Contact Us    Contact Us     |     Feedback
MOBILE VIEW  | 

NITROGEN DIOXIDE

Export To Excel

Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Nitrogen dioxide is a "criteria air pollutant" produced from combustion of fossil fuels and spontaneous reaction of other oxides of nitrogen.

Specific Substances

    A) No Synonyms were found in group or single elements
    1.2.1) MOLECULAR FORMULA
    1) N-O2

Available Forms Sources

    A) FORMS
    1) Nitrogen dioxide is a "criteria air pollutant" (Clayton & Clayton, 1994). It is a reddish-brown gas which condenses to a brown liquid at temperatures below 21.15 degrees C (Budavari, 1996; Lewis, 1997). It can occur at levels as high as 0.45 ppm in polluted urban air (Clayton & Clayton, 1994).
    2) Nitrogen dioxide can disproportionate in air to form a mixture of nitrogen oxides, and the commercial pressurized product called nitrogen tetroxide is actually an equilibrium mixture of nitrogen dioxide and N2O4 (Budavari, 1996). Nitrogen dioxide decomposes in water to form NITRIC ACID and NITRIC OXIDE (Budavari, 1996).
    3) Oxides of nitrogen can react with AMINES to form carcinogenic and mutagenic N-NITROSAMINES. They can also react with POLYNUCLEAR AROMATIC HYDROCARBONS (PAHs) to form nitro-aromatic compounds, some of which are potent mutagens (Hisamatsu, 1984; Tokowa, 1981; Pitts, 1978). Thus, chemical reactivity may be an important consideration in nitrogen dioxide toxicity. The toxicology of nitrogen dioxide has been reviewed (Morrow, 1984; p 151; Pitts, 1978; NIOSH, 1976).
    4) Nitrogen oxides are formed endogenously in the lung and respiratory tract by the enzyme nitric oxide synthetase. They may play a role in airway and smooth muscle relaxation, and nitric oxide inhalation therapy may actually be beneficial in some persons with asthma, adult respiratory distress syndrome (ARDS), or pulmonary hypertension. The interrelationships between endogenous and inhaled nitrogen oxides have been reviewed (Gaston et al, 1994).
    5) Nitrogen dioxide at potentially toxic (greater than 5 ppm) concentrations can form spontaneously under certain conditions when nitric oxide is used therapeutically in the ventilator treatment of lung disease (Losa et al, 1997).
    6) Most studies of nitrogen dioxide are in reference to air pollution and acid rain, involving mixed exposures with other chemicals.
    7) Many occupational exposures to nitrogen dioxide occur as a result of its formation from the decomposition of nitrates, as in silage (silo filler's disease) (ACGIH, 1992). Symptomatic exposures are also reported in indoor ice arenas due to the use of combustion powered ice conditioning equipment (zambonis) (Karlson-Stiber et al, 1996).
    8) The odor threshold is in the range of 0.04 to 5 ppm, and this may not be sufficient to protect susceptible individuals (Hathaway et al, 1996; Clayton & Clayton, 1994). In any event, odor alone should never be used to determine if an environment is safe.
    B) SOURCES
    1) Nitrogen dioxide is a "criteria air pollutant" produced from combustion of fossil fuels and spontaneous reaction of other oxides of nitrogen (Clayton & Clayton, 1994).
    C) USES
    1) Nitrogen dioxide is used commercially as a chemical intermediate, catalyst, nitrating agent, oxidizing agent, polymerization inhibitor, oxidizer for rocket fuels, and in bleaching flour (Lewis, 1997; Budavari, 1996).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Because nitric oxide and nitrogen dioxide almost always occur together, this review is based on the properties of nitrogen oxides. Nitrogen dioxide forms nitric acid upon contact with water. It is more acutely toxic than nitric oxide.
    B) Exposure to nitrogen oxides results in acute and chronic changes of the pulmonary system including pulmonary edema, pneumonitis, bronchitis, bronchiolitis, emphysema and possibly methemoglobinemia. Usually, no symptoms occur, except a slight cough, fatigue, and nausea. However, potentially fatal pulmonary edema can occur following minimal early symptoms.
    1) Acute effects may or may not develop within one to two hours after exposure, and include tachypnea, tachycardia, fine crackles and wheezing, and cyanosis. Another acute scenario involves dyspnea and coughing which subside over two to three weeks.
    2) The second stage involves abrupt development of fever and chills, more severe dyspnea, cyanosis, and pulmonary edema. There is no correlation between severity of the first and second stages.
    3) Recovery may be either complete or may involve some degree of impairment of pulmonary function.
    C) Nitrogen dioxide exposure does occur with the use of nitric oxide inhalation therapy in infants. Exposure of nurses and respiratory therapists occurs as well, but is generally transient.
    0.2.3) VITAL SIGNS
    A) Dyspnea and weak, rapid, pulse may develop after a delay of several hours.
    0.2.20) REPRODUCTIVE
    A) Nitrogen dioxide has been fetotoxic in rats and affected behavior and growth statistics in newborn mice. Methemoglobin inducers are considered harmful to the fetus.
    0.2.21) CARCINOGENICITY
    A) Nitrogen dioxide is apparently not directly carcinogenic, but may enhance or modify the growth of lung tumors in animals.

Laboratory Monitoring

    A) Monitor pulmonary function. Posterior/anterior chest x-ray may be diagnostic and prognostic. Monitor methemoglobin.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Nitrogen dioxide exists as a liquid below 21 degrees C. Ingestion is unlikely at higher temperatures.
    B) EMESIS should NOT BE INDUCED, because of the corrosive nature of this material. Activated charcoal is unlikely to be of benefit and may obscure endoscopic findings if GI tract irritation or burns are present.
    C) 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.
    D) Patients who have ingested liquid nitrogen dioxide may be a risk for developing pulmonary edema, due to the possibility of fumes escaping into the pharynx and respiratory system.
    E) 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.
    F) 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.
    G) 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.
    H) 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) Treatment of toxic pulmonary edema caused by nitric oxide inhalation should be directed towards reversal of ventilatory failure by using oxygen in assisting ventilation. In patients with toxic bronchiolitis, steroids may be beneficial in decreasing the amount of inflammation. Methemoglobinemia and mild acidosis may be present, but specific treatment for these conditions will probably not be necessary.
    C) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    D) 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.
    E) 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.
    F) 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.
    G) Because pulmonary symptoms may be delayed, all patients with significant exposure should be carefully observed for AT LEAST 48 HOURS.
    0.4.4) EYE EXPOSURE
    A) Eye exposure to nitric oxide normally does not occur to a significant extent. However, this substance is a strong eye irritant due to the formation of nitric acid, which can permanently alter proteins. Because this reaction is relatively slow, permanent injury may possibly be prevented by IMMEDIATE DECONTAMINATION.
    B) 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) 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.
    2) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
    3) All patients with significant dermal exposure should be carefully observed for possible development of delayed clinical signs and symptoms. Follow treatment recommendations in the INHALATION EXPOSURE section where appropriate.

Range Of Toxicity

    A) TOXIC DOSE: Death due to airway obstruction secondary to edema of the glottis has not been well documented, but is estimated to occur at concentrations greater than 100 ppm. The odor of nitrogen dioxide is perceptible at concentrations as low as 0.11 ppm. Symptoms appear at 13 ppm.

Clinical Effects

Summary Of Exposure

    A) Because nitric oxide and nitrogen dioxide almost always occur together, this review is based on the properties of nitrogen oxides. Nitrogen dioxide forms nitric acid upon contact with water. It is more acutely toxic than nitric oxide.
    B) Exposure to nitrogen oxides results in acute and chronic changes of the pulmonary system including pulmonary edema, pneumonitis, bronchitis, bronchiolitis, emphysema and possibly methemoglobinemia. Usually, no symptoms occur, except a slight cough, fatigue, and nausea. However, potentially fatal pulmonary edema can occur following minimal early symptoms.
    1) Acute effects may or may not develop within one to two hours after exposure, and include tachypnea, tachycardia, fine crackles and wheezing, and cyanosis. Another acute scenario involves dyspnea and coughing which subside over two to three weeks.
    2) The second stage involves abrupt development of fever and chills, more severe dyspnea, cyanosis, and pulmonary edema. There is no correlation between severity of the first and second stages.
    3) Recovery may be either complete or may involve some degree of impairment of pulmonary function.
    C) Nitrogen dioxide exposure does occur with the use of nitric oxide inhalation therapy in infants. Exposure of nurses and respiratory therapists occurs as well, but is generally transient.

