Contact Us    Contact Us     |     Feedback
MOBILE VIEW  | 

PHOSGENE OXIME

Export To Excel

Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Phosgene oxime, or dichloroformoxime, is a halogenated oxime used as a blistering agent for chemical terrorist/warfare purposes. This chemical is also considered a "Nettle Rush" gas or nettle agent. In liquid or vapor form it causes an almost immediate dermal effect with corrosive skin and tissue lesions.
    B) Military Classification: Blister Agent
    C) Military abbreviation: CX

Specific Substances

    1) Agent CX
    2) CX
    3) Dichloroformoxime
    4) Molecular Formula: CH-Cl2-NO
    1.2.1) MOLECULAR FORMULA
    1) CHCl2NOH
    2) CHCl2NO

Available Forms Sources

    A) FORMS
    1) Halogenated oximes include phosgene oxime, diiodoformoxime, dibromoformoxime, and monochloroformoxime. Phosgene oxime is the most irritant of the series. The latter agents are also urticants and were discovered long before World War II, but are not considered as chemical/terrorist warfare threats because they are not nearly as toxic as phosgene oxime.
    2) Phosgene oxime may appear as a liquid or as a colorless, low-melting point crystalline solid, readily soluble in water. It has an appreciable vapor pressure. As a dry solid, this chemical decomposes spontaneously and needs to be stored at low temperatures ((US Army, 1996)).
    B) USES
    1) Phosgene oxime was developed for use as a terrorist/warfare agent, and is classified as a vesicant. It is not a true vesicant since it does not cause skin blisters; therefore, a nettle or urticant agent is a better description. It can be dispersed as a liquid or vapor causing almost immediate tissue damage upon contact (U.S. Army , 1995; U.S. Army, 1997).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Phosgene oxime is classified as a vesicant, an agent which causes a corrosive type of skin and tissue lesion. It is not a true vesicant since it does not cause blisters; therefore, it is best described as a uriticant or nettle agent. It is characterized by immediate pain and tissue damage within seconds. Extreme pain may last for several days. Damage to the eyes, skin, and airways is similar to that caused by mustard gas. The crystalline solid form will produce enough vapor to cause symptoms.
    B) INHALATION - Severe respiratory irritant in low concentrations. Irritation begins at 0.2 mg/min/m(3) and becomes unbearable at 3 mg/min/m(3). Respiratory effects include pulmonary edema and death due to respiratory arrest.
    C) OCULAR - Vapors at low concentrations cause severe eye irritation. Ocular exposures to higher concentrations can cause incapacitating inflammation, and blindness.
    D) SKIN - High concentrations cause severe skin irritation with rapidly developing necrotizing wounds. Immediate pain is followed by blanching with an erythematous ring in 30 seconds, a wheal in 30 minutes, and necrosis in 24 hours or later.
    0.2.4) HEENT
    A) High concentrations can cause corneal lesions, dimming of vision, and blindness. Both liquid and vapor contact can cause immediate mucous membrane irritation and pain.
    0.2.6) RESPIRATORY
    A) Both the vapor and contact with the liquid causes immediate pain and irritation of the upper airways. Inhalation or systemic absorption may cause respiratory tract irritation, dyspnea, and pulmonary edema.
    0.2.13) HEMATOLOGIC
    A) Unlike mustard gas, phosgene oxime does NOT cause damage to the bone marrow.
    0.2.14) DERMATOLOGIC
    A) Exposure to liquid or vapor producing pain will also cause skin necrosis at the site of contact.
    0.2.20) REPRODUCTIVE
    A) 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) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Laboratory Monitoring

    A) Perform routine laboratory studies on persons requiring hospital admission such as CBC, liver enzymes, kidney function tests, glucose, and serum electrolytes.
    B) Monitor arterial blood gases, pulse oximetry, pulmonary function, and chest x-ray in patients following significant exposures. Non-cardiogenic pulmonary edema is a toxic effect of phosgene oxime and may develop several hours after exposure.
    C) Because effects can be delayed, serial chest x-rays and pulse oximetry (or ABGs) are recommended for inhalation exposures.
    D) Monitor fluid balance if pulmonary edema is present.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) DO NOT INDUCE EMESIS. Nausea and vomiting should be treated with antiemetics.
    B) MUCOSAL DECONTAMINATION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. The exact 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. Patients should not be forced to drink after ingestion of an acid, nor should they be allowed to drink larger volumes since this may induce vomiting, and thereby re-exposure of the injured tissues to the corrosive acid. Dilution may only be helpful if performed in the first seconds to minutes after ingestion.
    C) GASTRIC DECONTAMINATION: Ipecac contraindicated. Activated charcoal is not recommended as it may interfere with endoscopy and will not reduce injury to GI mucosa. Consider insertion of a small, flexible nasogastric or orogastric tube to suction gastric contents after recent large ingestion of a strong acid; the risk of further mucosal injury or iatrogenic esophageal perforation must be weighed against potential benefits of removing any remaining acid from the stomach.
    D) ENDOSCOPY: Because acid ingestion may cause severe gastric burns with relatively few initial signs and symptoms, endoscopic evaluation is recommended within 24 hours in any patient with a definite history of ingesting a strong acid, even if asymptomatic. If burns are found, follow 10 to 20 days later with a barium swallow.
    E) PHARMACOLOGIC TREATMENT: The use of corticosteroids is controversial. Patients with first degree burns generally do well and rarely develop strictures. Corticosteroids are generally not beneficial in these patients. Some authors have advocated the use of corticosteroids for second degree, deep-partial thickness burns within 48 hours of ingestion in patients without gastrointestinal bleeding or evidence of perforation. However, no well-controlled human study has documented efficacy. Corticosteroids are generally not beneficial in patients with second degree, superficial-partial thickness burns. Some authors have recommended steroids in patients with third degree burns. 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. Antibiotics are indicated for suspected perforation or infection and in patients receiving corticosteroids.
    F) 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.
    0.4.3) INHALATION EXPOSURE
    A) There is no antidote for phosgene. Treatment is symptomatic and supportive.
    B) 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.
    C) Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    D) 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) Treatment is symptomatic and supportive. Flush eyes immediately with water or isotonic sodium bicarbonate (if available) for at least an hour or until the cul-de-sacs are free of particulate matter and returned to neutrality (confirm with pH paper).
    B) EYE ASSESSMENT: The extent of eye injury (degree of corneal opacification and perilimbal whitening) may not be apparent for 48 to 72 hours after the burn.
    C) All patients with significant eye exposure should be carefully monitored for possible development of systemic signs and symptoms. Follow treatment recommendations in INHALATION EXPOSURE section where appropriate.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) Treatment is symptomatic and supportive. There is no antidote for phosgene oxime exposure. Most burns are second degree, but it is possible to have third degree burns with a liquid exposure. Treat necrotic lesions as a thermal burn. Skin lesions may require many months to heal.
    2) 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).
    3) Treat dermal irritation or burns with standard topical therapy, including dressings and topical antibiotic ointments.
    4) 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.

Range Of Toxicity

    A) Phosgene oxime is not known to have been used on a battlefield, and information regarding its effects on humans is limited. Concentrations below 8% appear to cause no or inconsistent effects.

Clinical Effects

Summary Of Exposure

    A) Phosgene oxime is classified as a vesicant, an agent which causes a corrosive type of skin and tissue lesion. It is not a true vesicant since it does not cause blisters; therefore, it is best described as a uriticant or nettle agent. It is characterized by immediate pain and tissue damage within seconds. Extreme pain may last for several days. Damage to the eyes, skin, and airways is similar to that caused by mustard gas. The crystalline solid form will produce enough vapor to cause symptoms.
    B) INHALATION - Severe respiratory irritant in low concentrations. Irritation begins at 0.2 mg/min/m(3) and becomes unbearable at 3 mg/min/m(3). Respiratory effects include pulmonary edema and death due to respiratory arrest.
    C) OCULAR - Vapors at low concentrations cause severe eye irritation. Ocular exposures to higher concentrations can cause incapacitating inflammation, and blindness.
    D) SKIN - High concentrations cause severe skin irritation with rapidly developing necrotizing wounds. Immediate pain is followed by blanching with an erythematous ring in 30 seconds, a wheal in 30 minutes, and necrosis in 24 hours or later.

