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Toluene diisocyanate (TDI), methylene diisocyanate (MDI), hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), 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).


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. Inhalation is the typical route of sensitization but skin contact may also play a role. Once a person is sensitized to one isocyanate, cross-reactivity to others often occurs.


The ACGIH-recommended 8-hour TLV–time-weighted averages (TWA) and the California OSHA permissible exposure limits (PELs) for TDI, MDI, HDI, and IPDI are all 0.005 ppm (Federal OSHA limits are less stringent for TDI and MDI and not established for HDI and IPDI). These exposure limits are intended to prevent acute irritant effects. In individuals with prior sensitivity, however, even this level may induce asthma responses. The level considered immediately dangerous to life or health (IDLH) for TDI is 2.5 ppm. Other isocyanates (eg, MDI, HDI) are less volatile, but exposure can occur from inhalation of spray aerosols and skin contact.


  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 be delayed several hours.

  2. Low-level chronic exposure may produce dyspnea, wheezing, and other signs and symptoms consistent with asthma. A late-phase symptom onset in a sensitized individual may occur hours following exposure (eg, overnight after a work day). Interstitial lung responses, with radiographic infiltrates and hypoxemia, may occur less commonly as a hypersensitivity pneumonitis syndrome.


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 ...

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