Vital Signs

    3.3.1) SUMMARY
    A) Dyspnea and weak, rapid, pulse may develop after a delay of several hours.
    3.3.2) RESPIRATIONS
    A) DYSPNEA may develop after a delay of 5 to 12 hours (Harbison, 1998). Nitrogen oxides interfere with gas exchange in the lungs and can cause asphyxiation (CHRIS , 2000).
    3.3.5) PULSE
    A) Weak, rapid, pulse may develop.

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) CONJUNCTIVITIS: Nitrogen dioxide is a severe eye irritant (Sax & Lewis, 1989).
    2) BURNS - Liquid nitrogen dioxide (as nitrogen tetroxide) may cause severe burns upon direct contact (Grant, 1993). Persistent corneal opacities occurred in rabbits exposed to nitrogen dioxide fumes at 70 ppm, while 20 ppm for four hours had no such effect (Grant, 1993).
    3.4.5) NOSE
    A) WITH POISONING/EXPOSURE
    1) IRRITATION: Higher concentrations are immediately irritating to the nose (Sax & Lewis, 1989).
    3.4.6) THROAT
    A) WITH POISONING/EXPOSURE
    1) IRRITATION: Irritation of the throat is seen with exposure to higher concentrations (Sax & Lewis, 1989). Frothy, thick sputum may be present (EPA, 1985).
    2) CORROSION: Corrosion of dental enamel may occur with chronic exposure (HSDB , 1991).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) TACHYARRHYTHMIA
    1) WITH POISONING/EXPOSURE
    a) Tachycardia may be present (EPA, 1985).
    B) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) A weak, rapid pulse, dilated heart, chest congestion, and circulatory collapse may be seen.

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) INJURY DUE TO ASPHYXIATION
    1) WITH POISONING/EXPOSURE
    a) MECHANISM OF INJURY: Nitric oxide is oxidized in air to form nitrogen dioxide, which then reacts with water in the respiratory tract to form nitric acid. The nitrates and nitrites formed from dissociation of nitric acid causes extensive local and systemic tissue damage (Ramirez & Dowell, 1971). Nitrogen oxides interfere with gas exchange in the lungs and can cause asphyxiation (CHRIS , 2000).
    B) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) SIGNS/SYMPTOMS: Cough, hyperpnea, and dyspnea will be seen after some delay, because the chemical reaction is slow (Sax & Lewis, 1989). Rapid and shallow respirations, mild or violent coughing with frothy expectoration, and physical signs of pulmonary edema may develop. Pulmonary edema may be delayed, occurring 4 to 24 hours following exposure to nitrous fumes.
    b) High concentrations in the range of 60 to 150 ppm may cause immediate coughing and burning in the chest (Sax & Lewis, 1989).
    c) An asphyxial death due to blockade of gas exchange in the lungs may ensue a few hours after the first evidence of pulmonary edema.
    d) Delayed pulmonary edema, rales, and wheezes may develop in the absence of immediate pulmonary damage (Douglas et al, 1989).
    C) DYSPNEA
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: Nitrogen dioxide (NO2) intoxication occurred in 31 out of 43 exposed individuals (72.1%) following the use of propane-powered ice-resurfacing equipment in an indoor ice arena with a nonfunctioning ventilation system. In preparation for hockey practice, the ice was resurfaced for a duration of 60 to 90 minutes. Resurfacing was completed at 11:30 am and hockey practice started between 6:00 and 8:00 pm. Initial reports of illness occurred the following morning. Cases of intoxication were defined as exposures reporting shortness of breath, coughing, hemoptysis, and chest pain or tightness within 48 hours of exposure. In one case, bilateral infiltrates and nodules were observed on chest CT. No additional cases were reported after the ventilation system was repaired (Centers for Disease Control and Prevention (CDC), 2012).
    1) Symptoms in the 31 affected patients included: cough in 26 (84%), shortness of breath in 24 (77%), chest tightness in 20 (65%), chest pain in 14 (45%), weakness or sore throat were each reported in 11 patients (36%), hemoptysis, throat irritation or headache were each reported in 8 patients (26%), 6 had abdominal pain (19%), 5 had eye irritation (16%), and dizziness and choking were each reported in one patient (Centers for Disease Control and Prevention (CDC), 2012).
    b) CASE SERIES: Three factory workers experienced symptoms of nitrogen dioxide toxicity and lung injury following an inhalation exposure from a broken nitrogen dioxide tank. Cases 1 and 2 (exposure time 150 and 220 minutes, respectively) presented with chills, dyspnea, and cough approximately 5 hours post exposure, and case 3 (exposure time 5 minutes) complained of cough and bloody sputum 1 day post exposure. On X-ray and CT scan, all 3 patients showed evidence of pulmonary edema without cardiomegaly. A complete recovery was seen in all 3 patients after steroid therapy (Tanaka et al, 2007).
    D) BRONCHOSPASM
    1) WITH POISONING/EXPOSURE
    a) Nitrogen dioxide and nitric oxide can cause bronchospasm (Epler, 1989).
    b) Asthmatics may be more sensitive to the effects of nitrogen dioxide. In one study, asthmatics exhibited increased airway reactivity to methacholine after exposure to 0.5 ppm nitrogen dioxide for one hour (Mohsenin, 1987). In another study, the effect was marginal at 0.2 ppm (Kleinman et al, 1983). Bronchoconstriction was observed in exercising asthmatics exposed to 0.3 ppm for 30 minutes (Utell, 1985).
    c) No statistically significant untoward response to nitrogen dioxide was noted in 21 mildly asthmatic volunteers exposed to up to 3 ppm of nitrogen dioxide in purified background air in an environmental-controlled chamber (Linn et al, 1986).
    E) PNEUMONITIS
    1) WITH POISONING/EXPOSURE
    a) BRONCHIOLITIS OBLITERANS: Cyanosis and crackles may occur 2 to 4 weeks after a mild acute exposure to nitrogen dioxide; bronchiole become obstructed with granulation tissue and fibrin plug (Epler, 1989).
    b) In its early stage, bronchiolitis obliterans is reversible with corticosteroid therapy for up to 12 months (Jones et al, 1973; Epler, 1989).
    c) LATE BRONCHIOLITIS OBLITERANS: This more severe form involves scarring and irreversible air flow obstruction and is more rare than the acute form (Epler, 1989).
    d) CASE SERIES: An amateur ice hockey team (n=15) was inadvertently exposed to elevated levels of carbon monoxide and nitrogen dioxide in a poorly ventilated ice arena. Of the 15 players, 12 were treated as outpatients while 3 developed pneumonitis. The primary symptoms were cough, dyspnea, chest pain, and hemoptysis. Infiltrates were observed on chest x-ray in 5 of 15 patients and one patient had evidence of peribronchovascular interstitial pattern on chest CT. His diagnostic studies were consistent with severe respiratory failure. In lung function studies, 4 patients developed restrictive ventilatory disorders, one had an obstructive disorder and one patient had a combined disorder. Most patients (n=8) were treated with IV or inhaled corticosteroids, beta2 agonists and antibiotics and several patients required oxygen therapy. In 14 patients, recovery was uneventful and treatment was discontinued within approximately one month. However, one patient required inhaled corticosteroid treatment for another 3 months to treat a persistent, mild-obstructive ventilatory disorder. Emission studies were conducted following exposure and both carbon monoxide (1.95 times for CO) and nitrogen dioxide (more than 10 times the normal limit) exceeded the recommended indoor air quality standards (Brat et al, 2013).
    F) SEQUELA
    1) WITH POISONING/EXPOSURE
    a) One to four weeks following a brief encounter with nitrous fumes, bronchiolar injury may cause a bronchiolar obstruction. Restrictive and obstructive pulmonary defects with hypoxemia and a reduction in carbon monoxide diffusion have been seen in days following nitrous fume exposures.
    b) Long-term pulmonary effects in man following a single acute exposure of nitrous fumes have not been documented, but the nitrous fumes have been shown to alter lung proteins so that they become antigenic.
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) Emphysematous lesions were produced in mice exposed to 10 ppm nitrogen dioxide for 2 hours/day, 5 days/week for up to 30 weeks. Even though nitrogen dioxide is more acutely toxic then nitric oxide, it was less potent than the latter in inducing emphysematous lesions under similar conditions of exposure (HSDB , 1991).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) FATIGUE
    1) WITH POISONING/EXPOSURE
    a) Fatigue, restlessness, lethargy, and loss of consciousness may be noted.
    B) CLOUDED CONSCIOUSNESS
    1) WITH POISONING/EXPOSURE
    a) Anxiety and mental confusion may occur.

