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Toxicological information

Sensitisation data (human)

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Administrative data

Endpoint:
sensitisation data (humans)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: reliable experimental method and documentation

Data source

Reference
Reference Type:
publication
Title:
No information
Author:
Welinder H et. al.
Year:
1988
Bibliographic source:
Clinical Allergy, 19: 85-93

Materials and methods

Type of sensitisation studied:
respiratory
Study type:
other: cohort study (retrospective)
Principles of method if other than guideline:
no guideline followed

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited): "The paints were based on one or two oligomers of HDI (Desmodur N-100 (DN) or N-3300;...with about 0.5 % monomer HDI."

Method

Type of population:
occupational
Subjects:
- Number of subjects exposed: 30 (car painters)
- Sex: male
- Age: average age of 35
Clinical history:
- Exposure history: They had been working as painters on average for 15 years, and with isocyanate paints on average for 8 years.

- Medical history (for respiratory hypersensitivity):
- Any other allergic or airway disorders: 8 were atopic
- Smoking history: 11 were smokers
Controls:
Referent samples in the antibody determinations were randomly selected from a group of twenty-two healthy workers, all men, employed in a food industry and with no history of isocyanate exposure.
Route of administration:
other: exposure probably by inhalation and dermal
Details on study design:
A questionnaire had to be filled out concerning atopy, chronic bronchitis, conjunctivitis, rhinitis, and asthma. Venous blood samples were collected for the serum levels of total IgE, IgG, IgM, IgA, and specific antibodies. Subjects who had symptoms or signs indicating work-related hypersensitivity underwent a further examination by a physician and, if necessary, bronchial challenge with methacholine, lung X-ray, and skin-prick tests.

Results and discussion

Results of examinations:
- Symptoms: 13 had suffered symptoms of rhinitis and/or conjunctivitis, 3 had attacks of cough, 7 had attacks of dyspnoea and/or chest tightness, 3 had chronic bronchitis. In total 10 had suffered symptoms from the bronchi. There was no association between exposure time or degree of protection, and symptoms. The atopics did not report more symptoms than non-atopics.
From a group of ten subjects who underwent further examinations two were attributed a clear clinical asthma. Patient 1 had suffered asthma since childhood, however, his asthma had been aggravated during the isocyanate exposure. Patient 2 developed asthma of late type during the time he had worked as a car painter.

- Antibody findings: No significant differences in the total antibody levels between exposed subjects and controls. No significant differences found in the RAST ratios of IgE antibodies against HDI-human serum albumin (HSA) between exposed workers and controls subjects. Car painters with symptoms, including the two asthmatics, did not have elevated specific IgE values, as compared to non-symptomatics. IgG antibodies against HDI-HSA slightly, but not significantly, increased in car painters. IgG antibodies against Desmodur N-100-HSA significantly increased in car painters, compared to controls. Six persons were found to have subclass IgG4 antibodies (IgG4-Desmodur N-100- HSA).

Mixed exposure. No clear relation to HDI Trimer exclusively.

Applicant's summary and conclusion

Executive summary:

In a study with 30 HDI prepolymer (also HDI Trimer) exposed workers the immunologic status is investigated. The presence of specific IgG antibodies is confirmed. Therefore an immunologic reaction against HDI prepolymer in general is indicated. The authors stated, that it is unknown if HDI prepolymer specific IgG antibodies play a pathogenic role, or just reflect exposure, or even block IgE and thus having a protecting function. No correlation between the presence of IgG antibodies and symptoms could be found.