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TOLUENE DIISOCYANATE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Toluene diisocyanate (TDI) is usually available in two isomers: 2,4-toluene diisocyanate and 2,6-toluene diisocyanate. Over 95% of the commercially available products used for industry contain 80% 2,4-TDI and 20% 2,6-TDI. The potential routes of human exposure are inhalation and dermal contact and is usually confined to workplace exposures.

Specific Substances

    A) SYNONYMS
    1) 2,4-TOLYENE DIISOCYANATE
    2) 4-METHYL-M-PHENYLENE ISOCYANATE
    3) 4-METHYL-META-PHENYLENE DIISOCYANATE
    4) AI3-15101
    5) BENZENE-, 1,3-DIISOCYANATOMETHYL-
    6) CRESORCINOL DIISOCYANATE
    7) DESMODUR T100
    8) DESMODUR-T
    9) DI-ISO-CYANATOLUENE
    10) DIFENYLMETHAAN-DISIOCYANAAT (DUTCH)
    11) DIIOSOCYANATOHEXANE
    12) DIISOCYANATOMETHYLBENZENE (1,3-)
    13) DIISOCYANATOMETHYLBENZENE
    14) DIISOCYANATOTOLUENE (1,3-)
    15) DIISOCYANATOTOLUENE
    16) DIPHENYL METHANE DIISOCYANATE
    17) DIPHENYLMETHYL DIISOCYANATE
    18) HYLENE T ORGANIC ISOCYANATE
    19) HYLENE TCPA
    20) HYLENE TLC
    21) HYLENE TM
    22) HYLENE TRF
    23) HYLENE-T
    24) ISOCYANIC ACID, METHYL-m-PHENYLENE ESTER
    25) ISOCYANIC ACID, METHYLPHENYLENE ESTER (1,3-)
    26) ISOCYANIC ACID, METHYLPHENYLENE ESTER
    27) METHYL-meta-PHENYLENE DIISOCYANATE
    28) METHYL-META-PHENYLENE ISOCYANATE
    29) METHYLENE-BISPHENYLENE DI-ISOCYANATE (M.D.I.)
    30) METHYLPHENYLENE ISOCYANATE (1,3-)
    31) METHYLPHENYLENE ISOCYANATE
    32) MIC (CAS 556-61-6)
    33) MONDUR TDS
    34) MONDUR-TD-80
    35) MONDUR-TD
    36) NACCONATE IOO
    37) NACCONATE-100
    38) NIAX TDI-P
    39) NIAX TDI
    40) NIAXISOCYANATE TDI
    41) RUBINATE TDI 80/20
    42) RUBINATE TDI
    43) T 100
    44) TDI 80-20
    45) TDI-80
    46) TDI-80
    47) TDI
    48) TOLUENE DIISOCYANATE (1,3-)
    49) TOLUENE DIISOCYANATE (65:35)
    50) TOLUENE DIISOCYANATE (80:20)
    51) TOLUENE DIISOCYANATE (CAS 26471-62-5)
    52) TOLUENE DIISOCYANATE
    53) TOLUENE DIISOCYANATE
    54) TOLUYLENE DIISOCYANATE
    55) TOLYLENE DIISOCYANATE (1,3-)
    56) TOLYLENE DIISOCYANATE
    57) TOLYLENE ISOCYANATE (1,3-)
    58) TOLYLENE ISOCYANATE
    59) CAS 584-84-9
    INCLUDED SUBSTANCES -- 2,4-TOLUENE DIISOCYANATE
    1) TDI
    2) Toluene-2,4-Diisocyanate
    3) 2,4-Tolylene Diisocyanate
    4) Meta-tolylene Diisocyanate
    5) 2,3-Diisocyanatotoluene
    6) Tolylene Diisocyanate
    RELATED COMPOUNDS -- METHYLENE DIPHENYL DIISOCYANATE
    1) MDI
    2) CAS 101-68-8
    RELATED COMPOUNDS -- HEXAMETHYLENE DIISOCYANATE
    1) HDI
    2) CAS 822-06-0
    RELATED COMPOUNDS -- ISOPHORONE DIISOCYANATE
    1) IPDI
    RELATED COMPOUNDS -- HYDROGENATED MDI
    1) Dicyclohexylmethane 4,4'-diisocyanate

    1.2.1) MOLECULAR FORMULA
    1) C9-H6-N2-O2

Available Forms Sources

    A) FORMS
    1) Toluene diisocyanate (TDI) is usually available in two isomers: 2,4-toluene diisocyanate and 2,6-toluene diisocyanate. Over 95% of the commercially available products used for industry contain 80% 2,4-TDI and 20% 2,6-TDI (National Toxicology Program, 2011; ACGIH, 1986).
    2) Hexamethylene diisocyanates (HDI) are available in many products as nonvolatile prepolymers and trace amounts of the monomer (Vandenplas et al, 1993).
    B) USES
    1) TDI is one of the isocyanates most employed in the manufacture of polyurethane foams, elastomers, and coating (National Toxicology Program, 2011; ACGIH, 1986).
    2) Foams are used in furniture, packaging, insulation, and boat building. Flexible foams are made up of TDI whereas the rigid foams have the less volatile MDI (Finkel, 1983).
    3) Polyurethane coatings are used in leather, wire, tank linings, masonry, paints, floor and wood finishes. HDI-containing paints may have 30 to 60% nonvolatile HDI prepolymers and traces of the HDI monomer (Vandenplas et al, 1993).
    4) Elastomers, which are abrasion- and solvent-resistant, are used in adhesives, coated fabrics, films, linings, clay pipe seals, and in abrasive wheels, and other mechanical items. MDI has been used as a wood bonding material (Herbert et al, 1995).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Toluene diisocyanate (TDI) is one of the isocyanates most employed in the manufacture of polyurethane foams, elastomers, and coatings.
    B) TOXICOLOGY: TDI is an irritant to mucous membranes of the eyes, the gastrointestinal and the respiratory tract. It also causes a marked inflammatory reaction on direct skin contact. In some individuals, low level repeated exposure to TDI can cause respiratory sensitization and asthma.
    C) EPIDEMIOLOGY: Most exposures are occupational either via inhalation or dermal contact.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: TDI is an irritant to the skin, lungs, conjunctiva and gastrointestinal tract.
    2) SEVERE TOXICITY: Laryngitis, chest pain, bronchospasm, sensation of oppression or constriction of the chest, bronchitis, emphysema, pneumonitis and cor pulmonale may result from exposure. Continued exposure to TDI in an asthmatic patient resulted in a fatality. Severe conjunctival irritation and lacrimation may result from exposure to liquid or high vapor concentrations. Glaucoma and iridocyclitis have been reported with a splash exposure.
    0.2.21) CARCINOGENICITY
    A) Toluene diisocyanate is considered a suspected or possible human carcinogen, based on sufficient evidence of carcinogenicity or tumors (tumors of the spleen, subcutaneous, hepatic, ovarian, peritoneum, and mammary gland tissues) in experimental animals.

Laboratory Monitoring

    A) Monitor vital signs and mental status, monitor pulmonary exam.
    B) Monitor pulse oximetry and/or arterial blood gases, chest radiograph and pulmonary function tests in patients with respiratory signs/symptoms.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment consists of predominantly symptomatic and supportive care. Monitor patient for respiratory distress. If a cough or breathing difficulty develops, evaluate for respiratory tract irritation, bronchitis and pneumonitis. If bronchospasm develops, administer inhaled (beta 2 adrenergic agonists) and oxygen as needed. Consider systemic corticosteroids in patients with significant bronchospasm. Sensitized individuals should be monitored for severe allergic reaction. These people are at risk for severe asthma and anaphylaxis and should be cautioned to avoid further exposure.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) In patients who develop severe toxicity, treatment should be primarily focused on airway management. Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta 2 adrenergic agonists and systemic steroids.
    C) DECONTAMINATION
    1) PREHOSPITAL: GI decontamination is not indicated, toxicity is from irritant effects and sensitization, not systemic absorption. Irrigate exposed eyes with water. Remove contaminated clothing and wash exposed skin with soap and water. Administer oxygen to patients with respiratory irritation after inhalation.
    2) HOSPITAL: GI decontamination is not indicated, toxicity is from irritant effects and sensitization, not systemic absorption. Irrigate exposed eyes copiously with 0.9% saline. Remove contaminated clothing and wash exposed skin with soap and water. Administer oxygen to patients with respiratory irritation after inhalation.
    D) AIRWAY MANAGEMENT
    1) Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta 2 adrenergic agonists and systemic steroids if bronchospasm develops.
    E) ANTIDOTE
    1) There is no specific antidote for treatment of TDI exposure.
    F) PATIENT DISPOSITION
    1) HOME CRITERIA: Patients who are asymptomatic or have minimal irritation after small exposures can be managed at home or the work place.
    2) OBSERVATION CRITERIA: Symptomatic patients, patients with known or suspected sensitization, or patients with known large exposures should be referred to a healthcare facility for evaluation and treatment, and observed for 6 hours for signs of toxicity.
    3) ADMISSION CRITERIA: Patients with significant symptoms should be admitted for treatment and monitoring. Patients with respiratory failure should be admitted to an ICU setting.
    4) CONSULT CRITERIA: Contact a medical toxicologist or poison center for any patient with severe toxicity. Consult an ophthalmologist for patients with severe eye irritation or splash exposure. Patients with an occupational exposure should be referred to an occupational physician and industrial hygienist.
    G) PITFALLS
    1) Failure to recognize and aggressively treat severe bronchospasm. Patients with inhalation exposure are at risk for sensitization and severe bronchospasm with subsequent exposure. Careful workplace evaluation is required in the event of occupational exposure.
    H) DIFFERENTIAL DIAGNOSIS
    1) Acute asthma attack, COPD with acute exacerbation, chlorine gas exposure, ammonia gas exposure, other irritant exposure.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) Randomized, double-blind cross-over studies showed minimal efficacy of bronchodilator therapy. This may be due to the absence of airway hyperresponsiveness in some TDI-induced asthma.
    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) TOXICITY: Available dose-response information concerning humans pertains to inhalational exposure. Concentrations of 2.5 ppm are considered Immediately Dangerous to Life or Health (IDLH). Continued exposure to TDI in an asthmatic patient resulted in a fatality.
    B) EXPOSURE LIMITS: Recommended short-term exposure limits for TDI in industry is 0.02 ppm. TDI does not have sufficient warning properties (eg, odor or eye irritancy) at air concentrations below the recommended short term exposure limit.

Clinical Effects

Summary Of Exposure

    A) USES: Toluene diisocyanate (TDI) is one of the isocyanates most employed in the manufacture of polyurethane foams, elastomers, and coatings.
    B) TOXICOLOGY: TDI is an irritant to mucous membranes of the eyes, the gastrointestinal and the respiratory tract. It also causes a marked inflammatory reaction on direct skin contact. In some individuals, low level repeated exposure to TDI can cause respiratory sensitization and asthma.
    C) EPIDEMIOLOGY: Most exposures are occupational either via inhalation or dermal contact.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: TDI is an irritant to the skin, lungs, conjunctiva and gastrointestinal tract.
    2) SEVERE TOXICITY: Laryngitis, chest pain, bronchospasm, sensation of oppression or constriction of the chest, bronchitis, emphysema, pneumonitis and cor pulmonale may result from exposure. Continued exposure to TDI in an asthmatic patient resulted in a fatality. Severe conjunctival irritation and lacrimation may result from exposure to liquid or high vapor concentrations. Glaucoma and iridocyclitis have been reported with a splash exposure.

