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DIGLYCIDYL ETHER

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Diglycidyl ether is a compound having two 2,3-epoxypropyl groups combined through an ether linkage (Finkel, 1983).

Specific Substances

    A) No Synonyms were found in group or single elements
    1.2.1) MOLECULAR FORMULA
    1) C6-H10-O3

Available Forms Sources

    A) SOURCES
    1) It may be a trace contaminant in epoxy derivatives of epichlorohydrin (Clayton & Clayton, 1993).
    B) USES
    1) Diglycidyl ether is used as a reactive epoxy resin diluent, an agent for treating textiles, a chemical intermediate, and a stabilizing agent for chlorinated organic compounds (Hathaway et al, 1991; EPA, 1985) ACGIH, 1991).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Diglycidyl ether is an irritant of eyes, skin, and mucous membranes. Clouding of the cornea may follow vapor exposure. Severe dermal burns that heal slowly may occur with direct skin contact. Dermal sensitization may develop.
    B) Central nervous system depression and coma have been observed in exposed experimental animals. Single injections and chronic dermal or inhalation exposure have produced bone marrow depression in experimental animals. Liver and kidney damage have been seen in exposed experimental animals. Pneumonitis has been observed in experimental animals, even with oral exposure.
    C) Ingestions have not been reported, but gastrointestinal tract irritation might be predicted to occur based on the other irritant properties of diglycidyl ether.
    D) Diglycidyl ether is mutagenic in several assays, and produces dermal epitheliomas following repeated dermal application in mice.
    E) Because of its toxicity, diglycidyl ether generally is not used outside experimental laboratories. No systemic effects have been reported in humans.
    0.2.4) HEENT
    A) Severe corneal irritation may be seen. In experimental animals, corneal opacities and loosening of the corneal epithelium from the stroma have been observed. Mucosal irritation of the nose and throat may be seen.
    0.2.6) RESPIRATORY
    A) Inhalation exposure causes irritation of the respiratory tract. Pulmonary edema might occur.
    0.2.7) NEUROLOGIC
    A) Ataxia and coma have been observed in exposed experimental animals.
    0.2.8) GASTROINTESTINAL
    A) Gastrointestinal tract irritation may be predicted based on the other irritant properties of diglycidyl ether.
    0.2.9) HEPATIC
    A) Hepatotoxicity has developed in exposed experimental animals. This effect has not been reported in exposed humans.
    0.2.10) GENITOURINARY
    A) Nephrotoxicity has developed in exposed experimental animals. This effect has not been reported in exposed humans.
    0.2.13) HEMATOLOGIC
    A) Bone marrow depression occurs in experimental animals.
    0.2.14) DERMATOLOGIC
    A) Dermal irritation and sensitization may be seen.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no reproductive studies were found for diglycidyl ether in humans. Decreased spermatogenesis or focal testicular necrosis have been noted in experimental animals.
    0.2.21) CARCINOGENICITY
    A) In mice, diglycidyl ether was found to be an equivocal tumorigenic agent by RTECS criteria.

Laboratory Monitoring

    A) Monitor complete blood count and liver and renal function tests in patients with significant exposure.
    B) 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) Observe patients with ingestion carefully for the possible development of esophageal or gastrointestinal tract irritation or burns. If signs or symptoms of esophageal irritation or burns are present, consider endoscopy to determine the extent of injury.
    C) If central nervous system depression or severe upper airway irritation occur, assure airway patency and oxygenation. Endotracheal intubation could be necessary.
    D) Observe patients carefully for signs of pneumonitis.
    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) 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.

Range Of Toxicity

    A) Lethal percutaneous doses in rats and rabbits: 1.0 and 1.5 grams per kilogram. Ten parts per million causes moderate irritation of the eyes and respiratory tract in humans, and 3 parts per million caused respiratory tract irritation in experimental animals.

Clinical Effects

Summary Of Exposure

    A) Diglycidyl ether is an irritant of eyes, skin, and mucous membranes. Clouding of the cornea may follow vapor exposure. Severe dermal burns that heal slowly may occur with direct skin contact. Dermal sensitization may develop.
    B) Central nervous system depression and coma have been observed in exposed experimental animals. Single injections and chronic dermal or inhalation exposure have produced bone marrow depression in experimental animals. Liver and kidney damage have been seen in exposed experimental animals. Pneumonitis has been observed in experimental animals, even with oral exposure.
    C) Ingestions have not been reported, but gastrointestinal tract irritation might be predicted to occur based on the other irritant properties of diglycidyl ether.
    D) Diglycidyl ether is mutagenic in several assays, and produces dermal epitheliomas following repeated dermal application in mice.
    E) Because of its toxicity, diglycidyl ether generally is not used outside experimental laboratories. No systemic effects have been reported in humans.

