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ETHYLENEDIAMINE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Ethylenediamine is a polyamine widely used in industry and as an aid in pharmaceutical preparations.
    B) It is a severe irritant and is corrosive to the eyes, skin, and mucous membranes.

Specific Substances

    1) 1,2-Diaminoethane
    2) 1,2-Ethanediamine
    3) 1,2-Ethylenediamine
    4) beta-aminoethylene
    5) Dimethylenediamine
    6) Ethylendiamine
    7) Ethylenediamine
    8) Ethylene diamine
    9) EDA
    10) NCI-c 60402
    11) NIOSH/RTECS KH 8578000
    12) MOLECULAR FORMULA: C2-H8-N2
    13) CAS 107-15-3
    1.2.1) MOLECULAR FORMULA
    1) C2-H8-N2

Available Forms Sources

    A) FORMS
    1) Ethylenediamine is a clear, colorless or slightly yellow, strongly alkaline, hygroscopic liquid with an ammonia-like odor. When it is exposed to air, it absorbs carbon dioxide with the evolution of white fumes (JEF Reynolds , 2000).
    B) USES
    1) Ethylenediamine is a chemical intermediate used in the manufacture of dyes, fungicides, waxes, insecticides, resins, casein, lacquer, and shellac. It is also used in many industrial processes (Hogan, 1990).
    2) Ethylenediamine is used as a pharmaceutical aid in pharmaceutical preparations. It forms a stable mixture with theophylline to produce aminophylline or aminophylline hydrate (JEF Reynolds , 2000). It is an ingredient of some topical creams.
    3) It is used in the chemical and pharmaceutical industries (JEF Reynolds , 2000).
    4) Ethylenediamine is a component of soldering flux used in electronics industry (Goh, 1985).
    5) Mycolog II(R) cream (Squibb) no longer contains ethylenediamine however, many generic versions still use the older formulation which utilizes ethylenediamine as a stabilizer (Fisher, 1989; Fisher, 1988a).
    6) Ethylenediamine has been used in veterinary medicine as a urinary acidifier (HSDB , 2000).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Ethylenediamine (EDA) is an eye and mucous membrane irritant and skin sensitizer. EDA hypersensitivity is common, particularly in patients with contact dermatitis.
    B) EDA hypersensitivity reactions can occur following administration of aminophylline to patients previously sensitized by topical or inhalation routes. Skin reaction can be local, generalized, or exfoliative and may be accompanied by bronchospasm.
    C) Patients allergic to aminophylline may safely be given other theophylline preparations, but should avoid compounds closely related to EDA such as hydroxyzine.
    D) Poisoning may occur following inhalation, dermal, and oral exposure.
    E) When heated to decomposition, ethylenediamine emits toxic fumes of oxides of nitrogen and ammonia.
    0.2.3) VITAL SIGNS
    A) Hypotension has been reported in experimental animals.
    0.2.4) HEENT
    A) Liquid splash may produce acute pain and serious eye injury. Vapor exposure may produce corneal edema causing halos to be seen around lights. Inhalation may cause irritation of respiratory mucosa.
    0.2.6) RESPIRATORY
    A) Hypersensitivity reactions including bronchospasm have occurred.
    B) Shortness of breath and rhinitis may be noted following inhalation exposure.
    0.2.7) NEUROLOGIC
    A) Headache and dizziness may occur following inhalation exposure.
    0.2.8) GASTROINTESTINAL
    A) Nausea and vomiting have been reported following inhalation exposure.
    0.2.9) HEPATIC
    A) Hepatic injury has been reported from repeated vapor exposures in experimental laboratory animals.
    0.2.10) GENITOURINARY
    A) Renal damage has been reported from repeated vapor exposures in experimental laboratory animals.
    0.2.13) HEMATOLOGIC
    A) Methemoglobinemia has been reported following exposure to maximum allowable concentrations.
    0.2.14) DERMATOLOGIC
    A) Localized contact dermatitis, exacerbation of topically-induced contact dermatitis, generalized maculopapular, erythematous, pruritic, burning dermatitis, and exfoliative dermatitis have been reported.
    B) Hair loss was reported in experimental laboratory animals from repeated vapor exposures.
    0.2.18) PSYCHIATRIC
    A) Aggressive behavior has been reported following administration of aminophylline.
    0.2.19) IMMUNOLOGIC
    A) EDA is a skin and respiratory sensitizer.
    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.
    B) No information about possible male reproductive effects in humans was found in available references at the time of this review.
    0.2.22) OTHER
    A) Cross reactions with other compounds have been suggested.

Laboratory Monitoring

    A) Elevated serum methemoglobin levels may be used as an indirect test for exposure in workers exposed to ethylenediamine. No methods for measurement of ethylenediamine in environmental samples were listed in available references at the time of this review.
    B) Monitor pulse oximetry and/or ABGs, chest x-ray, and pulmonary function tests in symptomatic patients.
    C) Monitor CBC, urinalysis, and liver and kidney function tests in patients with significant exposure.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Do not induce emesis. Dilution with milk or water may be beneficial. Observe patient for signs of GI irritation or burns. Monitor patient for systemic toxicity.
    B) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    C) ALLERGIC REACTION: MILD/MODERATE: Antihistamines with or without inhaled beta agonists, corticosteroids or epinephrine. SEVERE: Oxygen, aggressive airway management, antihistamines, epinephrine, corticosteroids, ECG monitoring, and IV fluids.
    D) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
    E) METHEMOGLOBINEMIA: Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.
    F) METHYLENE BLUE: INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules and 10 mg/1 mL (1% solution) vials. Additional doses may sometimes be required. Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection. NEONATES: DOSE: 0.3 to 1 mg/kg.
    G) Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) BRONCHOSPASM - Administer beta adrenergic agonists. Monitor peak expiratory flow rate, monitor for hypoxia and respiratory failure, and administer oxygen as necessary.
    C) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) Hypersensitivity reactions may occur with any exposure in a sensitized individual.
    B) A 5% aqueous solution of ethylenediamine has been reported to induce minor eye injury when splashed into the eye. A 15% solution of EDA may seriously damage the cornea.

Clinical Effects

Summary Of Exposure

    A) Ethylenediamine (EDA) is an eye and mucous membrane irritant and skin sensitizer. EDA hypersensitivity is common, particularly in patients with contact dermatitis.
    B) EDA hypersensitivity reactions can occur following administration of aminophylline to patients previously sensitized by topical or inhalation routes. Skin reaction can be local, generalized, or exfoliative and may be accompanied by bronchospasm.
    C) Patients allergic to aminophylline may safely be given other theophylline preparations, but should avoid compounds closely related to EDA such as hydroxyzine.
    D) Poisoning may occur following inhalation, dermal, and oral exposure.
    E) When heated to decomposition, ethylenediamine emits toxic fumes of oxides of nitrogen and ammonia.

Vital Signs

    3.3.1) SUMMARY
    A) Hypotension has been reported in experimental animals.
    3.3.4) BLOOD PRESSURE
    A) Ethylenediamine causes depression of blood pressure in experimental animals (Clayton & Clayton, 1994).

Heent

    3.4.1) SUMMARY
    A) Liquid splash may produce acute pain and serious eye injury. Vapor exposure may produce corneal edema causing halos to be seen around lights. Inhalation may cause irritation of respiratory mucosa.
    3.4.3) EYES
    A) Acute pain and serious injury may result from splashes of ethylenediamine into the eye. When the liquid was applied to rabbit's eyes, it produced a grade 8 injury on a scale of 1 to 10 after 24 hours.
    1) This injury was less severe than that produced by ammonium hydroxide (Carpenter & Smyth, 1946).
    B) A 5% aqueous solution has been reported to induce minor injury (ACGIH, 1986). A 15% aqueous solution may seriously damage the cornea (ACGIH, 1986).
    C) Exposure to amine vapors may produce edema of the epithelium of the cornea causing colored halos to be seen around lights (Grant & Schuman, 1993).
    3.4.5) NOSE
    A) Irritation of nasal and respiratory mucosa is reported at concentrations of 200 and 400 ppm (Dernehl, 1951). An exposure for a few seconds at 100 ppm was found to be inoffensive in human subjects (Dernehl, 1951).
    3.4.6) THROAT
    A) Ethylenediamine is a mucous membrane irritant (ACGIH, 1986).