Vital Signs

    3.3.3) TEMPERATURE
    A) Fever occurred following an intravenous injection of 0.02 mg TDI/kg (Scheel et al, 1964).
    1) Fever has also been reported in patients with isocyanate-induced alveolitis (Baur, 1991).

Heent

    3.4.3) EYES
    A) CONJUNCTIVITIS: Severe conjunctival irritation and lacrimation may occur following exposure to liquid or high vapor concentrations (Siribaddana et al, 1998; Axford et al, 1976). Burning or pricking sensations from exposure to lower concentrations have been reported (Grant & Schuman, 1993). The reported threshold for eye irritation is 0.05 to 0.1 ppm (US DHHS, 1988).
    B) IRIDOCYCLITIS AND SECONDARY GLAUCOMA: Iridocyclitis and secondary glaucoma occurred in a workman who unintentionally splashed TDI in one eye (Grant & Schuman, 1993).
    C) IRRITATION/ANIMALS: A drop of meta- and para-toluene diisocyanate on rabbit eyes caused immediate pain, lacrimation, swelling of the lids, and conjunctival irritation (Grant & Schuman, 1993).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) COR PULMONALE
    1) WITH POISONING/EXPOSURE
    a) Cor pulmonale has occurred as a result of exposure to large amounts of TDIs (Axford et al, 1976).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) TOXIC EFFECT OF GAS, FUMES AND/OR VAPORS
    1) WITH POISONING/EXPOSURE
    a) General presentations of exposed patients may include burning or irritation of the nose and throat, a choking sensation (which may be accompanied by blood-streaked sputum), laryngitis, retrosternal soreness, and chest pain (Siribaddana et al, 1998; Elkins et al, 1962; NIOSH, 1973).
    b) Depending upon duration of exposure and level of concentration above 0.5 ppm, respiratory symptoms develop with a latent period of 4 to 8 hours (Rye, 1973).
    c) The symptomatology of inhalational exposure to TDI is stereotypical (ILO, 1983).
    1) At the end of a few days to two months of exposure, lacrimation and irritation of the conjunctivae and pharynx occur. A dry nocturnal cough, substernal pains, and dyspnea may result later.
    2) Symptoms worsen in the evening and are less prominent in the morning with minimal mucus expectoration.
    3) Symptoms diminish after several days away from the site of exposure but recur upon return to work.
    d) The characteristic substernal pain may be due to the paroxysmal or persistent cough often associated with inhalation.
    e) CASE REPORT: Hallucinations, delusions and impaired consciousness were noted at admission in a 27-year-old man following inhalational exposure to dimethylacetamide, ethylenediamine, and diphenylmethane diisocyanate in a confined space for a continuous 4 to 6 hours per day for 3 days. Pulmonary edema with hypoxemia (pH 7.37, PaCO2 34.4 mm Hg, PaO2 36.1 mmHg, HCO3 19.5 mEq/L) developed as well as hyperemic edema of the tracheobronchial tree. He made a full recovery (Su et al, 2000).
    B) DISORDER OF RESPIRATORY SYSTEM
    1) WITH POISONING/EXPOSURE
    a) NON-SPECIFIC AIRWAY HYPERRESPONSIVENESS: TDI exposure can cause airway hyperresponsiveness which may persist despite cessation of exposure (Saetta et al, 1992).
    b) Non-specific airway hyperresponsiveness, such as measured through methacholine or cold air challenge, can occur in persons with or without TDI-induced asthma. Nonspecific hyperresponsiveness may persist in persons who have recovered (eg, no response to TDI challenge) from TDI-induced asthma (Paggiaro et al, 1993).
    c) Two reports found that persons with TDI-induced asthma were more likely to react to a methacholine challenge test (Moscato et al, 1991; Jones et al, 1992). A negative response to a methacholine challenge was also measured in some patients with TDI-induced asthma (Moscato et al, 1991).
    C) ALLERGIC PNEUMONIA
    1) WITH POISONING/EXPOSURE
    a) Hypersensitivity pneumonitis to TDI and other isocyanates is less common than asthma.
    b) CASE REPORT: Hypersensitivity pneumonitis was confirmed by biopsy of a 41-year-old automobile paint sprayer who presented with dyspnea, cyanosis, fever, crepitant rales, reticulonodular radiographic infiltrates, restrictive pulmonary function, and elevated TDI-specific IgG (Yoshizawa et al, 1989). He improved markedly with prednisolone and oxygen.
    c) CASE REPORT: A 53-year-old steel plant maintenance worker who occasionally glued pipes together presented with cough, fever, malaise, interstitial pneumonitis, eosinophilia, decreased FEF 25%-75%, and elevated IgG antibody levels specific for diphenylmethane diisocyanate (MDI) (Walker et al, 1989).
    d) CASE REPORT: A 34-year-old spray painter presented with hemoptysis, dyspnea, bilateral pulmonary opacities, respiratory failure, and high levels of IgG and IgE antibodies against HDI-HSA (hexamethylene diisocyanate human serum albumin) and TDI-HSA (Patterson et al, 1990). He fully recovered after 2 days of assisted ventilation and 11 days of steroids.
    e) CASE SERIES: Alveolitis has been reported following isocyanate exposure, but is uncommon. Findings in 12 isocyanate-exposed workers included shortness of breath, fever, isocyanate-specific IgG antibodies, decreased vital capacity, abnormal chest x-ray, and BAL and transbronchial biopsy evidence of lymphocytic alveolitis (Baur, 1991).
    D) CHEMICAL-INDUCED ASTHMA
    1) WITH POISONING/EXPOSURE
    a) An asthmatic-like syndrome (chemical bronchitis with severe bronchospasm, sensation of oppression or constriction of chest) can occur after exposure (Axford et al, 1976).
    b) Respiratory sensitization and asthma are key effects of TDI exposure.
    1) Overall, due to improved work place monitoring and occupational controls, the incidence of diisocyanate asthma has decreased due to a decline in airborne TDI. Occasional reports of TDI induced asthma appears to be associated with TDI concentrations that exceed 80 ppb for short periods. Likewise, high short-term exposures may also lead to respiratory sensitization (Arnold et al, 2012).
    2) CASE SERIES: A study was conducted in a new polyurethane foam production factory in Europe to assess toluene diisocyanate (TDI) exposure in newly hired workers (n=49) using questionnaires, spirometry and TDI-specific serology during their first year of employment. During the study period, fixed point air sampling in the foaming hall and cutting areas showed that airborne TDI concentrations were low (ie, below the limit of detection of 0.1 ppb) in over 87% of the recordings in the cutting areas and over 95% of the readings from the foaming hall, respectively. Although there were no reports of air sampling exceeding the threshold limit value (TLV) for a 8 hour work day, there were intermittent, recurrent episodes of higher exposure levels (maximum, 10 ppb) during peak periods of foam production. Overall, the prevalence of asthma symptoms and/or immunologic sensitization to TDI was low in workers that completed their first year of employment. Over the study period, 12 (24.5%) of the original 49 workers were lost to follow-up with no other workers enrolled and 7 (14.2%) workers developed new asthma symptoms (n=3), TDI-specific IgG (n=1), new airflow obstruction (n=1) and/or a decline in FEV1 greater than or equal to 15% (n=3). Of note the workers lost to follow-up had a higher prevalence of current asthma symptoms compared to those workers who completed the 12 month follow-up (25% vs 2.7%; p=0.04). The findings suggest further longitudinal evaluation of workers and the need for better evaluation of potential TDI-health risks (Gui et al, 2014).
    3) ONSET: The onset of symptoms experienced by the TDI sensitized individual may be insidious, becoming progressively more pronounced with continued exposure over days to months. The initial symptoms of dyspnea and cough can progress to severe asthma and bronchitis (ACGIH, 1986; Bruckner et al, 1968; Porter et al, 1975; Weill H, Butcher B & Dharmarajan V et al, 1981; Williamson, 1965).
    4) Based on the onset of symptoms, asthmatic reactions to isocyanate challenge have been classified as immediate (eg, within 30 min), late (eg, after 1 or more hours) or dual (both), having immediate and late symptom onset (Fabbri, 1990; Saetta et al, 1992; Moscato et al, 1991). Workers exposed to low TDI levels may also experience minimal or no respiratory symptoms only to suddenly experience an acute and severe asthmatic reaction (Banks et al, 1986).
    5) Late and dual asthmatic reactions to TDI have been associated with early elevations of neutrophils, eosinophils, leukotriene B4, CD8 positive lymphocytes, and albumin in bronchoalveolar lavage fluid (Fabbri et al, 1985; Fabbri et al, 1987; Fabbri, 1990) (Zocca et al, 1990) (Finotto et al, 1991). Neutrophil counts appear to be significantly higher in the bronchial mucosa in the TDI- induced asthma patients as compared with allergy-induced asthma patients (Park et al, 2002). The bronchial mucosa contains inflammatory cell infiltrates and increased subepithelial collagen deposition (Saetta et al, 1992).
    6) PROGNOSIS: A better prognosis (less severe symptoms, decreased requirements for medication, improved PFTs, or complete recovery) may relate to:
    a) Exposure at a younger age
    b) Shorter duration of exposure (eg, 10 years or less)
    c) Shorter duration of disease prior to diagnosis and treatment
    d) Shorter duration of exposure post diagnosis (eg, not longer than 3 years of exposure post diagnosis)
    e) Immediate or dual pattern of asthmatic response to TDI
    f) Early, complete removal from exposure after the onset of asthma
    7) A POORER PROGNOSIS (symptoms severe; no improvement) may relate to:
    a) Late pattern of asthmatic response
    b) Delayed diagnosis and treatment
    c) Continued exposure after diagnosis
    8) REFERENCES: (Fabbri & Mapp, 1991; Moscato et al, 1991; Paggiaro et al, 1993; Pisati et al, 1993).
    9) A small study did not find any prognostic value in age, symptom duration or time since last exposure (Vandenplas et al, 1993). In three studies, the presence of atopy did not appear to be significantly related to the presence of TDI or MDI induced asthma (Moscato et al, 1991; Vandenplas et al, 1993).
    10) Increased diurnal variation in peak expiratory flow rate has been demonstrated in exposed workers who did not have TDI induced asthma (Lee & Phoon, 1992). Environmental monitoring demonstrated that these men were exposed above the STEL of 0.02 ppm.
    11) MARKERS
    a) Markers of TDI induced asthma include: antigen specific histamine releasing factor produced by peripheral blood mononuclear cells, elevated serum eosinophil cationic protein, specific IgG-albumin conjugates (but not specific IgE-albumin conjugates), and mast cells and cytokines in the airway mucosa (Maestrelli et al, 1995) (Stefano et al, 1993) (Park et al, 1999; Mapp et al, 1994; Herd & Bernstein, 1994).
    12) CASE SERIES