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA
    1) WITH POISONING/EXPOSURE
    a) Nausea may occur.
    B) ABDOMINAL PAIN
    1) WITH POISONING/EXPOSURE
    a) Abdominal pain may be noted.

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) JAUNDICE
    1) WITH POISONING/EXPOSURE
    a) Jaundice, along with increase in bile pigments in the blood and urine, and hepatic lesions, have been rarely reported to occur with nitrogen oxides poisoning. (Finkel, 1983).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) RENAL ABSCESS
    1) WITH POISONING/EXPOSURE
    a) Renal lesions have been reported to occur with nitrogen oxide poisoning, possibly secondary to hemolysis from methemoglobinemia. This is a relatively rare occurrence compared to the incidence of pulmonary effects (Finkel, 1983).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) METHEMOGLOBINEMIA
    1) WITH POISONING/EXPOSURE
    a) Welders exposed to 3.9 to 5.4 ppm nitrogen dioxide had 2.3 to 2.6 percent methemoglobin (HSDB , 2000). Methemoglobin levels as high as 71.3 percent have been reported from human exposures to nitrous fumes (Touze et al, 1983).
    b) Methemoglobin concentrations up to 44 percent have been reported in postmortem blood samples from individuals exposed to silo gas (Clayton & Clayton, 1994).
    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) Methemoglobinemia has been produced by nitrogen dioxide in dogs (Sittig, 1985). Clinically significant methemoglobinemia may also be noted with exposure to higher oxides of nitrogen (Clutton-Brock, 1967).
    b) Nitrogen dioxide was less effective than nitric oxide for inducing methemoglobin in mice (Oda et al, 1980).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) Nitric oxide is a severe skin irritant (Sax & Lewis, 1989).
    B) CHEMICAL BURN
    1) WITH POISONING/EXPOSURE
    a) Liquid nitrogen dioxide (as nitrogen tetroxide) may cause severe burns upon direct contact (Grant, 1993).
    C) CYANOSIS
    1) WITH POISONING/EXPOSURE
    a) Cyanosis may be noted as a delayed symptom (Finkel, 1983; Clayton & Clayton, 1994).

Reproductive

    3.20.1) SUMMARY
    A) Nitrogen dioxide has been fetotoxic in rats and affected behavior and growth statistics in newborn mice. Methemoglobin inducers are considered harmful to the fetus.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) RATS - In rat studies, observed toxic effects included fetal death, fetotoxicity, behavioral changes in the newborn and changes in the weaning or lactation index, growth statistics and litter size. In mouse studies, changes in growth statistics and behavioral changes were observed in the newborn (RTECS , 2000).
    2) Several studies have been done on the embryotoxic or teratogenic effects of nitrogen dioxide, possibly mixed with other chemicals, but the conclusions were not available at the time of this review (Sakai, 1984; Tabacova, 1984; Freeman, 1974).
    3) In a study of CD-1 mice exposed to NO2 from 0 to 45 ppm NO2 from gestation day 7 to day 18 found decreased birth weight and decreased neuromuscular coordination in offspring (Singh, 1988).
    4) A rat study of NO2 exposure throughout gestation to concentrations of 0.05 to 10 mg/m3 (0.26-5.3 ppm) found dose-dependent changes in neuromotor development (coordination deficits, retarded locomotion, reduced activity) (Tabacova et al, 1985).
    3.20.3) EFFECTS IN PREGNANCY
    A) METHEMOGLOBINEMIA
    1) HUMANS - Exposure to nitrogen dioxide can induce methemoglobinemia (HSDB , 2000; Dabney et al, 1990). In general, the fetus is more susceptible to methemoglobin formation than the adult and fetal methemoglobin is reduced back to normal hemoglobin more slowly than adult hemoglobin. The fetus may also be more susceptible to alterations in oxygen transport (Mansouri, 1985). The time of maximum susceptibility is thought to be the last trimester, when the fetal need for oxygen is greatest.
    B) ABORTION
    1) HUMANS - There is some evidence linking spontaneous abortions with presence of nitrous oxide in operating rooms, where nitrogen dioxide may also be present (Barlow & Sullivan, 1982). At the present time the role of nitrogen oxides in adverse human reproductive effects, if any, is not resolved.
    C) ANIMAL STUDIES
    1) Menstrual cycle changes were observed in female rats (RTECS , 2000).
    2) Lipid peroxidation was increased in rats exposed to nitrogen dioxide in utero, indicating that the nitrogen dioxide may have been available to the fetus (Balabaeva & Tabakova, 1985)
    3) Exposure of pregnant rats to airborne concentrations of 0.43, 0.045, and 0.018 ppm of nitrogen dioxide increased intrauterine deaths and stillbirths, decreased birth weights, and produced certain unspecified developmental abnormalities (Gofmekler, 1977). Other studies have been done on the embryotoxic or teratogenic effects of nitrogen dioxide, possibly mixed with other chemicals, but the conclusions were not available at the time of this review (Sakai, 1984; Tabacova, 1984; Freeman, 1974).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS10102-44-0 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.2) SUMMARY/HUMAN
    A) Nitrogen dioxide is apparently not directly carcinogenic, but may enhance or modify the growth of lung tumors in animals.
    3.21.3) HUMAN STUDIES
    A) CARCINOMA
    1) Oxides of nitrogen can react with AMINES to form carcinogenic and mutagenic N-NITROSAMINES. They can also react with POLYNUCLEAR AROMATIC HYDROCARBONS (PAHs) to form nitro-aromatic compounds, some of which are potent mutagens (Hisamatsu, 1984; Tokowa, 1981; Pitts, 1978).
    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) Nitrogen dioxide does not appear to induce lung tumors directly in animals, but may modify their growth positively or negatively, depending on the experimental conditions used (Witschi, 1988).

Genotoxicity

    A) Nitrogen dioxide has been genotoxic at the level of DNA damage, unscheduled DNA synthesis, mutations, chromosome aberrations, and sister chromatid exchanges. These may be indirect effects due to the reaction of nitrates or nitrites in the body with other substances to form genotoxins.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor pulmonary function. Posterior/anterior chest x-ray may be diagnostic and prognostic. Monitor methemoglobin.
    4.1.2) SERUM/BLOOD
    A) ACID/BASE
    1) Arterial blood gases and methemoglobin concentrations should be monitored.
    4.1.4) OTHER
    A) OTHER
    1) PULMONARY FUNCTION TESTS
    a) Monitor pulmonary function tests.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) Posterior/anterior chest x-ray may be diagnostic and prognostic.
    B) CT RADIOGRAPH
    1) High-resolution CT (HCRT) may be useful in diagnosing nitrogen dioxide exposure. HCRT results showed centrilobular nodules in one case series (Tanaka et al, 2007).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Monitor pulmonary function. Posterior/anterior chest x-ray may be diagnostic and prognostic. Monitor methemoglobin.