Heent

    3.4.1) SUMMARY
    A) High concentrations can cause corneal lesions, dimming of vision, and blindness. Both liquid and vapor contact can cause immediate mucous membrane irritation and pain.
    3.4.3) EYES
    A) Phosgene oxime is violently irritating to the eyes. It causes intense, immediate pain and local tissue destruction on contact with skin, eyes, and mucuous membranes. Very low concentrations can cause lacrimation, inflammation, and temporary blindness (Sidell et al, 1998; (US Army, 1996); USACHPPM , 2001).
    B) High concentrations can cause corneal lesions, dimming of vision, and blindness (USACHPPM , 2001; (US Army, 1996)).
    3.4.5) NOSE
    A) Both liquid and vapor contact can cause immediate, intense and almost intolerable pain and local tissue destruction on contact with skin, eyes, and mucuous membranes.(Sidell et al, 1998) U.S Army, 2001).
    3.4.6) THROAT
    A) In both liquid and vapor forms, contact with mucous membranes can cause immediate moderate to severe pain and irritation of the mouth and throat (Sidell et al, 1998).

Respiratory

    3.6.1) SUMMARY
    A) Both the vapor and contact with the liquid causes immediate pain and irritation of the upper airways. Inhalation or systemic absorption may cause respiratory tract irritation, dyspnea, and pulmonary edema.
    3.6.2) CLINICAL EFFECTS
    A) IRRITATION SYMPTOM
    1) Phosgene oxime is an upper airways irritant. Both liquid and vapor contact cause immediate pain and irritation to mucous membranes of the upper airways (Sidell et al, 1998; U.S. Army , 1995; (US Army, 1996)).
    B) ACUTE LUNG INJURY
    1) Inhalation or systemic absorption may cause respiratory tract irritation, dyspnea and pulmonary edema. Non-cardiogenic pulmonary edema may occur after inhalation and after skin application. Following a large amount of phosgene oxime on the skin, pulmonary edema may occur after a several hour delay. Generally, the longer the onset time, the less severe the poisoning. Deaths, which are predicted to be rare, would be due to respiratory arrest (U.S. Army , 1995; U.S. Army, 1997).
    a) Necrotizing bronchiolitis and thrombosis of pulmonary venules may accompany pulmonary edema; pulmonary thromboses are prominent (U.S. Army, 1997).

Gastrointestinal

    3.8.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) GASTRITIS HEMORRHAGIC
    a) No human data is available, but animal studies suggest hemorrhagic inflammatory changes in the gastrointestinal tract following exposures to phosgene oxime (U.S. Army , 1995).

Hematologic

    3.13.1) SUMMARY
    A) Unlike mustard gas, phosgene oxime does NOT cause damage to the bone marrow.
    3.13.2) CLINICAL EFFECTS
    A) BONE MARROW FINDING
    1) LACK OF EFFECT
    a) Unlike mustard gas, phosgene oxime does NOT cause damage to the bone marrow (Sidell et al, 1998).

Dermatologic

    3.14.1) SUMMARY
    A) Exposure to liquid or vapor producing pain will also cause skin necrosis at the site of contact.
    3.14.2) CLINICAL EFFECTS
    A) SKIN NECROSIS
    1) Any exposure to liquid or vapor producing pain will also cause skin necrosis at the site of contact. Dermal contact to liquid or vapor results in immediate, extreme pain followed by blanching with an erythematous ring in 60 seconds; wheal follows in 30 minutes; skin is edematous in one hour; within 24 hours original blanched area acquires brown pigmentation; at one week, eschar forms in pigmented area; at about 3 weeks, desquamation with necrosis followed by crust formation and purulent exudate occurs. Skin lesions resemble those caused by a strong acid. Extreme pain can persist for days (U.S. Army , 1995; (US Army, 1996); U.S. Army, 1997)
    a) The zone of erythema radiates from the point of application, which develops within 60 seconds following a few milligrams of phosgene oxime dropped onto the skin, and resembles a wagon wheel in appearance ((US Army, 1996)).
    b) Skin injuries can take 1 to 3 months to heal. About 20% of exposed victims are expected to show healing delayed beyond 2 months. Itching may be prominent throughout healing process ((US Army, 1996)).
    c) In some cases, healing was not complete after 4-6 months following the exposure incident (U.S. Army, 1997).
    B) DISCOLORATION OF SKIN
    1) Following either liquid or vapor contact, visible, grayish tissue damage may be seen within several minutes (U.S. Army, 1997).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.3) 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 CAS1794-86-1 (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) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Genotoxicity

    A) At the time of this review, no data were available to assess the mutagenic or genotoxic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Perform routine laboratory studies on persons requiring hospital admission such as CBC, liver enzymes, kidney function tests, glucose, and serum electrolytes.
    B) Monitor arterial blood gases, pulse oximetry, pulmonary function, and chest x-ray in patients following significant exposures. Non-cardiogenic pulmonary edema is a toxic effect of phosgene oxime and may develop several hours after exposure.
    C) Because effects can be delayed, serial chest x-rays and pulse oximetry (or ABGs) are recommended for inhalation exposures.
    D) Monitor fluid balance if pulmonary edema is present.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) Serial chest x-rays should be evaluated for early signs of pulmonary edema.
    a) BACKGROUND: Pulmonary edema may be evident on chest x-ray within 2 hours of high dose exposure, 4 to 6 hours of moderate exposure, and approximately 8 to 24 hours after low dose exposure (Sidell et al, 2000); effects can vary.
    b) RADIOGRAPHIC FINDINGS: Blurred perihilar enlargement and diffuse opacities are common following phosgene exposure.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.3) DISPOSITION/INHALATION EXPOSURE
    6.3.3.5) OBSERVATION CRITERIA/INHALATION
    A) A monitoring or observation period of 12 to 24 hours post exposure has been suggested.

