENT OF MILD TO MODERATE ORAL TOXICITY
    1) Perform early (within 12 hours) endoscopy in patients with stridor, drooling, vomiting, significant oral burns, difficulty swallowing or abdominal pain, and in all patients with deliberate ingestion. If burns are absent or Grade I severity, patient may be discharged when able to tolerate liquids and soft foods by mouth. If mild Grade II burns, admit for intravenous fluids, slowly advance diet as tolerated. Perform barium swallow or repeat endoscopy several weeks after ingestion (sooner if difficulty swallowing) to evaluate for stricture formation.
    C) SEVERE ORAL TOXICITY
    1) Resuscitate with 0.9% saline; blood products may be necessary. Early airway management in patients with upper airway edema or respiratory distress. Early (within 12 hours) gastrointestinal endoscopy to evaluate for burns. Early bronchoscopy in patients with respiratory distress or upper airway edema. Early surgical consultation for patients with severe Grade II or Grade III burns, large deliberate ingestions, or signs, symptoms or laboratory findings concerning for tissue necrosis or perforation.
    D) DILUTION
    1) Dilute with 4 to 8 ounces of water may be useful if it can be performed shortly after ingestion in patients who are able to swallow, with no vomiting or respiratory distress; then the patient should be NPO until assessed for the need for endoscopy. Neutralization, activated charcoal, and gastric lavage are all contraindicated.
    E) AIRWAY MANAGEMENT
    1) Aggressive airway management in patients with deliberate ingestions or any indication of upper airway injury.
    F) ENDOSCOPY
    1) Should be performed as soon as possible (preferably within 12 hours, not more than 24 hours) in any patient with deliberate ingestion, adults with any signs or symptoms attributable to inadvertent ingestion, and in children with stridor, vomiting, or drooling after inadvertent ingestion. Endoscopy should also be considered in children with dysphagia or refusal to swallow, significant oral burns, or abdominal pain after unintentional ingestion. Children and adults who are asymptomatic after inadvertent ingestion do not require endoscopy. The grade of mucosal injury at endoscopy is the strongest predictive factor for the occurrence of systemic and GI complications and mortality. The absence of visible oral burns does NOT reliably exclude the presence of esophageal burns.
    G) CORTICOSTEROIDS
    1) The use of corticosteroids to prevent stricture formation is controversial. Corticosteroids should not be used in patients with Grade I or Grade III injury, as there is no evidence that it is effective. Evidence for Grade II burns is conflicting, and the risk of perforation and infection is increased with steroid use.
    H) STRICTURE
    1) A barium swallow or repeat endoscopy should be performed several weeks after ingestion in any patient with Grade II or III burns or with difficulty swallowing to evaluate for stricture formation. Recurrent dilation may be required. Some authors advocate early stent placement in these patients to prevent stricture formation.
    I) SURGICAL MANAGEMENT
    1) Immediate surgical consultation should be obtained on any patient with Grade III or severe Grade II burns on endoscopy, significant abdominal pain, metabolic acidosis, hypotension, coagulopathy, or a history of large ingestion. Early laparotomy can identify tissue necrosis and impending or unrecognized perforation, early resection and repair in these patients is associated with improved outcome.
    J) PATIENT DISPOSITION
    1) OBSERVATION CRITERIA: Patients with alkaline corrosive ingestion should be sent to a health care facility for evaluation. Patients who remain asymptomatic over 4 to 6 hours of observation, and those with endoscopic evaluation that demonstrates no burns or only minor Grade I burns and who can tolerate oral intake can be discharged home.
    2) ADMISSION CRITERIA: Symptomatic patients, and those with endoscopically demonstrated Grade II or higher burns should be admitted. Patients with respiratory distress, Grade III burns, acidosis, hemodynamic instability, gastrointestinal bleeding, or large ingestions should be admitted to an intensive care setting.
    K) PITFALLS
    1) The absence of oral burns does NOT reliably exclude the possibility of significant esophageal burns.
    2) Patients may have severe tissue necrosis and impending perforation requiring early surgical intervention without having severe hypotension, rigid abdomen, or radiographic evidence of intraperitoneal air.
    3) Patients with any evidence of upper airway involvement require early airway management before airway edema progresses.
    4) The extent of eye injury (degree of corneal opacification and perilimbal whitening) may not be apparent for 48 to 72 hours after the burn. All patients with corrosive eye injury should be evaluated by an ophthalmologist.
    L) DIFFERENTIAL DIAGNOSIS
    1) Acid ingestion, gastrointestinal hemorrhage, or perforated viscus.
    0.4.3) INHALATION EXPOSURE
    A) DECONTAMINATION
    1) Administer oxygen as necessary. Monitor for respiratory distress.
    B) AIRWAY MANAGEMENT
    1) Manage airway aggressively in patients with significant respiratory distress, stridor or any evidence of upper airway edema. Monitor for hypoxia or respiratory distress.
    C) BRONCHOSPASM
    1) Treat with oxygen, inhaled beta agonists and consider systemic corticosteroids.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION
    1) Exposed eyes should be irrigated with copious amounts of 0.9% saline for at least 30 minutes, until pH is neutral and the cul de sacs are free of particulate material.
    2) An eye examination should always be performed, including slit lamp examination. Ophthalmologic consultation should be obtained. Antibiotics and mydriatics may be indicated.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION
    a) Remove contaminated clothes and any particulate matter adherent to skin. Irrigate exposed skin with copious amounts of water for at least 15 minutes or longer, depending on concentration, amount and duration of exposure to the chemical. A physician may need to examine the area if irritation or pain persist.