Oral Exposure

    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) Nitrogen dioxide exists as a liquid below 21 degrees C. Ingestion is unlikely at higher temperatures. Gastric decontamination is not likely to be useful, as the toxin will vaporize at body temperature.
    2) EMESIS should NOT BE INDUCED, because of the corrosive nature of the nitric acid formed in the stomach from nitrogen dioxide. Activated charcoal is unlikely to be of benefit and may obscure endoscopic findings if GI tract irritation or burns are present.
    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).
    6.5.3) TREATMENT
    A) 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.
    B) ACUTE LUNG INJURY
    1) Patients who have ingested liquid nitrogen dioxide may be a risk for developing pulmonary edema, due to the possibility of fumes escaping into the pharynx and entering the respiratory system.
    2) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    3) 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)
    4) 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).
    5) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    6) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    7) 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).
    8) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    C) 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.
    D) HOSPITAL ADMISSION
    1) Patients who are initially symptomatic should be observed in a controlled setting for at least 24 to 48 hours for delayed respiratory effects (Ellenhorn & Barceloux, 1988; Sax & Lewis, 1989).
    E) OBSERVATION REGIMES
    1) Patients that have been observed for several hours following an exposure, and remain asymptomatic, may be treated as outpatients. The patient should be instructed to return to the a health care facility if any symptoms develop (Ellenhorn & Barceloux, 1988).
    2) Patients that were initially symptomatic who become asymptomatic after 24 to 36 hours of observation may be released with arrangement of follow-up appointment to assess pulmonary status (Ellenhorn & Barceloux, 1988).
    3) Close outpatient follow-up should be continued in patients who develop adult respiratory distress since these patients are at high risk to develop bronchiolitis obliterans within several weeks (Ellenhorn & Barceloux, 1988).

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) RESPIRATORY PROTECTION -
    1) Personnel should take necessary precautions to prevent becoming victims themselves, because exposure is usually via inhalation.
    B) DECONTAMINATION -
    1) 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.
    2) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    3) 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) SUPPORT
    1) Exposure is usually via inhalation. Initial symptoms may be mild. progressive inflammation of the lungs may arise 5 to 72 hours after the exposure. Advanced respiratory and cardiovascular support may be required.
    B) ACUTE LUNG INJURY
    1) Treatment of toxic pulmonary edema caused by nitrogen dioxide inhalation should be directed toward the reversal of ventilatory failure by using oxygen and assisting ventilation.
    2) Although clinical improvement and improvement in pulmonary function tests have been attributed to the administration of corticosteroids (Ramirez & Dowell, 1971), there is no convincing evidence that steroids alter the course of nitrogen dioxide-induced pulmonary edema or prevent subsequent bronchitis or bronchiolitis.
    C) 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.
    D) EXPERIMENTAL THERAPY
    1) CHLORPHENTERMINE -
    a) Hastings et al (1987) suggested pretreatment with chlorphentermine offered partial protection against NO2 toxicity in a mouse model.
    b) CONCLUSION - This treatment is NOT recommended at this time. Additional studies in are needed to demonstrate the safety and efficacy of this treatment.
    2) ASCORBIC ACID
    a) Nash (1990) proposed that a 1 gram oral dose of ascorbic acid would temporarily protect against the subsequent toxic effects by competing with the sensitive sites for freshly absorbed nitrogen dioxide gas.
    b) CONCLUSION: This treatment is NOT recommended at this time. Additional studies in are needed to demonstrate the safety and efficacy of this treatment.
    3) HYPERBARIC OXYGEN
    a) Was found to increase mortality in mice exposed to 1,100 ppm nitrogen dioxide then treated with oxygen pressurized at 1.8 atmospheres (Pelled et al, 1973).
    4) DEFEROXAMINE
    a) DEFEROXAMINE given intravenously prior to exposure to an airborne concentration of 175 ppm of nitrogen dioxide afforded some protection from acute lung injury in rats. Whether or not it would have similar effects in humans is unknown (Meulenbelt et al, 1993).
    E) HOSPITAL ADMISSION
    1) Patients who are initially symptomatic should be observed in a controlled setting for at least 24 to 48 hours for delayed respiratory effects (Ellenhorn & Barceloux, 1988; Sax & Lewis, 1989).
    F) OBSERVATION REGIMES
    1) Patients that have been observed for several hours following an exposure, and remain asymptomatic, may be treated as outpatients. The patient should be instructed to return to the a health care facility if any symptoms develop (Ellenhorn & Barceloux, 1988).
    2) Patients that were initially symptomatic who become asymptomatic after 24 to 36 hours of observation may be released with arrangement of follow-up appointment to assess pulmonary status (Ellenhorn & Barceloux, 1988).
    3) Close outpatient follow-up should be continued in patients who develop adult respiratory distress since these patients are at high risk to develop bronchiolitis obliterans within several weeks (Ellenhorn & Barceloux, 1988).
    G) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) Eye exposure to nitric oxide normally does not occur to a significant extent. However, this substance is a strong eye irritant due to the formation of nitric acid, which can permanently alter proteins. Because this reaction is relatively slow, permanent injury may possibly be prevented by IMMEDIATE DECONTAMINATION.
    B) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).
    6.8.2) TREATMENT
    A) OBSERVATION REGIMES
    1) All patients with significant eye exposure should be carefully observed for possible development of delayed clinical signs and symptoms. Follow treatment recommendations in the INHALATION EXPOSURE section where appropriate.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) BURN
    1) APPLICATION
    a) These recommendations apply to patients with MINOR chemical burns (FIRST DEGREE; SECOND DEGREE: less than 15% body surface area in adults; less than 10% body surface area in children; THIRD DEGREE: less than 2% body surface area). Consultation with a clinician experienced in burn therapy or a burn unit should be obtained if larger area or more severe burns are present. Neutralizing agents should NOT be used.
    2) DEBRIDEMENT
    a) After initial flushing with large volumes of water to remove any residual chemical material, clean wounds with a mild disinfectant soap and water.
    b) DEVITALIZED SKIN: Loose, nonviable tissue should be removed by gentle cleansing with surgical soap or formal skin debridement (Moylan, 1980; Haynes, 1981). Intravenous analgesia may be required (Roberts, 1988).
    c) BLISTERS: Removal and debridement of closed blisters is controversial. Current consensus is that intact blisters prevent pain and dehydration, promote healing, and allow motion; therefore, blisters should be left intact until they rupture spontaneously or healing is well underway, unless they are extremely large or inhibit motion (Roberts, 1988; Carvajal & Stewart, 1987).
    3) TREATMENT
    a) TOPICAL ANTIBIOTICS: Prophylactic topical antibiotic therapy with silver sulfadiazine is recommended for all burns except superficial partial thickness (first-degree) burns (Roberts, 1988). For first-degree burns bacitracin may be used, but effectiveness is not documented (Roberts, 1988).
    b) SYSTEMIC ANTIBIOTICS: Systemic antibiotics are generally not indicated unless infection is present or the burn involves the hands, feet, or perineum.
    c) WOUND DRESSING:
    1) Depending on the site and area, the burn may be treated open (face, ears, or perineum) or covered with sterile nonstick porous gauze. The gauze dressing should be fluffy and thick enough to absorb all drainage.
    2) Alternatively, a petrolatum fine-mesh gauze dressing may be used alone on partial-thickness burns.
    d) DRESSING CHANGES:
    1) Daily dressing changes are indicated if a burn cream is used; changes every 3 to 4 days are adequate with a dry dressing.
    2) If dressing changes are to be done at home, the patient or caregiver should be instructed in proper techniques and given sufficient dressings and other necessary supplies.
    e) Analgesics such as acetaminophen with codeine may be used for pain relief if needed.
    4) TETANUS PROPHYLAXIS
    a) The patient's tetanus immunization status should be determined. Tetanus toxoid 0.5 milliliter intramuscularly or other indicated tetanus prophylaxis should be administered if required.
    B) 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.
    C) HOSPITAL ADMISSION
    1) Patients who are initially symptomatic should be observed in a controlled setting for at least 24 to 48 hours for delayed respiratory effects (Ellenhorn & Barceloux, 1988; Sax & Lewis, 1989).
    D) OBSERVATION REGIMES
    1) Patients that have been observed for several hours following an exposure, and remain asymptomatic, may be treated as outpatients. The patient should be instructed to return to the a health care facility if any symptoms develop (Ellenhorn & Barceloux, 1988).
    2) Patients that were initially symptomatic who become asymptomatic after 24 to 36 hours of observation may be released with arrangement of follow-up appointment to assess pulmonary status (Ellenhorn & Barceloux, 1988).
    3) Close outpatient follow-up should be continued in patients who develop adult respiratory distress since these patients are at high risk to develop bronchiolitis obliterans within several weeks (Ellenhorn & Barceloux, 1988).
    E) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Range Of Toxicity

Summary

    A) TOXIC DOSE: Death due to airway obstruction secondary to edema of the glottis has not been well documented, but is estimated to occur at concentrations greater than 100 ppm. The odor of nitrogen dioxide is perceptible at concentrations as low as 0.11 ppm. Symptoms appear at 13 ppm.