Monitoring

    A) Perform routine laboratory studies on persons requiring hospital admission such as CBC, liver enzymes, kidney function tests, glucose, and serum electrolytes.
    B) Monitor arterial blood gases, pulse oximetry, pulmonary function, and chest x-ray in patients following significant exposures. Non-cardiogenic pulmonary edema is a toxic effect of phosgene oxime and may develop several hours after exposure.
    C) Because effects can be delayed, serial chest x-rays and pulse oximetry (or ABGs) are recommended for inhalation exposures.
    D) Monitor fluid balance if pulmonary edema is present.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED -
    1) Ipecac-induced emesis is NOT recommended because of the irritant and corrosive nature of phosgene oxime.
    B) ACTIVATED CHARCOAL -
    1) Activated charcoal is of unknown benefit in phosgene oxime ingestion. Since the primary toxicity is expected to be local corrosive injury rather than systemic effects from absorption, activated charcoal is not routinely recommended in the unlikely event of ingestion (it may obscure endoscopy findings and induce emesis).
    C) 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).
    D) 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.
    E) DERMAL EXPOSURE -
    1) If the military M291 Skin Decontaminating Kit for skin decontamination is available, it should be used as soon as possible. If the M291 Skin Decontaminating Kit is not available, skin decontamination should be done with copious amounts of water or isotonic sodium bicarbonate. Adsorbent powders, such as fullers' earth, have been suggested for physical decontamination of the skin.
    F) EYE EXPOSURE -
    1) Flush eyes immediately with water, 0.9% saline or isotonic sodium bicarbonate (if available) for at least an hour or until the cul-de-sacs are free of particulate matter and returned to neutrality (confirm with pH paper).
    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) EMESIS is to be AVOIDED, because of the irritant and corrosive nature of this material.
    B) DILUTION
    1) If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. The exact 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).
    2) USE OF DILUENTS IS CONTROVERSIAL: While experimental models have suggested that immediate dilution may lessen caustic injury (Homan et al, 1993; Homan et al, 1994; Homan et al, 1995), this has not been adequately studied in humans.
    3) DILUENT TYPE: Use any readily available nontoxic, cool liquid. Both milk and water have been shown to be effective in experimental studies of caustic ingestion (Maull et al, 1985; Rumack & Burrington, 1977; Homan et al, 1995; Homan et al, 1994; Homan et al, 1993).
    4) ADVERSE EFFECTS: Potential adverse effects include vomiting and airway compromise (Caravati, 2004).
    5) CONTRAINDICATIONS: Do NOT attempt dilution in patients with respiratory distress, altered mental status, severe abdominal pain, nausea or vomiting, or patients who are unable to swallow or protect their airway. Diluents should not be force fed to any patient who refuses to swallow (Rao & Hoffman, 2002).
    C) GASTRIC LAVAGE
    1) Consider insertion of a small, flexible nasogastric tube to aspirate gastric contents soon after a significant ingestion. The risk of worsening mucosal injury must be weighed against the potential benefit.
    D) ACTIVATED CHARCOAL
    1) Activated charcoal is of unknown benefit in phosgene oxime ingestion. Since the primary toxicity is expected to be local corrosive injury rather than systemic effects from absorption, activated charcoal is not routinely recommended in the unlikely event of ingestion (it may obscure endoscopy findings and induce emesis).
    6.5.3) TREATMENT
    A) BURN
    1) Severe irritation or vesication of the esophagus or gastrointestinal tract would be predicted to occur following liquid phosgene oxime ingestion. There is no information available specifically pertaining to the ingestion of phosgene oxime; the following recommendations are derived from information regarding exposure to acids.
    B) ENDOSCOPIC PROCEDURE
    1) SUMMARY: Obtain consultation concerning endoscopy as soon as possible and perform endoscopy within the first 24 hours when indicated.
    2) INDICATIONS: Most studies associating the presence or absence of gastrointestinal burns with signs and symptoms after caustic ingestion have involved primarily alkaline ingestions. Because acid ingestion may cause severe gastric injury with fewer associated initial signs and symptoms, endoscopic evaluation is recommended in any patient with a definite history of ingestion of a strong acid, even if asymptomatic.
    3) RISKS: Numerous large case series attest to the relative safety and utility of early endoscopy in the management of caustic ingestion.
    a) REFERENCES: Gaudreault et al, 1983; Symbas et al, 1983; Crain et al, 1984; (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; Nuutinen et al, 1994)
    4) 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).
    5) 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.
    6) FOLLOW UP - If burns are found, follow 10 to 20 days later with barium swallow or esophagram.
    C) 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).
    D) SURGICAL PROCEDURE
    1) In severe cases of gastrointestinal necrosis or perforation, emergent surgical consultation should be obtained. The need for gastric resection or laparotomy in the stable patient is controversial (Chodak & Passaro, 1978; Dilawari et al, 1984).
    2) LAPAROTOMY/LAPAROSCOPY - Early laparotomy or laparoscopy should be considered in patients with endoscopic evidence of severe esophageal or gastric burns after acid ingestion to evaluate for the presence of transmural gastric or esophageal necrosis (Estrera et al, 1986; Meredith et al, 1988; Wu & Lai, 1993). Emergent laparotomy should be strongly considered in any patient with hypotension, altered mental status, or acidemia (Hovarth et al, 1991).
    a) STUDY - In a retrospective study of patients with extensive transmural gastroesophageal necrosis after caustic ingestion, all 4 patients treated in the conventional manner (endoscopy, 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).
    b) Wu & Lai (1993) reported the results of emergency surgical resection of the alimentary tract in 28 patients who had extensive corrosive injuries due to the ingestion of acids or other caustics. Operative mortality was most frequently associated with sepsis. Non-fatal bleeding, infections, biliary or bronchial fistulas were other noted complications. Morbidity and mortality were related to the severity of the damage and the extent of surgery required.
    1) Immediate postoperative management included antibiotics, extensive respiratory care, tracheobronchial toilet, maintenance of fluid, electrolyte and acid-base balance, and jejunostomy feeding or total parenteral nutrition.
    E) GENERAL TREATMENT
    1) Treatment guidelines for patients sustaining systemic effects following significant oral exposure may be found in the INHALATION EXPOSURE treatment section.