Respiratory

    3.6.1) SUMMARY
    A) Hypersensitivity reactions including bronchospasm have occurred.
    B) Shortness of breath and rhinitis may be noted following inhalation exposure.
    3.6.2) CLINICAL EFFECTS
    A) TOXIC EFFECT OF GAS, FUMES AND/OR VAPORS
    1) WITH POISONING/EXPOSURE
    a) With chronic exposure, bronchospasm, asthma, lung congestion, and pulmonary edema may be seen. With acute exposure, dyspnea and rhinitis may occur.
    b) CASE REPORT - Hallucinations, delusions and impaired consciousness were noted at admission in a 27-year-old male following inhalational exposure to dimethylacetamide, ethylenediamine, and diphenylmethane diisocyanate in a confined space for a continuous 4-6 hours per day for 3 days. Pulmonary edema with hypoxemia (pH 7.37, PaCO2 34.4 mm Hg, PaO2 36.1 mmHg, HCO3 19.5 mEq/L) developed as well as hyperemic edema of the tracheobronchial tree. He made a full recovery (Su et al, 2000).
    B) BRONCHOSPASM
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES - Three of 130 factory workers were found to have asthma associated with occupational exposure and sensitization to ethylenediamine. Atopic subjects were not preferentially affected and none of affected workers had attacks of asthma prior to employment (Hagmar et al, 1982).
    b) Bronchospasm has been reported following preparation of aminophylline suppositories (Tas & Weissberg, 1958) and following occupational exposures to ethylenediamine.
    c) CASE REPORT - Lam & Chan-Yeng (1980) reported the occurrence of coughing, wheezing, and dyspnea in a 30-year-old male 4 hours after exposure to photographic chemicals containing EDA. Inhalation provocation tests with EDA 1:25 for 15 minutes reproduced the reaction (Lam & Chan-Yeung, 1980).
    d) Gelfand (1963) reported an immediate type of bronchospastic reaction in workers in the rubber, lacquer, and shellac industries. Reactions occurred immediately after inhalation provocation and persisted for 0.5 to 2 hours. All had immediate positive intradermal skin reactions. It is likely that this represented a primary irritant reaction and not hypersensitivity (Gelfand, 1963).
    e) Ethylenediamine is extremely alkaline and can produce toxic irritant changes following intradermal testing (Kradjan & Lakshminarayan, 1981).
    f) In the lacquer and shellac industries, wheezing, heaviness in the chest, and severe asthma occur with exposure to ethylenediamine (HSDB , 2000).
    g) CASE REPORTS - Delayed asthmatic response was reported in two patients working in the same factory after several months of exposure to ethylenediamine vapors.
    1) Coughing, wheezing, and dyspnea would occur after exposure to EDA, did not occur when not working, and reoccurred after re-exposure. Slight elevations of total IgE and eosinophils were also noted (Nakazawa & Matsui, 1990; Lewinsohn & Ott, 1991).
    C) DYSPNEA
    1) WITH POISONING/EXPOSURE
    a) Shortness of breath has occurred following inhalation exposure (JEF Reynolds , 2000).
    D) RHINITIS
    1) WITH POISONING/EXPOSURE
    a) Rhinitis may be provoked from inhalation of ethylenediamine or aminophylline dust (Zuidema, 1985).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RESPIRATORY DISORDER
    a) RATS - Lung congestion was noted in rats chronically exposed to ethylenediamine (Pozzani & Carpenter, 1954).
    2) PULMONARY EDEMA
    a) Pulmonary edema with hemorrhage and bronchopneumonia have been observed in rabbits repeatedly exposed to ethylamines; similar effects occur in experimental animals exposed to ethylenediamine (HSDB , 2000).

Neurologic

    3.7.1) SUMMARY
    A) Headache and dizziness may occur following inhalation exposure.
    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) Dizziness and headache have been reported following inhalation exposure to fumes (JEF Reynolds , 2000).

Gastrointestinal

    3.8.1) SUMMARY
    A) Nausea and vomiting have been reported following inhalation exposure.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Nausea and vomiting may occur following inhalation exposure to fumes (JEF Reynolds , 2000).

Hepatic

    3.9.1) SUMMARY
    A) Hepatic injury has been reported from repeated vapor exposures in experimental laboratory animals.
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATOCELLULAR DAMAGE
    a) RATS - Liver damage occurred in experimental laboratory rats exposed repeatedly to 484 ppm of ethylenediamine vapors. Lesser degrees of injury was produced at 225 and 132 ppm.
    1) No injury was noted from 125 ppm continued for thirty 7-hour exposures (Pozzani & Carpenter, 1954). Hepatotoxicity has NOT been reported in human exposures.

Genitourinary

    3.10.1) SUMMARY
    A) Renal damage has been reported from repeated vapor exposures in experimental laboratory animals.
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) ALBUMINURIA
    a) RATS - Renal tubular damage and proteinuria occurred in experimental laboratory rats from intraperitoneal doses of 300 mg/kg (Tabor & Rosenthal, 1956).

Hematologic

    3.13.1) SUMMARY
    A) Methemoglobinemia has been reported following exposure to maximum allowable concentrations.
    3.13.2) CLINICAL EFFECTS
    A) METHEMOGLOBINEMIA
    1) WITH POISONING/EXPOSURE
    a) Methemoglobinemia has been reported in workers exposed to the maximum allowable concentration of ethylenediamine in the working area (Bainova et al, 1987). Absorption was via the dermal route.

Dermatologic

    3.14.1) SUMMARY
    A) Localized contact dermatitis, exacerbation of topically-induced contact dermatitis, generalized maculopapular, erythematous, pruritic, burning dermatitis, and exfoliative dermatitis have been reported.
    B) Hair loss was reported in experimental laboratory animals from repeated vapor exposures.
    3.14.2) CLINICAL EFFECTS
    A) GENERALIZED EXFOLIATIVE DERMATITIS
    1) WITH THERAPEUTIC USE
    a) CASE REPORTS - Severe exfoliative dermatitis has been reported in several patients (Petrozzi & Shore, 1976; Bernstein & Lorinez, 1979; Elias & Levinson, 1981) Neirenberg & Glazener, 1982).
    1) Generalized erythema occurred within 1 to 2 days of oral, rectal, or intravenous aminophylline therapy, which progressed to pedal and palmar exfoliation over the next 7 to 10 days. Rechallenge in 3 patients produced an accelerated reaction within 6 to 8 hours.
    B) CONTACT DERMATITIS
    1) WITH THERAPEUTIC USE
    a) CASE REPORTS - Localized contact dermatitis was first reported in 2 pharmacists who were preparing aminophylline suppositories. A maculopapular rash appeared on the hands and face, followed by formation of vesicles, scaling, weeping, and lichenification (Baer et al, 1973; Tas & Weissberg, 1958).
    b) Local reactions due to Mycolog(R)l cream were subsequently reported in 13 patients with positive patch tests to EDA (Provost & Jillson, 1967; Hogan, 1990). Another 10 cases were reported by Epstein & Maibach (1968).
    c) Inadvertent prolonged topical contact with an ethylenediamine-containing cream resulted in a lymphoblastic psoriaform dermatitis resembling a premycotic condition (Wall, 1982).
    d) Exacerbation of topically-induced contact dermatitis has been reported following systemic administration of aminophylline.
    1) CASE SERIES - Provost & Jillson (1967) reported dermal erythema and exacerbation of underlying patchy eczema in 2 patients, 18 and 48 hours following oral administration of aminophylline.
    e) Generalized maculopapular, erythematous, pruritic, burning dermatitis has been reported following systemic administration (mostly IV) of aminophylline to patients previously sensitized to EDA (DeShazo & Stevenson, 1981).
    f) DeShazo & Stevenson (1981) reported 2 cases (DeShazo & Stevenson, 1981).
    1) The first was a 5-year-old boy with a history of previous diaper rash due to Mycolog(R) cream. Within 24 hours of receiving oral aminophylline he developed lymphadenopathy and a generalized rash which persisted for 10 days with desquamation.
    2) The other case involved a 44-year-old male who had used Mycolog(R) cream in the past with no problem and developed a generalized rash 12 to 24 hours after his first dose of IV aminophylline with desquamation over the next 7 days (Hogan, 1989).
    g) Another case of generalized rash occurring twice in the same patient following administration of IV aminophylline was reported by Lawyer et al (1980). In this patient the rash was exacerbated after oral administration of hydroxyzine.
    h) Positive reactions to ethylenediamine have been observed in adult volunteers after patch testing (HSDB , 2000).
    i) Keczkes et al (1982) described 4 patients with a positive patch test to ethylenediamine that remained sensitive on retesting 10 years after the positive test reaction occurred (Keczkes et al, 1982).
    j) CASE SERIES - Nielsen & Jorgensen (1987) reported 16 patients retested 10 years after a 3+ positive patch test to ethylenediamine. Approximately 25% of these patients had lost their sensitivity to ethylenediamine following avoidance of contact with it (Nielsen & Jorgensen, 1987).
    C) CHEMICAL BURN
    1) WITH POISONING/EXPOSURE
    a) Ethylenediamine is alkaline and may produce skin irritation and blistering when the liquid is splashed or spilled onto the skin (ACGIH, 1986; Dernehl, 1951; JEF Reynolds , 2000).
    D) ECZEMA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - Vesicular eczema was reported on the palms and proximal nail folds of a maintenance man after using a floor polish remover containing 3% ethylenediamine for several months. Three months after discontinuing use of the remover the dermatitis was improved, but not entirely clear (English & Rycroft, 1989).
    E) CONTACT DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES - Keczkes et al (1982) described 4 patients with a positive patch test to ethylenediamine who remained sensitive on retesting 10 years after the positive test reaction occurred. Not all substances produced 100% response after 10 years. Ethylenediamine did produce a positive test in all 4 patients tested (Keczkes et al, 1982).
    b) CASE SERIES - Nielsen & Jorgensen (1987) reported 16 patients retested 10 years after a 3+ positive patch test to ethylenediamine. Approximately 25% of these patients had lost their sensitivity to ethylenediamine following avoidance of contact (Nielsen & Jorgensen, 1987).
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) ALOPECIA
    a) RATS - Repeated exposures of ethylenediamine vapors at 484 ppm produced hair loss in experimental laboratory rats (Pozzani & Carpenter, 1954). Hair loss has NOT been reported in human exposures.

