1-isocyanato-2(or 4)-(4-isocyanatobenzyl)benzene and their reaction products with [(methylethylene)bis(oxy)]dipropanol and butane-1,3-diol and propylene glycol

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Does not include experimental toxicological data

Cross-reference

Reason / purpose:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1995

Materials and methods

Study type:

other: Observational study

Test guideline

Qualifier:

no guideline followed

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

Commercial Diisocyanates

Method

Type of population:

occupational

Subjects:

Cohort = 1780.

Company physicians' case histories of 1780 isocyanate workers of car and chemical companies were evaluated. Specific exposure information is not provided. Sixteen (16) were subjects suspected of having isocyanate-induced hypersensitivity pneumonitis.

Clinical history:

Not Applicable

Controls:

Not Applicable

Details on study design:

Chest x-ray films were taken, levels of IgE and IgG antibodies to isocyanate-human serum albumin were estimated; conjugates and isocyanate challenge tests, bronchoalveolar lavage fluid analyses, and/or lung histologic investigations were performed.

Results and discussion

Results of examinations:

Each of the 14 study patients who had hypersensitivity pneumonitis had work-related dyspnea and fever occurring several hours after the start of work with isocyanates. Typical clinical findings were the reduction of lung diffusing capacity (n = 10), reticular or nodular lung patterns in the x-ray film (n = 9), and serum IgG antibodies specific to isocyanate- human serum albumin conjugates (n = 10). Restrictive ventilation patterns in the inhalation challenge tests (n 5), lymphocytic and/or neutrophilic alveolitis seen in bronchoalveolar lavage fluid analyses (n = 7), and lymphohistiocytic patterns mostly associated with mild fibrosis in lung histology (n = 5) confirmed the diagnosis.

Any other information on results incl. tables

Hypersensitivity pneumonitis is caused by the inhalation of different organic substances and mediated by cytotoxic mechanisms and various cellular and humoral immune responses. Although the individual pathogenetic role of these responses is not clear, it can be assumed that parameters used diagnostically such as specific IgG antibodies (which may lead to the formation of immune complexes and the activation of the complement cascade) and antigen-specific lymphocyte reactions are also operative in this chronic interstitial lung disease. Symptoms and clinical findings of the 14 cases described here are in line with the generally accepted pathogenesis and diagnostic criteria of hypersensitivity pneumonitis.

Applicant's summary and conclusion

Conclusions:

Diisocyanate has been described mainly as causing sensitizing and non-sensitizing asthma, and to a lesser extent hypersensitivity pneumonitis, which is a type of parenchymal lung disease. MDI is the diisocyanate most often implicated. Although the condition is fairly rare, awareness and a sound medical surveillance program are very important so that definite diagnoses of exposed workers can be obtained and appropriate preventive measures can be introduced.