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.
    D) Rescuers in the field should wear appropriate respiratory equipment to prevent exposure.
    6.7.2) TREATMENT
    A) SUPPORT
    1) There is no antidote for phosgene oxime exposure. Treatment is symptomatic and supportive. Inhalational exposure can result in respiratory tract irritation and pulmonary edema. Provide airway management when necessary.
    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) Decontamination after ocular exposures are critical since phosgene oxime is absorbed within seconds. Immediately flush the eyes with water for 5 to 10 minutes. Do not cover the eyes with bandages. If photophobia causes discomfort, dark or opaque goggles can be worn ((CDC, 2001)).
    B) Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline, water or isotonic sodium bicarbonate (which ever is more rapidly available) immediately. Once irrigation has begun, instill a drop of local anesthetic for comfort; switching from water to slightly warmed sterile saline or isotonic sodium bicarbonate may also improve patient comfort (Ernst et al, 1998; Grant & Schuman, 1993).
    1) Continue irrigation for at least an hour or until the superior and inferior cul-de-sacs have returned to neutrality (pH of 7.0) and remain so for 30 minutes after irrigation is discontinued (Brodovsky et al, 2000). Immediate and prolonged irrigation after corrosive eye injury is associated with improved visual acuity, shorter hospital stay and fewer surgical interventions (Kuckelkorn et al, 1995; Saari et al, 1984).
    2) Search the conjunctival sac for solid particles and remove them while continuing irrigation (Grant & Schuman, 1993).
    6.8.2) TREATMENT
    A) INJURY OF GLOBE OF EYE
    1) There is no information available specifically pertaining to eye exposure to phosgene oxime; the following recommendations are derived from information regarding exposure to acids.
    2) EVALUATION
    a) ASSESSMENT CAUSTIC EYE BURNS: It may take 48 to 72 hours after the burn to assess correctly the degree of ocular damage (Brodovsky et al, 2000a).
    b) The 1965 Roper-Hall classification uses the size of the corneal epithelial defect, the degree of corneal opacification and extent of limbal ischemia to evaluate the extent of the chemical ocular injury (Brodovsky et al, 2000a; Singh et al, 2013):
    1) GRADE 1 (prognosis good): Corneal epithelial damage; no limbal ischemia.
    2) GRADE 2 (prognosis good): Cornea hazy; iris details visible, ischemia less than one-third of limbus.
    3) GRADE 3 (prognosis guarded): Total loss of corneal epithelium; stromal haze obscures iris details; ischemia of one-third to one-half of limbus.
    4) GRADE 4 (prognosis poor): Cornea opaque; iris and pupil obscured, ischemia affects more than one-half of limbus.
    c) A newer classification (Dua) is based on clock hour limbal involvement as well as a percentage of bulbar conjunctival involvement (Singh et al, 2013):
    1) GRADE 1 (prognosis very good): 0 clock hour of limbal involvement and 0% conjunctival involvement.
    2) GRADE 2 (prognosis good): Less than 3 clock hour of limbal involvement and less than 30% conjunctival involvement.
    3) GRADE 3 (prognosis good): Greater than 3 and up to 6 clock hour of limbal involvement and greater than 30% to 50% conjunctival involvement.
    4) GRADE 4 (prognosis good to guarded): Greater than 6 and up to 9 clock hour of limbal involvement and greater than 50% to 75% conjunctival involvement.
    5) GRADE 5 (prognosis guarded to poor): Greater than 9 and less than 12 clock hour of limbal involvement and greater than 75% and less than 100% conjunctival involvement.
    6) GRADE 6 (very poor): Total limbus (12 clock hour) involved and 100% conjunctival involvement.
    3) MINOR INJURY
    a) SUMMARY
    1) If ocular damage is minor, artificial tears/lubricants, topical cycloplegics, and antibiotics may be all that are needed.
    b) ARTIFICIAL TEARS
    1) To promote re-epithelization, preservative-free artificial tears/lubricants (eg, hyaluronic acid hourly) may be used (Fish & Davidson, 2010; Tuft & Shortt, 2009).
    c) TOPICAL CYCLOPLEGIC
    1) Use to guard against development of posterior synechiae and ciliary spasm (Brodovsky et al, 2000b; Grant & Schuman, 1993). Cyclopentolate 0.5% or 1% eye drops may be administered 4 times daily to control pain (Tuft & Shortt, 2009; Spector & Fernandez, 2008).
    d) TOPICAL ANTIBIOTICS
    1) An antibiotic ophthalmic ointment or drops should be used for as long as epithelial defects persist (Brodovsky et al, 2000b; Grant & Schuman, 1993). Topical erythromycin or tetracycline ointment may be used (Spector & Fernandez, 2008).
    e) PAIN CONTROL
    1) If pain control is required, oral or parenteral NSAIDs or narcotics are preferred to topical ocular anesthetics, which may cause local corneal epithelial damage if used repeatedly (Spector & Fernandez, 2008; Grant & Schuman, 1993). However, topical 0.5% proparacaine has been recommended (Spector & Fernandez, 2008).
    4) SEVERE INJURY
    a) SUMMARY
    1) If the damage is minor, the above may be all that is needed. For grade 3 or 4 injuries, one or more of the following may be used, only with ophthalmologic consultation: acetazolamide, topical timolol, topical steroids, citrate, ascorbate, EDTA, cysteine, NAC, penicillamine, tetracycline, or soft contact lenses.
    b) ARTIFICIAL TEARS
    1) To promote re-epithelization, preservative-free artificial tears/lubricants (eg, hyaluronic acid hourly) may be used (Fish & Davidson, 2010; Tuft & Shortt, 2009).
    c) PAIN CONTROL
    1) If pain control is required, oral or parenteral NSAIDs or narcotics are preferred to topical ocular anesthetics, which may cause local corneal epithelial damage if used repeatedly (Spector & Fernandez, 2008; Grant & Schuman, 1993). However, topical 0.5% proparacaine has been recommended (Spector & Fernandez, 2008).
    d) CARBONIC ANHYDRASE INHIBITOR
    1) Acetazolamide (250 mg orally 4 times daily) may be given to control increased intraocular pressure (Singh et al, 2013; Tuft & Shortt, 2009; Spector & Fernandez, 2008).
    e) TOPICAL STEROIDS
    1) DOSE: Dexamethasone 0.1% ointment 4 times daily to reduce inflammation. If persistent epithelial defect is present, discontinue dexamethasone by day 14 to reduce the risk of stromal melt (Tuft & Shortt, 2009). Other sources suggest that corticosteroids should be stopped if the epithelium has not covered surface defects by 5 to 7 days (Grant & Schuman, 1993a).
    2) Topical prednisolone 0.5% has also been used. A further increase in corneoscleral melt may occur if topical steroids are used alone. In one study, topical prednisolone 0.5% was used in combination with topical ascorbate 10%; no increase in corneoscleral melt was observed when topical steroids were used until re-epithelization (Singh et al, 2013; Fish & Davidson, 2010).
    3) In one retrospective study, fluorometholone 1% drops were administered every 2 hours initially, then decreased to four times daily when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete (Brodovsky et al, 2000).
    a) STUDY: The combination of intensive topical corticosteroids, topical citrate and ascorbate, and oral citrate and ascorbate was associated with improved best corrected visual acuity and a trend towards more rapid corneal reepithelialization in Grade 3 alkali burns in one retrospective study (Brodovsky et al, 2000).
    f) ASCORBATE
    1) Oral or topical ascorbate may be used to promote epithelial healing and reduce the risk of stromal necrosis (Fish & Davidson, 2010).
    2) DOSE: Ascorbate 10% 4 times daily topically or 1 g orally (2 g/day) (Singh et al, 2013; Tuft & Shortt, 2009).
    3) Ascorbate is needed for the formation of collagen and the concentration of ascorbate in the anterior chamber is decreased when the ciliary body is damaged by alkali burns (Tuft & Shortt, 2009; Grant & Schuman, 1993a). In one retrospective study, ascorbate drops (10%) were administered every 2 hours, then decreased to 4 times a day when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete. These patients also received 500 mg of oral ascorbate 4 times daily, until discharge from the hospital (Brodovsky et al, 2000).
    a) STUDY: The combination of intensive topical corticosteroids, topical citrate and ascorbate, and oral citrate and ascorbate was associated with improved best corrected visual acuity and a trend towards more rapid corneal reepithelialization in Grade 3 alkali burns in one retrospective study (Brodovsky et al, 2000).
    g) CITRATE
    1) Topical citrate may be used to promote epithelial healing and reduce the risk of stromal necrosis (Fish & Davidson, 2010).
    2) DOSE: Potassium citrate 10% 4 times daily topically (Tuft & Shortt, 2009).
    3) Citrate chelates calcium, and thereby interferes with the harmful effects of neutrophil accumulation, such as release of proteolytic enzymes and superoxide free radicals, phagocytosis and ulceration (Grant & Schuman, 1993a). In one retrospective study, 10% citrate drops were administered every 2 hours, then decreased to 4 times a day when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete. These patients also received a urinary alkalinizer containing 720 mg of citric acid anhydrous and 630 mg of sodium citrate anhydrous 3 times daily, until discharge from the hospital (Brodovsky et al, 2000).
    a) STUDY: The combination of intensive topical corticosteroids, topical citrate and ascorbate, and oral citrate and ascorbate was associated with improved best corrected visual acuity and a trend towards more rapid corneal reepithelialization in Grade 3 alkali burns in one retrospective study (Brodovsky et al, 2000).
    h) COLLAGENASE INHIBITORS
    1) Inhibitors of collagenase can inhibit collagenolytic activity, prevent stromal ulceration, and promote wound healing. Several effective agents, such as cysteine, n-acetylcysteine, sodium ethylenediamine tetra acetic acid (EDTA), calcium EDTA, penicillamine, and citrate, have been recommended (Singh et al, 2013; Tuft & Shortt, 2009; Perry et al, 1993; Seedor et al, 1987).
    2) TETRACYCLINE: Has been found to have an anticollagenolytic effect. Systemic tetracycline 50 mg/kg/day reduced the incidence of alkali-induced corneal ulcerations in rabbits (Seedor et al, 1987).
    3) DOXYCYCLINE: Decreased epithelial defects and collagenase activity in a rabbit model of alkali burns to the eye (Perry et al, 1993). DOSE: 100 mg twice daily (Tuft & Shortt, 2009).
    i) ANTIBIOTICS
    1) An antibiotic ophthalmic ointment or drops should be used for as long as epithelial defects persist (Brodovsky et al, 2000b; Grant & Schuman, 1993). Topical erythromycin or tetracycline ointment may be used (Spector & Fernandez, 2008). In patients with severe burns, a topical fluoroquinolone antibiotic drop 4 times daily may also be used (Tuft & Shortt, 2009). A topical fourth generation fluoroquinolone has been recommended as an antimicrobial prophylaxis in patients with large epithelial defect (Fish & Davidson, 2010).
    j) TOPICAL CYCLOPLEGIC
    1) Cyclopentolate 0.5% or 1% eye drops may be administered 4 times daily to control pain (Tuft & Shortt, 2009; Spector & Fernandez, 2008).
    k) SOFT CONTACT LENSES
    1) A bandage contact lens (eg, silicone hydrogel) may make the patient more comfortable and protect the surface (Fish & Davidson, 2010; Tuft & Shortt, 2009). Hydrophilic high oxygen permeability lenses are preferred (Singh et al, 2013). Soft lenses with intermediate water content and inherent rigidity may facilitate reepithelialization. The use of 0.5 normal sodium chloride drops hourly and artificial tears or lubricant eyedrops instilled 4 times a day may help maintain adequate hydration and lens mobility.
    5) SURGICAL THERAPY
    a) SURGICAL THERAPY CAUSTIC EYE INJURY
    1) Early insertion of methylmethacrylate ring or suturing saran wrap over palpebral and cul-de-sac conjunctiva may prevent fibrinosis adhesions and reduce fibrotic contracture of conjunctiva, but the advantage of such treatments is not clear.
    2) Limbal stem cell transplantation has been used successfully in both the acute stage of injury and the chronically scarred healing phase in patients with persistent epithelial defects after chemical burns (Azuara-Blanco et al, 1999; Morgan & Murray, 1996; Ronk et al, 1994).
    3) In some patients, amniotic membrane transplantation (AMT) has been successful in improving corneal healing and visual acuity in patients with persistent epithelial defects after chemical burns. It can restore the conjunctival surface and decrease limbal stromal inflammation (Fish & Davidson, 2010; Sridhar et al, 2000; Su & Lin, 2000; Meller et al, 2000; Azuara-Blanco et al, 1999).
    4) Control glaucoma. Remove any cataracts formed (Fish & Davidson, 2010; Tuft & Shortt, 2009).
    5) In patients with severe injury, tenonplasty can be performed to promote epithelialization and prevent melting (Tuft & Shortt, 2009).
    6) A keratoprosthesis placement has also been indicated in severe cases (Fish & Davidson, 2010). Penetrating keratoplasty is usually delayed as long as possible as results appear to be better with a greater lag time between injury and keratoplasty (Grant & Schuman, 1993).
    6) OTHER
    a) SYSTEMIC TOXICITY - No cases of systemic phosgene oxime poisoning following only eye exposure have been reported. All patients with significant eye exposure should be carefully monitored for possible development of systemic signs and symptoms. Follow treatment recommendations in INHALATION EXPOSURE section where appropriate.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) Due to rapid reaction of phosgene oxime with tissue, decontamination is expected to not be entirely effective after pain has been produced. If the military M291 Skin Decontaminating Kit for skin decontamination is available, it should be used as soon as possible (Anon, 1996).
    2) If the M291 Skin Decontaminating Kit is not available, skin decontamination should be done with copious amounts of water or isotonic sodium bicarbonate to remove any phosgene oxime which has not yet reacted with tissue. Adsorbent powders, such as fullers' earth, have been suggested for physical decontamination of the skin (Anon, 1996).
    3) Chemical inactivation with chloramine and phenol Towelettes, carried by the military, are INEFFECTIVE.
    6.9.2) TREATMENT
    A) SUPPORT
    1) Treatment is symptomatic and supportive. There is no antidote for phosgene oxime exposure. Ulcerated necrotic skin lesions should be treated as a thermal burn. Analgesics may be required for severe dermal pain.
    B) 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.
    C) GENERAL TREATMENT
    1) Treatment guidelines for patients sustaining systemic effects following significant dermal exposure may be found in the INHALATION EXPOSURE treatment section.
    D) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Range Of Toxicity