    a) In a long-term follow-up study of workers with TDI-induced occupational asthma, 46 individuals with a confirmed diagnosis (ie, a positive response to the specific inhalation challenge in the laboratory with TDI vapors) participated in the follow-up study (average duration 11 +/- 3.6 years), most workers had a general improvement in asthma after being removed from exposure. However, greater than 80% of workers continued to report asthma symptoms. Most individuals worked in a furniture or carpentry plant. The total duration of occupational exposure at the time of diagnosis was 22.3 +/- 13.3 years. During follow-up, a total of 32 patients had been completely removed from exposure for 6 +/- 6.9 years and were found to have less episodes of shortness of breath and dyspnea compared to patients (n=14) that continued to be exposed. Likewise, PD20FEV1 methacholine was significantly improved in workers with a lower FEV1 (a determinant of asthma outcome) at diagnosis compared to workers with a higher FEV1 at the time of diagnosis (Talini et al, 2013).
    13) CASE REPORTS
    a) TDI: A 43-year-old man with a 6 year history of TDI-induced asthma developed a fatal asthma attack while mixing 2 components of a polyurethane paint. Although he had previously been advised to change jobs, he continued to work with the paints while taking anti-asthmatic drugs at home and work (Fabbri et al, 1988).
    b) MDI: POLYURETHANE FOAM: This is principally associated with occupational asthma. An unusual case of respiratory hypersensitivity and asthmatic response has been attributed to the use of a MDI-containing polyurethane foam in the home. Possible prior occupational exposure to isocyanates may have occurred during the burning of polyurethane packs (Dietemann-Molard et al, 1991). In this case, the MDI challenge test was positive, FEV1 was decreased 53%, and TDI and MDI-specific IgEs were present.
    c) MDI: PHENOL FORMALDEHYDE: Workers in a plant which produced board by bonding aspen and balsam wood with MDI and phenol formaldehyde had significantly greater reductions in FEV(1)/FVC ratio and increased symptoms (cough, dyspnea, wheezing, chest tightness) than oilfield and gas plant workers (Herbert et al, 1995).
    d) HEXAMETHYLENE DIISOCYANATE PREPOLYMERS: Hexamethylene diisocyanate (HDI) monomers have been replaced by HDI prepolymers in some products in order to reduce the respiratory hazards of HDI since the prepolymers are less volatile than the monomers. One study (N=20) reported that asthma was induced by the HDI monomer, prepolymers or a commercial mixture of the prepolymers and monomer (Vanderplas et al, 1993).
    E) BRONCHITIS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Occupational non-asthmatic neutrophilic bronchitis was diagnosed in a 34-year-old clerk after being exposed to TDI at her work place, a manufacturing company that used TDI extensively, for 18 months. Her symptoms included a chronic dry cough that improved when she was away from the work place. A sputum induction study was performed before and 24 hours after exposure which showed a neutrophil increase. Other studies were normal (ie, spirometry and a reversibility and methacholine challenge tests), and no other causes for a chronic cough could be found (Pala et al, 2011).
    b) Chronic bronchitis may occur with high exposures (Axford et al, 1976; Jones et al, 1992).
    F) EMPHYSEMA
    1) WITH POISONING/EXPOSURE
    a) Emphysema has occurred as a result of high exposures (Axford et al, 1976).
    G) COR PULMONALE
    1) WITH POISONING/EXPOSURE
    a) Cor pulmonale has occurred as a result of high exposures (Axford et al, 1976).
    H) SEQUELA
    1) WITH POISONING/EXPOSURE
    a) Long-term respiratory symptoms with slight impairment of ventilatory function is reported. In some of these cases, irreversible damage has been documented (Adams, 1970; Banks et al, 1990; Innocenti et al, 1981; Luo et al, 1990; Mapp et al, 1988; Moller et al, 1986; Paggiaro et al, 1984; Venables et al, 1985; Weill H, Butcher B & Dharmarajan V et al, 1981).
    b) Pulmonary function abnormalities consistent with air flow obstruction (decreased FEV1/FVC) and wheezing were reported in automobile painters exposed to TDI and methylene isocyanate (Parker et al, 1991). Exposure concentrations ranged from 0.005 to 0.06 ppm (mean of 0.005 ppm). The ACGIH recommended exposure level for TDI (8 hour time weighted average) is 0.005 ppm (ACGIH, 1995). Chronic obstructive lung disease may occur despite cessation of exposure (Baur, 1991).
    c) CASE SERIES: Lozewicz et al (1987) reported 82% of 50 patients they were able to follow, continued to have respiratory symptoms 4 or more years after avoidance of exposure, and nearly one-half of these patients required treatment at least once per week.
    d) One study suggested that patients with certain HLA genes (DQB1*0104 and DQB1*0503) may be predisposed to developing asthma after TDI exposure (Mapp et al, 2000).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RESPIRATORY DISORDER
    a) Tracheobronchitis occurred in animals with 30 exposures to 1 to 2 ppm TDI given for 6 hours each time (ACGIH, 1986).
    b) Acute lung injury and hemorrhage were noted on autopsy of rodents following repeated exposure to TDI (ACGIH, 1986).
    c) Respiratory rate was reduced by 50% after single 6 hour exposures of guinea pigs to 0.18 and 0.5 ppm TDI (Stevens & Palmer, 1970).
    d) Fibrous lesions were noted in rat lungs after exposure to 0.1 ppm TDI, 6 hours/day, 5 days/week for up to 58 exposures (Niewenhuis et al, 1965).
    e) Guinea-pigs exposed to 10% TDI daily for 7 days then to 5% TDI weekly for 4 weeks developed interstitial pneumonitis-like lesions that were not observed in after single exposures to TDI (Yamada et al, 1995).
    2) BRONCHOSPASM
    a) Nonspecific airway hyperresponsiveness has been induced in guinea pigs following inhalation of MDI at doses which caused significant irritation. Prior sensitization was produced by MDI inhalation and topical or intradermal MDI administration (Pauluhn & Mohr, 1994; Rattray et al, 1994).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: Firefighters exposed to TDI and possibly other substances experienced euphoria, loss of coordination, and loss of consciousness (Le Quesne et al, 1976; McKerrow et al, 1970; O'Donoghue, 1985).
    B) ALTERED MENTAL STATUS
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: Long-lasting symptoms of personality change, irritability, depression, loss of memory, and impotency (psychogenic) were also reported in firefighters (Le Quesne et al, 1976; McKerrow et al, 1970; O'Donoghue, 1985).
    b) CASE SERIES: Irritability, cerebellar ataxia, anxiety, memory loss, depression, euphoria and delusions were reported in TDI exposed workers (Siribaddana et al, 1998).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) VOMITING
    1) WITH POISONING/EXPOSURE
    a) Nausea and vomiting may occur from inhalation of vapor or aerosol (Axford et al, 1976; Siribaddana et al, 1998).
    B) ABDOMINAL PAIN
    1) WITH POISONING/EXPOSURE
    a) Abdominal pain may result from inhalational exposure (Axford et al, 1976). Epigastric and substernal pain may be secondary to the paroxysmal or persistent cough associated with inhalation.
    C) INTESTINAL OBSTRUCTION
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 16-year-old boy working at a sponge production factory was acutely exposed to inhalational toluene 2,4 diisocyanate gas for 2 hours about 6 days prior to hospital admission. His history was significant for lymphoma and surgery for gastric lymphoma at age 10; a recent annual exam for lymphoma was normal. Upon admission, symptoms included nausea, vomiting, periumbilical pain, fever and chills. Constipation occurred 4 days after exposure. An abdominal CT showed disseminated dilatation of the intestinal loops, thickening of the ileal wall, and collapse of the distal colon suggesting an intestinal obstruction. Exploratory surgery showed no mass nor severe adhesions; however, mild adhesions from prior surgery were observed. Enterolysis and milking of the distended loops were performed. The patient recovered uneventfully. A cause and effect relationship between TDI exposure and intestinal obstruction could not be determined (Shadnia et al, 2013).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) BULLOUS ERUPTION
    1) WITH POISONING/EXPOSURE
    a) Irritation of the skin with blister formation, erythema and edema can occur (US DHHS, 1988).
    B) DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) Studies suggest that dermatitis is more common following contact to TDI than allergic contact dermatitis.
    b) A textile worker developed an allergic dermatitis while processing wool. Patch testing revealed reactions to dicyclohexylmethane-4,4'-diisocyanate (Thompson & Belsito, 1997).
    C) ALLERGIC CONTACT DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) In occupational studies, allergic contact dermatitis and skin sensitization are rarely reported in workers in manufacturing industries following TDI exposure (Arnold et al, 2012).
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SKIN SENSITIZER
    a) In animal studies, TDI is a skin sensitizer (Arnold et al, 2012).
    2) IRRITATION
    a) Rabbit skin exposed to 500 mg of TDI developed a severe reaction in the open Draize test (reviewed in RTECS(R), 1995). Studies have shown that TDI exposures can produce moderate dermal irritation when applied to both intact and abraded skin (Arnold et al, 2012).
    3) ALLERGIC REACTION
    a) Sensitization from topical or intradermal administration of MDI with subsequent airway hyperresponsiveness following MDI inhalation has been reported in guinea pigs (Pauluhn & Mohr, 1994; Rattray et al, 1994).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) MUSCLE PAIN
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: Muscle pain was a common complaint in a series of TDI exposed workers (Siribaddana et al, 1998).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) WITH POISONING/EXPOSURE
    a) Toluene diisocyanate can cause respiratory (common) and possibly dermal sensitization (Arnold et al, 2012; US DHHS, 1988; Baur, 1991; National Research Council, 1992). It has been suggested that topical exposure to TDI can activate an immune response; however it remains unclear whether dermally-mediated activation is adequate to initiate respiratory sensitization (Arnold et al, 2012).
    b) SKIN TEST REACTIONS/ANTIBODIES: Positive skin test reactions to TDI-conjugates with human serum albumin and positive TDI-specific IgE and IgG antibodies have been reported but the exact mechanism involved is still unknown (Butcher et al, 1977; Cartier et al, 1989; Finkel, 1983; Karol et al, 1979; Karol, 1980) (Keskinen et al, 1988) (Selden et al, 1989).
    c) Individuals who have TDI antibodies do not always develop hypersensitivity symptoms, and persons who are hypersensitive to TDI do not always have detectable TDI-specific antibodies (National Research Council, 1992).
    d) HEXAMETHYLENE DIISOCYANATE (HDI): HDI-specific IgG antibodies were elevated in a car painter who had 3 episodes of hypersensitivity pneumonitis-like disease after exposure to acrylic lacquers with hexamethylene diisocyanate (HDI) as the curing agent (Selden et al, 1989).
    B) WHITE BLOOD CELL ABNORMALITY
    1) WITH POISONING/EXPOSURE
    a) SERUM CHEMOTAXIS FACTOR: Release of a serum chemo-attracting factor for neutrophils and activation of neutrophils occurred in workers with late asthmatic reaction to TDI (Valentino et al, 1988).