Range Of Toxicity

    A) Serious burns are less likely if the pH is less than 11.5. Injury is greater with large exposures and high concentrations.
    B) With highly concentrated liquids, esophageal burns may occur in up to 100% of patients, even after accidental ingestion.
    C) Nasal mucosa and eye irritation occur at an airborne concentration of 10 parts per million. The odor is barely recognizable at 5 parts per million.

Clinical Effects

Summary Of Exposure

    A) USES: Diepoxybutane, an alkaline corrosive, is an epoxide compound used as a chemical intermediate, a cross-linking agent for textile fibers, in polymer curing, as an alkylating chemical in research, for preventing microbial spoilage, and in the preparation of various pharmaceutical agents and erythritol.
    B) TOXICOLOGY: Diepoxybutane may cause liquefaction necrosis. It can saponify the fats in the cell membrane, destroying the cell and allowing deep penetration into mucosal tissue. In gastrointestinal tissue, an initial inflammatory phase may be followed by tissue necrosis (sometimes resulting in perforation), then granulation and finally stricture formation.
    C) EPIDEMIOLOGY: Diepoxybutane is generally available for industrial use only. Exposure is unusual.
    D) WITH POISONING/EXPOSURE
    1) Diepoxybutane is an alkaline corrosive. Although there is limited information regarding specific human toxicity following exposure, the following effects may occur, based on documented human exposures with other alkaline corrosives.
    2) MILD TO MODERATE ORAL TOXICITY: Patients with mild ingestions may only develop irritation or grade I (superficial hyperemia and edema) burns of the oropharynx, esophagus or stomach; acute or chronic complications are unlikely. Patients with moderate toxicity may develop grade II burns (superficial blisters, erosions and ulcerations) and are at risk for subsequent stricture formation, particularly esophageal. Some patients (particularly young children) may develop upper airway edema.
    a) Alkaline corrosive ingestion may produce burns to the oropharynx, upper airway, esophagus and occasionally stomach. Spontaneous vomiting may occur. The absence of visible oral burns does NOT reliably exclude the presence of esophageal burns. The presence of stridor, vomiting, drooling, and abdominal pain are associated with serious esophageal injury in most cases.
    b) PREDICTIVE: The grade of mucosal injury at endoscopy is the strongest predictive factor for the occurrence of systemic and GI complications and mortality.
    3) SEVERE ORAL TOXICITY: May develop deep burns and necrosis of the gastrointestinal mucosa. Complications often include perforation (esophageal, gastric, rarely duodenal), fistula formation (tracheoesophageal, aortoesophageal), and gastrointestinal bleeding. Hypotension, tachycardia, tachypnea and, rarely, fever may develop. Stricture formation (esophageal, less often oral or gastric) is likely to develop long term. Esophageal carcinoma is another long term complication. Upper airway edema is common and often life threatening. Severe toxicity is generally limited to deliberate ingestions in adults in the US, because alkaline products available in the home are generally of low concentration.
    4) INHALATION EXPOSURE: Mild exposure may cause cough and bronchospasm. Severe inhalation may cause upper airway edema and burns, stridor, and rarely acute lung injury.
    5) OCULAR EXPOSURE: Ocular exposure can produce severe conjunctival irritation and chemosis, corneal epithelial defects, limbal ischemia, permanent visual loss and in severe cases perforation.
    6) DERMAL EXPOSURE: Mild exposure causes irritation and partial thickness burns. Prolonged exposure or high concentration products can cause full thickness burns.