Immunologic

    3.19.1) SUMMARY
    A) EDA is a skin and respiratory sensitizer.
    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) WITH POISONING/EXPOSURE
    a) Ethylenediamine is a respiratory and dermal sensitizer. A shorter latency period between first ethylenediamine exposure and subsequent appearance of respiratory symptoms was reported in workers that are current smokers (Aldrich et al, 1987).
    b) Both immediate and delayed hypersensitivity reactions may occur (Berman & Ross, 1983).
    c) Photoallergic dermatitis has also been reported (Romaguera et al, 1986; Burry, 1986).
    d) A patient developed severe exfoliative erythroderma after intravenous aminophylline. Investigations suggested the reaction was a cell-mediated hypersensitivity to ethylenediamine (Elias & Levinson, 1981).
    e) Results of a study in experimental animals suggested the potential usefulness of the lymphocyte transformation test for in vitro diagnosis of ethylenediamine-induced hypersensitivity in humans (Babiuk et al, 1987).
    f) Because of the hypersensitivity to diamines, including ethylenediamine, it is difficult to establish a threshold limit that will insure prevention of hypersensitive reactions (HSDB , 2000).

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.
    B) No information about possible male reproductive effects in humans was found in available references at the time of this review.
    3.20.2) TERATOGENICITY
    A) HUMANS
    1) The unborn may be especially sensitive to ethylenediamine, because it can induce METHEMOGLOBINEMIA. The fetal form of hemoglobin, which is still present at birth, is more easily oxidized to methemoglobin, and levels of methemoglobin reductase are lower in the fetus than in the adult (Ross & Desforges, 1959).
    B) ANIMAL STUDIES
    1) No evidence of ethylenediamine-induced teratogenic effects was observed in timed-pregnant rats fed ethylenediamine dihydrochloride (1, 0.25, 0.05, or 0 g/kg/day) on gestation days 6 through 15 (DePass et al, 1987). In mouse studies, changes in growth statistics were observed (HSDB , 2000; RTECS , 2000).
    3.20.3) EFFECTS IN PREGNANCY
    A) ANIMAL STUDIES
    1) Ethylenediamine did not cause any treatment related adverse effects on the following reproductive indices studied in rats (Yang et al, 1984):
    a) Fraction of pregnancies resulting in litters with live pups
    b) Fertility index; days from first mating to parturition
    c) Gestation survival index for 0 to 4 days, 4 to 14 days, and 4 to 21 days
    d) Pups born live per litter
    e) Pup body weight by litter at lactation days 4 and 14
    f) And individual body weight for pups at weaning day 21.
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) HUMANS
    1) LACK OF INFORMATION
    a) At the time of this review, no data were available to assess the potential effects of exposure to this agent during lactation.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS107-15-3 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.4) ANIMAL STUDIES
    A) ANIMAL STUDIES
    1) MICE - Dermal application of ethylenediamine 1% solution (25 microliters) to the skin of mice for their lifetime produced no evidence for cutaneous oncogenicity (DePass et al, 1984).

Genotoxicity

    A) No positive effect on unscheduled DNA synthesis was noted in experimental studies. Mutations have been observed in S typhimurium but not in the Chinese hamster ovary mutation assay. A dose-related effect in the sister chromatid exchange test has not been noted.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Elevated serum methemoglobin levels may be used as an indirect test for exposure in workers exposed to ethylenediamine. No methods for measurement of ethylenediamine in environmental samples were listed in available references at the time of this review.
    B) Monitor pulse oximetry and/or ABGs, chest x-ray, and pulmonary function tests in symptomatic patients.
    C) Monitor CBC, urinalysis, and liver and kidney function tests in patients with significant exposure.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count and liver and kidney function tests is suggested for patients with significant exposure.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) If respiratory tract irritation is present, monitor arterial blood gases and chest x-ray.
    2) PULMONARY FUNCTION TESTS
    a) If respiratory tract irritation is present, it may be useful to monitor pulmonary function tests.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) If respiratory tract irritation is present, monitor chest x-ray.

Methods

    A) CHROMATOGRAPHY
    1) Reversed-phase high pressure liquid chromatography (HPLC) with UV detection has been used to determine plasma and urine levels of ethylenediamine in a volunteer following oral and intravenous administration of aminophylline (HSDB , 2000). The lower limit of detection was 0.05 mug/mL.
    B) OTHER
    1) PATCH TEST - 2% ethylenediamine in petrolatum may be useful to differentiate causes of dermatitis.
    2) INDIRECT MEASURE - Elevated serum methemoglobin levels may be used as an indirect test of response in workers exposed to ethylenediamine.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.
    6.3.3) DISPOSITION/INHALATION EXPOSURE
    6.3.3.1) ADMISSION CRITERIA/INHALATION
    A) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.
    6.3.4) DISPOSITION/EYE EXPOSURE
    6.3.4.1) ADMISSION CRITERIA/EYE
    A) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.
    6.3.4.3) CONSULT CRITERIA/EYE
    A) Because of the potential for serious eye injury following direct ocular contact, prolonged initial flushing and early ophthalmologic evaluation are advisable.
    6.3.5) DISPOSITION/DERMAL EXPOSURE
    6.3.5.1) ADMISSION CRITERIA/DERMAL
    A) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.
    6.3.5.5) OBSERVATION CRITERIA/DERMAL
    A) Some chemicals can produce systemic poisoning by absorption through intact skin. Carefully observe patients with dermal exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.

