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Toluene diisocyanate (TDI), methylene diisocyanate (MDI), and related chemicals are industrial components in the polymerization of urethane coatings and insulation materials. Urethanes have widespread uses in sealants, coatings, finishes, glues, and even medical applications (eg, casts). Most two-part urethane products contain some amount of one of these chemicals, and lesser amounts contaminate one-part systems. Methyl isocyanate (the toxin released in the disaster in Bhopal, India) is a carbamate insecticide precursor; it is not used in urethanes, has actions different from those of the TDI group of chemicals, and is not discussed here (see Table IV–4).

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  1. Mechanism of toxicity. TDI and related isocyanates act as irritants and sensitizers at very low concentrations. The mechanism is poorly understood. They may act as haptens or through cell-mediated immune pathways. Once a person is sensitized to one isocyanate, cross-reactivity to others often occurs.

  2. Toxic dose. The ACGIH-recommended workplace limit (threshold limit value—short-term exposure limit [TLV-STEL]) and the OSHA limit (permissible exposure limit—ceiling [PEL-C]) for TDI are both 0.02 ppm (0.14 mg/m3). The ACGIH-recommended 8-hour TLV–time-weighted average (TWA) is considerably lower at 0.005 ppm (0.036 mg/m3). These exposure limits prevent acute irritant effects. In individuals with prior TDI sensitivity, however, even this level may induce asthma responses. The level considered immediately dangerous to life or health (IDLH) is 2.5 ppm. Other isocyanates (eg, MDI, hexamethylene diisocyanate [HDI]) are less volatile, but overexposure can occur from inhalation of spray aerosols and potentially through direct skin contact. The ACGIH TLV-TWA values for MDI and HDI are the same as those for TDI.

  3. Clinical presentation

    1. Acute exposure to irritant levels causes skin and upper respiratory tract toxicity. Burning eyes and skin, cough, and wheezing are common. Noncardiogenic pulmonary edema may occur with severe exposure. Symptoms may occur immediately with exposure or may occasionally be delayed several hours.

    2. Low-level chronic exposure may produce dyspnea, wheezing, and other signs and symptoms consistent with asthma. Interstitial lung responses, with radiographic infiltrates and hypoxemia, may occur less commonly as a hypersensitivity pneumonitis syndrome.

  4. Diagnosis requires a careful occupational history. Pulmonary function testing may document an obstructive deficit or less commonly restriction (if pneumonitis is present), or the results may be normal. Variable airflow or changing measures of airway reactivity (methacholine or histamine challenge) temporally linked to exposure strongly support the diagnosis of isocyanate-induced asthma.

    1. Specific levels. There are no routine clinical blood or urine tests for isocyanates.

      1. Test inhalation challenge to isocyanate is not advised except in experienced laboratories owing to the danger of severe asthma attack.

      2. Isocyanate antibody testing, although used in research, is difficult to interpret in an individual patient and may not correlate with non-IgE responses.

    2. Other useful laboratory studies include co-oximetry or arterial blood gases, chest radiography, and pulmonary function tests.

  5. Treatment

    1. Emergency and supportive measures

      1. After acute high-intensity inhalational exposure, maintain an open airway (See Airway), give bronchodilators as needed for wheezing (See Hypoxia), and observe for 8–12 hours for pulmonary edema (See Hypoxia...

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