Heent

    3.4.1) SUMMARY
    A) Conjunctival irritation to severe eye injury may be observed. Irritation of the upper respiratory tract mucosa may be seen.
    3.4.3) EYES
    A) IRRITATION - Diepoxybutane caused eyelid swelling and conjunctival irritation in one case of human exposure (Clayton & Clayton, 1982).
    1) Direct contact with the liquid caused severe conjunctival irritation in rabbits (Grant, 1986).
    2) Vapor exposure at 3 to 12 parts per million caused severe injury with loosening and sloughing of the corneal epithelium, corneal stroma opacification, and some vascularization and permanent scarring of the cornea in rabbits (Grant, 1986).
    B) Diepoxybutane was found to be a severe eye irritant in the rabbit using the Standard Draize Test (RTECS, 1996).
    3.4.5) NOSE
    A) MUCOSAL IRRITATION - Irritation of the upper respiratory tract mucosa was reported in one human exposure case (Clayton & Clayton, 1982). Severe mucosal irritation has been seen in exposed experimental animals (Clayton & Clayton, 1982).
    3.4.6) THROAT
    A) MUCOSAL IRRITATION - Irritation of the upper respiratory tract mucosa was reported in one human exposure case (Clayton & Clayton, 1982). Severe mucosal irritation has been seen in exposed experimental animals (Clayton & Clayton, 1982).

Respiratory

    3.6.1) SUMMARY
    A) Severe respiratory tract irritation and pulmonary edema may occur.
    3.6.2) CLINICAL EFFECTS
    A) IRRITATION SYMPTOM
    1) Irritation of the upper respiratory tract mucosa was reported in one human exposure case (Clayton & Clayton, 1982).
    B) ACUTE LUNG INJURY
    1) Severe respiratory tract irritation leading to pulmonary edema and death has occurred in exposed experimental animals (IARC, 1976; Clayton & Clayton, 1982).

Gastrointestinal

    3.8.1) SUMMARY
    A) A potential exists for severe irritation or burns of the esophagus or gastrointestinal tract following ingestion.
    3.8.2) CLINICAL EFFECTS
    A) GASTROINTESTINAL IRRITATION
    1) No human ingestion cases have been reported, but irritation or burns of the esophagus or gastrointestinal tract might be predicted based on this agent's other irritant properties.

Genitourinary

    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) TESTIS DISORDER
    a) INSECT SPERM ABNORMALITIES - Diepoxybutane exposure caused ring-x loss in the sperm and spermatids of Drosophila melanogaster (Zimmering, 1983).

Hematologic

    3.13.1) SUMMARY
    A) Bone marrow depression has been observed in rat studies.
    3.13.2) CLINICAL EFFECTS
    A) MYELOSUPPRESSION
    1) After several intramuscular injections of diepoxybutane, rats developed relative lymphopenia and leukopenia (Clayton & Clayton, 1982). This effect has not been reported in exposed humans.
    B) ERYTHROCYTE DEFORMABILITY
    1) DECREASED FIBROBLAST CLONOGENICITY - Exposure to 5 micrograms per milliliter of diepoxybutane in culture media caused a 50 percent reduction in clonogenicity of normal fibroblasts and a complete absence of clonogenicity in fibroblasts from patients with Fanconi anemia (Shaham et al, 1987).

Dermatologic

    3.14.1) SUMMARY
    A) Severe dermal irritation or burns may occur.
    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) Severe skin irritation with blistering has been noted from direct contact with this material in experimental animals (IARC, 1976).
    2) Diepoxybutane was found to be a severe skin irritant in the Standard and the Open Draize tests (RTECS, 1996).

Endocrine

    3.16.1) SUMMARY
    A) Thymic atrophy and splenic involution has been observed in experimental animals.
    3.16.2) CLINICAL EFFECTS
    A) DISORDER OF ENDOCRINE SYSTEM
    1) THYMUS AND SPLEEN INJURY - Experimental animals exposed by inhalation to near-fatal concentrations had thymic atrophy and splenic involution (Clayton & Clayton, 1982). These effects have not been reported in exposed humans.

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    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 this agent.
    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 exposure to this agent during pregnancy or lactation.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS1464-53-5 (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) Not Listed
    3.21.2) SUMMARY/HUMAN
    A) Diepoxybutane is not regarded as a potential human carcinogen.
    3.21.3) HUMAN STUDIES
    A) ANIMAL STUDIES
    1) Diepoxybutane has produced squamous cell skin carcinomas and local sarcomas in rodents exposed by injection or dermal contact (IARC, 1976). Oral administration to rats did not produce tumors (Clayton & Clayton, 1982). No human cancer cases linked to diepoxybutane exposure have been reported (IARC, 1976).
    2) In one rat study, diepoxybutane was found to be an equivocal tumorigenic agent by RTECS criteria with musculoskeletal tumors. In the mouse, it was found to be an equivocal tumorigenic agent by RTECS criteria with skin and appendages tumors in one study and an equivocal tumorigenic agent by RTECS criteria for lymphomas in another study (RTECS, 1996).
    3) Diepoxybutane was anticipated to be a carcinogen in the NTP Fifth Annual Report on Carcinogens, 1989 (RTECS, 1996).
    3.21.4) ANIMAL STUDIES
    A) ANIMAL STUDIES
    1) Diepoxybutane is an experimental animal carcinogen.