Heent

    3.4.1) SUMMARY
    A) Severe corneal irritation may be seen. In experimental animals, corneal opacities and loosening of the corneal epithelium from the stroma have been observed. Mucosal irritation of the nose and throat may be seen.
    3.4.3) EYES
    A) CONJUNCTIVITIS - Severe corneal irritation may be seen with either direct contact or vapor exposure (Grant, 1986). Corneal opacities and loosening of the corneal epithelium from the stroma have been observed following vapor exposure in experimental animals (Grant, 1986).
    B) IRRITATION - Diglycidyl ether induced severe eye irritation in the rabbit in the Standard Draize Test (RTECS , 1995).
    3.4.5) NOSE
    A) MUCOSAL IRRITATION - Inhalation exposure causes irritation of the mucosa of the nose and throat (Hathaway et al, 1991).
    3.4.6) THROAT
    A) MUCOSAL IRRITATION - Inhalation exposure causes irritation of the mucosa of the nose and throat (Hathaway et al, 1991).

Respiratory

    3.6.1) SUMMARY
    A) Inhalation exposure causes irritation of the respiratory tract. Pulmonary edema might occur.
    3.6.2) CLINICAL EFFECTS
    A) IRRITATION SYMPTOM
    1) Inhalation exposure causes irritation of the respiratory tract (Hathaway et al, 1991). Pulmonary edema might occur in serious exposures.
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) PNEUMONITIS
    a) Pneumonitis and pulmonary hemorrhage have been observed in experimental animals, even when diglycidyl ether was administered orally (Clayton & Clayton, 1993). This effect has not been reported in exposed humans.

Neurologic

    3.7.1) SUMMARY
    A) Ataxia and coma have been observed in exposed experimental animals.
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CNS DEPRESSION
    a) Central nervous system depression with ataxia and coma is seen in experimental animals administered diglycidyl ether (Clayton & Clayton, 1982) ACGIH, 1991). This effect has not been reported in exposed humans.

Gastrointestinal

    3.8.1) SUMMARY
    A) Gastrointestinal tract irritation may be predicted based on the other irritant properties of diglycidyl ether.
    3.8.2) CLINICAL EFFECTS
    A) GASTRITIS
    1) Ingestions have not been reported, but irritation or burns of the esophagus or gastrointestinal tract might be predicted based on the other irritant properties of diglycidyl ether.

Hepatic

    3.9.1) SUMMARY
    A) Hepatotoxicity has developed in exposed experimental animals. This effect has not been reported in exposed humans.
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATOCELLULAR DAMAGE
    a) Exposed experimental animals have developed liver injury (Clayton & Clayton, 1993). This effect has not been reported in exposed humans.

Genitourinary

    3.10.1) SUMMARY
    A) Nephrotoxicity has developed in exposed experimental animals. This effect has not been reported in exposed humans.
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) Exposed experimental animals have developed kidney injury (Clayton & Clayton, 1993). This effect has not been reported in exposed humans.
    2) TESTIS DISORDER
    a) MALE REPRODUCTIVE EFFECTS - Decreased spermatogenesis or focal testicular necrosis have been noted in some animal experiments (Clayton & Clayton, 1993) ACGIH, 1991).

Hematologic

    3.13.1) SUMMARY
    A) Bone marrow depression occurs in experimental animals.
    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) MARROW DEPRESSION
    a) Bone marrow depression and leukocytopenia followed by leukocytosis have been observed with both acute and chronic diglycidyl ether administration in experimental animals (Clayton & Clayton, 1993) ACGIH, 1991). These effects have not been reported in exposed humans.

Dermatologic

    3.14.1) SUMMARY
    A) Dermal irritation and sensitization may be seen.
    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) Dermal irritation or severe, slow healing skin burns may occur following direct contact (Hathaway et al, 1991) ACGIH, 1991).
    B) DERMATITIS
    1) Diglycidyl ether is a strong skin sensitizing agent (Gosselin et al, 1984; Clayton & Clayton, 1993).
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) IRRITATION
    a) Diglycidyl ether induced moderate to severe skin irritation in the rabbit in the Standard Draize Test (RTECS , 1995).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no reproductive studies were found for diglycidyl ether in humans. Decreased spermatogenesis or focal testicular necrosis have been noted in experimental animals.
    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 diglycidyl ether.
    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 diglycidyl ether exposure during pregnancy or lactation.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS2238-07-5 (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) In mice, diglycidyl ether was found to be an equivocal tumorigenic agent by RTECS criteria.
    3.21.3) HUMAN STUDIES
    A) CARCINOMA
    1) ANIMAL STUDIES
    a) Repeated dermal exposure causes epitheliomas in mice (Clayton & Clayton, 1993). Repeated injection did not produce tumors in rats (ACGIH, 1986).
    b) In mouse studies, diglycidyl ether was found to be an equivocal tumorigenic agent by RTECS criteria with skin and appendage tumors (RTECS , 1995).