Minimum Lethal Exposure

    A) CONCENTRATION LEVEL
    1) Death due to airway obstruction secondary to edema of the glottis has not been well documented, but is estimated to occur at concentrations greater than 100 ppm (Tse & Bockman, 1970).
    2) The odor of nitrogen dioxide is perceptible at concentrations as low as 0.11 ppm.
    3) Symptoms appear at 13 ppm.
    4) A concentration of 200 ppm may be fatal (Budavari, 1996).
    5) Exposures in the range of 100 to 150 ppm for a few minutes are dangerous, and 200 to 700 ppm can be fatal after brief exposure (Sax & Lewis, 1989).
    6) Although asymptomatic, normal adult human volunteers demonstrated changes in bronchoalveolar lavage findings consistent with inflammatory changes when exposed to 2 ppm nitrogen dioxide for 4 hours (Devlin et al, 1999).

Maximum Tolerated Exposure

    A) CONCENTRATION LEVEL
    1) SUMMARY
    a) One attempt to arrive at an ambient air standard for nitrogen dioxide, which was based on results of studies since 1966, concluded that the maximal no-effect dose is approximately 0.6 ppm without any safety factor.
    b) Applying various safety factors as currently practiced by various regulatory agencies would lead to air standards in the parts per billion range (Morrow, 1975).
    c) The lowest effective concentration to produce bronchoconstriction in asthmatics is 200 mcg/m(3), derived from meta-analysis (Berglund et al, 1994).
    2) Death due to airway obstruction secondary to edema of the glottis has not been well documented, but is estimated to occur at concentrations greater than 100 ppm.
    3) The odor of nitrogen dioxide is perceptible to most at 0.22 ppm, but some individuals can detect it as low as 0.11 ppm (ACGIH, 1991).
    4) Symptoms appear at 13 ppm.
    5) Mucous membrane irritation occurs at 1 to 13 ppm (Clayton & Clayton, 1994).
    B) CASE REPORTS
    1) OCCUPATIONAL
    a) Workers who were exposed to 30 to 35 ppm nitrogen dioxide for several years showed no apparent ill effects (ACGIH, 1991).
    b) Nurses and respiratory therapists had transient exposures to nitrogen dioxide of up to 3.1 ppm, but 15 minute and full shift averages were below the 0.5 ppm detection limit, suggesting transient exposures (Phillips et al, 1999).
    2) ADULT
    a) A group of 22 adult volunteers who were exposed to 1 or 2 parts per million nitrogen dioxide under controlled conditions for 2 hours per day over 3 consecutive days had increased frequencies of infection by attenuated influenza A/Korea/82 virus compared to a control group, but the differences were not statistically significant.
    1) These exposure conditions did not produce any significant changes in pulmonary function or nonspecific airway reactivity to a methacholine challenge (Goings et al, 1989).
    b) An outbreak of respiratory illness associated with use of propane powered ice-resurfacing machines was reported among adolescent hockey players. Simulated reenactment produced nitrogen dioxide levels as high as 1250 ppb (Rosenlund & Bluhm, 1999).
    C) CASE SERIES
    1) An amateur ice hockey team (n=15) was inadvertently exposed to elevated levels of carbon monoxide and nitrogen dioxide in a poorly ventilated ice arena. Of the 15 players, 12 were treated as outpatients while 3 developed pneumonitis. The primary symptoms were cough, dyspnea, chest pain, and hemoptysis. Infiltrates were observed on chest x-ray in 5 of 15 patients and one patient had evidence of peribronchovascular interstitial pattern on chest CT. His diagnostic studies were consistent with severe respiratory failure. In lung function studies, 4 patients developed restrictive ventilatory disorders, one had an obstructive disorder and one patient had a combined disorder. Most patients (n=8) were treated with IV or inhaled corticosteroids, beta2 agonists and antibiotics and several patients required oxygen therapy. In 14 patients, recovery was uneventful and treatment was discontinued within approximately one month. However, one patient required inhaled corticosteroid treatment for another 3 months to treat a persistent, mild-obstructive ventilatory disorder. Emission studies were conducted following exposure and both carbon monoxide (1.95 times for CO) and nitrogen dioxide (more than 10 times the normal limit) exceeded the recommended indoor air quality standards (Brat et al, 2013).

Workplace Standards

    A) ACGIH TLV Values for CAS10102-44-0 (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) Nitrogen dioxide
    a) TLV:
    1) TLV-TWA: 3 ppm
    2) TLV-STEL: 5 ppm
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A4
    2) Codes: Not Listed
    3) Definitions:
    a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    c) TLV Basis - Critical Effect(s): URT and LRT irr
    d) Molecular Weight: 46.01
    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) Under Study
    1) Nitrogen dioxide
    a) TLV:
    1) TLV-TWA:
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: Not Listed
    2) Codes: Not Listed
    3) Definitions: Not Listed
    c) TLV Basis - Critical Effect(s):
    d) Molecular Weight:
    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 CAS10102-44-0 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Nitrogen dioxide
    2) REL:
    a) TWA:
    b) STEL: 1 ppm (1.8 mg/m(3))
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s):
    3) IDLH:
    a) IDLH: 20 ppm
    b) Note(s): Not Listed

    C) Carcinogenicity Ratings for CAS10102-44-0 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Nitrogen dioxide
    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) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Nitrogen dioxide
    3) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Nitrogen dioxide
    4) 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
    5) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Nitrogen dioxide
    6) MAK (DFG, 2002): Not Listed
    7) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS10102-44-0 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Nitrogen dioxide
    2) Table Z-1 for Nitrogen dioxide:
    a) 8-hour TWA:
    1) ppm: 5
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 9
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value: (C) - An employee's exposure to this substance shall at no time exceed the exposure limit given.
    4) Skin Designation: No
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: OHM/TADS, 2000
    1) TCLo- (INHALATION)HUMAN:
    a) 64 ppm
    B) References: RTECS, 2000
    1) TCLo- (INHALATION)HUMAN:
    a) 2 ppm for 4 H
    b) 6200 ppb for 10M
    c) 90 ppm for 40M

Physicochemical

Physical Characteristics

    A) Nitrogen dioxide is a colorless solid, a yellow liquid, and a brown gas (Weast, 1989).
    B) It is a reddish-brown gas with an irritating odor. It is a liquid below 21.15 degrees C (Budavari, 1996).

Molecular Weight

    A) 46.01 (Clayton & Clayton, 1994)