Genotoxicity

    A) Diepoxybutane has been positive in a number of genotoxicity studies.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Obtain a complete blood count in symptomatic patients following an alkaline corrosive ingestion.
    B) In patients with signs and symptoms suggesting severe burns, perforation, or bleeding (or adults with deliberate, high volume or high concentration ingestions), obtain renal function tests, serum electrolytes, INR, PTT, type and crossmatch for blood, and monitor urine output. Serum lactate and base deficit may also be useful in these patients.
    C) Monitor pulse oximetry or arterial blood gases in patients with signs and symptoms suggestive of upper airway edema or burns.
    D) Obtain an upright chest x-ray in patients with signs and symptoms suggesting severe burns, perforation, or bleeding (or adults with deliberate, high volume or high concentration ingestions) to evaluate for pneumomediastinum or free air under the diaphragm. The absence of these findings DOES NOT rule out the possibility of necrosis or perforation of the esophagus or stomach. Obtain a chest radiograph in patients with pulmonary signs or symptoms.
    E) Several weeks after ingestion, barium contrast radiographs of the upper GI tract are useful in patients who sustained grade II or III burns, to evaluate for strictures.
    4.1.2) SERUM/BLOOD
    A) HEMATOLOGIC
    1) Obtain a complete blood count in patients with symptomatic alkaline corrosive ingestion.
    B) COAGULATION STUDIES
    1) In patients with signs and symptoms suggesting severe burns, perforation, or bleeding, obtain renal function tests, PT or INR, PTT, and type and crossmatch for blood.
    4.1.3) URINE
    A) OTHER
    1) Monitor urine output in patients with significant gastrointestinal burns, perforation, or bleeding.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) Monitor pulse oximetry or arterial blood gases in patients with signs and symptoms suggestive of upper airway burns.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) Obtain an upright chest x-ray in patients with significant signs and symptoms to evaluate for pneumomediastinum or free air under the diaphragm.
    2) The absence of these findings does not rule out the possibility of necrosis or perforation of the esophagus or stomach (Davis et al, 1972; Allen et al, 1970).
    3) Obtain a chest x-ray in patients with significant pulmonary signs or symptoms.
    4) A water-soluble contrast material should be used initially to exclude esophageal perforation in patients with GI burns associated with alkaline ingestions, as water soluble contrast causes less injury than barium if it extravasates into tissue (Chen et al, 1988; Kirsh & Ritter, 1976) .
    5) Barium esophagogram performed once perforation has been excluded may be useful to evaluate extent of injury or presence of strictures (Leape et al, 1971; Lowe et al, 1979; Chen et al, 1988).

Methods

    A) CHROMATOGRAPHY
    1) Diepoxybutane may be detected in ambient air by either gas-liquid chromatography or a pyridinium chloride-chloroform method for epoxy groups (Clayton & Clayton, 1993).
    B) OTHER
    1) Personnel monitoring badges are available for epoxides with detection limits in the ppb range (Clayton & Clayton, 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, and those with endoscopically demonstrated Grade II or higher burns should be admitted. Patients with respiratory distress, Grade III burns, acidosis, hemodynamic instability, gastrointestinal bleeding, or large ingestions should be admitted to an intensive care setting.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with alkaline corrosive ingestion should be sent to a health care facility for evaluation. Patients who remain asymptomatic over 4 to 6 hours of observation, and those with endoscopic evaluation that demonstrates no burns or only minor Grade I burns and who can tolerate oral intake can be discharged home.

Monitoring

    A) Obtain a complete blood count in symptomatic patients following an alkaline corrosive ingestion.
    B) In patients with signs and symptoms suggesting severe burns, perforation, or bleeding (or adults with deliberate, high volume or high concentration ingestions), obtain renal function tests, serum electrolytes, INR, PTT, type and crossmatch for blood, and monitor urine output. Serum lactate and base deficit may also be useful in these patients.
    C) Monitor pulse oximetry or arterial blood gases in patients with signs and symptoms suggestive of upper airway edema or burns.
    D) Obtain an upright chest x-ray in patients with signs and symptoms suggesting severe burns, perforation, or bleeding (or adults with deliberate, high volume or high concentration ingestions) to evaluate for pneumomediastinum or free air under the diaphragm. The absence of these findings DOES NOT rule out the possibility of necrosis or perforation of the esophagus or stomach. Obtain a chest radiograph in patients with pulmonary signs or symptoms.
    E) Several weeks after ingestion, barium contrast radiographs of the upper GI tract are useful in patients who sustained grade II or III burns, to evaluate for strictures.