Genotoxicity

    A) Diglycidyl ether was mutagenic and caused chromosome aberrations in several assay systems.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor complete blood count and liver and renal function tests in patients with significant exposure.
    B) 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.
    B) HEMATOLOGIC
    1) Monitor complete blood count in patients with significant exposure.
    C) ACID/BASE
    1) Monitor arterial blood gases in patients with significant inhalation exposure or respiratory tract irritation.
    4.1.4) OTHER
    A) OTHER
    1) DERMAL
    a) Dermal patch testing may be useful in the evaluation of patients (especially atopic individuals) with suspected skin sensitization to diglycidyl ether.

Radiographic Studies

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

Methods

    A) CHROMATOGRAPHY
    1) Diglycidyl ether can be adsorbed onto charcoal and analyzed by gas liquid chromatography (Sittig, 1985).
    B) OTHER
    1) No NIOSH Analytical method has been established (NIOSH, 1995).

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) All patients who are symptomatic following ingestion of diglycidyl ether should be admitted to the hospital and carefully monitored for the possible development of pneumonitis or severe esophageal or gastrointestinal tract irritation or burns.
    6.3.3) DISPOSITION/INHALATION EXPOSURE
    6.3.3.1) ADMISSION CRITERIA/INHALATION
    A) All patients with significant inhalation exposure or respiratory tract irritation should be admitted to the hospital and carefully monitored for the possible development of severe respiratory tract irritation or pulmonary edema.

Monitoring

    A) Monitor complete blood count and liver and renal function tests in patients with significant exposure.
    B) Monitor arterial blood gases and chest x-ray in patients with inhalation exposure.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) GENERAL - Move victims of inhalation exposure from the toxic environment and administer 100% humidified supplemental oxygen with assisted ventilation as required. Exposed skin and eyes should be copiously flushed. Induced emesis should be avoided. Carefully observe patients with ingestion exposure for the development of significant esophageal or gastrointestinal tract irritation or burns.
    B) 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) 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.
    C) 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).
    D) 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.
    E) ORAL EXPOSURE -
    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.
    2) Significant esophageal or gastrointestinal tract irritation or burns may occur following ingestion. The possible benefit of early removal of some ingested material by cautious gastric lavage must be weighed against potential complications of bleeding or perforation.
    3) 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.
    4) If central nervous system depression or severe upper airway irritation occur, assure airway patency and oxygenation. Endotracheal intubation could be necessary.
    5) Observe patients carefully for signs of pneumonitis.
    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) Induced emesis should be avoided.
    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 with ingestion exposure carefully for the development of signs of esophageal or gastrointestinal tract irritation or burns (nausea, vomiting, diarrhea, abdominal pain, bleeding, perforation, etc).
    2) Observe patients with ingestion carefully for the possible development of esophageal or gastrointestinal tract irritation or burns. If signs or symptoms of esophageal irritation or burns are present, consider endoscopy to determine the extent of injury.
    C) AIRWAY MANAGEMENT
    1) If central nervous system depression or severe upper airway irritation occur, assure airway patency and oxygenation. Endotracheal intubation could be necessary.
    D) MONITORING OF PATIENT
    1) Monitor complete blood count and liver and renal function tests.
    E) MYELOSUPPRESSION
    1) If severe bone marrow depression should occur, blood component transfusion could be required.
    F) PNEUMONITIS
    1) Pneumonitis has been seen in experimental animals with oral exposure (Clayton & Clayton, 1993). Observe patients carefully for signs of pneumonitis (cough, fever, sputum production, chest pain), and obtain chest x-ray, sputum cultures, and gram stain should they occur. Antibiotics and chest physiotherapy could be required.
    G) HOSPITAL ADMISSION
    1) All patients who are symptomatic following ingestion of diglycidyl ether should be admitted to the hospital and carefully monitored for the possible development of pneumonitis or severe esophageal or gastrointestinal tract irritation or burns.

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 could 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) OPHTHALMIC EXAMINATION AND EVALUATION
    1) Severe corneal injury may occur. 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) 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.
    B) ACUTE ALLERGIC REACTION
    1) Patients with dermal hypersensitivity reactions may require treatment with systemic corticosteroids or antihistamines.
    C) 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 diglycidyl ether poisoning.

