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DIMETHYLNITROSAMINE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Dimethylnitrosamine is a methylating agent capable of causing carcinomas, especially of the liver and lungs, and to a lesser degree, the kidneys following chronic exposures. Acute exposures may result in severe liver damage, coagulopathy and hemorrhage.

Specific Substances

    1) Dimethylnitrosamine
    2) Dimethylamine, N-Nitroso-
    3) Dimethylnitrosamin (German)
    4) Dimethyl Nitrosamine
    5) N-Dimethyl-Nitrosamine
    6) N,N-Dimethylnitrosamine
    7) Dimethylnitrosoamine
    8) DMN
    9) DMNA
    10) Methanamine, N-Methyl-N-Nitroso-
    11) NDMA
    12) N-Methyl-N-Nitrosomethanamine
    13) Nitrosodimethylamine
    14) N-Nitrosodimethylamine
    15) N-Nitroso-N,N-Dimethylamine
    16) Nitrous Dimethylamide
    17) CAS 62-75-9
    18) DMN (DIMETHYLNITROSAMINE)
    19) DMNA (DIMETHYLNITROSAMINE)
    20) NITROUS DIMETHYLAMINE
    1.2.1) MOLECULAR FORMULA
    1) C2-H6-N2-O

Available Forms Sources

    A) FORMS
    1) Dimethylnitrosamine (DMNA) is no longer produced commercially in the USA (HSDB , 2000).
    B) SOURCES
    1) DMNA has been found in dialysate made from water purified by deionizers (Simenhoff et al, 1983).
    2) Trace amounts have been found in tobacco smoke concentrate, cured meat products, and smoked meats (Budavari, 1996).
    3) Dimethylnitrosamine is often found in fish meal (Lewis, 1993).
    4) Nitrosamines can be formed in soil, air, water, food, and in the gastrointestinal tract from naturally occurring nitrates and nitrites reacting with amines under acidic conditions. Environmental exposure can be extensive (Clayton & Clayton, 1994).
    5) Dimethylnitrosamine is an air pollutant, especially in the tire and rubber industries (Hathaway et al, 1996). The use of nitrosamines as vulcanizing retarders and/or blowing agents has been replaced (Clayton & Clayton, 1993).
    6) Besides the expected high levels found in nitrate-cured meats, dimethylnitrosamine can occur at 300 ppb in soya bean oil (Clayton & Clayton, 1993).
    C) USES
    1) Dimethylnitrosamine was formerly used as an industrial solvent (in the production of fibers and plastics), as an antioxidant and nematocide, in lubricants and condensers, and in the production of rocket fuels (HSDB , 2000).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Dimethylnitrosamine (DMNA) is an hepatotoxin and a probable human carcinogen. There are few reports of acute overexposure in humans.
    B) Fever, headache, malaise, vomiting, conjunctivitis, photophobia, periorbital ecchymosis, coagulopathy, subarachnoid hemorrhage, pulmonary edema, seizures, cerebral edema, hepatitis, hepatomegaly, ascites, hepatic necrosis, and thrombocytopenia have been reported following acute exposure.
    C) Inhalation may produce immediate effects of skin, nose, and eye irritation.
    0.2.4) HEENT
    A) Ingestion has caused conjunctival injection, periorbital ecchymosis, and conjunctival hemorrhages. Scleral jaundice may occur following oral or inhalational exposure. Corneal damage and uveitis may occur after a latent period.
    0.2.5) CARDIOVASCULAR
    A) Myocardial hemorrhages have occurred following oral exposure.
    0.2.6) RESPIRATORY
    A) Pulmonary edema, congestion, and hemorrhagic areas have been reported.
    0.2.7) NEUROLOGIC
    A) Seizures, cerebral edema, headache, and malaise have been reported.
    0.2.8) GASTROINTESTINAL
    A) Vomiting, gastrointestinal hemorrhage, and peritonitis have occurred.
    0.2.9) HEPATIC
    A) The liver is the primary target organ. Centrilobular liver necrosis, hepatomegaly, jaundice, ascites, and hepatitis have been reported after ingestion and inhalational exposures. Diffuse hemorrhages around central veins of the liver may occur.
    0.2.10) GENITOURINARY
    A) Red blood cells have been seen in the kidney tubules following ingestion.
    0.2.13) HEMATOLOGIC
    A) Thrombocytopenia, coagulopathy and hemorrhage have developed after exposures.
    0.2.19) IMMUNOLOGIC
    A) Lymph node fibrosis has been reported following inhalation.
    B) Humoral and cellular immunity can be suppressed in experimental animals. Toxicity may involve autoimmunity.
    0.2.20) REPRODUCTIVE
    A) Fetal death, fetotoxicity, and other teratogenic effects were observed in rat and mouse studies. Pre- and post-implantation mortality and abortion were observed in rats. Abnormal changes in sperm morphology were detected in mice.
    0.2.21) CARCINOGENICITY
    A) Dietary dimethylnitrosamine intake has been associated with a higher risk of gastric cancer.

Laboratory Monitoring

    A) No toxic serum levels have been established. Monitor liver enzymes, platelet count, INR or prothrombin time and bleeding time, and blood glucose levels.
    B) Specific OSHA requirements have been promulgated for the medical surveillance of employees exposed to DMNA.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) ACTIVATED CHARCOAL -
    1) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    B) GASTRIC LAVAGE -
    1) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    a) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    C) ACUTE LUNG INJURY
    1) 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) SEIZURES -
    1) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    a) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    b) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    E) HEMORRHAGE -
    1) Transfusions of packed red blood cells, fresh frozen plasma or platelets may be necessary if bleeding is extensive or platelet count is below 20,000/mm(3).
    F) MONITORING PARAMETERS -
    1) Obtain baseline liver studies. It may be advisable to monitor for several months following the exposure.
    G) SYMPTOMATIC/SUPPORTIVE TREATMENT -
    1) Appropriate supportive measures should be considered.
    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.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) A potentially lethal dose (extrapolated from animal data) is 1.8 gm for an average adult or 0.3 gm for a 10 kg child.

Clinical Effects

Summary Of Exposure

    A) Dimethylnitrosamine (DMNA) is an hepatotoxin and a probable human carcinogen. There are few reports of acute overexposure in humans.
    B) Fever, headache, malaise, vomiting, conjunctivitis, photophobia, periorbital ecchymosis, coagulopathy, subarachnoid hemorrhage, pulmonary edema, seizures, cerebral edema, hepatitis, hepatomegaly, ascites, hepatic necrosis, and thrombocytopenia have been reported following acute exposure.
    C) Inhalation may produce immediate effects of skin, nose, and eye irritation.

Vital Signs

    3.3.3) TEMPERATURE
    A) FEVER has been reported in animals; mild fever was reported in a case of a human oral exposure (ITI, 1975; Cooper & Kimbrough, 1980).

Heent

    3.4.1) SUMMARY
    A) Ingestion has caused conjunctival injection, periorbital ecchymosis, and conjunctival hemorrhages. Scleral jaundice may occur following oral or inhalational exposure. Corneal damage and uveitis may occur after a latent period.
    3.4.3) EYES
    A) HEMORRHAGE - Ingestion has caused coagulopathy with conjunctival injection, photophobia, periorbital ecchymosis, conjunctival hemorrhage, and non-reactive pupils secondary to subarachnoid hemorrhage (Cooper & Kimbrough, 1980).
    B) ICTERUS - Conjunctival and scleral icterus have been reported following oral and inhalation exposures (Cooper & Kimbrough, 1980; Freund, 1937).
    C) IRRITATION - Acute inhalation has caused immediate eye irritation in animal studies (Freund, 1937).
    D) LATENT TOXICITY - Corneal damage and uveitis may be delayed in onset (Clayton & Clayton, 1994). Grant & Schuman (1993) reported both corneal damage and uveitis following a latent period after exposure to nitrosamine gases. Permanent injury and depigmentation of the iris are also reported to occur.

