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Toxicological information

Sensitisation data (human)

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Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Limited documentation

Data source

Reference
Reference Type:
publication
Title:
Allergic contact dermatitis from dicyclohexylmethane-4,4'-diisocyanate
Author:
Frick M, Björkner B, Hamnerius N and Zimerson E
Year:
2003
Bibliographic source:
Contact Dermatitis 48, 6, 305-309

Materials and methods

Type of sensitisation studied:
skin
Study type:
case report
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Clinical patch test with a standard series (comprising a modified European standard series), an isocyanate series and work material conducted with workers
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
source and purity of test material not described

Method

Type of population:
occupational
Ethical approval:
not specified
Subjects:
- A glue, mainly based on dicyclohexylmethane-4,4'-diisocyanate (70 %),  was suspected of being the cause of an outbreak of severe eczema at a  
factory manufacturing medical equipment from August 1999 to April 2001.  16 out of approximately 100 persons working in the relevant 
department  were referred to medical consultation. 
- These 16 workers with recent episodes of eczema were patch tested with  a standard series, an isocyanate series, and work material.
Controls:
Additionally, dermatitis patients served as controls and were patch tested only with DMDI and DMDA.
Route of administration:
dermal
Details on study design:
accidental and unintentional occupational exposure

Results and discussion

Results of examinations:
Medical history of some workers and test substances which may cause contact allergy, employment time before elicitation and site of lesion of the patients described in the publication. Number of positive reactions after patch tests are described for the tested substances.

MAIN RESULTS: No. positive (total no. tested) and concentration (%w/w) tested 13 (17) patients reacted to dicyclohexylmethane-4,4'-diisocyanate (1% and 0.1% t ested)    
9 (17) patients reacted to hexane-1,6-diisocyanate (0.1% tested)    
5 (17) patients reacted to bis-(4-aminocyclohexyl)methane  (0.1% tested)  
5 (17) patients reacted to bis-(4-aminophenyl)methane (0.5% tested)
4 (17) patients reacted to isophoronediisocyanate (1% tested)     
0 (17) patients reacted to diphenylmethane-4,4'-diisocyanate or toluene  diisocyanate (2% tested ; each) ( further concentrations and substances/glue were/was tested)

Any other information on results incl. tables

4 tested workers reacted to the test substance Isophoronediisocyanate (IPDI). As far as authors know, none of them had contact with this substance before

Applicant's summary and conclusion

Conclusions:
The authors conclude, that aliphatic diisocyanates are strong cutaneous sensitizers and aromatic diisocyanates are weak cutaneous sensitizer. The test substance Isophoronediisocyanate (IPDI) showed positive patch-test reaction in 4 workers, but none of the workers had contact with IPDI before. This could be explained with cross reactivity between the isocyanates of the glue, used by the workers and the test substance IPDI.
Executive summary:

A glue, mainly based on dicyclohexylmethane-4,4'-diisocyanate (70 %),  was suspected of being the cause of an outbreak of severe eczema at a   factory manufacturing medical equipment from August 1999 to April 2001.  16 out of approximately 100 persons working in the relevant  department  were referred to medical consultation.  Patch tests were conducted at 16 workers that used isocyanate-containing glue with a standard series, an isocyanate series and work material. One isocyanate in the isocyanate series was Isophoronediisocyanate (IPDI). The test substance IPDI was applied in a concentration of 1 % (w/w). The authors conclude, that aliphatic diisocyanates are strong cutaneous sensitizers and aromatic diisocyanates are weak cutaneous sensitizer. The test substance Isophoronediisocyanate (IPDI) showed positive patch-test reaction in 4 workers, but none of the workers had contact with IPDI before. To our opinion this could be explained with cross reactivity between the isocyanates of the glue, used by the workers and the test substance IPDI.