Monitoring

    A) Elevated serum methemoglobin levels may be used as an indirect test for exposure in workers exposed to ethylenediamine. No methods for measurement of ethylenediamine in environmental samples were listed in available references at the time of this review.
    B) Monitor pulse oximetry and/or ABGs, chest x-ray, and pulmonary function tests in symptomatic patients.
    C) Monitor CBC, urinalysis, and liver and kidney function tests in patients with significant exposure.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED
    1) Ethylenediamine is an irritant. DO NOT INDUCE VOMITING. Dilution with water or milk may be beneficial following an ingestion of a significant amount.
    B) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) Ethylenediamine is an irritant. DO NOT INDUCE VOMITING. Dilution with water or milk may be beneficial following an ingestion of a significant amount.
    B) ACTIVATED CHARCOAL
    1) No information was found on adsorption of ethylenediamine to activated charcoal. Activated charcoal may be of theoretical benefit following a significant ingestion of ethylenediamine.
    a) Use of activated charcoal may interfere with esophagoscopy should it be indicated to detect burns or perforation induced from the irritant properties of ethylenediamine.
    2) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    3) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) Treatment is symptomatic and supportive. There is no specific antidote for ethylenediamine intoxication.
    B) 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).
    C) IRRITATION SYMPTOM
    1) Observe patients with ingestion carefully for the possible development of esophageal or gastrointestinal tract irritation or burns. If signs or symptoms of esophageal irritation or burns are present, consider endoscopy to determine the extent of injury.
    D) OBSERVATION REGIMES
    1) Carefully observe patients with ingestion exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    E) ANAPHYLAXIS
    1) SUMMARY
    a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
    2) BRONCHOSPASM
    a) ALBUTEROL
    1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    3) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm.
    b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).
    4) MILD CASES
    a) DIPHENHYDRAMINE
    1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
    2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    5) MODERATE CASES
    a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).
    6) SEVERE CASES
    a) EPINEPHRINE
    1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
    2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TLet al,null).
    7) AIRWAY MANAGEMENT
    a) OXYGEN: 5 to 10 liters/minute via high flow mask.
    b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
    c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TLet al,null).
    d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
    e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
    f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    8) MONITORING
    a) CARDIAC MONITOR: All complicated cases.
    b) IV ACCESS: Routine in all complicated cases.
    9) HYPOTENSION
    a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.
    1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
    2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).
    10) H1 and H2 ANTIHISTAMINES
    a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
    1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).
    b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
    c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).
    11) DYSRHYTHMIAS
    a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TLet al,null). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.
    12) OTHER THERAPIES
    a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TLet al,null).
    F) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    G) METHEMOGLOBINEMIA
    1) SUMMARY
    a) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.
    2) METHYLENE BLUE
    a) INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules (Prod Info PROVAYBLUE(TM) intravenous injection, 2016) and 10 mg/1 mL (1% solution) vials (Prod Info methylene blue 1% intravenous injection, 2011). REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. NOTE: Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection (Prod Info methylene blue 1% intravenous injection, 2011; Herman et al, 1999). NEONATES: DOSE: 0.3 to 1 mg/kg (Hjelt et al, 1995).
    b) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004)
    c) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M disease, sulfhemoglobinemia, or G-6-PD deficiency. Methylene blue is reduced by methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to leukomethylene blue. This in turn reduces methemoglobin. Red blood cells of patients with G-6-PD deficiency do not produce enough NADPH to convert methylene blue to leukomethylene blue (do Nascimento et al, 2008).
    d) DRUG INTERACTION: Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome (U.S. Food and Drug Administration, 2011; Stanford et al, 2010; Prod Info methylene blue 1% IV injection, 2011).
    3) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)
    a) DOSE: 2 to 4 mg/kg intravenously over 5 minutes. Dose may be repeated in 30 minutes (Nemec, 2011; Lindenmann et al, 2006; Kiese et al, 1972).
    b) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose (Dunipace et al, 1992; Hix & Wilson, 1987; Winek et al, 1969; Teunis et al, 1970; Marquez & Todd, 1959).
    c) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    6.7.2) TREATMENT
    A) BRONCHOSPASM
    1) BRONCHOSPASM SUMMARY
    a) Administer beta2 adrenergic agonists. Consider use of inhaled ipratropium and systemic corticosteroids. Monitor peak expiratory flow rate, monitor for hypoxia and respiratory failure, and administer oxygen as necessary.
    2) ALBUTEROL/ADULT DOSE
    a) 2.5 to 5 milligrams diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response, administer 2.5 to 10 milligrams every 1 to 4 hours as needed OR administer 10 to 15 milligrams every hour by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.5 milligram by nebulizer every 30 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).
    3) ALBUTEROL/PEDIATRIC DOSE
    a) 0.15 milligram/kilogram (minimum 2.5 milligrams) diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.25 to 0.5 milligram by nebulizer every 20 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).
    4) ALBUTEROL/CAUTIONS
    a) The incidence of adverse effects of beta2-agonists may be increased in older patients, particularly those with pre-existing ischemic heart disease (National Asthma Education and Prevention Program, 2007). Monitor for tachycardia, tremors.
    5) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm. PREDNISONE: ADULT: 40 to 80 milligrams/day in 1 or 2 divided doses. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 or 2 divided doses (National Heart,Lung,and Blood Institute, 2007).
    B) OBSERVATION REGIMES
    1) Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) IRRITATION SYMPTOM
    1) Respiratory tract irritation, if severe, can progress to noncardiogenic pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases.
    2) There are no controlled studies indicating that early administration of corticosteroids can prevent the development of noncardiogenic pulmonary edema in patients with inhalation exposure to respiratory irritant substances, and long-term use may cause adverse effects (Boysen & Modell, 1989).
    a) However, based on anecdotal experience, some clinicians do recommend early administration of corticosteroids (such as methylprednisolone 1 gram intravenously as a single dose) in an attempt to prevent the later development of pulmonary edema.
    1) Anecdotal experience with dimethyl sulfate inhalation showed possible benefit of methylprednisolone in the TREATMENT of noncardiogenic pulmonary edema (Ip et al, 1989).
    3) Anecdotal experience also indicated that systemic corticosteroids may have possible efficacy in the TREATMENT of drug-induced noncardiogenic pulmonary edema (Zitnik & Cooper, 1990; Stentoft, 1990; Chudnofsky & Otten, 1989) or noncardiogenic pulmonary edema developing after cardiopulmonary bypass (Maggart & Stewart, 1987).
    4) It is not clear from the published literature that administration of systemic corticosteroids early following inhalation exposure to respiratory irritant substances can PREVENT the development of noncardiogenic pulmonary edema. The decision to administer or withhold corticosteroids in this setting must currently be made on clinical grounds.
    D) 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).
    E) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) IRRITATION SYMPTOM
    1) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
    B) DERMATITIS
    1) When selecting topical corticosteroids, avoid using medications containing ethylenediamine.
    2) When selecting antihistamines for systemic use for treatment of hypersensitivity reactions, avoid using antihistamines that are derivatives of ethylenediamine such as antazoline, hydroxyzine, methapyrilene, pyrilamine, tripelennnamine, and thenyldiamine.
    C) SKIN ABSORPTION
    1) Some chemicals can produce systemic poisoning by absorption through intact skin. Carefully observe patients with dermal exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    D) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Range Of Toxicity

Summary

    A) Hypersensitivity reactions may occur with any exposure in a sensitized individual.
    B) A 5% aqueous solution of ethylenediamine has been reported to induce minor eye injury when splashed into the eye. A 15% solution of EDA may seriously damage the cornea.

Minimum Lethal Exposure

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

Maximum Tolerated Exposure

    A) ROUTE OF EXPOSURE
    1) Hypersensitivity reactions have occurred from single intravenous or oral doses of aminophylline in a sensitized patient (Hardy et al, 1983; Thompson et al, 1984) and following use of topical preparations containing 0.1 percent ethylenediamine (Fisher, 1986).
    2) In humans, inhalation of 100 parts per million was inoffensive; 200 parts per million caused slight nasal irritation and tingling of the face; 400 parts per million for 5 to 10 seconds caused intolerable nasal irritation (Proctor & Hughes, 1978; Hathaway et al, 1996).
    B) OCCUPATIONAL
    1) A retrospective study of 197 employees of an ethyleneamine production unit of a factory, between the years 1947 and 1983, noted 141 ethyleneamine related medical visits.
    a) Among the 141 visits 17 percent was respiratory symptoms, 11 percent ophthalmic, and 75 percent dermatologic. No excesses of mortality was identified among the ethyleneamine production unit workers as compared to referent groups (Lewinsohn & Ott, 1991).
    C) ANIMAL DATA
    1) The smallest daily dose of ethylenediamine which caused toxic signs when fed to rats in drinking water during a 90-day exposure was 0.12 gram/kilogram (Smyth et al, 1951).