Cardiovascular

    3.5.1) SUMMARY
    A) Myocardial hemorrhages have occurred following oral exposure.
    3.5.2) CLINICAL EFFECTS
    A) HEMORRHAGE
    1) Myocardial and endocardial hemorrhages have been reported in patients with severe hepatic necrosis and coagulopathy after oral exposure (Cooper & Kimbrough, 1980).

Respiratory

    3.6.1) SUMMARY
    A) Pulmonary edema, congestion, and hemorrhagic areas have been reported.
    3.6.2) CLINICAL EFFECTS
    A) ACUTE LUNG INJURY
    1) Pulmonary edema, congestion, atelectasis, and irregular dark hemorrhagic areas in the lungs were reported in a child who died after ingestion (Cooper & Kimbrough, 1980).
    B) PNEUMONIA
    1) Pneumonitis of the right base is diagnosed following a chest roentgenogram in a 26-year-old male chemist following inhalation exposure over a month period (Freund, 1937).
    C) PULMONARY HEMORRHAGE
    1) Autopsy examinations revealed petechial hemorrhages of the lungs and diaphragm and extensive intra-alveolar hemorrhages with edema in 2 persons with severe hepatic necrosis and coagulopathy following oral lethal ingestions (Cooper & Kimbrough, 1980).
    2) Hemorrhages of the bronchi and trachea were noted at necropsy in a 26-year- old male chemist following approximately a one month inhalational exposure (Freund, 1937).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) PULMONARY EDEMA
    a) Autopsy of a dog exposed to inhalational dimethylnitrosamine for 30 minutes revealed acute diffuse pulmonary edema with terminal passive congestion (Freund, 1937).

Neurologic

    3.7.1) SUMMARY
    A) Seizures, cerebral edema, headache, and malaise have been reported.
    3.7.2) CLINICAL EFFECTS
    A) SEIZURE
    1) Seizures were reported in conjunction with liver failure after ingestion (Cooper & Kimbrough, 1980).
    B) CEREBRAL EDEMA
    1) Cerebral edema and right subarachnoid hemorrhages were reported at necropsy in 2 persons poisoned with oral ingestions (Cooper & Kimbrough, 1980).
    C) HEADACHE
    1) Headache has been reported following acute exposures (Freund, 1937; Cooper & Kimbrough, 1980).
    D) MALAISE
    1) Malaise was reported after ingestion (Cooper & Kimbrough, 1980).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SEIZURES
    a) Seizures were reported in mice and a dog 18 hours following a 30 minute inhalation of dimethylnitrosamine (Freund, 1937).

Gastrointestinal

    3.8.1) SUMMARY
    A) Vomiting, gastrointestinal hemorrhage, and peritonitis have occurred.
    3.8.2) CLINICAL EFFECTS
    A) GASTROENTERITIS
    1) Vomiting, which is often prolonged (1 to 2 days), may occur after ingestion. Abdominal cramps and diarrhea may also occur (Cooper & Kimbrough, 1980).
    B) GASTROINTESTINAL HEMORRHAGE
    1) Petechial hemorrhages in the colon and bloody fluid in the stomach were reported in a child with hepatic necrosis and coagulopathy who died after ingestion (Cooper & Kimbrough, 1980).
    C) PERITONITIS
    1) A significant proliferative productive peritonitis was reported at necropsy in a chemist following daily inhalational exposures over approximately a one month period (Freund, 1937).

Hepatic

    3.9.1) SUMMARY
    A) The liver is the primary target organ. Centrilobular liver necrosis, hepatomegaly, jaundice, ascites, and hepatitis have been reported after ingestion and inhalational exposures. Diffuse hemorrhages around central veins of the liver may occur.
    3.9.2) CLINICAL EFFECTS
    A) INJURY OF LIVER
    1) The liver is the target organ for dimethylnitrosamine. Extensive damage, primarily focusing on the centrilobular area of the liver, includes necrosis and cirrhosis with ultimate partial bile duct obstruction (Clayton & Clayton, 1994; Cooper & Kimbrough, 1980; Freund, 1937).
    B) LARGE LIVER
    1) Hepatomegaly has been reported after ingestion (Cooper & Kimbrough, 1980; Freund, 1937).
    C) JAUNDICE
    1) Icterus has occurred in patients after ingestion (Cooper & Kimbrough, 1980).
    D) HEPATIC NECROSIS
    1) Massive necrosis of the liver was reported at necropsy in a 1-year-old boy following a homicidal ingestion overdose. A complete loss of hepatocytes in the centrilobular areas were reported (Cooper & Kimbrough, 1980). The same authors report another case at necropsy with extensive necrosis of the hepatocytes in the center of the lobules, with prominent congestion and hemorrhage.
    2) Freund (1937) reports 2 cases of inhalational exposures in chemists, over a one month period. A diagnosis of toxic parenchymatous hepatitis with ascites was made. In the one who died, an autopsy revealed acute degeneration of the parenchyma with focal and diffuse areas of necrosis.
    E) ASCITES
    1) Ascites has also been reported (Freund, 1937) ACGIH, 1980).
    F) HEMORRHAGE
    1) Multiple periportal miliary hemorrhages and diffuse hemorrhages around the central veins have been reported at autopsy in several cases (Cooper & Kimbrough, 1980; Freund, 1937).
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATIC CIRRHOSIS
    a) Micronodular liver cirrhosis, induced in rats after 3 weeks of low dose treatment with dimethylnitrosamine, was suggested to be an immune-mediated response (Jezequel et al, 1989).
    2) HEPATIC CARCINOMA
    a) Liver tumors, usually of vascular origin (hemangiosarcomas), are easily induced in animals with single high doses of dimethylnitrosamine, short-term exposures, or low dose chronic exposures (Terracini et al, 1978; (Coccia et al, 1988; Reznik, 1975; Stenback et al, 1986; Tomatis et al, 1964; Anderson et al, 1989; Cardesa et al, 1973; Lijinsky & Reuber, 1981; Mohr et al, 1974; Klaunig et al, 1988). DNA alkylation has been found in the livers (Coccia et al, 1988; Kamendulis & Corcoran, 1995; Tates et al, 1983; Barbin et al, 1983). Bile duct neoplasms were reported in high frequency in a study involving over 4000 rats (Peto et al, 1991).

Genitourinary

    3.10.1) SUMMARY
    A) Red blood cells have been seen in the kidney tubules following ingestion.
    3.10.2) CLINICAL EFFECTS
    A) RENAL TUBULAR DISORDER
    1) Numerous red blood cells were seen in kidney collection tubules on autopsy in a 24-year-old male following ingestion of dimethylnitrosamine (Cooper & Kimbrough, 1980).

Hematologic

    3.13.1) SUMMARY
    A) Thrombocytopenia, coagulopathy and hemorrhage have developed after exposures.
    3.13.2) CLINICAL EFFECTS
    A) THROMBOCYTOPENIC DISORDER
    1) Severe thrombocytopenia has been reported following ingestion, with platelet counts below 20,000/mm(3). Evidence of hemorrhage was seen in brain, gastrointestinal tract, heart, lungs, and liver in patients who died after ingestion exposure (Cooper & Kimbrough, 1980).
    B) HEMORRHAGE
    1) A 24-year-old adult developed severe epistaxis, gingival bleeding, conjunctival injection, periorbital ecchymosis, and cerebral hemorrhage after ingestion (Cooper & Kimbrough, 1980). Bruising and ecchymosis are common.
    2) Hemorrhages of the lungs, liver, gastrointestinal tract, and pericardium were reported at necropsy in a 26-year-old male chemist following inhalational exposures to dimethylnitrosamine (Freund, 1937).
    3) Multiple periportal miliary hemorrhages and diffuse hemorrhages around the central veins have been reported at autopsy in several cases (Cooper & Kimbrough, 1980; Freund, 1937).
    4) Numerous red blood cells have been seen in kidney collection tubules following ingestion in a 24-year-old male (Cooper & Kimbrough, 1980).
    C) BLOOD COAGULATION PATHWAY FINDING
    1) Coagulopathy with prolonged PT and elevated fibrin split products has been reported in patients with sever hepatic necrosis after ingestion (Cooper & Kimbrough, 1980).
    D) LACK OF EFFECT
    1) The bone marrow was not affected in several cases of oral and inhalational exposures (Cooper & Kimbrough, 1980; Freund, 1937).

