Isocyanates are highly reactive, low-molecular-weight chemicals that include toluene diisocyanate (TDI), methylene diisocyanate (MDI), hexamethylene diisocyanate (HDI), and isophorone diisocyanate (IPDI). They are industrial components in the polymerization of urethane coatings and insulation materials. Urethanes have widespread uses in sealants, coatings such as paint and varnishes, flexible and rigid foams, finishes, glues and even medical applications (eg, casts).

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-3).

TDI and related isocyanates are irritants and sensitizers at low concentrations. The mechanism is poorly understood but may be related to the formation of isocyanate-protein adducts. Inhalation is the typical route of sensitization but there is evidence that both respiratory and dermal exposures can lead to sensitization. Once a person is sensitized to one isocyanate, cross-reactivity to others often occurs.

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. Contact dermatitis can result in symptoms of rash, itchiness and hives. 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 patient and may not correlate with illness.
2. Other useful laboratory studies may include co-oximetry or arterial blood gases or chest radiography in selected clinical scenarios.

1. Emergency and supportive measures
   1. After acute high-intensity inhalational exposure, maintain an open airway, give bronchodilators as needed for wheezing, and observe for 8-12 hours for pulmonary edema.
   2. Once airway hyperreactivity has been documented, further exposure to isocyanate is contraindicated. Involve public health or OSHA agencies to determine whether other workers also are at increased risk through improper workplace controls.
2. Specific drugs and antidotes. There is no specific antidote.
3. Decontamination after high-level exposure
   1. Inhalation. Remove the victim from exposure and give supplemental oxygen if available.
   2. Skin and eyes. Remove contaminated clothing (liquid or heavy vapor exposure) and wash exposed skin with copious soap and water. Irrigate exposed eyes with saline or tepid water.
4. Enhanced elimination. There is no role for these procedures.