Reproductive

    3.20.5) FERTILITY
    A) IMPOTENCE
    1) CASE SERIES - Firefighters exposed to TDI and possibly other substances suffered from impotence for some time after exposure. This was thought to be due to an indirect neurologic effect rather than to direct toxicity to the male genitalia (Le Quesne et al, 1976).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS26471-62-5 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) IARC Classification
    a) Listed as: Toluene diisocyanates
    b) Carcinogen Rating: 2B
    1) The agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans. This category is used for agents, mixtures and exposure circumstances for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent, mixture or exposure circumstance for which there is inadequate evidence of carcinogenicity in humans but limited evidence of carcinogenicity in experimental animals together with supporting evidence from other relevant data may be placed in this group.
    B) IARC Carcinogenicity Ratings for CAS1321-38-6 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.2) SUMMARY/HUMAN
    A) Toluene diisocyanate is considered a suspected or possible human carcinogen, based on sufficient evidence of carcinogenicity or tumors (tumors of the spleen, subcutaneous, hepatic, ovarian, peritoneum, and mammary gland tissues) in experimental animals.
    3.21.3) HUMAN STUDIES
    A) CARCINOMA
    1) A study of 218 male workers exposed to TDI found an excess of respiratory infections and a slightly higher than expected incidence of cancer; however, the increased cancer was not confirmed in cases of extended absence from work (EPA, 1984). A group of 4154 Swedish workers exposed to TDI in manufacturing polyurethane foam, had slight increases in mortality from rectal cancer and non-Hodgkin's lymphoma (Hagmar et al, 1993a).
    2) Mortality from rectal cancer and non-Hodgkin's lymphoma were increased in a group of 4611 men and women from 4 polyurethane foam plants exposed for at least 3 months from the late 1950's through 1987, but the increase was not statistically significant. Non-Hodgkin's lymphoma and Hodgkin's disease showed some correlation with time since first employment. The findings are not considered conclusive, however, and will require more years of follow-up (Schnorr et al, 1996).
    3) An increase in prostate cancer was reported in a study of 7023 Swedish workers at polyurethane foam manufacturing plants, but it was not statistically significant (odds ratio=2.66). A weaker association was present for colon cancer, and in contrast to the previous study, no links were apparent for increased rectal cancer or non-Hodgkin's lymphoma (Hagmar et al, 1993b).
    4) A NIOSH industry-wide study has been proposed to look for excess mortality from cancer, especially lung cancer, in TDI workers (EPA, 1983).
    3.21.4) ANIMAL STUDIES
    A) NEOPLASM
    1) Tumors of the pancreas, liver, mammary glands, and vascular system were reported in rats and mice used in an inadequately described study (National Toxicology Program, 1982).
    2) Toluene diisocyanate is considered a suspected or possible human carcinogen, based on sufficient evidence of carcinogenicity or tumors (tumors of the spleen, subcutaneous, hepatic, ovarian, peritoneum, and mammary gland tissues) in experimental animals (IARC, 1987; US DHHS, 1994) ACGIH, 1995).
    3) TDI has caused tumors in mice and rats when given orally (Loeser, 1983), but these results are controversial. TDI was not carcinogenic when administered by inhalation at doses up to 0.15 ppm (Loeser, 1983).
    B) LACK OF EFFECT
    1) NON-CARCINOGENICITY OF CHRONIC EXPOSURE - Rats and mice exposed to 0.05 or 0.15 ppm TDI, 6 hours daily, 5 days/week for 2 years did not develop tumors (IARC, 1986; Owen P, 1980).
    2) It has been postulated that the reason tumors have been observed in rodent studies involving oral administration of TDI, but not after inhalation of TDI is that the acidic environment in the stomach causes conversion of TDI to toluene diamine, a known mutagen and rodent carcinogen. In other tissues, TDI reacts with NH2 groups which may polymerize to form oligoureas (Doe & Hoffmann, 1995).

Genotoxicity

    A) Sister chromatid exchange values were considerably higher in peripheral blood lymphocytes of 26 workers exposed to TDI in 1 study. There were mixed results in 2 studies of DNA fragmentation patterns after exposure to isocyanates. Micronucleus test values in peripheral blood lymphocytes of workers (n=26) exposed to TDI were almost 3 times greater than in a control group (Marczynski et al, 2005; Bilban, 2004; Marczynski et al, 2003).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs and mental status, monitor pulmonary exam.
    B) Monitor pulse oximetry and/or arterial blood gases, chest radiograph and pulmonary function tests in patients with respiratory signs/symptoms.
    4.1.2) SERUM/BLOOD
    A) No specific lab work (CBC, electrolytes, urinalysis) is needed unless otherwise clinically indicated.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) Monitor pulse oximetry and/or arterial blood gases, chest radiograph and pulmonary function tests in patients with respiratory signs/symptoms.
    2) DERMAL
    a) RAST testing for IgE antibodies against p-tolyl monoisocyanate antigens is unreliable because of false positives and false negatives (Proctor et al, 1988).
    b) The presence of a TDI-specific antibody indicates exposure but is not an indicator of TDI hypersensitivity. Individuals who have TDI antibodies do not always develop hypersensitivity symptoms, and persons who are hypersensitive to TDI do not always have detectable TDI-specific antibodies (National Research Council, 1992).
    c) Neither TDI-specific IgE nor prior positive skin test to TDI was a predictor of TDI-induced bronchoconstriction (Karol et al, 1994).
    3) OTHER
    a) BRONCHOPROVOCATION SPECIFIC CHALLENGE: When positive, bronchoprovocative challenge with TDI provides a definitive, but risky, diagnostic tool (Proctor et al, 1988). It has a sensitivity of only 68% and cross-reactions between TDI and MDI can affect bronchial provocation test results (Banks et al, 1989; Innocenti et al, 1988).
    b) BRONCHOPROVOCAATION NON-SPECIFIC CHALLENGE: Methacholine responsiveness correlated better with TDI sensitivity than TDI-specific IgE or skin tests, but was not sufficient to make a diagnosis of TDI sensitivity. Negative or positive methacholine challenge results can occur in persons with TDI-induced asthma (Moscato et al, 1991; Jones et al, 1992).
    c) AIRBORNE EXPOSURE: In occupational studies, work place exposure to TDI during manufacture of polyurethane foam production showed a good correlation between airborne TDI and toluene diamine (TDA) in urine (Cocker, 2011).
    1) METHOD: A direct method of analyzing toluenediamines in hydrolyzed urine involves extraction with toluene, purification with a strong cation-exchange sorbent, and separation by either ion-suppression or ion-pair chromatography. With electrochemical detection, 2,6-TDA and 2,4-TDA can be detected at 0.1 and 0.15 mcg/L, respectively. Using this method, levels of urinary toluenediamines were shown to be elevated in workers from a polyurethane foam factory, relative to unexposed controls (Carbonnelle et al, 1996).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with significant symptoms should be admitted for treatment and monitoring. Patients with respiratory failure should be admitted to an ICU setting.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Patients who are asymptomatic or have minimal irritation after small exposures can be managed at home or the work place.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Contact a medical toxicologist or poison center for any patient with severe toxicity. Consult an ophthalmologist for patients with severe eye irritation or splash exposure. Patients with an occupational exposure should be referred to an occupational physician and industrial hygienist.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Symptomatic patients, patients with known or suspected sensitization, or patients with known large exposures should be referred to a healthcare facility for evaluation and treatment, and observed for 6 hours for signs of toxicity.

Monitoring

    A) Monitor vital signs and mental status, monitor pulmonary exam.
    B) Monitor pulse oximetry and/or arterial blood gases, chest radiograph and pulmonary function tests in patients with respiratory signs/symptoms.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) GI decontamination is not indicated, toxicity is from irritant effects and sensitization, not systemic absorption.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) GI decontamination is not indicated, toxicity is from irritant effects and sensitization, not systemic absorption.
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) Monitor vital signs and mental status, monitor pulmonary exam.
    2) Monitor pulse oximetry and/or arterial blood gases, chest radiograph and pulmonary function tests in patients with respiratory signs/symptoms.
    B) BRONCHOSPASM
    1) Bronchodilators and oxygen may be used in acute attacks.
    2) BRONCHOSPASM SUMMARY
    a) Administer beta2 adrenergic agonists. Consider use of inhaled ipratropium and systemic corticosteroids. Monitor peak expiratory flow rate, monitor for hypoxia and respiratory failure, and administer oxygen as necessary.
    3) ALBUTEROL/ADULT DOSE
    a) 2.5 to 5 milligrams diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response, administer 2.5 to 10 milligrams every 1 to 4 hours as needed OR administer 10 to 15 milligrams every hour by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.5 milligram by nebulizer every 30 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).
    4) ALBUTEROL/PEDIATRIC DOSE
    a) 0.15 milligram/kilogram (minimum 2.5 milligrams) diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.25 to 0.5 milligram by nebulizer every 20 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).
    5) ALBUTEROL/CAUTIONS
    a) The incidence of adverse effects of beta2-agonists may be increased in older patients, particularly those with pre-existing ischemic heart disease (National Asthma Education and Prevention Program, 2007). Monitor for tachycardia, tremors.
    6) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm. PREDNISONE: ADULT: 40 to 80 milligrams/day in 1 or 2 divided doses. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 or 2 divided doses (National Heart,Lung,and Blood Institute, 2007).
    7) Several placebo-controlled randomized double-blind crossover studies have been conducted to investigate the efficacy of various bronchodilators.
    a) Theophylline (6.5 mg/kg twice a day) only has a partial effect (Mapp et al, 1987).
    b) Verapamil (120 mg twice a day), ketotifen, salbutamol alone, atropine (0.008 to 0.012 mg/kg atropine sulfate administered subcutaneously 30 minutes before TDI challenge and 90 minutes after TDI exposure), and cromolyn (20 mg 4 times daily via a spinhaler) have no protective effect (De Marzo et al, 1988; Mapp et al, 1987; Paggiaro et al, 1987; Tossin et al, 1989).
    8) Prednisone and aerosolized beclomethasone (1 mg twice daily) have been shown to prevent late asthmatic reactions or increased airway responsiveness in TDI-sensitized patients (De Marzo et al, 1988; Fabbri et al, 1985).
    9) Non-steroidal antiinflammatory agents did not prevent the reactions associated with late TDI-induced asthma (Fabbri et al, 1985).
    C) ACUTE ALLERGIC REACTION
    1) Sensitized individuals should be cautioned to avoid further exposure as serious allergic reactions may result.
    D) EXPERIMENTAL THERAPY
    1) MATRIX METALLOPROTEINASE INHIBITOR: Matrix metalloproteinase-9 (MMP-9) is the major proteinase that induces bronchial remodeling in asthma, as well as, induces the migration of eosinophils and neutrophils across the basement membrane. A murine TDI-induced asthma model, using female mice, showed increased inflammatory cells (neutrophils and eosinophils), histologic changes (eg, increased inflammatory cells around the bronchioles, thickened airway epithelium, and accumulation of mucus and debris in the bronchioles), airway hyperresponsiveness, and increased MMP-9 activity in the inflammatory cells in the airway lumen. Administration of a matrix metalloproteinase inhibitor (MMP-I) reduced the numbers of neutrophils and eosinophils in the bronchoalveolar lavage (BAL) fluid at 72 hours after TDI inhalation, as well as, reduced the level and activity of MMP-9 in the BAL fluid at 72 hours after TDI inhalation, indicating that an MMP-I may be a useful alternative for treatment of TDI-induced asthma(Lee et al, 2001).