Endocrine

    3.16.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HYPOGLYCEMIA
    a) Hypoglycemic shock and death was reported in a dog 18 hours after a 30 min inhalational exposure to dimethylnitrosamine. The authors speculate this is related to destruction of the glycogenic function of the liver. Muscle glycogen reserves are diminished, thus also resulting in muscle fasciculations (Freund, 1937).

Immunologic

    3.19.1) SUMMARY
    A) Lymph node fibrosis has been reported following inhalation.
    B) Humoral and cellular immunity can be suppressed in experimental animals. Toxicity may involve autoimmunity.
    3.19.2) CLINICAL EFFECTS
    A) LYMPHEDEMA
    1) Diffuse fibrosis and edema of the lymph nodes was reported at necropsy in a 26-year-old male chemist following approximately one month inhalational exposure (Freund, 1937).
    3.19.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) IMMUNE SYSTEM DISORDER
    a) HUMORAL IMMUNITY - CD-1 mice given up to 20 ppm chronically showed depression of IgM response to sheep red blood cells (Des Jardins et al, 1992).
    b) CELLULAR IMMUNITY - Allogeneic stimulation of cells in the mixed lymphocyte reaction were suppressed with 10 and 20 ppm dimethylnitrosamine in CD-1 mice (Des Jardins et al, 1992).
    c) AUTOIMMUNITY - Dimethylnitrosamine enhanced expression of the major histocompatibility antigen component Ia in macrophages and lymphocytes of mice, prior to development of micronodular hepatic cirrhosis. This implies that DMNA-induced hepatotoxicity may involve an autoimmune-mediated mechanism (Jezequel et al, 1989).

Reproductive

    3.20.1) SUMMARY
    A) Fetal death, fetotoxicity, and other teratogenic effects were observed in rat and mouse studies. Pre- and post-implantation mortality and abortion were observed in rats. Abnormal changes in sperm morphology were detected in mice.
    3.20.2) TERATOGENICITY
    A) FETOTOXICITY
    1) Toxic effects, including fetotoxicity, fetal death, and specific developmental abnormalities were observed in rats. In the mouse, stillbirth, changes in the viability index, and biochemical and metabolic changes were observed (RTECS , 2000).
    2) Increased perinatal deaths occurred in offspring of mice given 0.1 ppm dimethylnitrosamine in the drinking water before and during pregnancy (Anderson et al, 1978).
    B) CARCINOMA
    1) Dimethylnitrosamine was a transplacental carcinogen; hepatocellular sarcomas and carcinomas occurred in offspring of pregnant mice given the maximum dose of dimethylnitrosamine which was not fetotoxic on day 16 or 19 of gestation (Anderson et al, 1989). Lung tumors were significantly higher in progeny of strain A female mice given 10 ppb in the drinking water from 4 weeks prior to mating to 22 weeks after birth (Anderson et al, 1979).
    C) LACK OF EFFECT
    1) LACK OF EFFECT
    a) Dimethylnitrosamine was not teratogenic in rats or hamsters (Schardein, 1993).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY DISORDER
    1) Dimethylnitrosamine was observed to cause pre-implantation mortality, post-implantation mortality, and abortion in the rat (RTECS , 2000).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS62-75-9 (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) IARC Classification
    a) Listed as: N-Nitrosodimethylamine
    b) Carcinogen Rating: 2A
    1) The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans. This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent (mixture) may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals and strong evidence that the carcinogenesis is mediated by a mechanism that also operates in humans. Exceptionally, an agent, mixture or exposure circumstance may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans.
    3.21.2) SUMMARY/HUMAN
    A) Dietary dimethylnitrosamine intake has been associated with a higher risk of gastric cancer.
    3.21.3) HUMAN STUDIES
    A) GASTRIC CARCINOMA
    1) In a case-control study of 92 patients, dietary intake of dimethylnitrosamine estimated from a food composition table was associated with higher risk of gastric cancer in a dose-related fashion. The odds ratio for the highest tertile of consumption was 7.00. Significantly, consumption of nitrites and nitrates was not associated with gastric cancer (Pobel et al, 1995).
    B) CARCINOMA
    1) LARYNGEAL/ESOPHAGEAL/ORAL CANCERS -
    a) A 79% increased risk of upper aerodigestive tract cancer was associated with consumption of foods high in dimethylnitrosamine in a case-control study of 645 patients in Washington state (Rogers et al, 1995).
    3.21.4) ANIMAL STUDIES
    A) HEPATIC CARCINOMA
    1) Liver tumors, usually of vascular origin (hemangiosarcomas), are easily induced in animals with single high doses of dimethylnitrosamine, short-term exposures, or low dose chronic exposures (Terracini et al, 1978; (Coccia et al, 1988; Reznik, 1975; Stenback et al, 1986; Tomatis et al, 1964; Anderson et al, 1989; Cardesa et al, 1973; Lijinsky & Reuber, 1981; Mohr et al, 1974; Klaunig et al, 1988). DNA alkylation has been found in the livers (Coccia et al, 1988; Kamendulis & Corcoran, 1995; Tates et al, 1983; Barbin et al, 1983). Bile duct neoplasms were reported in high frequency in a study involving over 4000 rats (Peto et al, 1991).
    B) RENAL CARCINOMA
    1) Renal mesenchymal tumors were induced in rats with a single IP dose of dimethylnitrosamine. Tumor incidence was dose-related. Methylation of guanine in the kidney DNA was also linearly dose-related (Driver et al, 1987).
    C) PULMONARY CARCINOMA
    1) Argus et al (1982) have induced lung lesions consisting of alveologenic tumors and adenomatosis in C57B1/6J mice. Hemangioendotheliomas were also found in the mice treated with dimethylnitrosamine as well as tumors in the fatty tissue surrounding the pancreas or adhering to the intestinal loops (Argus et al, 1982).
    D) CARCINOMA
    1) Dimethylnitrosamine is a potent carcinogen (Simenhoff et al, 1983), being carcinogenic in all species tested. Target organs differ by species, but lung, liver, and kidney tumors have been described (ACGIH, 1980).
    2) It is in Group B2 (potency group 2 and "medium" hazard ranking), according to the US EPA's Carcinogen Assessment Group guidelines (Anon, 1993).
    3) SUMMARY
    a) Dimethylnitrosamine has been carcinogenic in rats, mice, hamsters, guinea pigs, rabbits, monkeys, and rainbow trout (Clayton & Clayton, 1994).
    1) CARCINOGENICITY IN RATS -
    a) In rats, dimethylnitrosamine was found to be an equivocal tumorigenic agent, carcinogenic, and neoplastic by RTECS criteria, with transplacental tumorigenesis, liver tumors, and lungs, thorax, or respiratory tumors. Kidney, ureteral, and bladder tumors were noted (RTECS , 2000).
    b) Liver tumors develop under conditions of long-term treatment at lower doses, while kidney tumors occur with higher doses of shorter duration (IARC, 1978; Driver et al, 1987).
    c) Inhalation of 0.04, 0.2, and 1.0 ppm of dimethylnitrosamine produced tumors mainly in the nasal cavity in rats (Klein et al, 1991).
    d) Doses of 0.1 and 1 ppm in the diet induced liver and bile duct tumors in rats; dose-response for liver tumors was linear, with no apparent threshold (Peto et al, 1991).
    e) Dimethylnitrosamine was carcinogenic in rats by the dermal route when applied in 3 doses of 1 to 10 mg; tumors were induced in the liver, lung, and kidney (Benemanskii & Levina, 1985).
    f) Rats developed hemangiosarcomas almost exclusively from exposure in the drinking water (Lijinsky & Reuber, 1981).
    2) CARCINOGENICITY IN MICE -
    a) In mice, dimethylnitrosamine was neoplastic and carcinogenic by RTECS criteria, with transplacental tumorigenesis, lung, thorax or respiratory tumors, bronchogenic carcinoma, increased incidence of tumors in susceptible strains, liver tumors, and tumors of the kidney, ureteral, and bladder (RTECS , 2000).
    b) Tumors of the kidney and lung developed in mice fed 0.005% dimethylnitrosamine for only 1 week (Terracini et al, 1966).
    c) Vascular tumors occurred in mice after IP injection of 6 mg/kg dimethylnitrosamine once a week for 10 weeks (Cardesa et al, 1973).
    d) Dimethylnitrosamine is a transplacental carcinogen in mice.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No toxic serum levels have been established. Monitor liver enzymes, platelet count, INR or prothrombin time and bleeding time, and blood glucose levels.
    B) Specific OSHA requirements have been promulgated for the medical surveillance of employees exposed to DMNA.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) No toxic serum levels have been established.
    2) LIVER ENZYMES - Liver failure is common, and liver enzymes should be monitored.
    3) Serum glucose levels should be monitored, especially in the presence of liver damage.
    B) COAGULATION STUDIES
    1) COAGULATION STUDIES - Exposed patients should have INR or prothrombin time and bleeding time monitored.
    C) HEMATOLOGIC
    1) Monitor complete blood count including platelet count.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) OSHA MEDICAL SURVEILLANCE METHODS (OSHA, 1990) - At no cost to the employee, a program of medical surveillance shall be established and implemented for employees considered for assignment to enter regulated areas, and for authorized employees.
    b) EXAMINATIONS - Before an employee is assigned to enter a regulated area, a preassignment physical examination by a physician shall be provided. The examination shall include the personal history of the employee, family and occupational background, including genetic and environmental factors.
    1) Authorized employees shall be provided periodic physical examinations, not less often than annually, following the preassignment examination.
    2) In all physical examinations, the examining physician shall consider whether there exist conditions of increased risk, including reduced immunological competence, those undergoing treatment with steroids or cytotoxic agents, pregnancy and cigarette smoking.
    c) RECORDS - Employers of employees examined pursuant to this paragraph shall cause to be maintained complete and accurate records of all such medical examinations. Records shall be maintained for the duration of the employee's employment. Upon termination of an employee's employment, including retirement or death, or in the event that the employer ceases business without a successor, records, or notarized true copies thereof, shall be forwarded by registered mail to the Director.
    1) Records required by this paragraph shall be provided upon request to employees, designated representatives, and the Assistant Secretary in accordance with 29 CFR 1910.20 (a)-(e) and (g)-(i). These records shall also be provided upon request to the Director.
    2) Any physician who conducts a medical examination required by this paragraph shall furnish to the employer a statement of the employee's suitability for employment in the specific exposure.
    d) Refer to the full text of CFR 1910.1016 for more information.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) Monitor chest x-ray for signs of pulmonary toxicity, including pulmonary edema, in symptomatic patients.