Summary

    A) Phosgene oxime is not known to have been used on a battlefield, and information regarding its effects on humans is limited. Concentrations below 8% appear to cause no or inconsistent effects.

Minimum Lethal Exposure

    A) ROUTE OF EXPOSURE
    1) Ct50 (EYE) HUMANS: 200 mg/min/m(3) (estimated; vapor) (Sidell et al, 1998)
    2) Ct50 (SKIN) HUMANS: 2500 mg/min/m(3) (erythema; vapor) (Sidell et al, 1998)
    3) LCt50 - (INHL) HUMANS: 3200 mg/min/m(3) (estimated; vapor) (Sidell et al, 1998; U.S. Army, 2001)
    4) LCt50 - (INHL) HUMANS: 1500-2000 mg/min/m(3) (estimated) (U.S. Army, 1995)
    5) LD50 - (SKIN) HUMANS: 25 mg/kg (estimated) (U.S. Army, 1995)

Maximum Tolerated Exposure

    A) ROUTE OF EXPOSURE
    1) DERMAL -
    a) It has been reported concentrations below 8% appear to cause no or inconsistent effects. When phosgene oxime is mixed with another chemical agent (e.g., VX), rapid skin damage due to phosgene oxime may render the skin more susceptible to the second agent (U.S. Army, 1997).
    b) Irritation begins at 0.2 mg/min/m(3) (12 seconds) (USACHPPM , 2001).
    c) Irritation is unbearable at 3 mg/min/m(3) (1 minute) (USACHPPM , 2001).

Workplace Standards

    A) ACGIH TLV Values for CAS1794-86-1 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS1794-86-1 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS1794-86-1 :
    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 ): Not Listed

    D) OSHA PEL Values for CAS1794-86-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Pharmacology Toxicology

Toxicologic Mechanism

    A) Phosgene oxime, an urticant or nettle agent, can cause a corrosive type of skin and tissue lesion. Any exposure to liquid or vapor producing pain will also cause skin necrosis at the site of contact. It does NOT cause blisters since it is not a true vesicant. Almost immediate tissue damage results on contact with either the vapor or liquid. The exact mechanism by which this chemical causes its effects is unknown, although it has been suggested that phosgene oxime reacts with SH and H2N groups (U.S. Army , 1995; (US Army, 1996)).
    B) Although the exact mechanism of action is unknown, it is thought that biological tissue damage may occur because of the necrotizing effects of the chlorine, or due to a direct effect of the oxime, or because of the carbonyl group. Skin lesions appear similar to those of a strong acid (U.S. Army, 1997).
    C) Although the cellular target is unknown, a direct injury mechanism, and an indirect injury mechanism are postulated (U.S. Army, 1997):
    1) DIRECT INJURY -
    1) Enzyme inactivation
    2) Cell death
    3) Corrosive injury
    4) Rapid local destruction of tissue (e.g., vesication)
    2) INDIRECT INJURY -
    1) Activation of alveolar macrophages
    2) Recruitment of neutrophils
    3) Release of H2O2
    4) Delayed tissue injury (e.g., pulmonary edema)

Physicochemical

Physical Characteristics

    A) Phosgene oxime is a liquid or a colorless, crystalline solid with an unpleasant and irritating odor that sublimes at ambient temperatures. At temperatures below 95 degrees F CX is a solid, but the vapor pressure of the solid is high enough to cause symptoms (U.S. Army , 1995; (US Army, 1996); Sidell et al, 1998).