Oral Exposure

    6.5.2) PREVENTION OF ABSORPTION
    A) Severe esophageal or gastrointestinal tract irritation or burns might occur following ingestion. Immediate dilution with milk or water might be beneficial.
    B) NASOGASTRIC TUBE
    1) INDICATIONS: Consider insertion of a small, flexible nasogastric tube to aspirate gastric contents after large, recent ingestion of caustics. The risk of worsening mucosal injury (including perforation) must be weighed against the potential benefit.
    2) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric emptying.
    b) AIRWAY PROTECTION: Alert patients - place in Trendelenburg and left lateral decubitus position, with suction available. Obtunded or unconscious patients - cuffed endotracheal intubation. COMPLICATIONS:
    1) Complications of gastric aspiration may include: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach (Vale, 1997). Combative patients may be at greater risk for complications.
    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) OBSERVATION REGIMES
    1) Carefully observe patients with ingestion exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) 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.
    D) ENDOSCOPIC PROCEDURE
    1) There is little information regarding the use of endoscopy, corticosteroids or surgery in the setting of concentrated diepoxybutane ingestion. The following information is derived from experience with other corrosives.
    2) SUMMARY: Obtain consultation concerning endoscopy as soon as possible, and perform endoscopy within the first 24 hours when indicated.
    3) INDICATIONS: Endoscopy should be performed in adults with a history of deliberate ingestion, adults with any signs or symptoms attributable to inadvertent ingestion, and in children with stridor, vomiting, or drooling after unintentional ingestion (Crain et al, 1984). Endoscopy should also be performed in children with dysphagia or refusal to swallow, significant oral burns, or abdominal pain after unintentional ingestion (Gaudreault et al, 1983; Nuutinen et al, 1994). Children and adults who are asymptomatic after accidental ingestion do not require endoscopy (Gupta et al, 2001; Lamireau et al, 2001; Gorman et al, 1992).
    4) RISKS: Numerous large case series attest to the relative safety and utility of early endoscopy in the management of caustic ingestion.
    a) REFERENCES: (Dogan et al, 2006; Symbas et al, 1983; Crain et al, 1984a; Gaudreault et al, 1983a; Schild, 1985; Moazam et al, 1987; Sugawa & Lucas, 1989; Previtera et al, 1990; Zargar et al, 1991; Vergauwen et al, 1991; Gorman et al, 1992)
    5) The risk of perforation during endoscopy is minimized by (Zargar et al, 1991):
    a) Advancing across the cricopharynx under direct vision
    b) Gently advancing with minimal air insufflation
    c) Never retroverting or retroflexing the endoscope
    d) Using a pediatric flexible endoscope
    e) Using extreme caution in advancing beyond burn lesion areas
    f) Most authors recommend endoscopy within the first 24 hours of injury, not advancing the endoscope beyond areas of severe esophageal burns, and avoiding endoscopy during the subacute phase of healing when tissue slough increases the risk of perforation (5 to 15 days after ingestion) (Zargar et al, 1991).
    6) GRADING
    a) Several scales for grading caustic injury exist. The likelihood of complications such as strictures, obstruction, bleeding, and perforation is related to the severity of the initial burn (Zargar et al, 1991):
    b) Grade 0 - Normal examination
    c) Grade 1 - Edema and hyperemia of the mucosa; strictures unlikely.
    d) Grade 2A - Friability, hemorrhages, erosions, blisters, whitish membranes, exudates and superficial ulcerations; strictures unlikely.
    e) Grade 2B - Grade 2A plus deep discreet or circumferential ulceration; strictures may develop.
    f) Grade 3A - Multiple ulcerations and small scattered areas of necrosis; strictures are common, complications such as perforation, fistula formation or gastrointestinal bleeding may occur.
    g) Grade 3B - Extensive necrosis through visceral wall; strictures are common, complications such as perforation, fistula formation, or gastrointestinal bleeding are more likely than with 3A.
    7) FOLLOW UP - If burns are found, follow 10 to 20 days later with barium swallow or esophagram.
    8) SCINTIGRAPHY - Scans utilizing radioisotope labelled sucralfate (technetium 99m) were performed in 22 patients with caustic ingestion and compared with endoscopy for the detection of esophageal burns. Two patients had minimal residual isotope activity on scanning but normal endoscopy and two patients had normal activity on scan but very mild erythema on endoscopy. Overall the radiolabeled sucralfate scan had a sensitivity of 100%, specificity of 81%, positive predictive value of 84% and negative predictive value of 100% for detecting clinically significant burns in this population (Millar et al, 2001). This may represent an alternative to endoscopy, particularly in young children, as no sedation is required for this procedure. Further study is required.
    9) MINIPROBE ULTRASONOGRAPHY - was performed in 11 patients with corrosive ingestion . Findings were categorized as grade 0 (distinct muscular layers without thickening, grade I (distinct muscular layers with thickening), grade II (obscured muscular layers with indistinct margins) and grade III (muscular layers that could not be differentiated). Findings were further categorized as to whether the worst appearing image involved part of the circumference (type a) or the whole circumference (type b). Strictures did not develop in patients with grade 0 (5 patients) or grade I (4 patients) lesions. Transient stricture formation developed in the only patient with grade IIa lesions, and stricture requiring repeated dilatation developed in the only patient with grade IIIb lesions (Kamijo et al, 2004).
    E) CORTICOSTEROID
    1) CORROSIVE INGESTION/SUMMARY: The use of corticosteroids for the treatment of caustic ingestion is controversial. Most animal studies have involved alkali-induced injury (Haller & Bachman, 1964; Saedi et al, 1973). Most human studies have been retrospective and generally involve more alkali than acid-induced injury and small numbers of patients with documented second or third degree mucosal injury.
    2) FIRST DEGREE BURNS: These burns generally heal well and rarely result in stricture formation (Zargar et al, 1989; Howell et al, 1992). Corticosteroids are generally not beneficial in these patients (Howell et al, 1992).
    3) SECOND DEGREE BURNS: Some authors recommend corticosteroid treatment to prevent stricture formation in patients with a second degree, deep-partial thickness burn (Howell et al, 1992). However, no well controlled human study has documented efficacy. Corticosteroids are generally not beneficial in patients with a second degree, superficial-partial thickness burn (Caravati, 2004; Howell et al, 1992).
    4) THIRD DEGREE BURNS: Some authors have recommended steroids in this group as well (Howell et al, 1992). A high percentage of patients with third degree burns go on to develop strictures with or without corticosteroid therapy and the risk of infection and perforation may be increased by corticosteroid use. Most authors feel that the risk outweighs any potential benefit and routine use is not recommended (Boukthir et al, 2004; Oakes et al, 1982; Pelclova & Navratil, 2005).
    5) CONTRAINDICATIONS: Include active gastrointestinal bleeding and evidence of gastric or esophageal perforation. Corticosteroids are thought to be ineffective if initiated more than 48 hours after a burn (Howell, 1987).