Workplace Standards

    A) ACGIH TLV Values for CAS107-15-3 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Ethylenediamine
    a) TLV:
    1) TLV-TWA: 10 ppm
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A4
    2) Codes: Skin
    3) Definitions:
    a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    b) Skin: This refers to the potential significant contribution to the overall exposure by the cutaneous route, including mucous membranes and the eyes, either by contact with vapors or, of likely greater significance, by direct skin contact with the substance. It should be noted that although some materials are capable of causing irritation, dermatitis, and sensitization in workers, these properties are not considered relevant when assigning a skin notation. Rather, data from acute dermal studies and repeated dose dermal studies in animals or humans, along with the ability of the chemical to be absorbed, are integrated in the decision-making toward assignment of the skin designation. Use of the skin designation provides an alert that air sampling would not be sufficient by itself in quantifying exposure from the substance and that measures to prevent significant cutaneous absorption may be warranted. Please see "Definitions and Notations" (in TLV booklet) for full definition.
    c) TLV Basis - Critical Effect(s):
    d) Molecular Weight: 60.1
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    B) NIOSH REL and IDLH Values for CAS107-15-3 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Ethylenediamine
    2) REL:
    a) TWA: 10 ppm (25 mg/m(3))
    b) STEL:
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s):
    3) IDLH:
    a) IDLH: 1000 ppm
    b) Note(s): Not Listed

    C) Carcinogenicity Ratings for CAS107-15-3 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Ethylenediamine
    a) A4 :Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    2) EPA (U.S. Environmental Protection Agency, 2011): D ; Listed as: Ethylene diamine
    a) D : Not classifiable as to human carcinogenicity.
    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 ; Listed as: Ethylenediamine
    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 CAS107-15-3 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Ethylenediamine
    2) Table Z-1 for Ethylenediamine:
    a) 8-hour TWA:
    1) ppm: 10
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 25
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: No
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: RTECS, 2000 ITI, 1985
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 200 mg/kg
    2) LD50- (SUBCUTANEOUS)MOUSE:
    a) 424 mg/kg
    3) LD50- (INTRAPERITONEAL)RAT:
    a) 76 mg/kg
    4) LD50- (ORAL)RAT:
    a) 500 mg/kg
    b) 1160 mg/kg
    5) LD50- (SUBCUTANEOUS)RAT:
    a) 300 mg/kg
    6) TCLo- (INHALATION)HUMAN:
    a) 200 ppm

Pharmacology Toxicology

Toxicologic Mechanism

    A) Aminophylline/ethylenediamine hypersensitivity is classically a somewhat delayed reaction, occurring 12 to 24 hours after drug exposure.
    1) This suggests an accelerated cell-mediated mechanism, but in vitro lymphocyte proliferation to aminophylline or aminophylline-epithelial protein conjugates has not been demonstrated.
    2) It is likely that antigen processing by dermal Langerhans cells is involved, but that viable cells may be necessary to detect a reaction in vitro (DeShazo & Stevenson, 1981; Elias & Levinson, 1981; DeShazo & Stevenson, 1981).
    B) Ethylenediamine has been reported to be an inhibitor of neuronal firing with a potency comparable to GABA (Anderson et al, 1973; Perkins & Stone, 1980; Phillis, 1977; Foster et al, 1981; Perkins et al, 1981).
    1) Strain & Flory (1981) therefore suggested that EDA may possess neurotoxic properties, particularly in neonates and in disease states where the blood-brain barrier is incomplete or altered. No neurotoxic effects have been noted in human exposures.
    C) When heated to decomposition, ethylenediamine emits toxic fumes of oxides of nitrogen and ammonia.

Physicochemical

Physical Characteristics

    A) Ethylenediamine is a thick, colorless alkaline liquid with an ammonia-like odor (JEF Reynolds , 2000; ACGIH, 1986).

Ph

    A) 11.9 (for a 25% aqueous solution at 25 degrees C) (ACGIH, 1986)

Molecular Weight

    A) 60.10 (Budavari, 1996)