Molecular Weight

    A) 113.94

References

General Bibliography

    1) 40 CFR 372.28: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Lower thresholds for chemicals of special concern. National Archives and Records Administration (NARA) and the Government Printing Office (GPO). Washington, DC. Final rules current as of Apr 3, 2006.
    2) 40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.
    3) 49 CFR 172.101 - App. B: Department of Transportation - Table of Hazardous Materials, Appendix B: List of Marine Pollutants. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 29, 2005.
    4) 62 FR 58840: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 1997.
    5) 65 FR 14186: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    6) 65 FR 39264: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    7) 65 FR 77866: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    8) 66 FR 21940: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2001.
    9) 67 FR 7164: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2002.
    10) 68 FR 42710: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2003.
    11) 69 FR 54144: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2004.
    12) AIHA: 2006 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook, American Industrial Hygiene Association, Fairfax, VA, 2006.
    13) Aceto T Jr, Terplan K, & Fiore RR: Chemical burns of the esophagus in children and glucocorticoid therapy. J Med 1970; 1:101-109.
    14) Adam JS & Brick HG: Pediatric caustic ingestion. Ann Otol Laryngol 1982; 91:656-658.
    15) American Conference of Governmental Industrial Hygienists : ACGIH 2010 Threshold Limit Values (TLVs(R)) for Chemical Substances and Physical Agents and Biological Exposure Indices (BEIs(R)), American Conference of Governmental Industrial Hygienists, Cincinnati, OH, 2010.
    16) Anderson KD, Touse TM, & Randolph JG: A controlled trial of corticosteroids in children with corrosive injury of the esophagus. N Engl J Med 1990; 323:637-640.
    17) Artigas A, Bernard GR, Carlet J, et al: The American-European consensus conference on ARDS, part 2: ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling.. Am J Respir Crit Care Med 1998; 157:1332-1347.
    18) Azuara-Blanco A, Pillai CT, & Dua HS: Amniotic membrane transplantation for ocular surface reconstruction. Br J Ophthalmol 1999; 83:399-402.
    19) Boukthir S, Fetni I, Mrad SM, et al: [High doses of steroids in the management of caustic esophageal burns in children]. Arch Pediatr 2004; 11(1):13-17.
    20) Brodovsky SC, McCarty AC, & Snibson G: Management of alkali burns an 11-year retrospective review. Ophthalmology 2000a; 107:1829-1835.
    21) Brodovsky SC, McCarty CA, & Snibson G: Management of alkali burns an 11-year retrospective review. Ophthalmology 2000; 107:1829-1835.
    22) Brodovsky SC, McCarty CA, & Snibson G: Management of alkali burns an 11-year review. Ophthalmology 2000b; 107:1829-1835.
    23) Brower RG, Matthay AM, & Morris A: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Eng J Med 2000; 342:1301-1308.
    24) Burgess JL, Kirk M, Borron SW, et al: Emergency department hazardous materials protocol for contaminated patients. Ann Emerg Med 1999; 34(2):205-212.
    25) CDC: Center for Disease Control US Department of Health and Human Services. Phosgene Oxime. Center for Disease Control. Atlanta, GA, USA. 2001. Available from URL: http://www.bt.cdc.gov/Agent/Blister/PhosgeneOxime.asp. As accessed Accessed 15, May 2001.
    26) Caravati EM: Alkali. In: Dart RC, ed. Medical Toxicology, Lippincott Williams & Wilkins, Philadelphia, PA, 2004.
    27) Carvajal HF & Stewart CE: Emergency management of burn patients: the first few hours. Emerg Med Reports 1987; 8:129-136.
    28) Cataletto M: Respiratory Distress Syndrome, Acute(ARDS). In: Domino FJ, ed. The 5-Minute Clinical Consult 2012, 20th ed. Lippincott Williams & Wilkins, Philadelphia, PA, 2012.
    29) Chodak GW & Passaro E: Acid ingestion: need for gastric resection. JAMA 1978; 239:229-226.
    30) Cleveland WW, Chandler JR, & Lawson RB: Treatment of caustic burns of the esophagus. JAMA 1963; 186:182-183.
    31) DFG: List of MAK and BAT Values 2002, Report No. 38, Deutsche Forschungsgemeinschaft, Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Wiley-VCH, Weinheim, Federal Republic of Germany, 2002.
    32) Dilawari JB, Singh S, & Rao PN: Corrosive acid ingestion in man, a clinical and endoscopic study. Gut 1984; 25:183-187.
    33) EPA: Search results for Toxic Substances Control Act (TSCA) Inventory Chemicals. US Environmental Protection Agency, Substance Registry System, U.S. EPA's Office of Pollution Prevention and Toxics. Washington, DC. 2005. Available from URL: http://www.epa.gov/srs/.
    34) EPMEDIC: Medical Management of Chemical Agent Patients-Blister Agents (Vesicants). Emergency Prepardness Medical Information Center. SanAntonio, TX, USA. 2001. Available from URL: http://mywebpage.netscape.com/Emrgncprepinfo/home.htm. As accessed Accessed May 15, 2001.
    35) Ernst AA, Thomson T, & Haynes ML: Warmed versus room temperature saline solution for ocular irrigation: a randomized clinical trial. Ann Emerg Med 1998; 32:676-679.
    36) Estrera A, Taylor W, & Mills LJ: Corrosive burns of the esophagus and stomach: a recommendation of an aggressive surgical approach. Ann Thorac Surg 1986; 41:276-283.
    37) Ferguson MK, Migliore M, & Staszak VM: Early evaluation and therapy for caustic esophageal injury. Am J Surg 1989; 157:116-120.
    38) Fish R & Davidson RS: Management of ocular thermal and chemical injuries, including amniotic membrane therapy. Curr Opin Ophthalmol 2010; 21(4):317-321.
    39) Gorman RL, Khin-Maung-Gyi MT, & Klein-Schwartz W: Initial symptoms as predictors of esophageal injury in alkaline corrosive ingestions. Am J Emerg Med 1992; 10:89-94.
    40) Grant WM & Schuman JS: Toxicology of the Eye, 4th ed, Charles C Thomas, Springfield, IL, 1993.
    41) Grant WM & Schuman JS: Toxicology of the Eye, 4th ed, Charles C Thomas, Springfield, IL, 1993a.
    42) Haas CF: Mechanical ventilation with lung protective strategies: what works?. Crit Care Clin 2011; 27(3):469-486.
    43) Haller JA & Bachman K: The comparative effect of current therapy on experimental caustic burns of the esophagus. Pediatrics 1964; 236-245.
    44) Haller JA, Andrews HG, & White JJ: Pathophysiology and management of acute corrosive burns of the esophagus. J Pediatr Surg 1971; 6:578-584.
    45) Hawkins DB, Demeter MJ, & Barnett TE: Caustic ingestion: controversies in management. A review of 214 cases. Laryngoscope 1980; 90:98-109.
    46) Haynes BW Jr: Emergency department management of minor burns. Top Emerg Med 1981; 3:35-40.
    47) Homan CS, Maitra SR, & Lane BP: Effective treatment of acute alkali injury of the esopahgus with early saline dilution therapy. Ann Emerg Med 1993; 22:178-182.
    48) Homan CS, Maitra SR, & Lane BP: Histopathologic evaluation of the therapeutic efficacy of water and mild dilution for esophageal acid injury. Acad Emerg Med 1995; 2:587-591.
    49) Homan CS, Maitra SR, & Lane BP: Therapeutic effects of water and milk for acute alkali injury of the esophagus. Ann Emerg Med 1994; 24:14-19.
    50) Hovarth OP, Olah T, & Zentai G: Emergency esophagogastrectomy for the treatment of hydrochloric acid injury. Ann Thorac Surg 1991; 52:98-101.
    51) Howell JM, Dalsey WC, & Hartsell FW: Steroids for the treatment of corrosive esophageal injury: a statistical analysis of past studies. Am J Emerg Med 1992; 10:421-425.
    52) Howell JM: Alkaline ingestions. Ann Emerg Med 1987; 15:820-825.
    53) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: 1,3-Butadiene, Ethylene Oxide and Vinyl Halides (Vinyl Fluoride, Vinyl Chloride and Vinyl Bromide), 97, International Agency for Research on Cancer, Lyon, France, 2008.
    54) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Formaldehyde, 2-Butoxyethanol and 1-tert-Butoxypropan-2-ol, 88, International Agency for Research on Cancer, Lyon, France, 2006.
    55) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Household Use of Solid Fuels and High-temperature Frying, 95, International Agency for Research on Cancer, Lyon, France, 2010a.
    56) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Smokeless Tobacco and Some Tobacco-specific N-Nitrosamines, 89, International Agency for Research on Cancer, Lyon, France, 2007.
    57) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Exposures, 92, International Agency for Research on Cancer, Lyon, France, 2010.
    58) IARC: List of all agents, mixtures and exposures evaluated to date - IARC Monographs: Overall Evaluations of Carcinogenicity to Humans, Volumes 1-88, 1972-PRESENT. World Health Organization, International Agency for Research on Cancer. Lyon, FranceAvailable from URL: http://monographs.iarc.fr/monoeval/crthall.html. As accessed Oct 07, 2004.
    59) International Agency for Research on Cancer (IARC): IARC monographs on the evaluation of carcinogenic risks to humans: list of classifications, volumes 1-116. International Agency for Research on Cancer (IARC). Lyon, France. 2016. Available from URL: http://monographs.iarc.fr/ENG/Classification/latest_classif.php. As accessed 2016-08-24.
    60) International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. World Health Organization. Geneva, Switzerland. 2015. Available from URL: http://monographs.iarc.fr/ENG/Classification/. As accessed 2015-08-06.
    61) Knox WG, Scott JR, & Zintel HA: Bouginage and steroids used singly or in combination in experimental corrosive esophagitis. Ann Surg 1967; 166:930-941.
    62) Kollef MH & Schuster DP: The acute respiratory distress syndrome. N Engl J Med 1995; 332:27-37.
    63) Kuckelkorn R, Kottek A, & Schrage N: Poor prognosis of severe chemical and thermal eye burns: the need for adequate emergency care and primary prevention. Int Arch Occup Environ Health 1995; 281-284.
    64) LoVecchio F, Hamilton R, & Sturman K: A meta-analysis of the use of steroids in the prevention of stricture formation from second degree caustic burns of the esophagus (abstract). J Toxicol-Clin Toxicol 1996; 35:579-580.
    65) Marshall F II: Caustic burns of the esophagus: ten year results of aggressive care. South Med J 1979; 72:1236-1237.
    66) Maull KI, Osman AP, & Maull CD: Liquid caustic ingestions: an in vitro study of the effects of buffer, neutralization, and dilution. Ann Emerg Med 1985; 4:1160-1162.
    67) Meller D, Pires RT, & Mack RJS: Amniotic membrane transplantation for acute chemical or thermal burns. Ophthalmology 2000; 107:980-990.
    68) Meredith JW, Kon ND, & Thompson JN: Management of injuries from liquid lye ingestion. J Trauma 1988; 28:1173-1180.
    69) Moazam F, Talbert JL, & Miller D: Caustic ingestion and its sequelae in children. South Med J 1987; 80:187-188.
    70) Morgan S & Murray A: Limbal autotransplantation in the acute and chronic phases of severe chemical injuries. Eye 1996; 10:349-354.
    71) Moylan JA: Burn care after thermal injury. Top Emerg Med 1980; 2:39-52.
    72) NFPA: Fire Protection Guide to Hazardous Materials, 13th ed., National Fire Protection Association, Quincy, MA, 2002.
    73) NHLBI ARDS Network: Mechanical ventilation protocol summary. Massachusetts General Hospital. Boston, MA. 2008. Available from URL: http://www.ardsnet.org/system/files/6mlcardsmall_2008update_final_JULY2008.pdf. As accessed 2013-08-07.
    74) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 1, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2001.
    75) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 2, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2002.
    76) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 3, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2003.
    77) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 4, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2004.
    78) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2,3-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    79) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2,4-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    80) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2-Butylene Oxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648083cdbb&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    81) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2-Dibromoethane (Proposed). United States Environmental Protection Agency. Washington, DC. 2007g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064802796db&disposition=attachment&contentType=pdf. As accessed 2010-08-18.