Methods

    A) MULTIPLE ANALYTICAL METHODS
    1) Various methods exist for analysis of dimethylnitrosamine, including thin layer chromatography, polarography, spectrophotometry, gas chromatography, high performance liquid chromatography, and thermal energy analysis (Clayton & Clayton, 1993).
    2) Kraft et al (1981) describe a gas chromatography technique for quantifying dimethylnitrosamine following urinary excretion in rats.
    3) Dimethylnitrosamine-DNA adducts can be detected immunologically with monoclonal or polyclonal antibodies (Asamoto et al, 1991). Detection of O6- or N7-methyl guanine would not be specific for dimethylnitrosamine, however, because other alkylating agents can form the same product.
    4) HPLC with fluorescence detection has been used to detect O6-methyl guanine and N7-methyl guanine in isolated DNA (Zhang, 1990).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Any exposure victim to DMNS should be admitted and monitored for liver damage and hemorrhagic tendencies.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Liver function studies should be monitored for at least 3 months following acute and chronic exposures.

Monitoring

    A) No toxic serum levels have been established. Monitor liver enzymes, platelet count, INR or prothrombin time and bleeding time, and blood glucose levels.
    B) Specific OSHA requirements have been promulgated for the medical surveillance of employees exposed to DMNA.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL -
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    B) GASTRIC LAVAGE
    1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    2) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    3) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    4) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    5) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    6.5.3) TREATMENT
    A) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    B) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    C) HEMORRHAGE
    1) Transfusions of packed red blood cells, fresh frozen plasma or platelets may be necessary if bleeding is extensive or platelet count is below 20,000/mm(3).
    D) SUPPORT
    1) Hepatic failure should be treated with appropriate supportive measures, which may include hemodialysis.
    E) FLUID/ELECTROLYTE BALANCE REGULATION
    1) If vomiting is persistent, monitor fluid and electrolyte status and replace as necessary.
    F) HYPOGLYCEMIA
    1) If hypoglycemia occurs, treat with dextrose infusion.
    G) MONITORING OF PATIENT
    1) Monitor liver function tests, even if asymptomatic for several months following an exposure.
    H) EXPERIMENTAL THERAPY
    1) Administration of insulin and glucagon significantly enhanced survival time, prothrombin time, and serum albumin levels in rats given dimethylnitrosamine every 24 hours (Fujiwara et al, 1988). Whether or not similar treatment would be effective for hepatic failure in humans is not known.
    2) Malotilate, given orally, prevented inflammation and decreased vascularization and interstitial collagen deposits in livers of dimethylnitrosamine-treated rats (Stenback et al, 1989).

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

Eye Exposure

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

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) PERSONNEL PROTECTION
    1) Remove contaminated clothing. Take measures to avoid secondary contamination of medical personnel because of the extreme toxicity of this material.
    B) 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).

Enhanced Elimination

    A) HEMODIALYSIS
    1) Hemodialysis may not be useful in dimethylnitrosamine poisoning because of rapid metabolism, but may be recommended in the presence of severe liver damage.

Range Of Toxicity

Summary

    A) A potentially lethal dose (extrapolated from animal data) is 1.8 gm for an average adult or 0.3 gm for a 10 kg child.

Minimum Lethal Exposure

    A) ACUTE
    1) The lowest lethal oral dose in humans has been reported at 10 milligrams per kilogram for an 80 week intermediate exposure (RTECS , 2000).
    2) A potentially lethal dose (extrapolated from animal data) is 1.8 grams for an average 60 kilogram adult or 0.3 grams for a 10 kilogram child (Cooper & Kimbrough, 1980).
    B) ANIMAL DATA
    1) Three dogs were exposed to 16 parts per million. Two expired and one survived with extensive liver damage (ACGIH, 1986).