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) 49 CFR 172.101: Department of Transportation - Table of Hazardous Materials. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 11, 2005.
    5) 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.
    6) 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.
    7) 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.
    8) 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.
    9) 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.
    10) 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.
    11) 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.
    12) 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.
    13) ACGIH: Documentation of the Threshold Limit Values, 5th ed, Am Conference of Govt Ind Hyg, Inc, Cincinnati, OH, 1986.
    14) AIHA: 2006 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook, American Industrial Hygiene Association, Fairfax, VA, 2006.
    15) Alaspaa AO, Kuisma MJ, Hoppu K, et al: Out-of-hospital administration of activated charcoal by emergency medical services. Ann Emerg Med 2005; 45:207-12.
    16) Aldrich FD, Strange AW, & Geesaman RE: Smoking and ethylene diamine sensitization in an industrial population. J Occup Med 1987; 29:311-315.
    17) 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.
    18) Anderson EG, Haas H, & Hosli L: Comparison of effects of noradrenaline and histamine with cyclic AMP on brain stem neurons. Brain Res 1973; 49:471-475.
    19) Ansell-Edmont: SpecWare Chemical Application and Recommendation Guide. Ansell-Edmont. Coshocton, OH. 2001. Available from URL: http://www.ansellpro.com/specware. As accessed 10/31/2001.
    20) 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.
    21) Babiuk C, Hastings KL, & Dean JH: Induction of ethylenediamine hypersensitivity in the guinea pig and the development of ELISA and lymphocyte blastogenesis techniques for its characterization. Fundam Appl Toxicol 1987; 9:623-634.
    22) Baer RL, Ramsey DL, & Biondi E: The most common contact allergens. Arch Dermatol 1973; 108:74-78.
    23) Bainova A, Khristeva V, & Madzhunov I: Dermal exposure to ethylenediamine in the petrochemical industry. Probl Khig 1987; 12:109-111.
    24) Bata Shoe Company: Industrial Footwear Catalog, Bata Shoe Company, Belcamp, MD, 1995.
    25) Berman BA & Ross RN: Ethylenediamine: Systemic eczematous contact-type dermatitis. Cutis 1983; 31:594-598.
    26) Bernstein JE & Lorinez AL: Ethylenediamine-induced exfoliative erythroderma. Arch Dermatol 1979; 115:360-361.
    27) Best Manufacturing: ChemRest Chemical Resistance Guide. Best Manufacturing. Menlo, GA. 2002. Available from URL: http://www.chemrest.com. As accessed 10/8/2002.
    28) Best Manufacturing: Degradation and Permeation Data. Best Manufacturing. Menlo, GA. 2004. Available from URL: http://www.chemrest.com/DomesticPrep2/. As accessed 04/09/2004.
    29) Boss Manufacturing Company: Work Gloves, Boss Manufacturing Company, Kewanee, IL, 1998.
    30) Boysen PG & Modell JH: Pulmonary edema, in: Textbook of Critical Care Medicine, 2nd ed. Shoemaker WC, Ayres S, Grenvik A et al (Eds), WB Saunders Company, Philadelphia, PA, 1989, pp 515-518.
    31) 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.
    32) Budavari S: The Merck Index, 12th ed, Merck & Co, Inc, Whitehouse Station, NJ, 1996.
    33) Burgess JL, Kirk M, Borron SW, et al: Emergency department hazardous materials protocol for contaminated patients. Ann Emerg Med 1999; 34(2):205-212.
    34) Burry JN: Photocontact dermatitis from ethylenediamine. Cont Derm 1986; 15:305-306.
    35) CHRIS : CHRIS Hazardous Chemical Data. US Department of Transportation, US Coast Guard. Washington, DC (Internet Version). Edition expires 1985; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    36) Calnan CD: Sensitivity to ethylenediamine, piperazine and hydroxyzine. Contact Derm 1975; 1:176.
    37) Caravati EM: Alkali. In: Dart RC, ed. Medical Toxicology, Lippincott Williams & Wilkins, Philadelphia, PA, 2004.
    38) Carpenter CP & Smyth HF Jr: Am J Ophthalmol 1946; 29:1363.
    39) 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.
    40) ChemFab Corporation: Chemical Permeation Guide Challenge Protective Clothing Fabrics, ChemFab Corporation, Merrimack, NH, 1993.
    41) Chudnofsky CR & Otten EJ: Acute pulmonary toxicity to nitrofurantoin. J Emerg Med 1989; 7:15-19.
    42) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    43) Clayton GD & Clayton FE: Patty's Industrial Hygiene and Toxicology, 4th ed, John Wiley & Sons, New York, NY, 1994.
    44) Clayton GD & Clayton FE: Patty's Industrial Hygiene and Toxicology, Vol 2B, Toxicology, 3rd ed, John Wiley & Sons, New York, NY, 1981.
    45) Comasec Safety, Inc.: Chemical Resistance to Permeation Chart. Comasec Safety, Inc.. Enfield, CT. 2003. Available from URL: http://www.comasec.com/webcomasec/english/catalogue/mtabgb.html. As accessed 4/28/2003.
    46) Comasec Safety, Inc.: Product Literature, Comasec Safety, Inc., Enfield, CT, 2003a.
    47) 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.
    48) Dagnone D, Matsui D, & Rieder MJ: Assessment of the palatability of vehicles for activated charcoal in pediatric volunteers. Pediatr Emerg Care 2002; 18:19-21.
    49) DePass LR, Fowler EH, & Yang RGH: Dermal oncogenicity studies on ethylenediamine in male C3H mice. Fundam Appl Toxicol 1984; 4:641-645.
    50) DePass LR, Yang RSH, & Woodside MD: Evaluation of the teratogenicity of ethylenediamine dihydrochloride in Fischer 344 rats by conventional and pair-feeding studies. Fundam Appl Toxicol 1987; 9:687-697.
    51) DeShazo RD & Stevenson HC: Generalized dermatitis to aminophylline. Ann Allergy 1981; 46:152-155.
    52) Dernehl CV: Clinical experiences with exposures to ethylene amines. Ind Med Surg 1951; 20:541.
    53) DuPont: DuPont Suit Smart: Interactive Tool for the Selection of Protective Apparel. DuPont. Wilmington, DE. 2002. Available from URL: http://personalprotection.dupont.com/protectiveapparel/suitsmart/smartsuit2/na_english.asp. As accessed 10/31/2002.
    54) DuPont: Permeation Guide for DuPont Tychem Protective Fabrics. DuPont. Wilmington, DE. 2003. Available from URL: http://personalprotection.dupont.com/en/pdf/tyvektychem/pgcomplete20030128.pdf. As accessed 4/26/2004.
    55) DuPont: Permeation Test Results. DuPont. Wilmington, DE. 2002a. Available from URL: http://www.tyvekprotectiveapprl.com/databases/default.htm. As accessed 7/31/2002.
    56) Dunipace AJ, Beaven R, Noblitt T, et al: Mutagenic potential of toluidine blue evaluated in the Ames test. Mutat Res 1992; 279(4):255-259.
    57) EPA: EPA chemical profile on ethylenediamine, Environmental Protection Agency, Washington, DC, 1985.
    58) 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/.
    59) ERG: Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident, U.S. Department of Transportation, Research and Special Programs Administration, Washington, DC, 2004.
    60) Elias JA & Levinson AI: Hypersensitivity reactions to ethylenediamine in aminophylline. Am Rev Respir Dis 1981; 123:550-552.
    61) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    62) English JSC & Rycroft RJG: Occupational sensitization to ethylenediamine in a floor polish remover. Contact Dermatitis 1989; 20:220-221.
    63) Epstein E & Maibach HI: Ethylenediamine allergic contact dermatitis. Arch Dermatol 1968; 98:476-477.
    64) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    65) Fisher A: Erythema multiform-like eruptions due to topical medications: part II. Cutis 1986; 37:158-161.
    66) Fisher AA: Does ethylenediamine hydrochloride cross react with ethylenediamine tetracetate?. Contact Derm 1975; 1:267.
    67) Fisher AA: Problems associated with "generic" topical medications. Cutis 1988a; 41:313-314.
    68) Fisher AA: Systemic eczematous 'contact type' dermatitis medicamentosa. Ann Allergy 1964; 24:406-420.
    69) Fisher AA: Unnecessary addition of ethylenediamine hydrochloride to "generic" nystatin creams. J Am Acad Dermatol 1989; 20:129-130.
    70) Foster P, Lloyd HGE, & Morgan P: Ethylenediamine acts upon GABA receptors and uptake sites. Br J Pharmacol 1981; 74:274.
    71) Gelfand HH: Respiratory allergy due to chemical compounds encountered in the rubber, lacquer, shellac, and beauty culture industries. J Allergy 1963; 34:374-381.
    72) Goh CL: Occupational dermatitis from soldering flux among workers in the electronics industry. Cont Derm 1985; 13:85-90.
    73) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    74) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    75) Grant WM & Schuman JS: Toxicology of the Eye, 4th ed, Charles C Thomas, Springfield, IL, 1993.
    76) Guardian Manufacturing Group: Guardian Gloves Test Results. Guardian Manufacturing Group. Willard, OH. 2001. Available from URL: http://www.guardian-mfg.com/guardianmfg.html. As accessed 12/11/2001.
    77) Guenther Skokan E, Junkins EP, & Corneli HM: Taste test: children rate flavoring agents used with activated charcoal. Arch Pediatr Adolesc Med 2001; 155:683-686.
    78) HSDB : Hazardous Substances Data Bank. National Library of Medicine. Bethesda, MD (Internet Version). Edition expires 1992; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    79) HSDB : Hazardous Substances Data Bank. National Library of Medicine. Bethesda, MD (Internet Version). Edition expires 2000; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    80) HSDB : Hazardous Substances Data Bank. National Library of Medicine. Bethesda, MD (Internet Version). Edition expires Oct/31/1993; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    81) Haas CF: Mechanical ventilation with lung protective strategies: what works?. Crit Care Clin 2011; 27(3):469-486.
    82) Hagmar L, Bellander T, & Bergoo B: Piperazine-induced occupational asthma. J Occup Med 1982; 24:193-197.
    83) Hardy C, Schofield O, & George CF: Allergy to aminophylline. Br Med J 1983; 286:2051-2052.
    84) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    85) Hathaway GJ, Proctor NH, & Hughes JP: Proctor & Hughes' Chemical Hazards of the Workplace, 4th ed, Van Nostrand Reinhold, New York, NY, 1996.
    86) Herman MI, Chyka PA, & Butlse AY: Methylene blue by intraosseous infusion for methemoglobinemia. Ann Emerg Med 1999; 33:111-113.
    87) Hix WR & Wilson WR: Toluidine blue staining of the esophagus: a useful adjunct in the panendoscopic evaluation of patients with squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 1987; 113(8):864-865.
    88) Hjelt K, Lund JT, Scherling B, et al: Methaemoglobinaemia among neonates in a neonatal intensive care unit. Acta Paediatr 1995; 84(4):365-370.
    89) Hogan DJ: Allergic contact dermatitis to ethylenediamine a continuing problem. Contact Dermatitis 1990; 8:133-136.
    90) Hogan DJ: Excipients in topical corticosteroid preparations in Canada. Canad Med Assoc J 1989; 141:1032.