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    D) Monitor for allergic reactions.
    6.7.2) TREATMENT
    A) MONITORING OF PATIENT
    1) Monitor vital signs and mental status, monitor pulmonary exam. Monitor pulse oximetry and/or arterial blood gases, chest radiograph and pulmonary function tests in patients with respiratory signs/symptoms.
    B) BRONCHOSPASM
    1) Bronchodilators and oxygen may be used in acute attacks.
    2) BRONCHOSPASM SUMMARY
    a) Administer beta2 adrenergic agonists. Consider use of inhaled ipratropium and systemic corticosteroids. Monitor peak expiratory flow rate, monitor for hypoxia and respiratory failure, and administer oxygen as necessary.
    3) ALBUTEROL/ADULT DOSE
    a) 2.5 to 5 milligrams diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response, administer 2.5 to 10 milligrams every 1 to 4 hours as needed OR administer 10 to 15 milligrams every hour by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.5 milligram by nebulizer every 30 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).
    4) ALBUTEROL/PEDIATRIC DOSE
    a) 0.15 milligram/kilogram (minimum 2.5 milligrams) diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.25 to 0.5 milligram by nebulizer every 20 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).
    5) ALBUTEROL/CAUTIONS
    a) The incidence of adverse effects of beta2-agonists may be increased in older patients, particularly those with pre-existing ischemic heart disease (National Asthma Education and Prevention Program, 2007). Monitor for tachycardia, tremors.
    6) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm. PREDNISONE: ADULT: 40 to 80 milligrams/day in 1 or 2 divided doses. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 or 2 divided doses (National Heart,Lung,and Blood Institute, 2007).
    7) Several placebo-controlled randomized double-blind crossover studies have been conducted to investigate the efficacy of various bronchodilators.
    a) Theophylline (6.5 mg/kg twice a day) only has a partial effect (Mapp et al, 1987). Another study found that administration of theophylline reduced the late asthmatic response induced by TDI in sensitized subjects but did not change responsiveness to methacholine in these same subjects (Crescioli et al, 1992).
    b) Verapamil (120 mg twice a day), ketotifen, salbutamol alone, atropine (0.008 to 0.012 mg/kg atropine sulfate administered subcutaneously 30 minutes before TDI challenge and 90 minutes after TDI exposure), and cromolyn (20 mg 4 times daily via a spinhaler) have no protective effect (De Marzo et al, 1988; Mapp et al, 1987; Paggiaro et al, 1987; Tossin et al, 1989).
    8) Prednisone and aerosolized beclomethasone (1 mg twice daily) have been shown to prevent late asthmatic reactions or increased airway responsiveness in TDI-sensitized patients (De Marzo et al, 1988; Fabbri et al, 1985). In another study beclomethasone treatment for 5 months reduced bronchospasm after methacholine challenge but not after TDI exposure in TDI sensitized asthmatics (Maestrelli et al, 1993).
    9) NSAIDs did not prevent reactions associated with late TDI-induced asthma (Fabbri et al, 1985).
    C) ACUTE ALLERGIC REACTION
    1) Sensitized individuals should be cautioned to avoid further exposure as serious allergic reactions may result.
    D) EXPERIMENTAL THERAPY
    1) MATRIX METALLOPROTEINASE INHIBITOR: Matrix metalloproteinase-9 (MMP-9) is the major proteinase that induces bronchial remodeling in asthma, as well as, induces the migration of eosinophils and neutrophils across the basement membrane. A murine TDI-induced asthma model, using female mice, showed increased inflammatory cells (neutrophils and eosinophils), histologic changes (eg, increased inflammatory cells around the bronchioles, thickened airway epithelium, and accumulation of mucus and debris in the bronchioles), airway hyperresponsiveness, and increased MMP-9 activity in the inflammatory cells in the airway lumen. Administration of a matrix metalloproteinase inhibitor (MMP-I) reduced the numbers of neutrophils and eosinophils in the bronchoalveolar lavage (BAL) fluid at 72 hours after TDI inhalation, as well as, reduced the level and activity of MMP-9 in the BAL fluid at 72 hours after TDI inhalation, indicating that an MMP-I may be a useful alternative for treatment of TDI-induced asthma(Lee et al, 2001).
    E) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) Irrigate exposed eyes copiously with 0.9% saline.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

Summary

    A) TOXICITY: Available dose-response information concerning humans pertains to inhalational exposure. Concentrations of 2.5 ppm are considered Immediately Dangerous to Life or Health (IDLH). Continued exposure to TDI in an asthmatic patient resulted in a fatality.
    B) EXPOSURE LIMITS: Recommended short-term exposure limits for TDI in industry is 0.02 ppm. TDI does not have sufficient warning properties (eg, odor or eye irritancy) at air concentrations below the recommended short term exposure limit.

Minimum Lethal Exposure

    A) SUMMARY
    1) Concentrations of 2.5 ppm are considered Immediately Dangerous to Life or Health (IDLH) in industrial settings (National Institute for Occupational Safety and Health, 2007).
    B) CASE REPORTS
    1) ADULT
    a) A fatal asthma attack has been reported in a person who continued to work with polyurethane paint, containing small amounts of TDI, despite a 6-year history of TDI-induced asthma, advice to cease exposure, and use of medication to control the asthma at work and at home (Fabbri et al, 1988). The autopsy showed overinflation of the lungs and mucous plugging of the small bronchi and bronchioles.

Maximum Tolerated Exposure

    A) CONCENTRATION LEVELS
    1) OSHA's PEL (permissible exposure limit) OR short term exposure limit (STEL) is 0.02 ppm (0.14 mg/m(3)) (National Institute for Occupational Safety and Health, 2007; ACGIH, 2012), and the Time Weighted Average (TWA) concentration for a conventional 8 hour workday is 0.005 ppm (ACGIH, 2012).
    2) TDI levels of 0.3 to 0.7 ppm were associated with a high incidence of illness, but no cases were observed from concentrations below 0.03 ppm (Hama, 1947).
    3) The maximum incidence of illnesses occurred when the average concentration of vapor was 0.1 ppm and very little trouble was reported at 0.01 ppm (Walworth & Virchow, 1959).
    4) RESPIRATORY FUNCTION
    a) SUMMARY: Long-term exposure to TDI above 20 ppb can result in a significant decline in FEV1 and Peak Expiratory Flow Rate over time; concentrations of 5 ppb appeared to be safe against the development of airway impairment and respiratory sensitization. Studies to elevate respiratory effects have indicated that levels between 5 and 20 ppb have resulted in no respiratory effects or have been inconclusive (Arnold et al, 2012).
    b) Occasional exposures to TDI beyond 0.02 ppm caused no significant deterioration in lung function (Erlicher H & Brochhagen FK, 1976).
    c) Occupational exposure to TDI of 3 parts per billion (21.3mcg/m(3)) in non-sensitized workers resulted in an increase in respiratory symptoms (e.g. rhinitis) without any deterioration in lung function; however, peak exposures of 30 parts per billion (213 mcg/m(3)) did result in an associated loss of ventilatory function in workers not sensitized to TDI (Nakashima et al, 2002).
    d) A dose-response relationship was demonstrated between acute pulmonary function changes and exposure of 112 workers to 0.0035 to 0.06 milligram TDI/cubic meter (IARC, 1979).
    e) Exposure of volunteers have shown that 0.05 to 0.1 parts per million TDI in the air can cause eye and nose irritation (Grant & Schuman, 1993).
    f) A normal age- and smoking-related rate of decline in forced expiratory volume in 1 second (FEV1) was demonstrated in subjects exposed to 0.001 to 0.0015 ppm TDI thus negating any effects of TDI at these levels (Musk et al, 1985).
    g) A daily mean exposure of 0.023 milligram/cubic meter produced impaired lung function and increased frequency of symptoms among nonsmokers but not among exposed smokers (Alexandersson et al, 1985).
    h) One study suggested that the total dose of exposure was more important than the either concentration or duration of exposure alone in determining the drop in FEV1 caused by TDI exposure in patients with isocyanate-induced asthma (Vandenplas et al, 1993).
    i) No respiratory symptoms or changes in pulmonary function were reported in workers who poured and molded polyurethane foam, breathing as much as 0.001 to 0.002 ppm TDI (Roper & Cromer, 1975).
    B) CASE REPORTS
    1) Occupational non-asthmatic neutrophilic bronchitis was diagnosed in a 34-year-old clerk after being exposed to TDI at her work place, a manufacturing company that used TDI extensively, for 18 months. Her symptoms included a chronic dry cough that improved when she was away from the work place. A sputum induction study was performed before and 24 hours after exposure which showed a neutrophil increase. Other studies were normal (ie, spirometry and a reversibility and methacholine challenge tests), and no other causes for a chronic cough could be found (Pala et al, 2011).

Workplace Standards

    A) ACGIH TLV Values for CAS26471-62-5 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) ACGIH TLV Values for CAS1321-38-6 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    C) NIOSH REL and IDLH Values for CAS26471-62-5 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    D) NIOSH REL and IDLH Values for CAS1321-38-6 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    E) Carcinogenicity Ratings for CAS26471-62-5 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: 2,4-/2,6-Toluene diisocyanate mixture (TDI)
    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): 2B ; Listed as: Toluene diisocyanates
    a) 2B : The agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans. This category is used for agents, mixtures and exposure circumstances for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent, mixture or exposure circumstance for which there is inadequate evidence of carcinogenicity in humans but limited evidence of carcinogenicity in experimental animals together with supporting evidence from other relevant data may be placed in this group.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Category 3A ; Listed as: Toluenediisocyanate
    a) Category 3A : Substances for which the criteria for classification in Category 4 or 5 are fulfilled but for which the database is insufficient for the establishment of a MAK value.
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): R ; Listed as: Toluene Diisocyanate
    a) R : RAHC = Reasonably anticipated to be a human carcinogen

    F) Carcinogenicity Ratings for CAS1321-38-6 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    G) OSHA PEL Values for CAS26471-62-5 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

    H) OSHA PEL Values for CAS1321-38-6 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (ORAL)RAT:
    1) 5,800 mg/kg (Zapp, 1957)

Pharmacology Toxicology

Toxicologic Mechanism

    A) TDI exposure tends to have a cumulative effect on most people. In human toxicology there are two classes of reaction to TDI: 1) primary irritation or pharmacodynamic action to which all exposed persons are susceptible to some degree and 2) sensitization reaction or allergic response in those persons who have become sensitized to TDI during earlier exposure (Butcher et al, 1977).
    1) TDI is a severe irritant to all living tissues with which it comes in contact in liquid or vapor form, especially to mucous membranes of the eyes, the gastrointestinal and the respiratory tract. It also has a marked inflammatory reaction on direct skin contact (Proctor et al, 1988).
    a) A common respiratory system response to inhaled TDI is both acute and chronic dimunition of ventilatory capacity, measured by a decrease in FEV1 even in the absence of other overt symptoms (Adams, 1970) 1975; (Moller et al, 1986; Venables et al, 1985; Weill H, Butcher B & Dharmarajan V et al, 1981).
    b) There have been no reports of human ingestion. Necropsy of rats revealed corrosive action on stomach as well as possible toxic effects on the liver (ACGIH, 1986).
    2) Respiratory sensitization occurs in susceptible persons after repeated exposure to TDI at levels of 0.02 ppm and below (Elkins et al, 1962). A chronic syndrome consisting of coughing, wheezing, tightness, or congestion in the chest and shortness of breath has been characterized with repeated exposures at such low concentrations (NIOSH, 1973).
    a) A sensitized individual, in addition to the aforementioned instant reactions, may be afflicted with marked tissue eosinophilia and acute pneumonitis with inflammatory edema of the lungs (Fabbri, 1985; (Fabbri et al, 1987) Zocca et al, 1990).
    b) Some individuals reported to have developed an allergic response have circulating antibodies to TDI or to TDI-animal protein conjugates (Butcher et al, 1977; Fabbri et al, 1987; Finkel, 1983) Karol et al, Karol, 1980, 1981).
    c) Further evidence in support of this is the demonstration of lymphocyte transformation in TDI-sensitized workers induced by TDI-conjugated proteins.
    3) TDI-induced late asthmatic reactions have been attributed to increased bronchovascular permeability caused by increased leukotriene B4 levels which also promote granulocyte adherence and leukocyte migration into tissues (Zocca et al, 1990).
    B) Because 1 micromole of TDI can stimulate methacholine-induced tracheal ring contraction, the pharmacological effect of TDI is believed to be due to an autonomic imbalance between cholinergic and beta-adrenergic neural control (Borm et al, 1989).
    C) Epithelial damage, thickening of basement membrane, and mild to moderate inflammatory reaction in the submucosa were demonstrated in TDI-sensitized patients who have ceased work within 4 to 40 months prior to bronchial biopsy (Paggiaro et al, 1990).