Workplace Standards

    A) ACGIH TLV Values for CAS62-75-9 (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) N-Nitrosodimethylamine
    a) TLV:
    1) TLV-TWA:
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A3
    2) Codes: L, Skin
    3) Definitions:
    a) A3: Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.
    b) L: Exposure by all routes should be carefully controlled to levels as low as possible.
    c) Skin: This refers to the potential significant contribution to the overall exposure by the cutaneous route, including mucous membranes and the eyes, either by contact with vapors or, of likely greater significance, by direct skin contact with the substance. It should be noted that although some materials are capable of causing irritation, dermatitis, and sensitization in workers, these properties are not considered relevant when assigning a skin notation. Rather, data from acute dermal studies and repeated dose dermal studies in animals or humans, along with the ability of the chemical to be absorbed, are integrated in the decision-making toward assignment of the skin designation. Use of the skin designation provides an alert that air sampling would not be sufficient by itself in quantifying exposure from the substance and that measures to prevent significant cutaneous absorption may be warranted. Please see "Definitions and Notations" (in TLV booklet) for full definition.
    c) TLV Basis - Critical Effect(s): Liver and kidney cancer; liver dam
    d) Molecular Weight: 74.08
    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 CAS62-75-9 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: N-Nitrosodimethylamine
    2) REL:
    a) TWA:
    b) STEL:
    c) Ceiling:
    d) Carcinogen Listing: (Ca) NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).
    e) Skin Designation: Not Listed
    f) Note(s): See Appendix A
    3) IDLH: Not Listed

    C) Carcinogenicity Ratings for CAS62-75-9 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A3 ; Listed as: N-Nitrosodimethylamine
    a) A3 :Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.
    2) EPA (U.S. Environmental Protection Agency, 2011): B2 ; Listed as: N-Nitrosodimethylamine
    a) B2 : Probable human carcinogen - based on sufficient evidence of carcinogenicity in animals.
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 2A ; Listed as: N-Nitrosodimethylamine
    a) 2A : The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans. This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent (mixture) may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals and strong evidence that the carcinogenesis is mediated by a mechanism that also operates in humans. Exceptionally, an agent, mixture or exposure circumstance may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Ca ; Listed as: N-Nitrosodimethylamine
    a) Ca : NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).
    5) MAK (DFG, 2002): Category 2 ; Listed as: N-Nitrosodimethylamine
    a) Category 2 : Substances that are considered to be carcinogenic for man because sufficient data from long-term animal studies or limited evidence from animal studies substantiated by evidence from epidemiological studies indicate that they can make a significant contribution to cancer risk. Limited data from animal studies can be supported by evidence that the substance causes cancer by a mode of action that is relevant to man and by results of in vitro tests and short-term animal studies.
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS62-75-9 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) Published Values ACGIH, 1986 HSDB, 2000 OHM/TADS, 1992 RTECS, 2000:
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 19 mg/kg
    2) LD50- (INTRAPERITONEAL)RAT:
    a) 26.5 mg/kg
    3) LD50- (ORAL)RAT:
    a) 58 mg/kg
    b) 27-41 mg/kg
    4) LD50- (SUBCUTANEOUS)RAT:
    a) 45 mg/kg

Pharmacology Toxicology

Toxicologic Mechanism

    A) DMNA is a potent methylating agent and is known to methylate guanine (Peterson & Hecht, 1991; Cooper & Kimbrough, 1980; Bianchini & Wild, 1994).
    B) Acute exposure to dimethylnitrosamine causes liver necrosis, while chronic exposure induces liver tumors through recurrent alkylation. Necrosis may happen as a result of DNA fragmentation, which was an early event in cultured mouse hepatocytes (Kamendulis & Corcoran, 1995).
    C) Reactive metabolites are responsible for the toxicity of dimethylnitrosamine (Clayton & Clayton, 1994).
    1) Different metabolites may be responsible for the genotoxicity and immunosuppressive activities of dimethylnitrosamine, because liver microsomal enzymes (S9 preparations) can produce the former, and intact hepatocytes produce the latter (Kim et al, 1989).
    2) Subsequent treatment with phenobarbital significantly increased the number of liver tumors induced by dimethylnitrosamine in mice (Klaunig et al, 1988), but not in hamsters (Stenback et al, 1986).
    3) The specific cytochrome P-450IIE1, responsible for activation of dimethylnitrosamine, is induced by ethanol, isopropanol, and acetone (Sohn et al, 1991; Anderson et al, 1992).
    4) No strain-, age-, or sex- differences were seen with levels of microsomal activating enzymes from mouse liver in the Salmonella mutagenicity assay (Ampy & Williams, 1986).
    5) In hamster liver preparations, both the microsomal and soluble cytosolic fractions were necessary to detect mutagenic activity in the Salmonella plate incorporation assay (Prival & Mitchell, 1981). This implies that more than one enzymatic step is necessary for activation of the pro-mutagen.
    D) AUTOIMMUNITY -
    1) Dimethylnitrosamine enhanced expression of the major histocompatibility antigen component Ia on mouse macrophages and lymphocytes, prior to development of micronodular hepatic cirrhosis. This implies that DMNA-induced hepatotoxicity may involve an autoimmune-mediated mechanism (Jezequel et al, 1989).
    2) Susceptibility to dimethylnitrosamine-induced tumors was a function of the H-2 haplotype in mice (Engelse et al, 1981).
    E) CARCINOGENESIS -
    1) A strong correlation was found between lung tumor yield and levels of O-methylguanine (a methyl DNA adduct derived from the nitrosamines) in lung DNA (Peterson & Hecht, 1991).
    2) DMNA exerts its carcinogenic effect after metabolism by cytochrome P-450 to an active metabolite which results in generation of mutagenic electrophiles implicated in carcinogenic effects (Camus et al, 1993).
    3) Dimethylnitrosamine-induced lung tumors in mice had a high frequency of mutationally-activated K-ras genes; in hybrid mice the activated gene was generally from the susceptible parent (Chen et al, 1994).
    4) The P53 gene was not involved in either spontaneous or dimethylnitrosamine-induced renal cell tumors in rats (Horesovsky et al, 1995).

Physicochemical

Physical Characteristics

    A) Dimethylnitrosamine is a yellow, oily liquid with a faint characteristic odor; it has also been described as having no appreciable odor (HSDB , 2000; Budavari, 1996; Clayton & Clayton, 1994) .

Ph

    A) Dimethylnitrosamine is neutral (Clayton & Clayton, 1994).

Molecular Weight

    A) 74.08 (Budavari, 1996)

