Registration Dossier

Diss Factsheets

Toxicological information

Sensitisation data (human)

Currently viewing:

Administrative data

sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
other information
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment

Data source

Reference Type:
The low prevalence of occupational asthma and antibody-dependent sensitization to diphenylmethane diisocyanate in a plant engineered for minimal exposure to diisocyanates
Bernstein DI, Korbee L, Stauder T, Bernstein JA, Scinto J, Herd ZL, Bernstein IL.
Bibliographic source:
J. Allergy Clin. Immunol..; 92: 387-396

Materials and methods

Type of sensitisation studied:
Study type:
other: cross-sectional study
Test guideline
no guideline available
Principles of method if other than guideline:
In a cross-sectional study, 243 workers exposed to MDI were screened for occupational asthma and antibody-dependent sensitization to MDI. Methods included a questionnaire, immunologic tests and measurements of peak expiratory flow rate.
GLP compliance:
not specified

Test material

Constituent 1
Reference substance name:
Cas Number:
Constituent 2
Reference substance name:
Isocyanic acid, polymethylenepolyphenylene ester
Isocyanic acid, polymethylenepolyphenylene ester
Constituent 3
Chemical structure
Reference substance name:
Isocyanic acid, polymethylenepolyphenylene ester
Cas Number:
Molecular formula:
Isocyanic acid, polymethylenepolyphenylene ester
Test material form:
aerosol dispenser: not specified
migrated information: aerosol


Type of population:
Ethical approval:
not specified
- Number of subjects exposed: 243
- Sex: men (175) and women (68)
- Duration of employment: 0-32 months with an average of 18.2 months
- Occupation: workers in the urethane mould lines (147), worker in administrative/transport/maintenance jobs (96)

Of note, from 1992 to 1992, 41 (17%) of the 243 employees left the mould area; only 4 (1.6%) were transferred for work-related medical reasons.
Route of administration:
Details on study design:

- Questionnaire
A questionnaire was taken by an interviewer, so as to reveal upper and lower respiratory symptoms, their time of onset, and their resolution or persistence after leaving the workplace. Questions elicited data pertaining to possible risk factors such as smoking and a personal history of seasonal respiratory symptoms during the spring, summer, and late fall. Questionnaire-derived diagnoses were assigned to each worker that included (1) probable or possible OA, (2) lower respiratory irritant responses; (3) non-OA, (4) urticaria or skin rash; (5) chronic bronchitis (nonoccupational); (6) occupational nasal symptoms and (7) nonoccupational nasal symptoms.

- Immunological tests
Sera from workers were assessedfor specific IgG and IgE antibodies to MDI-HSA.

- Lung function measurements
All workers who reported at least one lower respiratory symptom of wheezing, coough or shortness of breath and those workers with MDI-HSA specific antibodies were instructed to perform serial peak expiratory flow rate (PEFR) sstudies.
In all workers with PEFR variability, a detailed medical evaluation by a physician experienced in the evaluation of OA was done.
Under a casecontrol design, serial PEFR studies were also conducted on 23 randomly selected workers who did not report lower respiratory symptoms on the questionnaire.

Results and discussion

Results of examinations:
During the entire 3 years that the plant had been in operation short-term exposure did not exceed the accepted threshold limit value of 0.005 ppm.

9 (4%) workers had diagnoses of possible OA, 26 (11%) had lower respiratory irritant symptoms; 4 (2%) had diagnoses of non-OA, 2 (1%) reported chronic bronchitis; work-related urticaria and angioedema were found in 2 (1%); 88 (36%) reported work-related nasal symptoms; 22 (9%) reported non-work-related nasal symptoms; and, finally, 111 (46%) workers reported no symptoms at all.
Overall, work-related lower respiratory symptoms (OA and lower respiratory irritant) were reported by 15% of 243 workers.
No significant associations were found between these diagnoses and the presence or absence of risk factors including smoking, atopic history and job description. Equally, there was no significant association with duration of exposure.

Of the 243 workers tested, only 2 had elevated levels of both serum specific IgE and IgG to MDI-HSA.

PEFR studies were performed in 43 workers who reported lower respiratory symptoms and in 23 workers free of symptoms who were randomly selected to serve as case controls. Of nine workers with questionnaire diagnoses of OA, three exhibited work-related PEFR variability, whereas two of four with non-OA exhibited non-work-related variability. Significant PEFR variability was not detected in workers classified with lower respiratory irritant symptoms. Interestingly, 2 of 23 of the “asymptomatic” case control subjects exhibited significant variability in PEFR. A significant association was found between questionnaire-derived diagnoses of asthma (occupational or non-occupational) and the presence of PERF variability.

Applicant's summary and conclusion

Strict control and monitoring of ambient MDI exposure was associated with a low prevalence of specific sensitization to MDI and a lower than expected prevalence of occupational asthma.
Executive summary:

This paper by Bernstein et al. (1993) described a cross-sectional study of 243 workers exposed to diphenylmethane diisocyanate (MDI) in a urethane mold plant that had been designed to minimize MDI exposure (levels were maintained below 0.005 ppm and were continuously monitored).

All participants were screened by questionnaire and tests for serum antibodies to MDI-human serum albumin (HSA). On the basis of questionnaire responses, diagnoses were derived that included occupational asthma (OA), non-OA, work-related and non-work-related rhinitis and lower respiratory irritant responses. Serial peak respiratory flow rate studies were performed for 2 weeks in 43 workers with and in 23 workers without lower respiratory symptoms.

Results of serial peak expiratory flow rate studies were abnormal in 3 (33%) of 9 workers with OA, in 2 (50%) of 4 with non-OA and in 2 (9%) of 23 case control subjects. A significant association was found between peak flow rate variability and a questionnaire asthma diagnosis. Physicians confirmed three cases of OA, one of which occurred in a control worker who was free of symptoms. In all three cases asthma symptoms remitted after the worker left the workplace. Serum specific IgE and IgG levels were elevated in 2 of 243 workers.

On the basis of these cases, specific work activities associated with exposure to MDI were identified and corrective measures were instituted. Strict control and monitoring of ambient MDI exposure was associated with a low prevalence of specific sensitization to MDI and a lower than expected prevalence of OA.