Physicochemical

Physical Characteristics

    A) TDI: Clear liquid at room temperature, turns straw-colored on standing, with fruity, pungent odor (AAR, 1987; ACGIH, 1986; ILO, 1983)
    B) MDI: Light yellow to white crystals or fused solid (ILO, 1983)

Molecular Weight

    A) TDI: 174.16 (ACGIH, 1986)
    B) MDI: 250.25 (ILO, 1983)
    C) HDI: 168.2 (ILO, 1983)
    D) NDI: 210.2 (ILO, 1983)

Other

    A) ODOR THRESHOLD
    1) 0.4-2.14 ppm (CHRIS , 2002)

References

General Bibliography

    1) 40 CFR 372.28: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Lower thresholds for chemicals of special concern. National Archives and Records Administration (NARA) and the Government Printing Office (GPO). Washington, DC. Final rules current as of Apr 3, 2006.
    2) 40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.
    3) 49 CFR 172.101 - App. B: Department of Transportation - Table of Hazardous Materials, Appendix B: List of Marine Pollutants. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 29, 2005.
    4) 49 CFR 172.101: Department of Transportation - Table of Hazardous Materials. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 11, 2005.
    5) 62 FR 58840: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 1997.
    6) 65 FR 14186: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    7) 65 FR 39264: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    8) 65 FR 77866: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    9) 66 FR 21940: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2001.
    10) 67 FR 7164: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2002.
    11) 68 FR 42710: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2003.
    12) 69 FR 54144: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2004.
    13) AAR: Emergency Handling of Hazardous Material in Surface Transportation, Hazardous Materials Systems (BOE). Association of American Railroads, Washington, DC, 1987.
    14) ACGIH : 2012 TLVs(R) and BEI(R) Based on the Documentation of the Threshold Limit Values for Chemical Substances and Physical Agents & Biological Exposure Indices, ACGIH, Cincinnati, OH, 2012.
    15) ACGIH: Documentation of the Threshold Limit Values and Biological Exposure Indices, 5th ed, Am Conference of Govt Ind Hyg, Inc, Cincinnati, OH, 1986.
    16) AIHA: 2006 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook, American Industrial Hygiene Association, Fairfax, VA, 2006.
    17) Adams WGF: Lung function of men engaged in the manufacture of toluene diisocyanate (TDI). Proc Roy Soc Med 1970; 63:378.
    18) Alexandersson R, Hedenstierna G, & Randma E: Symptoms and lung function in low-exposure to TDI by polyurethane foam manufacturing. Internat Arch Occup Environ Health 1985; 55:149-157.
    19) 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.
    20) Andersen M: Scand J Work Environ Health 1980; 6:221-226.
    21) 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.
    22) Arnold SM , Collins MA , Graham C , et al: Risk assessment for consumer exposure to toluene diisocyanate (TDI) derived from polyurethane flexible foam. Regul Toxicol Pharmacol 2012; 64(3):504-515.
    23) Axford AT, McKerrow CB, & Jones AP: Accidental exposure to isocyanate fumes in a group of firemen. Br J Ind Med 1976; 33:65-71.
    24) Banks DE, Butcher BT, & Salvaggio JE: Isocyanate-induced respiratory disease. Ann Allergy 1986; 57:389-396.
    25) Banks DE, Rando RJ, & Barkman HW Jr: Persistence of toluene diisocyanate-induced asthma despite negligible workplace exposures. Chest 1990; 97:121-125.
    26) Banks DE, Sastre J, & Butcher BT: Role of inhalation challenge testing in the diagnosis of isocyanate-induced asthma. Chest 1989; 95:414-423.
    27) Barkman HW Jr: Chest 1984; 86:340.
    28) Bata Shoe Company: Industrial Footwear Catalog, Bata Shoe Company, Belcamp, MD, 1995.
    29) Baur X: Isocyanates. Clin Exp Allergy 1991; 21(suppl 1):241-246.
    30) Baur X: Occupational asthma due to isocyanates. Lung 1996; 174:23-30.
    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) Bilban M: Mutagenic testing of workers exposed to toluene-diisocyanates during plastics production process. Am J Ind Med 2004; 45(5):468-474.
    34) Borm PJA, Bast A, & Zuiderveld OP: In vitro effect of toluene diisocyanate on beta adrenergic and muscarinic receptor function in lung tissue of the rat. Br J Ind Med 1989; 46:56-59.
    35) Boss Manufacturing Company: Work Gloves, Boss Manufacturing Company, Kewanee, IL, 1998.
    36) Brooks SM: Occupational asthma. Toxicol Lett 1995; 82/83:39-45.
    37) Bruckner HC, Avery SB, & Stetson DM: Clinical and immunological appraisal of workers exposed to diisocyanate. Arch Environ Health 1968; 16:619-625.
    38) Burgess JL, Kirk M, Borron SW, et al: Emergency department hazardous materials protocol for contaminated patients. Ann Emerg Med 1999; 34(2):205-212.
    39) Butcher BT, Jones RN, & O'Neill CE: Longitudinal studies of workers employed in the manufacture of toluene diisocyanate. Am Rev Respir Dis 1977; 116:411-421.
    40) Butcher BT, O'Neill CE, & Reed MA: Radioallergosorbent testing of toluene diisocyanate-reactive individuals using p-tolyl isocyanate antigen. J Allergy Clin Immunol 1980; 66:213-216.
    41) CHRIS : CHRIS Hazardous Chemical Data. US Department of Transportation, US Coast Guard. Washington, DC (Internet Version). Edition expires 2002; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    42) Carbonnelle P, Boukortt S, & Lison D: Determination of toluenediamines in urine of workers occupationally exposed to isocyanates by high-performance liquid chromatography. Analyst 1996; 121:663-669.
    43) Cartier A, Grammer L, & Malo JL: Specific serum antibodies against isocyantes: association with occupational asthma. J Allergy Clin Immunol 1989; 84:507-514.
    44) ChemFab Corporation: Chemical Permeation Guide Challenge Protective Clothing Fabrics, ChemFab Corporation, Merrimack, NH, 1993.
    45) Cocker J : Biological monitoring for isocyanates. Ann Occup Hyg 2011; 55(2):127-131.
    46) 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.
    47) Comasec Safety, Inc.: Product Literature, Comasec Safety, Inc., Enfield, CT, 2003a.
    48) Crescioli S, De Marzo N, & Boschetto P: Theophylline inhibits late asthmatic reactions induced by toluene diisocyanate in sensitised subjects. Europ J PHarmacol 1992; 2228:45-50.
    49) Cullen MR, Redlich CA, & Beckett WS: Feasibility study of respiratory questionnaire and peak flow recordings in autobody shop workers exposed to isocyanate-containing spray paint - observations and limitations. Occup Medicine-Oxford 1996; 46:197-204.
    50) Czuppon AB, Marczynski B, & Baur X: Detection of protein changes in serum of workers following inhalation exposure to toluene diisocyanate vapors. Toxicol Ind Health 1992; 8:407-413.
    51) 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.
    52) De Marzo N, Fabri LM, & Crescioli S: Dose-dependent inhibitory effect of inhaled beclomethasone on late asthmatic reactions and increased airway responsiveness to methacholine induced by toluene diisocyanate in sensitized patients. Pul Pharm 1988; 1:15-20.
    53) Dietemann-Molard A, Kopferschmitt-Kubler MC, & Meyer PD: Allergic asthma due to domestic use of insulating polyurethane foam. Lancet 1991; 338:953.
    54) 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.
    55) 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.
    56) DuPont: Permeation Test Results. DuPont. Wilmington, DE. 2002a. Available from URL: http://www.tyvekprotectiveapprl.com/databases/default.htm. As accessed 7/31/2002.
    57) EPA: Chemical Hazard Information Profile (Draft Report). Toluene Diisocyanate, US Environmental Protection Agency, Washington, DC, 1984, pp 63.
    58) EPA: Search results for Toxic Substances Control Act (TSCA) Inventory Chemicals. US Environmental Protection Agency, Substance Registry System, U.S. EPA's Office of Pollution Prevention and Toxics. Washington, DC. 2005. Available from URL: http://www.epa.gov/srs/.
    59) ERG: Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident, U.S. Department of Transportation, Research and Special Programs Administration, Washington, DC, 2004.
    60) Elkins HB, McCarl GW, & Brugsch HG: Massachusetts experience with toluene diisocyanate. Am Ind Hyg Assoc J 1962; 23:265-272.
    61) Erlicher H & Brochhagen FK: Urethane in the Environments. Proceedings of the Plastic and Rubber Institute Conference (Sept 21-22), 1976.
    62) Fabbri LM & Mapp C: Bronchial hyperresponsiveness, airway inflammation and occupational asthma induced by toluene diisocyanate. Clin Exp Allergy 1991; 21(suppl 1):42-47.
    63) Fabbri LM, Boschetto P, & Zocca E: Bronchoalveolar neutrophilia during late asthmatic reactions induced by toluene diisocyanate. Am Rev Respir Dis 1987; 136:36-42.
    64) Fabbri LM, Chiesura-Corona P, & Dal Vecchio L: Prednisone inhibits late asthmatic reactions and the associated increase in airway responsiveness by toluene diisocyanate in sensitized subjects. Am Rev Respir Dis 1985; 132:1010-1014.
    65) Fabbri LM, Danieli D, & Crescioli P: Fatal asthma in a subject sensitized to toluene diisocyanate. Am Rev Respir Dis 1988; 137:1494-1498.
    66) Fabbri LM, Saeta M, & Picotti G: Late asthmatic reactions, airway inflammation and chronic asthma in toluene-diisocyanate-sensitized subjects. Respiration 1991; 58(Suppl):18-21.
    67) Fabbri LM: Airway inflammation and late asthmatic reactions. Eur Respir J 1990; 3:367-368.
    68) Finkel AJ: Hamilton and Hardy's Industrial Toxicology, 4th ed, John Wright, PSG Inc, Boston, MA, 1983.
    69) Finotto S, Fabbri LM, & Rado V: Increase in numbers of CD8 positive lymphocytes and eosinophils in peripheral blood of subjects with late asthmatic reactions induced by toluene diisocyanate. Br J Ind Med 1991; 48:116-121.
    70) Grant WM & Schuman JS: Toxicology of the Eye, 4th ed, Charles C Thomas, Springfield, IL, 1993.
    71) 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.
    72) Gui W, Wisnewski AV, Neamtiu I, et al: Inception cohort study of workers exposed to toluene diisocyanate at a ployurethane foam factory. AM J Ind Med 2014; 57(11):1207-1215.
    73) Hagmar L, Stromberg U, & Welinder H: Incidence of cancer and exposure to toluene diisocyanate and methylene diphenyldiisocyanate - a cohort based case-referent study in the polyurethane foam manufacturing industry. Br J Ind Med 1993b; 50:1003-1007.
    74) Hagmar L, Welinder H, & Mikoczy Z: Cancer incidence and mortality in the Swedish polyurethane foam manufacturing industry. Br J Ind Med 1993a; 50:537-543.
    75) Hama GM: Arch Ind Health 1947; 16:232.
    76) Herbert FA, Hessel PA, & Melenka SL: Pulmonary effects of simultaneous exposures to MDI formaldehyde and wood dust on workers in an oriented strand board plant. JOEM 1995; 37:461-465.
    77) Herd ZL & Bernstein DI: Antigen-specific stimulation of histamine releasing factors in diisocyanate-induced occupational asthma. Am J Resp Crit Care Med 1994; 150:988-994.
    78) Huang J, Aoyama K, & Ueda A: Experimental study on respiratory sensitivity to inhaled toluene diisocyanate. Arch Toxicol 1993; 67:373-378.
    79) 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.
    80) 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.
    81) 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.
    82) 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.
    83) 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.
    84) 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.
    85) IARC: Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man, International Agency for Research on Cancer, World Health Organization, Geneva, Switzerland, 1979.
    86) IARC: Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man, International Agency for Research on Cancer, World Health Organization, Geneva, Switzerland, 1986.