    82) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,3,5-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    83) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 2-Ethylhexyl Chloroformate (Proposed). United States Environmental Protection Agency. Washington, DC. 2007b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648037904e&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    84) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Acrylonitrile (Proposed). United States Environmental Protection Agency. Washington, DC. 2007c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648028e6a3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    85) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Adamsite (Proposed). United States Environmental Protection Agency. Washington, DC. 2007h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    86) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Agent BZ (3-quinuclidinyl benzilate) (Proposed). United States Environmental Protection Agency. Washington, DC. 2007f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ad507&disposition=attachment&contentType=pdf. As accessed 2010-08-18.
    87) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Allyl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648039d9ee&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    88) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Aluminum Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    89) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Arsenic Trioxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2007m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480220305&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    90) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Automotive Gasoline Unleaded (Proposed). United States Environmental Protection Agency. Washington, DC. 2009a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cc17&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    91) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Biphenyl (Proposed). United States Environmental Protection Agency. Washington, DC. 2005j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064801ea1b7&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    92) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bis-Chloromethyl Ether (BCME) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006n. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648022db11&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    93) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Boron Tribromide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ae1d3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    94) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bromine Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2007d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648039732a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    95) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bromoacetone (Proposed). United States Environmental Protection Agency. Washington, DC. 2008e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809187bf&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    96) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Calcium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    97) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Carbonyl Fluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ae328&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    98) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Carbonyl Sulfide (Proposed). United States Environmental Protection Agency. Washington, DC. 2007e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648037ff26&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    99) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Chlorobenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2008c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803a52bb&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    100) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Cyanogen (Proposed). United States Environmental Protection Agency. Washington, DC. 2008f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809187fe&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    101) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Dimethyl Phosphite (Proposed). United States Environmental Protection Agency. Washington, DC. 2009. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbf3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    102) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Diphenylchloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    103) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648091884e&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    104) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyl Phosphorodichloridate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480920347&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    105) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2008g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809203e7&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    106) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    107) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Germane (Proposed). United States Environmental Protection Agency. Washington, DC. 2008j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963906&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    108) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Hexafluoropropylene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064801ea1f5&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    109) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ketene (Proposed). United States Environmental Protection Agency. Washington, DC. 2007. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ee7c&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    110) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Magnesium Aluminum Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    111) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Magnesium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    112) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Malathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2009k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809639df&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    113) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Mercury Vapor (Proposed). United States Environmental Protection Agency. Washington, DC. 2009b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a8a087&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    114) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl Isothiocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963a03&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    115) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl Parathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2008l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963a57&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    116) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl tertiary-butyl ether (Proposed). United States Environmental Protection Agency. Washington, DC. 2007a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064802a4985&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    117) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methylchlorosilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2005. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5f4&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    118) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    119) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyldichlorosilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2005a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c646&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    120) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN1 CAS Reg. No. 538-07-8) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    121) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN2 CAS Reg. No. 51-75-2) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    122) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN3 CAS Reg. No. 555-77-1) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    123) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Tetroxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008n. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648091855b&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    124) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Trifluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963e0c&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    125) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Parathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2008o. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963e32&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    126) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Perchloryl Fluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e268&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    127) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Perfluoroisobutylene (Proposed). United States Environmental Protection Agency. Washington, DC. 2009d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e26a&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    128) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008p. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096dd58&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    129) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyl Mercaptan (Proposed). United States Environmental Protection Agency. Washington, DC. 2006d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020cc0c&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    130) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    131) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phorate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008q. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096dcc8&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    132) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phosgene (Draft-Revised). United States Environmental Protection Agency. Washington, DC. 2009e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a8a08a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    133) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phosgene Oxime (Proposed). United States Environmental Protection Agency. Washington, DC. 2009f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e26d&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    134) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Potassium Cyanide (Proposed). United States Environmental Protection Agency. Washington, DC. 2009g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbb9&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    135) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Potassium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    136) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Propargyl Alcohol (Proposed). United States Environmental Protection Agency. Washington, DC. 2006e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec91&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    137) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Selenium Hexafluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2006f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec55&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    138) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Silane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d523&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    139) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sodium Cyanide (Proposed). United States Environmental Protection Agency. Washington, DC. 2009h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbb9&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    140) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sodium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    141) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Strontium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    142) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sulfuryl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2006h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec7a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    143) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tear Gas (Proposed). United States Environmental Protection Agency. Washington, DC. 2008s. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e551&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    144) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tellurium Hexafluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e2a1&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    145) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tert-Octyl Mercaptan (Proposed). United States Environmental Protection Agency. Washington, DC. 2008r. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e5c7&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    146) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tetramethoxysilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d632&disposition=attachment&contentType=pdf. As accessed 2010-08-17.