    6) DOSE: Administer daily oral doses of 0.1 milligram/kilogram of dexamethasone or 1 to 2 milligrams/kilogram of prednisone. Continue therapy for a total of 3 weeks and then taper (Haller et al, 1971; Marshall, 1979). An alternative regimen in children is intravenous prednisolone 2 milligrams/kilogram/day followed by 2.5 milligrams/kilogram/day of oral prednisone for a total of 3 weeks then tapered (Anderson et al, 1990).
    7) ANTIBIOTICS: Animal studies suggest that the addition of antibiotics can prevent the infectious complications associated with corticosteroid use in the setting of caustic burns. Antibiotics are recommended if corticosteroids are used or if perforation or infection is suspected. Agents that cover anaerobes and oral flora such as penicillin, ampicillin, or clindamycin are appropriate (Rosenberg et al, 1953).
    8) STUDIES
    a) ANIMAL
    1) Some animal studies have suggested that corticosteroid therapy may reduce the incidence of stricture formation after severe alkaline corrosive injury (Haller & Bachman, 1964; Saedi et al, 1973a).
    2) Animals treated with steroids and antibiotics appear to do better than animals treated with steroids alone (Haller & Bachman, 1964).
    3) Other studies have shown no evidence of reduced stricture formation in steroid treated animals (Reyes et al, 1974). An increased rate of esophageal perforation related to steroid treatment has been found in animal studies (Knox et al, 1967).
    b) HUMAN
    1) Most human studies have been retrospective and/or uncontrolled and generally involve small numbers of patients with documented second or third degree mucosal injury. No study has proven a reduced incidence of stricture formation from steroid use in human caustic ingestions (Haller et al, 1971; Hawkins et al, 1980; Yarington & Heatly, 1963; Adam & Brick, 1982).
    2) META ANALYSIS
    a) Howell et al (1992), analyzed reports concerning 361 patients with corrosive esophageal injury published in the English language literature since 1956 (10 retrospective and 3 prospective studies). No patients with first degree burns developed strictures. Of 228 patients with second or third degree burns treated with corticosteroids and antibiotics, 54 (24%) developed strictures. Of 25 patients with similar burn severity treated without steroids or antibiotics, 13 (52%) developed strictures (Howell et al, 1992).
    b) Another meta-analysis of 10 studies found that in patients with second degree esophageal burns from caustics, the overall rate of stricture formation was 14.8% in patients who received corticosteroids compared with 36% in patients who did not receive corticosteroids (LoVecchio et al, 1996).
    c) Another study combined results of 10 papers evaluating therapy for corrosive esophageal injury in humans published between January 1991 and June 2004. There were a total of 572 patients, all patients received corticosteroids in 6 studies, in 2 studies no patients received steroids, and in 2 studies, treatment with and without corticosteroids was compared. Of 109 patients with grade 2 esophageal burns who were treated with corticosteroids, 15 (13.8%) developed strictures, compared with 2 of 32 (6.3%) patients with second degree burns who did not receive steroids (Pelclova & Navratil, 2005).
    3) Smaller studies have questioned the value of steroids (Ferguson et al, 1989; Anderson et al, 1990), thus they should be used with caution.
    4) Ferguson et al (1989) retrospectively compared 10 patients who did not receive antibiotics or steroids with 31 patients who received both antibiotics and steroids in a study of caustic ingestion and found no difference in the incidence of esophageal stricture between the two groups (Ferguson et al, 1989).
    5) A randomized, controlled, prospective clinical trial involving 60 children with lye or acid induced esophageal injury did not find an effect of corticosteroids on the incidence of stricture formation (Anderson et al, 1990).
    a) These 60 children were among 131 patients who were managed and followed-up for ingestion of caustic material from 1971 through 1988; 88% of them were between 1 and 3 years old (Anderson et al, 1990).
    b) All patients underwent rigid esophagoscopy after being randomized to receive either no steroids or a course consisting initially of intravenous prednisolone (2 milligrams/kilogram per day) followed by 2.5 milligrams/kilogram/day of oral prednisone for a total of 3 weeks prior to tapering and discontinuation (Anderson et al, 1990).
    c) Six (19%), 15 (48%), and 10 (32%) of those in the treatment group had first, second and third degree esophageal burns, respectively. In contrast, 13 (45%), 5 (17%), and 11 (38%) of the control group had the same levels of injury (Anderson et al, 1990).
    d) Ten (32%) of those receiving steroids and 11 (38%) of the control group developed strictures. Four (13%) of those receiving steroids and 7 (24%) of the control group required esophageal replacement. All but 1 of the 21 children who developed strictures had severe circumferential burns on initial esophagoscopy (Anderson et al, 1990).
    e) Because of the small numbers of patients in this study, it lacked the power to reliably detect meaningful differences in outcome between the treatment groups (Anderson et al, 1990).
    6) ADVERSE EFFECTS
    a) The use of corticosteroids in the treatment of caustic ingestion in humans has been associated with gastric perforation (Cleveland et al, 1963) and fatal pulmonary embolism (Aceto et al, 1970).
    F) SURGICAL PROCEDURE
    1) SUMMARY: Initially if severe esophageal burns are found a string may be placed in the stomach to facilitate later dilation. Insertion of a specialized nasogastric tube after confirmation of a circumferential burn may prevent strictures. Dilation is indicated after 2 to 4 weeks if strictures are confirmed. If dilation is unsuccessful colonic intraposition or gastric tube placement may be needed. Early laparotomy should be considered in patients with evidence of severe esophageal or gastric burns on endoscopy.
    2) STRING - If a second degree or circumferential burn of the esophagus is found a string may be placed in the stomach to avoid false channel and to provide a guide for later dilation procedures (Gandhi et al, 1989).
    3) STENT - The insertion of a specialized nasogastric tube or stent immediately after endoscopically proven deep circumferential burns is preferred by some surgeons to prevent stricture formation (Mills et al, 1978; (Wijburg et al, 1985; Coln & Chang, 1986).
    a) STUDY - In a study of 11 children with deep circumferential esophageal burns after caustic ingestion, insertion of a silicone rubber nasogastric tube for 5 to 6 weeks without steroids or antibiotics was associated with stricture formation in only one case (Wijburg et al, 1989).
    4) DILATION - Dilation should be performed at 1 to 4 week intervals when stricture is present(Gundogdu et al, 1992). Repeated dilation may be required over many months to years in some patients. Successful dilation of gastric antral strictures has also been reported (Hogan & Polter, 1986; Treem et al, 1987).
    5) COLONIC REPLACEMENT - Intraposition of colon may be necessary if dilation fails to provide an adequate sized esophagus (Chiene et al, 1974; Little et al, 1988; Huy & Celerier, 1988).
    6) LAPAROTOMY/LAPAROSCOPY - Several authors advocate laparotomy or laparoscopy in patients with endoscopic evidence of severe esophageal or gastric burns to evaluate for the presence of transmural gastric or esophageal necrosis (Cattan et al, 2000; Estrera et al, 1986; Meredith et al, 1988; Wu & Lai, 1993).
    a) STUDY - In a retrospective study of patients with extensive transmural esophageal necrosis after caustic ingestion, all 4 patients treated in the conventional manner (esophagoscopy, steroids, antibiotics, and repeated evaluation for the occurrence of esophagogastric necrosis and perforation) died while all 3 patients treated with early laparotomy and immediate esophagogastric resection survived (Estrera et al, 1986).