    87) IARC: Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man, International Agency for Research on Cancer, World Health Organization, Geneva, Switzerland, 1987.
    88) ICAO: Technical Instructions for the Safe Transport of Dangerous Goods by Air, 2003-2004. International Civil Aviation Organization, Montreal, Quebec, Canada, 2002.
    89) ILC Dover, Inc.: Ready 1 The Chemturion Limited Use Chemical Protective Suit, ILC Dover, Inc., Frederica, DE, 1998.
    90) ILO: ILO Encyclopaedia of Occupational Health and Safety, 3rd ed, Vol I. Parmeggiani L (Ed), International Labour Organization, Geneva, Switzerland, 1983.
    91) ITI: Toxic and Hazardous Industrial Chemicals Safety Manual, The International Technical Information Institute, Tokyo, Japan, 1988.
    92) ITIC/USEPA: Information Review No. 231, Toluene Diisocyanates. Government Printing Office, 1981.
    93) Innocenti A, Cirla AM, & Pisati G: Cross-reaction between aromatic isocyanates (TDI and MDI): a specific bronchial provocation test study. Clin Allergy 1988; 18:323-329.
    94) Innocenti A, Franzinelli A, & Sartorelli E: Long-term study of workers with asthma caused by polyurethane resins. Med Lavoro 1981; 3:231.
    95) 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.
    96) 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.
    97) Jones RN, Rando RJ, & Glindmeyer HW: Abnormal lung function in polyurethane foam producers. Am Rev Respir Dis 1992; 146:871-877.
    98) 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.
    99) Karol MH, Sandberg T, & Riley EJ: Longitudinal study of tolyl-reactive IgE antibodies in workers hypersensitive to TDI. J Occup Med 1979; 21:354-358.
    100) Karol MH, Tollerud DJ, & Campbell TP: Predictive value of airways hyperresponsiveness and circulating IgE for identifying types of responses to toluene diisocyanate inhalation challenge. Am J Respir Crit Care Med 1994; 149:611-615.
    101) Karol MH: CRC Crit Rev Toxicol 1986; 16:349-379.
    102) Karol MH: Study of guinea pig and human antibodies to toluene diisocyanate. Am Rev Respir Dis 1980; 122:965-970.
    103) 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.
    104) LaCrosse-Rainfair: Safety Products, LaCrosse-Rainfair, Racine, WI, 1997.
    105) Le Quesne PM, Axford AT, & McKerrow CB: Neurologic complications after a single severe exposure to toluene diisocyanate. Br J Ind Med 1976; 33:72-78.
    106) Lee HS & Phoon WH: Diurnal variation in peak respiratory flow rate among workers exposed to toluene diisocyantae in the polyurethane foam manufacturing industry. Br J Ind Med 1992; 49:423-427.
    107) Lee YC, Song CH, Lee HB, et al: A murine model of toluene diisocyanate-induced asthma can be treated with matrix metalloproteinase inhibitor. J Allergy Clin Immunol 2001; 108:1021-1026.
    108) Loeser E: Toxicol Lett 1983; 15:71-81.
    109) Luo JCJ, Nelsen KG, & Fischbein A: Persistent reactive airway dysfunction syndrome after exposure to toluene diisocyanate. Br J Ind Med 1990; 47:239-241.
    110) 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.
    111) 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.
    112) Maestrelli P, De Marzo N, & Saetta M: Effects of inhaled beclomethasone on airway responsiveness in occupational asthma placebo-controlled study of subjects sensitized to toluene diisocyanate. Am Rev Respir Dis 1993; 148:407-412.
    113) Maestrelli P, Di Stefano A, & Occari P: crytokines in the airway mucosa of subjects with asthma induced by toluene diisocyanate. Am J Respir Crit Care Med 1995; 151:607-612.
    114) Maitre A, Berode M, & Perdrix A: Biological monitoring of occupational exposure to toluene diisocyanate. Internat Arch Occup Environ Health 1993; 65:97-100.
    115) Mapp CE, Beghe B, & Balboni A: associated between HLA genes and susceptibility to toluene diicocyanate-induced asthma. Clin Exp Allergy 2000; 30:651-656.
    116) Mapp CE, Boschetto P, & Dal Vecchio L: Protective effect of antiasthma drugs on late asthmatic reaction and increased responsiveness induced by toluene diisocyanate in sensitized subjects. Am Rev Respir Dis 1987; 136:1403-1407.
    117) Mapp CE, Corona PC, & De Marzo N: Persistent asthma due to isocyanates. a follow-up study of subjects with occupational asthma due to toluene diisocyanate (TDI). Am Rev Respir Dis 1988; 137:1326-1329.
    118) Mapp CE, Plegani M, & Faggian: Eosinophin cationic protein (ECP), histamine and tryptase in peripheral blood before and during inhalation challenge with toluene diisocyanate (TDI) in sensitized subjects. Clin Exp Allergy 1994; 24:730-736.
    119) Mapp CE, Silva JR, & Lucchini RE: Inflammatory events in the blood and airways of guinea pigs immunized to toluene diisocyanate. Am J Resp Crit Care Med 1996; 154:201-208.
    120) Mar-Mac Manufacturing, Inc: Product Literature, Protective Apparel, Mar-Mac Manufacturing, Inc., McBee, SC, 1995.
    121) Marczynski B, Czuppon AB, & Schreiber GH: DNA double-strand breaks and apoptosis after in vitro exposure to toluene diisocyanate. Toxicol In Vitro 1993; 7:531-535.
    122) Marczynski B, Merget R, Mensing T, et al: DNA strand breaks in the lymphocytes of workers exposed to diisocyanates: indications of individual differences in susceptibility after low-dose and short-term exposure. Arch Toxicol 2005; 79(6):355-362.
    123) Marczynski B, Merget R, Teschner B, et al: Changes in low molecular weight DNA fragmentation in white blood cells after diisocyanate exposure of workers. Arch Toxicol 2003; 77(8):470-476.
    124) 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.
    125) McKerrow CT, Davies HJ, & Jones PA: Symptoms and lung function following acute and chronic exposure to toluene diisocyanate. Proc Roy Soc Med 1970; 63:376-378.
    126) 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.
    127) Moller DR, Brooks SM, & McKay RT: Chronic asthma due to toluene diisocyanate. Chest 1986; 90:494-499.
    128) Montgomery Safety Products: Montgomery Safety Products Chemical Resistant Glove Guide, Montgomery Safety Products, Canton, OH, 1995.
    129) Moscato G, Dellabianca A, & Corsico A: Bronchial responsiveness to ultrasonic fog in occupational asthma due to toluene diisocyanate. Chest 1993; 104:1127-1132.
    130) Moscato G, Dellabianca A, & Vinci G: Toluene diisocyanate-induced asthma: clinical findings and bronchial responsiveness studies in 113 exposed subjects with work-related respiratory symptoms. J Occup Med 1991; 33:720-725.
    131) Musk AW, Peters JM, & Bernstein L: Absence of respiratory effects in subjects exposed to low concentrations of TDI and MDI: a re-evaluation. J Occup Med 1985; 27:917-920.
    132) NFPA: Fire Protection Guide to Hazardous Materials, 13th ed., National Fire Protection Association, Quincy, MA, 2002.
    133) NIOSH: Criteria for a Recommended Standard: Occupational exposure to Toluene Diisocyanate. DHEW Pub No (HSM) 73-11022, National Institute for Occupational Safety and Health, Cincinnati, OH, 1973.
    134) 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.
    135) 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.
    136) 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.
    137) 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.
    138) Nakashima K, Takeshita T, & Morimoto K: Diagnosis and prevention of diseases induced by isocyanate. Environ Health Prevent Med 2002; 7:40-46.
    139) 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.
    140) 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.
    141) 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.
    142) 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.
    143) 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.
    144) 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.
    145) 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.
    146) 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.
    147) 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.
    148) 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.
    149) 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.
    150) 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.
    151) 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.
    152) 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.
    153) 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.
    154) 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.
    155) 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.
    156) 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.
    157) 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.
    158) 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.
    159) 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.
    160) 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.
    161) 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.
    162) 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.
    163) 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.
    164) 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.
    165) 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.
    166) 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.
    167) 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.
    168) 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.
    169) 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.
    170) 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.
    171) 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.
    172) 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.
    173) 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.
    174) 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.
    175) 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.
    176) 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.
    177) 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.
    178) 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.
    179) 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.
    180) 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.
    181) 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.
    182) 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.
    183) 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.
    184) 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.
    185) 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.
    186) 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.
    187) 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.
    188) 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.
    189) 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.
    190) 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.
    191) 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.
    192) 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.
    193) 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.
    194) 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.
    195) 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.
    196) 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.
    197) 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.
    198) 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.
    199) 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.
    200) 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.
    201) 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.
    202) 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.
    203) 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.
    204) 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.
    205) 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.
    206) 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.
    207) 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.
    208) 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.