    147) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethoxysilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d632&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    148) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethyl Phosphite (Proposed). United States Environmental Protection Agency. Washington, DC. 2009j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7d608&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    149) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethylacetyl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008t. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e5cc&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    150) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Zinc Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    151) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for n-Butyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064808f9591&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    152) National Heart,Lung,and Blood Institute: Expert panel report 3: guidelines for the diagnosis and management of asthma. National Heart,Lung,and Blood Institute. Bethesda, MD. 2007. Available from URL: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
    153) National Institute for Occupational Safety and Health: NIOSH Pocket Guide to Chemical Hazards, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Cincinnati, OH, 2007.
    154) National Research Council : Acute exposure guideline levels for selected airborne chemicals, 5, National Academies Press, Washington, DC, 2007.
    155) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 6, National Academies Press, Washington, DC, 2008.
    156) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 7, National Academies Press, Washington, DC, 2009.
    157) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 8, National Academies Press, Washington, DC, 2010.
    158) Nuutinen M, Uhari M, & Karvali T: Consequences of caustic ingestions in children. Acta Paediatr 1994; 83:1200-1205.
    159) Oakes DD, Sherck JP, & Mark JBD: Lye ingestion. J Thorac Cardiovasc Surg 1982; 83:194-204.
    160) Pelclova D & Navratil T: Do corticosteroids prevent oesophageal stricture after corrosive ingestion?. Toxicol Rev 2005; 24(2):125-129.
    161) Perry HD, Hodes LW, & Seedor JA: Effect of doxycycline hyclate on corneal epithelial wound healing in the rabbit alkali-burn model. Preliminary observations. Cornea 1993; 12:379-82.
    162) Previtera C, Giusti F, & Gugliemi M: Predictive value of visible lesions (cheeks, lips, oropharynx) in suspected caustic ingestion: may endoscopy reasonably be omitted in completely negative pediatric patients?. Pediatr Emerg Care 1990; 6:176-178.
    163) Rao RB & Hoffman RS: Caustics and Batteries, in Goldfrank LR, Flomenbaum NE, Lewin NA et al (eds): Goldfrank's Toxicologic Emergencies, 7th ed, McGraw-Hill, New York, NY, 2002.
    164) Reyes HM, Lin CY, & Schluhk FF: Experimental treatment of corrosive esophageal burns. J Pediatr Surg 1974; 9:317-327.
    165) Roberts JR: Minor burns (Pt II). Emerg Med Ambulatory Care News 1988; 10:4-5.
    166) Ronk JF, Ruiz-Esmenjaud S, & Osorio M: Limbal conjunctival autograft in subacute alkaline corneal burn. Cornea 1994; 13:465-468.
    167) Rosenberg N, Kunderman PJ, & Vroman L: Prevention of experimental esophageal stricture by cortisone II. Arch Surg 1953; 66:593-598.
    168) Rumack BH & Burrington JD: Caustic ingestions: a rational look at diluents. J Toxicol Clin Toxicol 1977; 11:27-34.
    169) Saari KM, Leinonen J, & Aine E: Management of chemical eye injuries with prolonged irrigation. Acta Ophthalmol Suppl 1984; 52-59.
    170) Saedi S, Nyhus LM, & Gabrys BF: Pharmacological prevention of esophageal stricture: an experimental study in the cat. Am Surg 1973a; 39:465-469.
    171) Saedi S, Nyhust LM, & Gabrys BF: Pharmacological prevention of esophageal stricture: an experimental study in the cat. Am Surg 1973; 39:465-469.
    172) Schild JA: Caustic ingestion in adult patients. Laryngoscope 1985; 95:1199-1201.
    173) Seedor JA, Perry HD, & McNamara TF: Systemic tetracycline treatment of alkali-induced corneal ulceration in rabbits. Arch Ophthalmol 1987; 105:268-271.
    174) Sidell FR, Patrick WC, & Dashiell TR: Jane's Chem-Bio Handbook, Jane's nformation Group, Alexandria, VA, 1998.
    175) Singh P, Tyagi M, Kumar Y, et al: Ocular chemical injuries and their management. Oman J Ophthalmol 2013; 6(2):83-86.
    176) Spector J & Fernandez WG: Chemical, thermal, and biological ocular exposures. Emerg Med Clin North Am 2008; 26(1):125-136.
    177) Sridhar MS, Bansal AK, & Sangwan VS: Amniotic membrans transplantation in acute chemical and thermal injury. Am J Ophthalmol 2000; 130:134-137.
    178) Stolbach A & Hoffman RS: Respiratory Principles. In: Nelson LS, Hoffman RS, Lewin NA, et al, eds. Goldfrank's Toxicologic Emergencies, 9th ed. McGraw Hill Medical, New York, NY, 2011.
    179) Su CY & Lin CP: Combined use of an amniotic membrane and tissue adhesive in treating corneal perforation: a case report. Ophtalmic Sufr Lasers 2000; 31:151-154.
    180) Sugawa C & Lucas CE: Caustic injury of the upper gastrointestinal tract in adults: a clinical and endoscopic study. Surgery 1989; 106:802-807.
    181) Tuft SJ & Shortt AJ: Surgical rehabilitation following severe ocular burns. Eye (Lond) 2009; 23(10):1966-1971.
    182) U.S. Army : Medical Management of Chemical Casualties Handbook, 2nd ed. United States Army Medical Research Institute of Chemical Defense. Aberdeen Proving Ground, MD. 1995. Available from URL: http://206.39.77.2/DMCR/NBC/chemcas/titlepg.htm. As accessed Accessed 14 Nov, 2000.
    183) U.S. Army : Textbook of Military Medicine: Medical Aspects of Chemical and Biological Warfare. Vesicants. Office of The Surgeon General Department of the Army at TMM Publications. Washington, D.C. 1997. Available from URL: http://www.vnh.org/MedAspChemBioWar/chapters/chapter_7.htm. As accessed Accessed 15 May, 2001.
    184) U.S. Army: The Army Chemical Agent Safety Program AR 385-61, Headquarters Department of the Army, Washington, DC, 1997a.
    185) U.S. Army: The Handbook on the Medical Aspects of NBC Defensive Operations FM 8-9. United States Army Medical Research Institute of Chemical Defense. Aberdeen Proving Ground, MD, USA. 1996. Available from URL: http://ccc.apgea.army.mil. As accessed Accessed May 15, 2001.
    186) U.S. Department of Energy, Office of Emergency Management: Protective Action Criteria (PAC) with AEGLs, ERPGs, & TEELs: Rev. 26 for chemicals of concern. U.S. Department of Energy, Office of Emergency Management. Washington, DC. 2010. Available from URL: http://www.hss.doe.gov/HealthSafety/WSHP/Chem_Safety/teel.html. As accessed 2011-06-27.
    187) U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project : 11th Report on Carcinogens. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Washington, DC. 2005. Available from URL: http://ntp.niehs.nih.gov/INDEXA5E1.HTM?objectid=32BA9724-F1F6-975E-7FCE50709CB4C932. As accessed 2011-06-27.
    188) U.S. Environmental Protection Agency: Discarded commercial chemical products, off-specification species, container residues, and spill residues thereof. Environmental Protection Agency's (EPA) Resource Conservation and Recovery Act (RCRA); List of hazardous substances and reportable quantities 2010b; 40CFR(261.33, e-f):77-.
    189) U.S. Environmental Protection Agency: Integrated Risk Information System (IRIS). U.S. Environmental Protection Agency. Washington, DC. 2011. Available from URL: http://cfpub.epa.gov/ncea/iris/index.cfm?fuseaction=iris.showSubstanceList&list_type=date. As accessed 2011-06-21.
    190) U.S. Environmental Protection Agency: List of Radionuclides. U.S. Environmental Protection Agency. Washington, DC. 2010a. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-sec302-4.pdf. As accessed 2011-06-17.
    191) U.S. Environmental Protection Agency: List of hazardous substances and reportable quantities. U.S. Environmental Protection Agency. Washington, DC. 2010. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-sec302-4.pdf. As accessed 2011-06-17.
    192) U.S. Environmental Protection Agency: The list of extremely hazardous substances and their threshold planning quantities (CAS Number Order). U.S. Environmental Protection Agency. Washington, DC. 2010c. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-part355.pdf. As accessed 2011-06-17.
    193) U.S. Occupational Safety and Health Administration: Part 1910 - Occupational safety and health standards (continued) Occupational Safety, and Health Administration's (OSHA) list of highly hazardous chemicals, toxics and reactives. Subpart Z - toxic and hazardous substances. CFR 2010 2010; Vol6(SEC1910):7-.
    194) U.S. Occupational Safety, and Health Administration (OSHA): Process safety management of highly hazardous chemicals. 29 CFR 2010 2010; 29(1910.119):348-.
    195) USACHPPM : U.S. Army Center for Health Promotion & Preventive Medicine. Detailed Facts About blister Agent Phosgene Oxime (CX). US Army Center for Health Promotion and Preventative Medicine. Aberdeen Proving Ground, MD. 2001. Available from URL: http://chppm-www.apgea.army.mil/dts/docs/detcx.pdf.
    196) United States Environmental Protection Agency Office of Pollution Prevention and Toxics: Acute Exposure Guideline Levels (AEGLs) for Vinyl Acetate (Proposed). United States Environmental Protection Agency. Washington, DC. 2006. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6af&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    197) Vergauwen P, Moulin D, & Buts JP: Caustic burns of the upper digestive and respiratory tracts. Eur J Pediatr 1991; 150:700-703.
    198) Willson DF, Truwit JD, Conaway MR, et al: The adult calfactant in acute respiratory distress syndrome (CARDS) trial. Chest 2015; 148(2):356-364.
    199) Wilson DF, Thomas NJ, Markovitz BP, et al: Effect of exogenous surfactant (calfactant) in pediatric acute lung injury. A randomized controlled trial. JAMA 2005; 293:470-476.
    200) Wu MH & Lai WW: Surgical management of extensive corrosive injuries of the alimentary tract. Surg Gynecol Obstetr 1993; 177:12-16.
    201) Yarington CT & Heatly CA: Steroids, antibiotics, and early esophagoscopy in caustic esophageal trauma. N Y State J Med 1963; 63:2960-2963.
    202) Zargar SA, Kochhar R, & Mehta S: The role of fiberoptic endoscopy in the management of corrosive ingestion and modified endoscopic classification of burns. Gastrointest Endosc 1991; 37:165-169.
    203) Zargar SA, Kochhar R, & Nagi B: Ingestion of corrosive acids: spectrum of injury to upper gastrointestinal tract and natural history. Gastroenterology 1989; 97:702-707.