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) AIRWAY MANAGEMENT
    1) If severe upper airway irritation and edema occur, endotracheal intubation could be required.
    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) 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) INJURY OF GLOBE OF EYE
    1) Severe eye injury could occur from either direct eye contact or vapor exposure (Grant, 1986). Prolonged flushing and early ophthalmologic consultation should be considered.
    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) 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.
    B) 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.
    C) BURN
    1) APPLICATION
    a) These recommendations apply to patients with MINOR chemical burns (FIRST DEGREE; SECOND DEGREE: less than 15% body surface area in adults; less than 10% body surface area in children; THIRD DEGREE: less than 2% body surface area). Consultation with a clinician experienced in burn therapy or a burn unit should be obtained if larger area or more severe burns are present. Neutralizing agents should NOT be used.
    2) DEBRIDEMENT
    a) After initial flushing with large volumes of water to remove any residual chemical material, clean wounds with a mild disinfectant soap and water.
    b) DEVITALIZED SKIN: Loose, nonviable tissue should be removed by gentle cleansing with surgical soap or formal skin debridement (Moylan, 1980; Haynes, 1981). Intravenous analgesia may be required (Roberts, 1988).
    c) BLISTERS: Removal and debridement of closed blisters is controversial. Current consensus is that intact blisters prevent pain and dehydration, promote healing, and allow motion; therefore, blisters should be left intact until they rupture spontaneously or healing is well underway, unless they are extremely large or inhibit motion (Roberts, 1988; Carvajal & Stewart, 1987).
    3) TREATMENT
    a) TOPICAL ANTIBIOTICS: Prophylactic topical antibiotic therapy with silver sulfadiazine is recommended for all burns except superficial partial thickness (first-degree) burns (Roberts, 1988). For first-degree burns bacitracin may be used, but effectiveness is not documented (Roberts, 1988).
    b) SYSTEMIC ANTIBIOTICS: Systemic antibiotics are generally not indicated unless infection is present or the burn involves the hands, feet, or perineum.
    c) WOUND DRESSING:
    1) Depending on the site and area, the burn may be treated open (face, ears, or perineum) or covered with sterile nonstick porous gauze. The gauze dressing should be fluffy and thick enough to absorb all drainage.
    2) Alternatively, a petrolatum fine-mesh gauze dressing may be used alone on partial-thickness burns.
    d) DRESSING CHANGES:
    1) Daily dressing changes are indicated if a burn cream is used; changes every 3 to 4 days are adequate with a dry dressing.
    2) If dressing changes are to be done at home, the patient or caregiver should be instructed in proper techniques and given sufficient dressings and other necessary supplies.
    e) Analgesics such as acetaminophen with codeine may be used for pain relief if needed.
    4) TETANUS PROPHYLAXIS
    a) The patient's tetanus immunization status should be determined. Tetanus toxoid 0.5 milliliter intramuscularly or other indicated tetanus prophylaxis should be administered if required.
    D) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) EFFICACY
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Range Of Toxicity