    209) 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.
    210) 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.
    211) 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.
    212) 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.
    213) 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.
    214) National Asthma Education and Prevention Program: Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol 2007; 120(5 Suppl):S94-S138.
    215) 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.
    216) 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.
    217) National Research Council : Acute exposure guideline levels for selected airborne chemicals, 5, National Academies Press, Washington, DC, 2007.
    218) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 6, National Academies Press, Washington, DC, 2008.
    219) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 7, National Academies Press, Washington, DC, 2009.
    220) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 8, National Academies Press, Washington, DC, 2010.
    221) National Research Council: Biologic Markers in Immunotoxicology, National Academy Press, Washington, DC, 1992.
    222) National Toxicology Program: Carcinogenesis Bioassay of Diisocyanate. NTP #10638W, US Department of Human Health Services, Research Triangle Park, NC, 1982.
    223) National Toxicology Program: Toluene diisocyanates. Rep Carcinog 2011; 12:414-416.
    224) 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.
    225) Niewenhuis R, Scheel LD, & Stemmer K: Toxicity of chronic low level exposures to toluene diisocyanate in animals. Am Ind Hyg Assoc J 1965; 26:143-149.
    226) 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.
    227) North: eZ Guide Interactive Software. North Safety. Cranston, RI. 2002a. Available from URL: http://www.northsafety.com/feature1.htm. As accessed 8/31/2002.
    228) O'Donoghue JL: Neurotoxicology of Industrial and Commercial Chemicals, 1 & 2, CRC Press, Inc, Boca Raton, FL, 1985, pp 136&34.
    229) Owen P: The toxicity and carcinogenicity to rats of toluene diisocyanate vapor administration by inhalation for a period of 113 weeks. HLE Project 484/1, 1980.
    230) Paggiaro PL, Bacci E, & Paoletti P: Bronchoalveolar lavage and morphology of the airways after cessation of exposure in asthmatic subjects sensitized to toluene diisocyanate. Chest 1990; 98:536-542.
    231) Paggiaro PL, Bacci E, & Talini D: Atropine does not inhibit late asthmatic responses induced by toluene diisocyanate in sensitized subjects. Am Rev Respir Dis 1987; 136:1237-1241.
    232) Paggiaro PL, Loi AM, & Rossi O: Follow-up study of patient with respiratory disease due to toluene diisocyanate (TDI). Clin Allergy 1984; 14:463-469.
    233) Paggiaro PL, Vagaggini B, & Dente FL: Bronchial hyperresponsiveness and toluene diisocyanate. Chest 1993; 103:1123-1128.
    234) Pala G , Pignatti P , & Moscato G : Occupational exposure to toluene diisocyanate and neutrophilic bronchitis without asthma. Clin Toxicol (Phila) 2011; 49(6):506-507.
    235) Park HS, Cho SH, Hong CS, et al: Isocyanate-induced occupational asthma in far-eas Asia: pathogenesis to prognosis. Clin Exp All 2002; 32:198-204.
    236) Park HS, Kim HY, & Nahm DH: Sepdific IgG, but not specific IgE, antibodies to toluene diicosyanate-human serum albumin conjugate are associated with toluene diisocyanate bronchoprovocation test results. J Allergy Clin Immunol 1999; 104:847-851.
    237) Parker DL, Waller K, & Himrich B: A cross-sectional study of pulmonary function in autobody repair workers. Am J Public Health 1991; 81:768-771.
    238) Patterson R, Nugent KM, & Harris KE: Immunologic hemorrhagic pneumonia caused by isocyanates. Am Rev Respir Dis 1990; 14:226-230.
    239) Pauluhn J & Mohr U: Assessment of respiratory hypersensitivity in guinea-pigs sensitized to diphenylmethane-4,4'-diisocyanate (MDI) challenge and challenged with MDI, acetylcholine or MDI-albumin conjugate. Toxicology 1994; 92:53-74.
    240) Persson P, Dalene M, & Skarping G: Biological monitoring of occupational exposure to toluene diisocyanate - measurement of toluenediamine in hydrolysed urine and plasma by gas chromatography-mass spectrometry. Br J Ind Med 1993; 50:1111-1118.
    241) Pisati G, Baruffini A, & Zedda S: Toluene diisocyanate induced asthma: outcome according to persistence or cessation of exposure. Br J Ind Med 1993; 50:60-64.
    242) Playtex: Fits Tough Jobs Like a Glove, Playtex, Westport, CT, 1995.
    243) Porter CV, Higgins RL, & Scheel LD: A retrospective study of clinical, physiologic, and immunologic changes in workers exposed to toluene diisocyanate. Am Ind Hyg Assoc J 1975; 36:159-168.
    244) Proctor NH, Hughes JP, & Fischman ML: Chemical Hazards of the Workplace, 2nd ed, JB Lippincott Co, Philadelphia, PA, 1988.
    245) RTECS : Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety and Health. Cincinnati, OH (Internet Version). Edition expires 2001; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    246) Rattray NJ, Botham PA, & Hext DR: Induction of respiratory hypersensitivity to diphenylmethane-4,4'-diisocyanate (MDI) in guinea pigs. Influence of route of exposure. Toxicology 1994; 88:15-30.
    247) Redlich CA, Homer RJ, & Smith BR: Immunologic responses to isocyanates in sensitized asthmatic subjects. Chest 1996; 109:6S-8S.
    248) River City: Protective Wear Product Literature, River City, Memphis, TN, 1995.
    249) Roper CP Jr & Cromer JW Jr: Health Hazard Evaluation Determination Report 74-118-218, HEW, PHS, CDC, NIOSH, Washington, DC, 1975.
    250) Rye WA: Human responses to isocyanate exposure. J Occup Med 1973; 15:306-307.
    251) Saetta M, Maestrella P, & Di Stefano A: Effect of cessation of exposure to toluene diisocyanate (TDI) on bronchial mucosa of subjects with TDI-induced asthma. Am Rev Respir Dis 1992; 145:169-174.
    252) 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.
    253) Sax NI & Lewis RJ: Dangerous Properties of Industrial Materials, 7th ed, Van Nostrand Reinhold Co, New York, NY, 1989.
    254) Scheel LD, Killens R, & Josephson A: Am Ind Hyg Assoc J 1964; 25:179.
    255) Schnorr TM, Steenland K, & Egeland GM: Mortality of workers exposed to toluene diisocyanate in the polyurethane foam industry. Occup Environ Med 1996; 53:703-707.
    256) Selden AI, Belin L, & Wass U: Isocyanate exposure and hypersensitivity pneumonitis - a report of probable case and prevalence of specific immunoglobulin G antibodies among exposed individuals. Scand J Work Environ Health 1989; 15:234-237.
    257) Servus: Norcross Safety Products, Servus Rubber, Servus, Rock Island, IL, 1995.
    258) Shadnia S, Ahmadimanesh M, Ghazi-Khansari M, et al: Intestinal obstruction in acute inhalational toluene 2,4-diisocyanate gas toxicity. Int J Occup Environ Med 2013; 4(3):164-166.
    259) Siribaddana SH, Wijesundera A, & Fernando R: Toluene diisocyanate exposure in a glove manufacturing plant. Clin Toxicol 1998; 36:95-98.
    260) Skarping G, Dalene M, & Lind P: Determination of toluenediamine isomers by capillary gas chromatography and chemical ionization mass spectrometry with special reference to the biological monitoring of 2,4- and 2,6-toluene diisocyanate. J Chromatogr A 1994; 663:199-210.
    261) Standard Safety Equipment: Product Literature, Standard Safety Equipment, McHenry, IL, 1995.
    262) Stevens MA & Palmer R: The effect of tolylene diisocyanate on certain laboratory animals. Proc Royal Soc Med 1970; 63:380-382.
    263) Styles JA: Br J Cancer 1978; 37:931-936.
    264) Su TC, Lin PH, & Chiu MJ: Dimethylacetamide, ethylenediamine, and diphenylmethane diisocyanate poisoning manifest as acute psychosis and pulmonary edema: treatment with hemoperfusion. Clin Toxicol 2000; 38:429-433.
    265) Talini D , Novelli F , Bacci E , et al: Mild improvement in symptoms and pulmonary function in a long-term follow-up of patients with toluene diisocyanate-induced asthma. Int Arch Allergy Immunol 2013; 161(2):189-194.
    266) Thompson T & Belsito DV: Allergic contact dermatitis from a diisocyanate in wool processing. Contact Dermatitis 1997; 37:239.
    267) 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.
    268) Tossin L, Chiesura-Corona P, & Fabbri LM: Ketotifen does not inhibit asthmatic reactions induced by toluene di-isocyanate in sensitized subjects. Clin Exp Allergy 1989; 19:177-182.
    269) 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.
    270) Trelleborg-Viking, Inc.: Trellchem Chemical Protective Suits, Interactive manual & Chemical Database. Trelleborg-Viking, Inc.. Portsmouth, NH. 2001.
    271) 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.
    272) 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.
    273) 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-.
    274) 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.
    275) 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.
    276) 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.
    277) 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.
    278) U.S. Occupational Safety and Health Administration: Part 1910 - Occupational safety and health standards (continued) Occupational Safety, and Health Administration's (OSHA) list of highly hazardous chemicals, toxics and reactives. Subpart Z - toxic and hazardous substances. CFR 2010 2010; Vol6(SEC1910):7-.
    279) U.S. Occupational Safety, and Health Administration (OSHA): Process safety management of highly hazardous chemicals. 29 CFR 2010 2010; 29(1910.119):348-.
    280) US DHHS: Managing Hazardous Materials Incidents. Agency for Toxic Substances and Disease Registry, US Department of Health and Human Services, 1994a.
    281) US DHHS: Occupational Safety and Health Guidelines for Chemical Hazards. DHHS (NIOSH) Publication No 88-118, Supplement I-OHG, 1988.
    282) US DHHS: Seventh Annual Report on Carcinogens, Summary 1994, National Toxicology Program, US Department of Health and Human Services, Washington, DC, 1994.
    283) United States Environmental Protection Agency Office of Pollution Prevention and Toxics: Acute Exposure Guideline Levels (AEGLs) for Vinyl Acetate (Proposed). United States Environmental Protection Agency. Washington, DC. 2006. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6af&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    284) Valentino M, Governa M, & Fiorini R: Increased neutrophil leukocyte chemotaxis induced by release of a serum factor in toluene-diisocyanate (TDI) asthma. Lung 1988; 166:317-325.
    285) Vandenplas O, Cartier A, & Lesage J: Prepolymers of hexamethylene diisocyanate as a cause of occupational asthma. J Allergy Clin Immunol 1993; 91:850-861.
    286) Venables KM, Dally MB, & Burge PS: Occupational asthma in a steel coating plant. Br J Ind Med 1985; 42:517-524.
    287) Walker CL, Grammer LC, & Shaughnessy MA: Diphenylmethane diisocyanate hypersensitivity pneumonitis: a serologic evaluation. J Occup Med 1989; 31:315-319.
    288) Walworth HT & Virchow WE: Am Ind Hyg Assoc J 1959; 20:205.
    289) Weill H, Butcher B & Dharmarajan V et al: NIOSH Contract No 210-75-0006, 1981.
    290) 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.
    291) Williamson KS: Studies in diisocyanate workers. Trans Assoc Ind Med Off 1965; 15:29-35.
    292) Workrite: Chemical Splash Protection Garments, Technical Data and Application Guide, W.L. Gore Material Chemical Resistance Guide, Workrite, Oxnard, CA, 1997.
    293) Yamada K, Amitani R, & Niimi A: Interstitial pneumonitis-like lesions in guinea-pigs following repeated exposure to toluene diisocyanate. Eur Respir J 1995; 8:1300-1306.
    294) Yoshizawa Y, Ohtsuka M, & Noguchi K: Hypersensitivity pneumonitis induced by toluene diisocyanate: sequelae of continuous exposure. Ann Int Med 1989; 110:31-34.