    91) Howland MA: Antidotes in Depth. In: Goldfrank LR, Flomenbaum N, Hoffman RS, et al, eds. Goldfrank's Toxicologic Emergencies. 8th ed., 8th ed. McGraw-Hill, New York, NY, 2006, pp 826-828.
    92) 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.
    93) 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.
    94) 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.
    95) 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.
    96) 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.
    97) 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.
    98) ICAO: Technical Instructions for the Safe Transport of Dangerous Goods by Air, 2003-2004. International Civil Aviation Organization, Montreal, Quebec, Canada, 2002.
    99) ILC Dover, Inc.: Ready 1 The Chemturion Limited Use Chemical Protective Suit, ILC Dover, Inc., Frederica, DE, 1998.
    100) ITI: Toxic and Hazardous Industrial Chemicals Safety Manual, The International Technical Information Institute, Tokyo, Japan, 1985.
    101) 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.
    102) 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.
    103) Ip M, Wong K-L, & Wong K-F: Lung injury in dimethyl sulfate poisoning. J Occup Med 1989; 31:141-143.
    104) JEF Reynolds : Martindale: The Extra Pharmacopeia (Internet version). The Pharmaceutical Press. London, UK (Internet Version). Edition expires 2000; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    105) JEF Reynolds : Martindale: The Extra Pharmacopeia. The Pharmaceutical Press. London, England (Internet Version). Edition expires 1993; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    106) Kappler, Inc.: Suit Smart. Kappler, Inc.. Guntersville, AL. 2001. Available from URL: http://www.kappler.com/suitsmart/smartsuit2/na_english.asp?select=1. As accessed 7/10/2001.
    107) Keczkes A, Basheer AM, & Wyatt EH: The persistence of allergic contact sensitivity: a 10-year follow-up in 100 patients. Br J Dermatol 1982; 107:461-465.
    108) Kiese M , Lorcher W , Weger N , et al: Comparative studies on the effects of toluidine blue and methylene blue on the reduction of ferrihaemoglobin in man and dog. Eur J Clin Pharmacol 1972; 4(2):115-118.
    109) Kimberly-Clark, Inc.: Chemical Test Results. Kimberly-Clark, Inc.. Atlanta, GA. 2002. Available from URL: http://www.kc-safety.com/tech_cres.html. As accessed 10/4/2002.
    110) Kleinman ME, Chameides L, Schexnayder SM, et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 14: pediatric advanced life support. Circulation 2010; 122(18 Suppl.3):S876-S908.
    111) Kollef MH & Schuster DP: The acute respiratory distress syndrome. N Engl J Med 1995; 332:27-37.
    112) Kradjan WA & Lakshminarayan S: Allergy to aminophylline: lack of predictability by skin testing. Am J Hosp Pharm 1981; 38:1031-1033.
    113) LaCrosse-Rainfair: Safety Products, LaCrosse-Rainfair, Racine, WI, 1997.
    114) Lam S & Chan-Yeung M: Ethylene diamine-induced asthma. Am Rev Respir Dis 1980; 121:151-155.
    115) Lawyer CH, Bardana EJ, & Rodgers R: Utilization of intravenous dihydroxypropyl theophylline (dyphylline) in an aminophylline-sensitive patient, and its pharmacokinetic comparison with theophylline. J Allergy Clin Immunol 1980; 65:353-357.
    116) Leung HW: Evaluation of the genotoxic potential of alkyleneamines. Mutat Res 1994; 320:31-43.
    117) Lewinsohn HC & Ott MG: A review of medical surveillance records of employees exposed to ethyleneamines. J Occup Med 1991; 33:148-154.
    118) Lieberman P, Nicklas R, Randolph C, et al: Anaphylaxis-a practice parameter update 2015. Ann Allergy Asthma Immunol 2015; 115(5):341-384.
    119) Lieberman P, Nicklas RA, Oppenheimer J, et al: The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol 2010; 126(3):477-480.
    120) Lindenmann J, Matzi V, Kaufmann P, et al: Hyperbaric oxygenation in the treatment of life-threatening isobutyl nitrite-induced methemoglobinemia--a case report. Inhal Toxicol 2006; 18(13):1047-1049.
    121) MAPA Professional: Chemical Resistance Guide. MAPA North America. Columbia, TN. 2003. Available from URL: http://www.mapaglove.com/pro/ChemicalSearch.asp. As accessed 4/21/2003.
    122) MAPA Professional: Chemical Resistance Guide. MAPA North America. Columbia, TN. 2004. Available from URL: http://www.mapaglove.com/ProductSearch.cfm?id=1. As accessed 6/10/2004.
    123) Maggart M & Stewart S: The mechanisms and management of noncardiogenic pulmonary edema following cardiopulmonary bypass. Ann Thorac Surg 1987; 43:231-236.
    124) Mar-Mac Manufacturing, Inc: Product Literature, Protective Apparel, Mar-Mac Manufacturing, Inc., McBee, SC, 1995.
    125) Marigold Industrial: US Chemical Resistance Chart, on-line version. Marigold Industrial. Norcross, GA. 2003. Available from URL: www.marigoldindustrial.com/charts/uschart/uschart.html. As accessed 4/14/2003.
    126) Marquez A & Todd M: Acute hemolytic anemia and agranulocytosis following intravenous administration of toluidine blue. Am Pract 1959; 10:1548-1550.
    127) Memphis Glove Company: Permeation Guide. Memphis Glove Company. Memphis, TN. 2001. Available from URL: http://www.memphisglove.com/permeation.html. As accessed 7/2/2001.
    128) Montgomery Safety Products: Montgomery Safety Products Chemical Resistant Glove Guide, Montgomery Safety Products, Canton, OH, 1995.
    129) NFPA: Fire Protection Guide to Hazardous Materials, 13th ed., National Fire Protection Association, Quincy, MA, 2002.
    130) 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.
    131) 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.
    132) 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.
    133) 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.
    134) 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.
    135) Nakazawa T & Matsui S: Ethylenediamine-induced late asthmatic responses. J Asthma 1990; 27:207-212.
    136) Naradzay J & Barish RA: Approach to ophthalmologic emergencies. Med Clin North Am 2006; 90(2):305-328.
    137) Nat-Wear: Protective Clothing, Hazards Chart. Nat-Wear. Miora, NY. 2001. Available from URL: http://www.natwear.com/hazchart1.htm. As accessed 7/12/2001.
    138) 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.
    139) 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.
    140) 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.
    141) 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.
    142) 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.
    143) 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.
    144) 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.
    145) 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.
    146) 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.
    147) 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.
    148) 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.
    149) 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.
    150) 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.
    151) 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.
    152) 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.
    153) 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.
    154) 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.
    155) 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.
    156) 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.
    157) 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.
    158) 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.
    159) 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.
    160) 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.
    161) 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.
    162) 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.
    163) 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.
    164) 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.
    165) 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.
    166) 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.
    167) 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.
    168) 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.
    169) 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.
    170) 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.
    171) 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.
    172) 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.
    173) 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.
    174) 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.
    175) 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.
    176) 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.
    177) 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.
    178) 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.
    179) 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.
    180) 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.
    181) 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.
    182) 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.
    183) 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.
    184) 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.
    185) 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.
    186) 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.
    187) 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.
    188) 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.
    189) 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.
    190) 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.
    191) 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.
    192) 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.
    193) 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.
    194) 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.
    195) 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.
    196) 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.
    197) 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.
    198) 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.
    199) 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.
    200) 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.
    201) 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.
    202) 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.
    203) 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.
    204) 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.
    205) 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.
    206) 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.
    207) 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.
    208) 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.
    209) 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.
    210) 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.
    211) 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.