References

General Bibliography

    1) 40 CFR 372.28: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Lower thresholds for chemicals of special concern. National Archives and Records Administration (NARA) and the Government Printing Office (GPO). Washington, DC. Final rules current as of Apr 3, 2006.
    2) 40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.
    3) 49 CFR 172.101 - App. B: Department of Transportation - Table of Hazardous Materials, Appendix B: List of Marine Pollutants. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 29, 2005.
    4) 49 CFR 172.101: Department of Transportation - Table of Hazardous Materials. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 11, 2005.
    5) 62 FR 58840: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 1997.
    6) 65 FR 14186: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    7) 65 FR 39264: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    8) 65 FR 77866: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    9) 66 FR 21940: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2001.
    10) 67 FR 7164: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2002.
    11) 68 FR 42710: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2003.
    12) 69 FR 54144: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2004.
    13) ACGIH: Documentation of the Threshold Limit Values and Biological Exposure Indices, 5th ed, Am Conference of Govt Ind Hyg, Inc, Cincinnati, OH, 1986.
    14) AIHA: 2006 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook, American Industrial Hygiene Association, Fairfax, VA, 2006.
    15) AMA Department of DrugsAMA Department of Drugs: AMA Evaluations Subscription, American Medical Association, Chicago, IL, 1992.
    16) Alaspaa AO, Kuisma MJ, Hoppu K, et al: Out-of-hospital administration of activated charcoal by emergency medical services. Ann Emerg Med 2005; 45:207-12.
    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) Ampy FR & Williams AO: Dimethylnitrosamine metabolism: I. In vitro activation of dimethylnitrosamine to mutagenic substance(s) by hepatic and renal tissues from three inbred strains of mice. Life Sci 1986; 39:923-930.
    19) Anderson LM, Giner Sorolla A, & Ebeling D: Effects of imipramine, nitrite, and dimethylnitrosamine on reproduction in mice. Res Commun Chem Pathol Pharmacol 1978; 19:311-327.
    20) Anderson LM, Hagiwara A, & Kovatch RM: Transplacental initiation of liver, lung, neurogenic and connective tissue tumors by N-nitroso compounds in mice. Fundam Appl Toxicol 1989; 12:604-620.
    21) Anderson LM, Koseniauskas R, & Burak ES: Reduced blood clearance and increased urinary excretion of N-nitrosodimethylamine in patas monkeys exposed to ethanol or isopropyl alcohol. Cancer Research 1992; 52:1463-1468.
    22) Anderson LM, Priest LJ, & Budinger JM: Lung tumorigenesis in mice after chronic exposure in early life to a low dose of dimethylnitrosamine. J Natl Cancer Inst 1979; 62:1553-1555.
    23) Anon: Evaluation of the Potential Carcinogenicity of N-Nitrosodimethylamine (62-75-9); Govt Reports Announcements & Index (GRA&I), Issue 17. National Technical Information Service (NTIS), 1993.
    24) 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.
    25) Argus MF, Hoch Ligeti C, & Arcos JC: Comparative pulmonary tumorigenesis in DBA/2J and C57Bl/6J mice by administration of 3-methylcholanthrene and dimethylnitrosamine singly and combined. Neoplasma 1982; 29:527-534.
    26) 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.
    27) Asamoto M, Mikheev AM, & Jiang YZ: Immunohistochemical detection of DNA alkylation adducts in rat and hamster liver after treatment with dimethylnitrosamine. Exp Pathol 1991; 41:71-88.
    28) Barbin A, Bereziat JC, & Bartsch H: Evaluation of DNA damage by the alkaline elution technique in liver, kidneys and lungs of rats and hamsters treated with N-nitrosodialkylamines. Carcinogenesis 1983; 4:541-545.
    29) Bata Shoe Company: Industrial Footwear Catalog, Bata Shoe Company, Belcamp, MD, 1995.
    30) Benemanskii VV & Levina VIa: Carcinogenic effect of N-nitrosodimethylamine after application to rat skin. Eksp Onkol 1985; 7:20-21.
    31) Best Manufacturing: ChemRest Chemical Resistance Guide. Best Manufacturing. Menlo, GA. 2002. Available from URL: http://www.chemrest.com. As accessed 10/8/2002.
    32) Best Manufacturing: Degradation and Permeation Data. Best Manufacturing. Menlo, GA. 2004. Available from URL: http://www.chemrest.com/DomesticPrep2/. As accessed 04/09/2004.
    33) Bianchini F & Wild CP: Effect of route of administration of environmental methylating agents on 7-methylguanine formation in white blood cells and internal organs - implications for molecular epidemiology. Cancer Lett 1994; 87:131-137.
    34) Boss Manufacturing Company: Work Gloves, Boss Manufacturing Company, Kewanee, IL, 1998.
    35) Brain KR, Walters KA, & James VJ: Percutaneous penetration of dimethylnitrosamine through human skin in vitro - application from cosmetic vehicles. Food Chem Toxicol 1995; 33:315-322.
    36) Brophy GM, Bell R, Claassen J, et al: Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17(1):3-23.
    37) 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.
    38) Budavari S: The Merck Index, 12th ed, Merck & Co, Inc, Rahway, NJ, 1996.
    39) Burgess JL, Kirk M, Borron SW, et al: Emergency department hazardous materials protocol for contaminated patients. Ann Emerg Med 1999; 34(2):205-212.
    40) Camus AM, Geneste O, & Honkakoski P: High variability of nitrosamine metabolism among individuals: role of cytochromes P450 2A6 and 2E1 in the dealkylation of N-nitrosodimethylamine and N-Nitrosodiethylamine in mice and humans. Molecular Carcinogenesis 1993; 7:268-275.
    41) Caravati EM, Knight HH, & Linscott MS: Esophageal laceration and charcoal mediastinum complicating gastric lavage. J Emerg Med 2001; 20:273-276.
    42) Cardesa A, Pour P, & Althoff J: Vascular tumors in female Swiss mice after intraperitoneal injection of dimethylnitrosamine. J Natl Cancer Inst 1973; 51:201-205.
    43) 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.
    44) Chamberlain JM, Altieri MA, & Futterman C: A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Ped Emerg Care 1997; 13:92-94.
    45) ChemFab Corporation: Chemical Permeation Guide Challenge Protective Clothing Fabrics, ChemFab Corporation, Merrimack, NH, 1993.
    46) Chen B, You L, & Wang Y: Allele-specific activation and expression of the K-ras gene in hybrid mouse lung tumors induced by chemical carcinogens. Carcinogenesis 1994; 15:2031-2035.
    47) Chin RF , Neville BG , Peckham C , et al: Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study. Lancet Neurol 2008; 7(8):696-703.
    48) Choonara IA & Rane A: Therapeutic drug monitoring of anticonvulsants state of the art. Clin Pharmacokinet 1990; 18:318-328.
    49) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    50) Clayton GD & Clayton FE: Patty's Industrial Hygiene and Toxicology, Toxicology, 3rd ed, 2, John Wiley and Sons, New York, NY, 1982.
    51) Clayton GD & Clayton FE: Patty's Industrial Hygiene and Toxicology, Volume 2A, Toxicology, 4th ed, John Wiley & Sons, New York, NY, 1993, pp 663-667.
    52) Clayton GD & Clayton FE: Patty's Industrial Hygiene and Toxicology, Volume 2E, Toxicology, 4th ed, John Wiley & Sons, New York, NY, 1994, pp 3430-3432.
    53) Coccia P, Salmona M, & Diomede L: Liver DNA alkylation after a single carcinogenic dose of dimethylnitrosamine to newborn and adult CFW Swiss mice. Chem Biol Interact 1988; 68:259-271.
    54) 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.
    55) Comasec Safety, Inc.: Product Literature, Comasec Safety, Inc., Enfield, CT, 2003a.
    56) Cooper SW & Kimbrough RD: Acute dimethylnitrosamine poisoning outbreak. J Sci 1980; 25:874-882.
    57) Cupitt LT: Fate of Toxic and Hazardous Materials in the air Environment. USEPA-600/3-80-084, 1980.
    58) 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.
    59) Dagnone D, Matsui D, & Rieder MJ: Assessment of the palatability of vehicles for activated charcoal in pediatric volunteers. Pediatr Emerg Care 2002; 18:19-21.
    60) Des Jardins R, Fournier M, & Denizeau F: Immunosuppression by chronic exposure to N-nitrosodimethylamine (NDMA) in mice. J Toxicol Environ Health 1992; 37:351-361.
    61) Driver HE, White IN, & Butler WH: Dose-response relationships in chemical carcinogenesis: renal mesenchymal tumours induced in the rat by single dose dimethylnitrosamine. Br J Exp Pathol 1987; 68:133-143.
    62) 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.
    63) 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.
    64) DuPont: Permeation Test Results. DuPont. Wilmington, DE. 2002a. Available from URL: http://www.tyvekprotectiveapprl.com/databases/default.htm. As accessed 7/31/2002.
    65) EPA: EPA chemical profile on dimethylnitrosamine, Environmental Protection Agency, Washington, DC, 1985.
    66) 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/.
    67) 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.
    68) Ehrenfeld JR, Ong J, & Farino W: Controlling Volatile Emissions at Hazardous Waste Sites, Noyes Publication, Park Ridge, NJ, 1986, pp 393-401.
    69) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    70) Engelse LD, Oomen LC, & Vander Valk MA: Studies on Lung Tumours. V. Susceptibility of Mice to Dimethylnitrosamine-Induced Tumour Formation in Relation to H-2 Haplotype. Int J Cancer 1981; 28:199-208.
    71) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    72) Fournier P: Biotransformation of dimethylnitrosamine. J Toxicol Clin Exp 1990; 10:283-296.
    73) Freund HA: Clinical manifestation and studies in parenchymatous hepatitis. Ann Intern Med 1937; 10:1144-1155.