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) AAR: Emergency Handling of Hazardous Material in Surface Transportation, Bureau of Explosives, Association of American Railroads, Washington, DC, 1987.
    14) ACGIH: Documentation of the Threshold Limit Values and Biological Exposure Indices, 6th ed, Am Conference of Govt Ind Hyg, Inc, Cincinnati, OH, 1992, pp 1108-1110.
    15) AIHA: 2006 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook, American Industrial Hygiene Association, Fairfax, VA, 2006.
    16) Abdushelishvili AV: Sb Tr Nauchno-Issled Inst Sanit Gig (Tiflis) 1977; 13:27-33.
    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) Anon: NIOSH Report, Contract No 210-7800009 (2), Publ No. PB 83-23471 6. Syracuse Research Corp (June), 1980.
    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) Balabaeva L & Tabakova S: Khig Zdraveopaz 1985; 28:41-46.
    22) Barlow SM & Sullivan FM: Reproductive Hazards of Industrial Chemicals, Academic Press, London, UK, 1982, pp 417-421.
    23) Bata Shoe Company: Industrial Footwear Catalog, Bata Shoe Company, Belcamp, MD, 1995.
    24) Bell S, Ashenden TW, & Rafarel CR: Effects of rural roadside levels of nitrogen dioxide on Polytrichum-Formosum Hedw. Environ Pollution 1992; 76:11-14.
    25) Best Manufacturing: ChemRest Chemical Resistance Guide. Best Manufacturing. Menlo, GA. 2002. Available from URL: http://www.chemrest.com. As accessed 10/8/2002.
    26) Best Manufacturing: Degradation and Permeation Data. Best Manufacturing. Menlo, GA. 2004. Available from URL: http://www.chemrest.com/DomesticPrep2/. As accessed 04/09/2004.
    27) Boss Manufacturing Company: Work Gloves, Boss Manufacturing Company, Kewanee, IL, 1998.
    28) Brat K, Merta Z, Plutinsky M, et al: Ice hockey lung - a case of mass nitrogen dioxide poisoning in the Czech Republic. Can Respir J 2013; 20(6):e100-e103.
    29) 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.
    30) Budavari S: The Merck Index, 11th ed, Merck & Co, Inc, Rahway, NJ, 1989, pp 1045.
    31) Budavari S: The Merck Index, 12th ed, Merck & Co, Inc, Whitehouse Station, NJ, 1996, pp 1135.
    32) Burgess JL, Kirk M, Borron SW, et al: Emergency department hazardous materials protocol for contaminated patients. Ann Emerg Med 1999; 34(2):205-212.
    33) CHRIS : CHRIS Hazardous Chemical Data. US Department of Transportation, US Coast Guard. Washington, DC (Internet Version). Edition expires 1990; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    34) CHRIS : CHRIS Hazardous Chemical Data. US Department of Transportation, US Coast Guard. Washington, DC (Internet Version). Edition expires 2000; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    35) Cape JN, Hargreaves KJ, & Storetonwest R: Nitrite in orographic cloud as an indicator of nitous acid in rural air. Atmospher Environ 1992; 26(Part A):2301-2307.
    36) Caravati EM: Alkali. In: Dart RC, ed. Medical Toxicology, Lippincott Williams & Wilkins, Philadelphia, PA, 2004.
    37) Carvajal HF & Stewart CE: Emergency management of burn patients: the first few hours. Emerg Med Reports 1987; 8:129-136.
    38) 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.
    39) Centers for Disease Control and Prevention (CDC): Exposure to nitrogen dioxide in an indoor ice arena - New Hampshire, 2011. MMWR Morb Mortal Wkly Rep 2012; 61(8):139-142.
    40) ChemFab Corporation: Chemical Permeation Guide Challenge Protective Clothing Fabrics, ChemFab Corporation, Merrimack, NH, 1993.
    41) Clayton GD & Clayton FE: Patty's Industrial Hygiene and Toxicology, Volume 2F, Toxicology, 4th ed, John Wiley & Sons, New York, NY, 1994, pp 4566-4591.
    42) Clutton-Brock J: Two cases of poisoning by contamination of nitrous oxide with higher oxides of nitrogen during anaesthesia. Br J Anaesth 1967; 39:388-392.
    43) 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.
    44) Comasec Safety, Inc.: Product Literature, Comasec Safety, Inc., Enfield, CT, 2003a.
    45) 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.
    46) Dabney BJ, Zelarney PT, & Hall AH: Evaluation and treatment of patients exposed to systemic asphyxiants. Emerg Care Q 1990; 6:65-80.
    47) Devlin RB, Horstman DP, & Gerrity TR: Inflammatory Response in Humans Exposed to 2.0 ppm Nitrogen Dioxide. Inhal Toxicol 1999; 11:2:89-109.
    48) Douglas WW, Hepper NGG, & Colby TV: Silo-Filler's disease. Mayo Clin Proc 1989; 64:291-304.
    49) 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.
    50) 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.
    51) DuPont: Permeation Test Results. DuPont. Wilmington, DE. 2002a. Available from URL: http://www.tyvekprotectiveapprl.com/databases/default.htm. As accessed 7/31/2002.
    52) 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.
    53) EPA: EPA chemical profile on nitrogen dioxide, Environmental Protection Agency, Washington, DC, 1985.
    54) 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/.
    55) 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.
    56) Ellenhorn MJ & Barceloux DG: Medical Toxicology: Diagnosis and Treatment of Human Poisoning, Elsevier, New York, NY, 1988.
    57) Epler GR: Silo-filler's disease: a new perspective. Mayo Clin Proc 1989; 64:368-370.
    58) Euler GL, Abbey DE, & Hodgkin JE: Chronic obstructive pulmonary disease symptom effects of long-term cumulative exposure to ambient levels of total oxidants and nitrogen dioxide in California Seventh-day Adventist residents. Arch Environ Health 1988; 43:279-285.
    59) Finkel AJ: Hamilton and Hardy's Industrial Toxicology, 4th ed, John Wright, PSG Inc, Boston, MA, 1983, pp 184-186.
    60) Freeman G: Am Rev Respir Dis 1974; 110:754-759.
    61) Gaston B, Drazen JM, & Loscalzo J: The biology of nitrogen oxides in the airways. Am J Respir Crit Care Med 1994; 149:538-551.
    62) Gil M & Cacho J: NO2 total column evolution during the 1989 spring at Antarctica peninsula. J Atmospher Chem 1992; 15:187-200.
    63) Gofmekler VA: Gig Sanit 1977; 12:22-27.
    64) Goings SAJ, Kulle TJ, & Bascom R: Effect of nitrogen dioxide exposure on susceptibility to influenze A virus infection in healthy adults. Am Rev Respir Dis 1989; 139:1075-1081.
    65) Gooch PC: Mutat Res 1977; 48:117-119.
    66) Grant WM: Toxicology of the Eye, 4th ed, Charles C Thomas, Springfield, IL, 1993.
    67) 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.
    68) HSDB : Hazardous Substances Data Bank. National Library of Medicine. Bethesda, MD (Internet Version). Edition expires 1991; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    69) 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.
    70) Haas CF: Mechanical ventilation with lung protective strategies: what works?. Crit Care Clin 2011; 27(3):469-486.
    71) Harbison RM: Hamilton and Hardy's Industrial Toxicology, 5th ed, Mosby, St. Louis, MO, 1998.
    72) Hathaway GJ, Proctor NH, & Hughes JP: Chemical Hazards of the Workplace, 4th ed, Van Nostrand Reinhold Company, New York, NY, 1996.
    73) Haynes BW Jr: Emergency department management of minor burns. Top Emerg Med 1981; 3:35-40.
    74) Herman MI, Chyka PA, & Butlse AY: Methylene blue by intraosseous infusion for methemoglobinemia. Ann Emerg Med 1999; 33:111-113.
    75) Hisamatsu Y: Mutat Res 1984; 130:364.
    76) Hisano K & Shiomi T: JPN J Genet (Idengaku Zasshi) 1980; 55:457.
    77) 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.
    78) Hjelt K, Lund JT, Scherling B, et al: Methaemoglobinaemia among neonates in a neonatal intensive care unit. Acta Paediatr 1995; 84(4):365-370.
    79) 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.
    80) 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.
    81) 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.
    82) 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.
    83) 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.
    84) 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.
    85) 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.
    86) ICAO: Technical Instructions for the Safe Transport of Dangerous Goods by Air, 2003-2004. International Civil Aviation Organization, Montreal, Quebec, Canada, 2002.
    87) ILC Dover, Inc.: Ready 1 The Chemturion Limited Use Chemical Protective Suit, ILC Dover, Inc., Frederica, DE, 1998.
    88) ITI: Toxic and Hazardous Industrial Chemicals Safety Manual, The International Technical Information Institute, Tokyo, Japan, 1988, pp 370-71-678.
    89) Inoue H: Mutat Res 1981; 88:281-290.
    90) 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.
    91) 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.
    92) Iqbal MM: Potential rates of denitrification in 2 field soils in southern England. J Agric Sci 1992; 118:223-227.
    93) Isomura K: Mutat Res 1984; 136:119-126.
    94) Ito S: Yokohama Igaku 1978; 29:237-245.
    95) Jazbec A, Simic D, & Hrsak J: Short-term effects of ambient nitrogen oxides on the number of emergency asthma cases in Zagreb, Croatia. Arh Hig Rada Toksikol 1999; 50(2):171-82.
    96) Jones GR, Proudfoot AT, & Hall JI: Pulmonary effects of acute exposure to nitrous fumes. Thorax 1973; 28:61-65.
    97) 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.
    98) Karlson-Stiber C, Hojer J, & Sjoholm A: Nitorgen dioxide pneumonitis in ice hockey players. J Intern Med 1996; 239:451-456.
    99) Kawamoto T, Matsuno K, & Arashidani K: Personal exposure to nitrogen dioxide from indoor heaters and cooking stoves. Arch Environ Contam Toxicol 1993; 25:534-538.