    212) National Asthma Education and Prevention Program: Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol 2007; 120(5 Suppl):S94-S138.
    213) 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.
    214) 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.
    215) National Research Council : Acute exposure guideline levels for selected airborne chemicals, 5, National Academies Press, Washington, DC, 2007.
    216) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 6, National Academies Press, Washington, DC, 2008.
    217) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 7, National Academies Press, Washington, DC, 2009.
    218) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 8, National Academies Press, Washington, DC, 2010.
    219) Neese Industries, Inc.: Fabric Properties Rating Chart. Neese Industries, Inc.. Gonzales, LA. 2003. Available from URL: http://www.neeseind.com/new/TechGroup.asp?Group=Fabric+Properties&Family=Technical. As accessed 4/15/2003.
    220) Nemec K: Antidotes in acute poisoning. Eur J Hosp Pharm Sci Pract 2011; 17(4):53-55.
    221) Ng TP, Lee HS, & Lee FY: Occupational asthma due to ethylene diamine. Ann Acad Med Singapore 1991; 20:399-402.
    222) Nielsen M & Jorgensen J: Persistence of contact sensitivity of ethylenediamine. Cont Derm 1987; 16:275-276.
    223) Niggemann B: Aggressives verhalten als nebenwirkung des athylenediamins (nicht aber des theophyllins). Monatsschr Kinderheilkd 1985; 133:487.
    224) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    225) North: Chemical Resistance Comparison Chart - Protective Footwear . North Safety. Cranston, RI. 2002. Available from URL: http://www.linkpath.com/index2gisufrm.php?t=N-USA1. As accessed April 30, 2004.
    226) North: eZ Guide Interactive Software. North Safety. Cranston, RI. 2002a. Available from URL: http://www.northsafety.com/feature1.htm. As accessed 8/31/2002.
    227) Nowak RM & Macias CG : Anaphylaxis on the other front line: perspectives from the emergency department. Am J Med 2014; 127(1 Suppl):S34-S44.
    228) Pascher F: Systemic reactions to topically applied drugs. Bull Acad Med 1973; 49:613-627.
    229) Peate WF: Work-related eye injuries and illnesses. Am Fam Physician 2007; 75(7):1017-1022.
    230) Peberdy MA , Callaway CW , Neumar RW , et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care science. Part 9: post–cardiac arrest care. Circulation 2010; 122(18 Suppl 3):S768-S786.
    231) Perkins MN & Stone TW: Aminophylline and theophylline derivatives as antagonists of neuronal depression by adenosine: a microiontophoretic study. Arch Internat Pharmacodyn 1980; 246:205-214.
    232) Perkins MN, Bowery NG, & Hill DR: Neuronal responses to ethylenediamine preferential blockade by Bicuculline. Neurosci Lett 1981; 23:325-327.
    233) Petrozzi JW & Shore RN: Generalized exfoliative dermatitis from ethylenediamine. Arch Dermatol 1976; 112:525-526.
    234) Phillis JW: The role of cyclic nucleotides in the CNS. Canad J Neurol Sci 1977; 4:151-195.
    235) Playtex: Fits Tough Jobs Like a Glove, Playtex, Westport, CT, 1995.
    236) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    237) Pozzani UC & Carpenter CP: Response of rats to repeated inhalation of ethylenediamine vapors. Arch Ind Hyg Occup Med 1954; 9:223-226.
    238) Proctor NH & Hughes JP: Chemical Hazards of the Workplace, JB Lippincott Co, Philadelphia, PA, 1978.
    239) Proctor NH, Hughes JP, & Fischman ML: Chemical Hazards of the Workplace, 2nd ed, JB Lippincott Co, Philadelphia, PA, 1988.
    240) Product Information: PROVAYBLUE(TM) intravenous injection, methylene blue intravenous injection. American Regent (per FDA), Shirley, NY, 2016.
    241) Product Information: diphenhydramine HCl intravenous injection solution, intramuscular injection solution, diphenhydramine HCl intravenous injection solution, intramuscular injection solution. Hospira, Inc. (per DailyMed), Lake Forest, IL, 2013.
    242) Product Information: dopamine hcl, 5% dextrose IV injection, dopamine hcl, 5% dextrose IV injection. Hospira,Inc, Lake Forest, IL, 2004.
    243) Product Information: methylene blue 1% IV injection, methylene blue 1% IV injection. American Regent, Inc (per manufacturer), Shirley, NY, 2011.
    244) Product Information: methylene blue 1% intravenous injection, methylene blue 1% intravenous injection. Akorn, Inc. (per manufacturer), Lake Forest, IL, 2011.
    245) Product Information: norepinephrine bitartrate injection, norepinephrine bitartrate injection. Sicor Pharmaceuticals,Inc, Irvine, CA, 2005.
    246) Provost TT & Jillson OF: Ethylenediamine contact dermatitis. Arch Dermatol 1967; 46:231-234.
    247) RTECS : Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety and Health. Cincinnati, OH (Internet Version). Edition expires 1992; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    248) RTECS : Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety and Health. Cincinnati, OH (Internet Version). Edition expires 2000; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    249) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    250) Raymond JZ & Gross PR: EDTA: Preservative dermatitis. Arch Derm 1969; 100:436-440.
    251) River City: Protective Wear Product Literature, River City, Memphis, TN, 1995.
    252) Romaguera C, Grimalt F, & Lecha M: Photoallergic dermatitis from ethylenediamine. Contact Dermatitis 1986; 14:130.
    253) Ross JD & Desforges JF: Reduction of methemoglobin by erythrocytes from cord blood: further evidence of deficient enzyme activity in the newborn period. Paediatrics 1959; 23:718-726.
    254) Safety 4: North Safety Products: Chemical Protection Guide. North Safety. Cranston, RI. 2002. Available from URL: http://www.safety4.com/guide/set_guide.htm. As accessed 8/14/2002.
    255) Sax NI: Dangerous Properties of Industrial Materials, 7th ed, Van Nostrand Reinhold Co, New York, NY, 1989.
    256) Servus: Norcross Safety Products, Servus Rubber, Servus, Rock Island, IL, 1995.
    257) Shepherd G & Keyes DC: Methylene blue. In: Dart,RC, ed. Medical Toxicology, 3rd ed. 3rd ed, Philadelphia, PA, 2004, pp -.
    258) Smyth HF Jr, Carpenter CP, & Weil CS: Range finding toxicity data: List IV. Arch Ind Hyg 1951; 4:119-122.
    259) Spiller HA & Rogers GC: Evaluation of administration of activated charcoal in the home. Pediatrics 2002; 108:E100.
    260) Standard Safety Equipment: Product Literature, Standard Safety Equipment, McHenry, IL, 1995.
    261) Stanford SC , Stanford BJ , & Gillman PK : Risk of severe serotonin toxicity following co-administration of methylene blue and serotonin reuptake inhibitors: an update on a case report of post-operative delirium. J Psychopharmacol 2010; 24(10):1433-1438.
    262) Stentoft J: The toxicity of cytarabine. Drug Saf 1990; 5:7-27.
    263) 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.
    264) Su TC, Lin PH, & Chiu MJ: Dimethylacetamide, ethylenediamine, and diphenylmethane diisocyanate poisoning manifest as acute psychosis and pulmonary edema: treatment with hemoperfusion. Clin Toxicol 2000; 38:429-433.
    265) Tabor CW & Rosenthal S: Pharmacology of spermine and spermidine. J Pharmacol Exp Ther 1956; 116:139.
    266) Tas J & Weissberg D: Allergy to aminophylline. Acta Allergol 1958; 12:39-42.
    267) Teunis BS, Leftwich EI, & Pierce LE: Acute methemoglobinemia and hemolytic anemia due to toluidine blue. Arch Surg 1970; 101:527-531.
    268) Thakore S & Murphy N: The potential role of prehospital administration of activated charcoal. Emerg Med J 2002; 19:63-65.
    269) Thompson PJ, Gibb WRG, & Cole P: Generalized allergic reaction to aminophylline. Thorax 1984; 39:600-603.
    270) Tingley: Chemical Degradation for Footwear and Clothing. Tingley. South Plainfield, NJ. 2002. Available from URL: http://www.tingleyrubber.com/tingley/Guide_ChemDeg.pdf. As accessed 10/16/2002.
    271) Trelleborg-Viking, Inc.: Chemical and Biological Tests (database). Trelleborg-Viking, Inc.. Portsmouth, NH. 2002. Available from URL: http://www.trelleborg.com/protective/. As accessed 10/18/2002.
    272) Trelleborg-Viking, Inc.: Trellchem Chemical Protective Suits, Interactive manual & Chemical Database. Trelleborg-Viking, Inc.. Portsmouth, NH. 2001.
    273) 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.
    274) 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.
    275) 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-.
    276) 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.
    277) 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.
    278) 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.
    279) 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.
    280) U.S. Food and Drug Administration: FDA Drug Safety Communication: Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications. U.S. Food and Drug Administration. Silver Spring, MD. 2011. Available from URL: http://www.fda.gov/Drugs/DrugSafety/ucm263190.htm. As accessed 2011-07-26.
    281) 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-.
    282) U.S. Occupational Safety, and Health Administration (OSHA): Process safety management of highly hazardous chemicals. 29 CFR 2010 2010; 29(1910.119):348-.
    283) 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.
    284) Vanden Hoek,TL; Morrison LJ; Shuster M et al: Part 12: Cardiac Arrest in Special Situations 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. American Heart Association. Dallas, TX. 2010. Available from URL: http://circ.ahajournals.org/cgi/reprint/122/18_suppl_3/S829. As accessed 2010-10-21.
    285) Wall LM: Lymphomatoid contact dermatitis due to ethylenediamine dihydrochloride. Contact Dermatitis 1982; 8:51-54.
    286) Wells Lamont Industrial: Chemical Resistant Glove Application Chart. Wells Lamont Industrial. Morton Grove, IL. 2002. Available from URL: http://www.wellslamontindustry.com. As accessed 10/31/2002.
    287) Willson DF, Truwit JD, Conaway MR, et al: The Adult Calfactant in Acute Respiratory Distress Syndrome (CARDS) Trial. Chest 2015; Epub:Epub.
    288) 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.
    289) Winek CL, Collom WD, & Martineau P: Toluidine blue intoxication. Clin Toxicol 1969; 2:1-3.
    290) Workrite: Chemical Splash Protection Garments, Technical Data and Application Guide, W.L. Gore Material Chemical Resistance Guide, Workrite, Oxnard, CA, 1997.
    291) Wright S & Harman RRM: Ethylenediamine and piperazine sensitivity. Br Med J 1983; 287:463-464.
    292) Yang RSH, Garman RH, & Weaver EV: Two-generation reproduction study of ethylenediamine in Fischer 344 rats. Fundam Appl Toxicol 1984; 4:539-546.
    293) Zitnik RJ & Cooper JA: Pulmonary disease due to antirheumatic agents. Clin Chest Med 1990; 11:139-150.
    294) Zuidema J: Ethylenediamine, profile of a sensitizing excipient. Pharm Weekbl (Sci) 1985; 7:134-140.
    295) do Nascimento TS, Pereira RO, de Mello HL, et al: Methemoglobinemia: from diagnosis to treatment. Rev Bras Anestesiol 2008; 58(6):651-664.