    74) Fujiwara K, Ogata I, & Mishiro S: Glucagon and insulin for the treatment of hepatic failure in dimethylnitrosamine-intoxicated rats. Scand J Gastroenterol 1988; 23:567-573.
    75) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    76) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    77) 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.
    78) Guenther Skokan E, Junkins EP, & Corneli HM: Taste test: children rate flavoring agents used with activated charcoal. Arch Pediatr Adolesc Med 2001; 155:683-686.
    79) HSDB : Hazardous Substances Data Bank. National Library of Medicine. Bethesda, MD (Internet Version). Edition expires 1990; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    80) HSDB : Hazardous Substances Data Bank. National Library of Medicine. Bethesda, MD (Internet Version). Edition expires 1992; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    81) 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.
    82) Haas CF: Mechanical ventilation with lung protective strategies: what works?. Crit Care Clin 2011; 27(3):469-486.
    83) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    84) Hathaway GJ, Proctor NH, & Hughes JP: Chemical Hazards of the Workplace, 3rd ed, Van Nostrand Reinhold Company, New York, NY, 1991, pp 439-440.
    85) Hathaway GJ, Proctor NH, & Hughes JP: Chemical Hazards of the Workplace, 4th ed, Van Nostrand Reinhold Company, New York, NY, 1996.
    86) Hegenbarth MA & American Academy of Pediatrics Committee on Drugs: Preparing for pediatric emergencies: drugs to consider. Pediatrics 2008; 121(2):433-443.
    87) Horesovsky G, Recio L, & Everitt J: P53 status in spontaneous and dimethylnitrosamine-induced renal cell tumors from rats. Mol Carcinog 1995; 12:236-240.
    88) Hvidberg EF & Dam M: Clinical pharmacokinetics of anticonvulsants. Clin Pharmacokinet 1976; 1:161.
    89) 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.
    90) 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.
    91) 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.
    92) 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.
    93) 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.
    94) 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.
    95) IARC: Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man: Some N-Nitroso Compounds, 17, International Agency for Research on Cancer, World Health Organization, Geneva, Switzerland, 1978, pp 125-175.
    96) ICAO: Technical Instructions for the Safe Transport of Dangerous Goods by Air, 2003-2004. International Civil Aviation Organization, Montreal, Quebec, Canada, 2002.
    97) ILC Dover, Inc.: Ready 1 The Chemturion Limited Use Chemical Protective Suit, ILC Dover, Inc., Frederica, DE, 1998.
    98) ITI: Toxic and Hazardous Industrial Chemicals Safety Manual, The International Technical Information Institute, Tokyo, Japan, 1975.
    99) 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.
    100) 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.
    101) Jezequel AM, Mancini R, & Rinaldesi ML: Dimethylnitrosamine-induced cirrhosis: Evidence for an immunological mechanism. J Hepatol 1989; 8:42-52.
    102) Kamendulis LM & Corcoran GB: Dimethylnitrosamine-induced DNA damage and toxic cell death in cultured mouse hepatocytes. J Toxicol Environ Health 1995; 46:31-46.
    103) 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.
    104) Kim BS, Yang KH, & Haggerty HG: Production of DNA single-strand breaks in unstimulated splenocytes by dimethylnitrosamine. Mutat Res 1989; 213:185-193.
    105) Kim RB, Oshea D, & Wilkinson GR: Interindividual variability of chlorzoxazone 6-hydroxylation in men and women and its relationship to CYP2E1 genetic polymorphisms. Clin Pharmacol Ther 1995; 57:645-655.
    106) 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.
    107) Klaunig JE, Weghorst CM, & Pereira MA: Effect of phenobarbital on diethylnitrosamine and dimethylnitrosamine induced hepatocellular tumors in male B6C3F1 mice. Cancer Lett 1988; 42:133-139.
    108) Klein RG, Janowsky I, & Pool Zobel BL: Effects of long-term inhalation of N-nitrosodimethylamine in rats. IARC Sci Publ 1991; 105:322-328.
    109) Kollef MH & Schuster DP: The acute respiratory distress syndrome. N Engl J Med 1995; 332:27-37.
    110) Kraft PL, Skipper PL, & Charnley G: Urinary excretion of dimethylnitrosamine: a quantitative relationship between dose and urinary excretion. Carcinogenesis 1981; 2:609-612.
    111) LaCrosse-Rainfair: Safety Products, LaCrosse-Rainfair, Racine, WI, 1997.
    112) Lewis RJ: Hawley's Condensed Chemical Dictionary, 12th ed, Van Nostrand Reinhold Company, New York, NY, 1993, pp 831.
    113) Lijinsky W & Reuber MD: Comparative carcinogenesis by some aliphatic nitrosamines in Fischer rats. Cancer Lett 1981; 14:297-302.
    114) Loddenkemper T & Goodkin HP: Treatment of Pediatric Status Epilepticus. Curr Treat Options Neurol 2011; Epub:Epub.
    115) 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.
    116) 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.
    117) Malik MAB & Tesfai K: Bull Environ Contam Toxicol 1981; 27:115-21.
    118) Manno EM: New management strategies in the treatment of status epilepticus. Mayo Clin Proc 2003; 78(4):508-518.
    119) Mar-Mac Manufacturing, Inc: Product Literature, Protective Apparel, Mar-Mac Manufacturing, Inc., McBee, SC, 1995.
    120) 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.
    121) 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.
    122) Mohr U, Haas H, & Hilfrich J: The carcinogenic effects of dimethylnitrosamine and nitrosomethylurea in European hamsters (Cricetus cricetus L). Br J Cancer 1974; 29:359-364.
    123) Montgomery Safety Products: Montgomery Safety Products Chemical Resistant Glove Guide, Montgomery Safety Products, Canton, OH, 1995.
    124) NFPA: Fire Protection Guide to Hazardous Materials, 13th ed., National Fire Protection Association, Quincy, MA, 2002.
    125) 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.
    126) 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.
    127) 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.
    128) 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.
    129) 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.
    130) Naradzay J & Barish RA: Approach to ophthalmologic emergencies. Med Clin North Am 2006; 90(2):305-328.
    131) 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.
    132) 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.
    133) 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.
    134) 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.
    135) 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.
    136) 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.
    137) 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.
    138) 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.
    139) 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.
    140) 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.
    141) 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.
    142) 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.
    143) 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.
    144) 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.
    145) 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.
    146) 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.
    147) 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.
    148) 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.
    149) 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.
    150) 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.
    151) 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.
    152) 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.
    153) 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.
    154) 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.
    155) 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.
    156) 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.
    157) 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.
    158) 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.
    159) 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.
    160) 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.
    161) 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.
    162) 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.
    163) 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.
    164) 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.
    165) 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.
    166) 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.
    167) 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.
    168) 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.
    169) 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.
    170) 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.
    171) 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.
    172) 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.
    173) 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.
    174) 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.
    175) 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.
    176) 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.
    177) 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.
    178) 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.
    179) 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.
    180) 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.
    181) 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.
    182) 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.
    183) 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.
    184) 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.
    185) 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.