    100) 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.
    101) 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.
    102) Kleinman MT, Bailey RM, & Linn WS: Effects of 0.2 ppm nitrogen dioxide on pulmonary function and response to bronchoprovocation in asthmatics. J Toxicol Environ Health 1983; 12:815-826.
    103) Kollef MH & Schuster DP: The acute respiratory distress syndrome. N Engl J Med 1995; 332:27-37.
    104) Kramer U, Koch T, & Ranft U: Traffic-related air pollution is associated with atopy in children living in urban areas. Epidemiology 2000; 11:1:64-70.
    105) Kripke BJ: Anesth Analg 1984; 63:526-528.
    106) LaCrosse-Rainfair: Safety Products, LaCrosse-Rainfair, Racine, WI, 1997.
    107) Lewis RJ: Hawley's Condensed Chemical Dictionary, 12th ed, Van Norstrand Reinhold Company, New York, NY, 1997.
    108) Lewis RJ: Sax's Dangerous Properties of Industrial Materials, 9th ed, Van Nostrand Reinhold Company, New York, NY, 1996.
    109) 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.
    110) Linn WS, Shamoo DA, & Avol EL: Dose-response study of asthmatic volunteers exposed to nitrogen dioxide during intermittent exercise. Arch Environ Health 1986; 41:292-296.
    111) Losa M, Tibballs J, & Carter B: Generation of nitrogen dioxide during nitric oxide therapy and mechanical ventilationof children with a Servo 900C ventilator. Intensive Care Med 1997; 23:450-455.
    112) 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.
    113) 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.
    114) Mansouri A: Methemoglobinemia. Am J Med Sci 1985; 289:200-209.
    115) Mar-Mac Manufacturing, Inc: Product Literature, Protective Apparel, Mar-Mac Manufacturing, Inc., McBee, SC, 1995.
    116) 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.
    117) Marquez A & Todd M: Acute hemolytic anemia and agranulocytosis following intravenous administration of toluidine blue. Am Pract 1959; 10:1548-1550.
    118) McConnell R, Berhane K, & Gilliland F: Air pollution and bronchitic symptoms in Southern California children with asthma. Environ Health Perspect 1999; 107(9):757-60.
    119) 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.
    120) Meulenbelt J, Dormans JAMA, & Vanbree L: Desferrioxamine treatment reduces histological evidence of lung damage in rats after acute nitrogen dioxide (NO2) intoxication. Human Exp Toxicol 1993; 12:389-395.
    121) Mohsenin V: Airway responses to nitrogen dioxide in asthmatic subjects. J Toxicol Environ Health 1987; 22:371-380.
    122) Montgomery Safety Products: Montgomery Safety Products Chemical Resistant Glove Guide, Montgomery Safety Products, Canton, OH, 1995.
    123) Morrow PE: An evaluation of recent NOx toxicity data and an attempt to derive an ambient air standard to NOx by established toxicological procedures. Environ Res 1975; 10:92-112.
    124) Morrow PE: J Toxicol Environ Health 1984; 13:205-227.
    125) Moylan JA: Burn care after thermal injury. Top Emerg Med 1980; 2:39-52.
    126) NFPA: Fire Protection Guide on Hazardous Materials, 10th ed, National Fire Protection Association, Boston, 1991.
    127) NFPA: Fire Protection Guide to Hazardous Materials, 13th ed., National Fire Protection Association, Quincy, MA, 2002.
    128) 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.
    129) NIOSH: Criteria For A Recommended Standard. Occupational Exposure to Oxides of Nitrogen (Nitrogen Dioxide and Nitric Oxide), PB 81-226995, National Institute for Occupational Safety and Health, Cincinnati, OH, 1976, pp 195.
    130) 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.
    131) 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.
    132) 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.
    133) 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.
    134) Naradzay J & Barish RA: Approach to ophthalmologic emergencies. Med Clin North Am 2006; 90(2):305-328.
    135) 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.
    136) 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.
    137) 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.
    138) 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.
    139) 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.
    140) 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.
    141) 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.
    142) 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.
    143) 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.
    144) 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.
    145) 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.
    146) 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.
    147) 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.
    148) 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.
    149) 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.
    150) 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.
    151) 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.
    152) 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.
    153) 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.
    154) 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.
    155) 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.
    156) 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.
    157) 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.
    158) 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.
    159) 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.
    160) 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.
    161) 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.
    162) 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.
    163) 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.
    164) 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.
    165) 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.
    166) 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.
    167) 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.
    168) 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.
    169) 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.
    170) 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.
    171) 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.
    172) 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.
    173) 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.
    174) 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.
    175) 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.
    176) 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.
    177) 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.
    178) 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.
    179) 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.
    180) 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.
    181) 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.
    182) 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.
    183) 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.
    184) 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.
    185) 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.
    186) 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.
    187) 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.
    188) 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.
    189) 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.
    190) 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.
    191) 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.
    192) 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.
    193) 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.
    194) 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.
    195) 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.
    196) 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.
    197) 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.
    198) 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.
    199) 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.
    200) 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.
    201) 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.
    202) 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.
    203) 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.
    204) 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.
    205) 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.
    206) 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.
    207) 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.
    208) 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.
    209) 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.
    210) 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.
    211) 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.
    212) National Research Council : Acute exposure guideline levels for selected airborne chemicals, 5, National Academies Press, Washington, DC, 2007.
    213) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 6, National Academies Press, Washington, DC, 2008.
    214) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 7, National Academies Press, Washington, DC, 2009.
    215) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 8, National Academies Press, Washington, DC, 2010.
    216) 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.
    217) Nemec K: Antidotes in acute poisoning. Eur J Hosp Pharm Sci Pract 2011; 17(4):53-55.
    218) 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.