Summary

    A) Serious burns are less likely if the pH is less than 11.5. Injury is greater with large exposures and high concentrations.
    B) With highly concentrated liquids, esophageal burns may occur in up to 100% of patients, even after accidental ingestion.
    C) Nasal mucosa and eye irritation occur at an airborne concentration of 10 parts per million. The odor is barely recognizable at 5 parts per million.

Minimum Lethal Exposure

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

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The maximum tolerated human exposure to this agent has not been delineated.
    2) Nasal mucosa and eye irritation occur at airborne vapor concentrations of 10 parts per million in humans, while the odor is barely recognizable at 5 parts per million (Clayton & Clayton, 1982). There are no odor or other warning properties at 1 part per million (a suggested threshold exposure concentration) (Clayton & Clayton, 1982).

Workplace Standards

    A) ACGIH TLV Values for CAS1464-53-5 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS1464-53-5 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS1464-53-5 :
    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): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): R ; Listed as: Diepoxybutane
    a) R : RAHC = Reasonably anticipated to be a human carcinogen

    D) OSHA PEL Values for CAS1464-53-5 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (ORAL)MOUSE:
    1) 72 mg/kg (RTECS, 1988)
    B) LD50- (ORAL)RAT:
    1) 78 mg/kg (RTECS, 1988)

Pharmacology Toxicology

Toxicologic Mechanism

    A) Diepoxybutane is a direct irritant of skin, eyes, and mucous membranes (Lewis, 1992).
    B) Epoxides usually exert their toxic effects via formation of reactive carbonium ions (Clayton & Clayton, 1993).
    C) Diepoxides such as diepoxybutane contain two functional groups and are potential crosslinking agents for nucleic acids and proteins (Clayton & Clayton, 1993).

Physicochemical

Physical Characteristics

    A) Diepoxybutane is a colorless to water-white, low viscosity liquid (HSDB, 2005; Clayton & Clayton, 1993) Lewis, 1992).

Molecular Weight

    A) 86.10

References

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