    186) 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.
    187) 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.
    188) 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.
    189) 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.
    190) 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.
    191) 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.
    192) 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.
    193) 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.
    194) 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.
    195) 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.
    196) 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.
    197) 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.
    198) 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.
    199) 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.
    200) 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.
    201) 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.
    202) 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.
    203) 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.
    204) 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.
    205) 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.
    206) 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.
    207) 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.
    208) National Research Council : Acute exposure guideline levels for selected airborne chemicals, 5, National Academies Press, Washington, DC, 2007.
    209) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 6, National Academies Press, Washington, DC, 2008.
    210) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 7, National Academies Press, Washington, DC, 2009.
    211) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 8, National Academies Press, Washington, DC, 2010.
    212) 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.
    213) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    214) 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.
    215) North: eZ Guide Interactive Software. North Safety. Cranston, RI. 2002a. Available from URL: http://www.northsafety.com/feature1.htm. As accessed 8/31/2002.
    216) OHM/TADS : Oil and Hazardous Materials/Technical Assistance Data System. US Environmental Protection Agency. Washington, DC (Internet Version). Edition expires 1992; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    217) OSHA: Occupational Safety and Health Administration. Subpart Z -- Toxic and Hazardous Substances - N-Nitrosodimethylamine. 29 CFR 1910, Department of Labor, Occupational Safety and Health Administration, Washington, DC, 1990, pp 1016.
    218) Oliver JE: J Environ Qual 1979; 8:596-601.
    219) Peate WF: Work-related eye injuries and illnesses. Am Fam Physician 2007; 75(7):1017-1022.
    220) Peterson LA & Hecht SS: O-Methylguanine is a critical determinant of 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone tumorigenesis in A/J mouse lung. Cancer Research 1991; 51:5557-5564.
    221) Peto R, Gray R, & Brantom P: Effects on 4080 rats of chronic ingestion of N-nitrosodiethylamine or N-nitrosodimethylamine: a detailed dose-response study. Cancer Res 1991; 51:6415-6451.
    222) Playtex: Fits Tough Jobs Like a Glove, Playtex, Westport, CT, 1995.
    223) Pobel D, Riboli E, & Cornee J: Nitrosamine, nitrate and nitrite in relation to gastric cancer - a case-control study in Marseille, France. Eur J Epidemiol 1995; 11:67-73.
    224) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    225) Polo J & Chow YL: J Natl Cancer Inst 1976; 56:997-1001.
    226) Prival MJ & Mitchell VD: Influence of microsomal and cytosolic fractions from rat, mouse, and hamster liver on the mutagenicity of dimethylnitrosamine in the Salmonella plate incorporation assay. Cancer Res 1981; 41:4361-4367.
    227) Product Information: diazepam IM, IV injection, diazepam IM, IV injection. Hospira, Inc (per Manufacturer), Lake Forest, IL, 2008.
    228) Product Information: lorazepam IM, IV injection, lorazepam IM, IV injection. Akorn, Inc, Lake Forest, IL, 2008.
    229) 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.
    230) 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.
    231) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    232) Reznik G: The carcinogenic effect of dimethylnitrosamine on the Chinese hamster (Cricetulus griseus). Cancer Lett 1975; 1:25-28.
    233) River City: Protective Wear Product Literature, River City, Memphis, TN, 1995.
    234) Rogers MAM, Vaughan TL, & Davis S: Consumption of nitrate, nitrite, and nitrosodimethylamine and the risk of upper aerodigestive tract cancer. Cancer Epidemiol Biomarkers Prev 1995; 4:29-36.
    235) 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.
    236) Sax NI & Lewis RJ: Dangerous Properties of Industrial Materials, 7th ed, Van Nostrand Reinhold Company, New York, NY, 1989, pp 1413-1414.
    237) Schardein JL: Chemically Induced Birth Defects, 2nd ed, Marcel Dekker, Inc, New York, NY, 1993, pp 755.
    238) Scott R, Besag FMC, & Neville BGR: Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomized trial. Lancet 1999; 353:623-626.
    239) Servus: Norcross Safety Products, Servus Rubber, Servus, Rock Island, IL, 1995.
    240) Shahidi F, Synowiecki J, & Sen N: Color characteristics and absence of N-nitrosamines in nitrite-cured seal meat. J Agr Food Chem 1992; 40:1398-1402.
    241) Simenhoff ML, Dunn SR, & Fiddler W: Generation of dimethylnitrosamine in water purification systems. JAMA 1983; 250:2020-2024.
    242) Sittig M: Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2nd ed, Noyes Publications, Park Ridge, NJ, 1985, pp 668-669.
    243) Sohn OS, Ishizaki H, & Yang CS: Metabolism of azoxymethane, methylazoxymethanol and N-nitrosodimethylamine by cytochrome P450IIE1. Carcinogenesis 1991; 12:127-131.
    244) Spiller HA & Rogers GC: Evaluation of administration of activated charcoal in the home. Pediatrics 2002; 108:E100.
    245) Sreenath TG, Gupta P, Sharma KK, et al: Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children: A randomized controlled trial. Eur J Paediatr Neurol 2009; Epub:Epub.
    246) Standard Safety Equipment: Product Literature, Standard Safety Equipment, McHenry, IL, 1995.
    247) Stenback F, Ala Kokko L, & Ryhanen L: Morphological, immunohistochemical and ultrastructural changes in dimethylnitrosamine [correction of dimenthylnitrosamine] induced liver injury. Effect of malotilate. Histol Histopathol 1989; 4:95-104.
    248) Stenback F, Mori H, & Furuya K: Pathogenesis of dimethylnitrosamine-induced hepatocellular cancer in hamster liver and lack of enhancement by phenobarbital. J Natl Cancer Inst 1986; 76:327-333.
    249) 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.
    250) Tate RL & Alexander M: J Natl Cancer Inst 1975; 54:327-330.
    251) Tates AD, Neuteboom I, & de Vogel N: The induction of chromosomal damage in rat hepatocytes and lymphocytes. I. Time-dependent changes of the clastogenic effects of diethylnitrosamine, dimethylnitrosamine and ethyl methanesulfonate. Mutat Res 1983; 107:131-151.
    252) Terracini B, Palestro G, & Gigliardi RM: Carcinogenicity of dimethylnitrosamine in Swiss mice. Br J Cancer 1966; 20:871-876.
    253) Thakore S & Murphy N: The potential role of prehospital administration of activated charcoal. Emerg Med J 2002; 19:63-65.
    254) 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.
    255) Tomatis L, Magee PN, & Shubik P: Induction of liver tumors in the Syurian golden hamster by feeding dimethylnitrosamine. J Natl Cancer Inst 1964; 33:341-345.
    256) 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.
    257) Trelleborg-Viking, Inc.: Trellchem Chemical Protective Suits, Interactive manual & Chemical Database. Trelleborg-Viking, Inc.. Portsmouth, NH. 2001.
    258) 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.
    259) 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.
    260) 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-.
    261) 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.
    262) 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.
    263) 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.
    264) 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.
    265) 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-.
    266) U.S. Occupational Safety, and Health Administration (OSHA): Process safety management of highly hazardous chemicals. 29 CFR 2010 2010; 29(1910.119):348-.
    267) 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.
    268) Vale JA, Kulig K, American Academy of Clinical Toxicology, et al: Position paper: Gastric lavage. J Toxicol Clin Toxicol 2004; 42:933-943.
    269) Vale JA: Position Statement: gastric lavage. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 1997; 35:711-719.
    270) Watanabe J, Yang JP, & Eguchi H: An RSA I polymorphism in the CYP2E1 gene does not affect lung cancer risk in a Japanese population. Jpn J Cancer Res 1995; 86:245-248.
    271) 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.
    272) Willson DF, Truwit JD, Conaway MR, et al: The Adult Calfactant in Acute Respiratory Distress Syndrome (CARDS) Trial. Chest 2015; Epub:Epub.
    273) 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.
    274) Workrite: Chemical Splash Protection Garments, Technical Data and Application Guide, W.L. Gore Material Chemical Resistance Guide, Workrite, Oxnard, CA, 1997.
    275) Yoo LJ, Barbour JF, & Libbey LM: Precursors of N-nitrosodimethylamine in malted barley 2. Determination of dimethylamine. J Agr Food Chem 1992; 40:2222-2225.
    276) Zhang PC: The determination of DNA adducts in liver and lung of mice exposed to dimethylnitrosamine (Chinese). Chung Hua Yu Fang I Hsueh Tsa Chih 1990; 24:136-138.