    219) North: eZ Guide Interactive Software. North Safety. Cranston, RI. 2002a. Available from URL: http://www.northsafety.com/feature1.htm. As accessed 8/31/2002.
    220) OHM/TADS : Oil and Hazardous Materials/Technical Assistance Data System. US Environmental Protection Agency. Washington, DC (Internet Version). Edition expires 1991; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    221) Oda H, Nogami H, & Nakajima T: Reaction of hemoglobin with nitric oxide and nitrogen dioxide in mice. J Toxicol Environ Health 1980; 6:673-678.
    222) Peate WF: Work-related eye injuries and illnesses. Am Fam Physician 2007; 75(7):1017-1022.
    223) Pelled B, Schechter Y, & Alroy G: Deleterious effect of oxygen at ambient and hyperbaric pressure in the treatment of nitrogen dioxide poisoned mice. Am Rev Res Dis 1973; 108:1152-1157.
    224) Peters JM, Avol E, & Navidi W: A study of twelve Southern California communities with differeing levels and types of air pollution. I. Prevalence of respiratory morbidity. Am J Respir Crit Care Med 1999; 159(3):760-7.
    225) Phillips ML, Hall TA, & Sekar K: Assessment of medical personnel exposure to nitrogen oxides during inhaled nitric oxide treatment of neonatal and pediatric patients. Pediatrics 1999; 104(5):1095-1100.
    226) Pitts JN Jr: Science 1978; 202:515-518.
    227) Playtex: Fits Tough Jobs Like a Glove, Playtex, Westport, CT, 1995.
    228) Product Information: PROVAYBLUE(TM) intravenous injection, methylene blue intravenous injection. American Regent (per FDA), Shirley, NY, 2016.
    229) Product Information: methylene blue 1% IV injection, methylene blue 1% IV injection. American Regent, Inc (per manufacturer), Shirley, NY, 2011.
    230) Product Information: methylene blue 1% intravenous injection, methylene blue 1% intravenous injection. Akorn, Inc. (per manufacturer), Lake Forest, IL, 2011.
    231) RTECS : Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety and Health. Cincinnati, OH (Internet Version). Edition expires 1991; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    232) 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.
    233) Ramirez RJ & Dowell AR: Silo-filler's disease: nitrogen dioxide-induced lung injury. Long term follow-up and review of literature. Ann Intern Med 1971; 74:569-576.
    234) Richters A & Damji KS: Changes in T-lymphocyte subpopulations and natural killer cells following exposure to ambient levels of nitrogen dioxide. J Toxicol Environ Health 1988; 25:247-256.
    235) River City: Protective Wear Product Literature, River City, Memphis, TN, 1995.
    236) Roberts JR: Minor burns (Pt II). Emerg Med Ambulatory Care News 1988; 10:4-5.
    237) Rosenlund M & Bluhm G: Health effects resulting from nitrogen dioxide exposure in an indoor ice arena. Arch Environ Health 1999; 54(1):52-7.
    238) 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.
    239) Sakai R: Internat J Environ Stud 1984; 23:113-120.
    240) Salome CM, Brown NJ, & Marks GB: Effect of nitrogen dioxide and other combustion products on asthmatic subjects in a home-like environment. Eur Respir J 1996; 9:910-918.
    241) Samet JM: Nitrogen dioxide and respiratory infection (Editorial). Am Rev Respir Dis 1989; 139:1073-1074.
    242) Sax NI & Lewis RJ: Dangerous Properties of Industrial Materials, 7th ed, Van Nostrand Reinhold Co, New York, NY, 1989, pp 2523.
    243) Schnizlein CT & Bice DE: Inhalation Toxicol Res Inst Annual Report 1978-1979, Henderson RF et al (Eds), Lovelace Biomed & Environ Res Inst, Albuquerque, NM, 1979.
    244) Servus: Norcross Safety Products, Servus Rubber, Servus, Rock Island, IL, 1995.
    245) Shalamberidze OP & Tsereteli NT: Gig Sanit 1971; 36:178-182.
    246) Shepherd G & Keyes DC: Methylene blue. In: Dart,RC, ed. Medical Toxicology, 3rd ed. 3rd ed, Philadelphia, PA, 2004, pp -.
    247) Shishido M & Yamada M: Kanagawa-Ken Taiki Osen Chosa Kenkyu Hokoku 1981; 23:190-198.
    248) Singh J: Nitrogen dioxide exposure alters neonatal development. Neurotoxicology 1988; 9:545-549.
    249) Sittig M: Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2nd ed, Noyes Publications, Park Ridge, NJ, 1985, pp 659-661.
    250) Sittig M: Handbook of Toxic and Hazardous Chemicals and Carcinogens, 3rd ed, Noyes Publications, Park Ridge, NJ, 1991.
    251) Skiba U, Hargreaves KJ, & Fowler D: Fluxes of nitric and nitrous oxides from agricultural soils in a cool temperate climate. Atmospher Environ 1992; 26(Part A):2477-2488.
    252) Standard Safety Equipment: Product Literature, Standard Safety Equipment, McHenry, IL, 1995.
    253) 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.
    254) 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.
    255) Strand V, Salomonsson P, & Lundahl J: Immediate and delayed effects of nitrogen dioxide exposure at an ambient level on bronchial responsiveness to histamine in subjects with asthma. Eur Respir J 1996; 9:733-740.
    256) Strand V, Svartengren M, & Rak S: Repeated exposure to an ambient level of NO2 enhances asthmatic response to a nonsymptomatic allergen dose. Eur Respir J 1998; 12(1):6-12.
    257) Sullivan TFP: Pollution Engineering 1987; 24.
    258) Tabacova S, Nikiforov B, & Balabaeva L: Postnatal effects of maternal exposure to nitrogen dioxide. Neurobehav Toxicol Teratol 1985; 7:785-789.
    259) Tabacova S: Teratology 1984; 29:33a-34a.
    260) Tanaka N, Emoto T, Matsumoto T, et al: Inhalational lung injury due to nitrogen dioxide: high-resolution computed tomography findings in 3 patients. J Comput Assist Tomogr 2007; 31(5):808-811.
    261) Teunis BS, Leftwich EI, & Pierce LE: Acute methemoglobinemia and hemolytic anemia due to toluidine blue. Arch Surg 1970; 101:527-531.
    262) 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.
    263) Tokowa H: Mutat Res 1981; 85:195-205.
    264) Totapally BR, Raszynski A, & Sussmane J: Nitric oxide and nitrogen dioxide concentrations during in vitro high-frequency oscillatory ventilation. J Crit Care 1999; 14(3):141-9.
    265) Touze MD, Desjrs P, & Baron D: Intoxication aigue collective par les vapeurs nitreuses (French). Toxicol Eur Res 1983; 5:220-224.
    266) 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.
    267) Trelleborg-Viking, Inc.: Trellchem Chemical Protective Suits, Interactive manual & Chemical Database. Trelleborg-Viking, Inc.. Portsmouth, NH. 2001.
    268) Tse RL & Bockman AA: Nitrogen dioxide toxicity. Report of four cases in firemen. JAMA 1970; 212:1341-1344.
    269) Tsuda H: Mutat Res 1981; 89:303-309.
    270) 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.
    271) 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.
    272) 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-.
    273) 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.
    274) 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.
    275) 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.
    276) 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.
    277) 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.
    278) 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-.
    279) U.S. Occupational Safety, and Health Administration (OSHA): Process safety management of highly hazardous chemicals. 29 CFR 2010 2010; 29(1910.119):348-.
    280) 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.
    281) Utell MJ: Effects of inhaled acid aerosols on lung mechanics: an analysis of human exposure studies. Environ Health Perspect 1985; 63:39-44.
    282) Vanoene H: Acid deposition and forest nutrient imbalances -- a modeling approach. Water Air Soil Pollut 1992; 63:33-50.
    283) Victorin K, Busk L, & Cederberg H: Genotoxic activity of 1,3-butadiene and nitrogen dioxide and their photochemical reaction products in Drosophila and in the mouse bone marrow micronucleus assay. Mutat Res 1990; 228:203-209.
    284) Victorin K: Review of the genotoxicity of nitrogen oxides. Mutat Res 1994; 317:43-55.
    285) Vinther FP: Measured and simulated denitrification activity in a cropped sandy loamy soil. Bio Fertil Soils 1992; 14:43-48.
    286) Wang JH, Devalia JL, & Duddle JM: Effect of six-hour exposure to nitrogen dioxide on early-phase nasal response to allergen challenge in patients with a history of seasonal allergic rhinitis. J Allergy Clin Immunol 1995; 96:669-676.
    287) Weast RC: Handbook of Chemistry and Physics 60th edition, CRC Press, Inc, Boca Raton, FL, 1989.
    288) 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.
    289) Whitaker V & Matvienko B: A method for the study of N2O evolution in tropical wetlands. Hydrobiologia 1992; 230:213-218.
    290) Willson DF, Truwit JD, Conaway MR, et al: The adult calfactant in acute respiratory distress syndrome (CARDS) trial. Chest 2015; 148(2):356-364.
    291) 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.
    292) Winek CL, Collom WD, & Martineau P: Toluidine blue intoxication. Clin Toxicol 1969; 2:1-3.
    293) Witschi H: Ozone, nitrogen dioxide and lung cancer: a review of some recent issues and problems. Toxicol 1988; 48:1-20.
    294) Workrite: Chemical Splash Protection Garments, Technical Data and Application Guide, W.L. Gore Material Chemical Resistance Guide, Workrite, Oxnard, CA, 1997.
    295) Zhou Q, Yao SC, & Russell A: Flue gas NOx reduction using ammonia radical injection. J Air Waste Manage Assoc 1992; 42:1193-1197.
    296) do Nascimento TS, Pereira RO, de Mello HL, et al: Methemoglobinemia: from diagnosis to treatment. Rev Bras Anestesiol 2008; 58(6):651-664.