Range Of Toxicity

Summary

    A) Lethal percutaneous doses in rats and rabbits: 1.0 and 1.5 grams per kilogram. Ten parts per million causes moderate irritation of the eyes and respiratory tract in humans, and 3 parts per million caused respiratory tract irritation in experimental animals.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.
    B) ROUTE OF EXPOSURE
    1) DERMAL - The lethal percutaneous doses in rats and rabbits after 24 hours of exposure are 1.0 and 1.5 grams per kilogram respectively (ACGIH, 1991).
    2) ORAL - Diglycidyl ether is more toxic by the oral route than when applied percutaneously (ACGIH, 1991).

Maximum Tolerated Exposure

    A) ROUTE OF EXPOSURE
    1) The odor of diglycidyl ether becomes recognizable at a concentration of about 5 parts per million, while 10 parts per million causes moderate irritation of the eyes and respiratory tract (ACGIH, 1991; (Clayton & Clayton, 1993).
    2) Inhalation exposure to 3 parts per million caused respiratory tract irritation in experimental animals (Clayton & Clayton, 1981).

Workplace Standards

    A) ACGIH TLV Values for CAS2238-07-5 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Diglycidyl ether (DGE)
    a) TLV:
    1) TLV-TWA: 0.01 ppm
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A4
    2) Codes: Not Listed
    3) Definitions:
    a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    c) TLV Basis - Critical Effect(s): Eye and skin irr; male repro dam
    d) Molecular Weight: 130.14
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    B) NIOSH REL and IDLH Values for CAS2238-07-5 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Diglycidyl ether
    2) REL:
    a) TWA: 0.1 ppm (0.5 mg/m(3))
    b) STEL:
    c) Ceiling:
    d) Carcinogen Listing: (Ca) NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).
    e) Skin Designation: Not Listed
    f) Note(s): See Appendix A
    3) IDLH:
    a) IDLH: 10 ppm
    b) Note(s): Ca
    1) Ca: NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A).

    C) Carcinogenicity Ratings for CAS2238-07-5 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Diglycidyl ether (DGE)
    a) A4 :Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Ca ; Listed as: Diglycidyl ether
    a) Ca : NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).
    5) MAK (DFG, 2002): Category 3B ; Listed as: Diglycidyl ether (DGE)
    a) Category 3B : Substances for which in vitro or animal studies have yielded evidence of carcinogenic effects that is not sufficient for classification of the substance in one of the other categories. Further studies are required before a final decision can be made. A MAK value can be established provided no genotoxic effects have been detected. (Footnote: In the past, when a substance was classified as Category 3 it was given a MAK value provided that it had no detectable genotoxic effects. When all such substances have been examined for whether or not they may be classified in Category 4, this sentence may be omitted.)
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS2238-07-5 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Diglycidyl ether (DGE)
    2) Table Z-1 for Diglycidyl ether (DGE):
    a) 8-hour TWA:
    1) ppm: 0.5
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 2.8
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value: (C) - An employee's exposure to this substance shall at no time exceed the exposure limit given.
    4) Skin Designation: No
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: RTECS, 1995 Lewis, 1992 Clayton & Clayton, 1993
    1) LD50- (INHALATION)MOUSE:
    a) 86 ppm for 4H
    2) LD50- (ORAL)MOUSE:
    a) 170-192 mg/kg
    3) LD50- (ORAL)RAT:
    a) 450-510 mg/kg
    4) LD50- (SKIN)RAT:
    a) 1000 mg/kg

Pharmacology Toxicology

Toxicologic Mechanism

    A) Diglycidyl ether is a direct irritant of eyes, skin, and mucous membranes (Hathaway et al, 1991; Finkel, 1983; Gosselin et al, 1984). It can also cause skin sensitization (Gosselin et al, 1984).
    B) Diglycidyl ether is a direct depressant of the central nervous system in experimental animals (Clayton & Clayton, 1982).
    C) Diglycidyl ether is mutagenic in several assay systems and carcinogenic when repeatedly applied to the skin of mice (Clayton & Clayton, 1993).
    D) Diglycidyl ether causes bone marrow suppression in experimental animals and has an adverse effect on rapidly developing cell lines such as spermatozoa (Clayton & Clayton, 1993).
    E) Diglycidyl ether is an alkylating agent (Loveless, 1951; Kihlman, 1956). Many of its adverse effects are consistent with alkylation of macromolecules being the primary mode of action.

Physicochemical

Physical Characteristics

    A) Diglycidyl ether is a colorless liquid with a strong, irritating odor (Hathaway et al, 1991) ACGIH, 1991; (Sax & Lewis, 1987).

Molecular Weight

    A) 130.14 (Sax & Lewis, 1987) ACGIH, 1991)

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