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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1991-04-15 to 1991-05-17
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
In contrast to the substance requiring REACH registration, the test substance is in agreement with the polymer definition. The difference is that the substance tested here has a higher content of blocked isophorone diisocyanate (IPDI, CAS RN 4098-71-9) monomer.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1981)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
A skin sensitization test according to OECD 406 has already excisted since 1991 and is sufficient for evaluation of the skin sensitisation potential of the test substance.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: crystalline solid
Details on test material:
Cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, caprolactam-blocked, produced by Hüls AG.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS: 
- Strain: Dunkin-Hartley, Pirbright White, BOR:DHPW (SPF)
- Sex: female
- Source: Fa. Winkelmann, Borchen (Germany)
- Age: healthy young adults
- Weight at study initiation: 330 g (mean test); 351 g (mean control)
- Controls: 10 animals; treatment: vehicle
- Housing: max. 5 animals per cage
- Room temperature: 20 +/- 3 °C
- Rel. humidity: 30 - 70 %
- Illumination: 12 h light/dark rythm
- Diet: Ssniff G4 complete diet for guinea pigs
- Water: Drinking water ad libitum
- Acclimatisation: 14 days
- Identification: coulour marks and cage tags

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
1st application: Induction 25 % occlusive epicutaneous
2nd application: Induction 25 % occlusive epicutaneous
3rd application: Induction 25 % occlusive epicutaneous
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
1st application: Induction 25 % occlusive epicutaneous
2nd application: Induction 25 % occlusive epicutaneous
3rd application: Induction 25 % occlusive epicutaneous
No. of animals per dose:
10 test animals
10 control animals
Details on study design:
ADMINISTRATION/EXPOSURE 
- Preparation of test substance for induction:  applied quantity approximately 0.5 g of the homogeneous preparation  test substance / vehicle
- Induction schedule:  3 identical inductions on days 0, 7, and 14:   6 hour occlusive patch (left side), concentration 25 %   assessment of dermal 
reactions 6 and 24 hours  after administration
- Challenge schedule: day 28   6 hour occlusive patch (right side)   assessment of dermal reactions 24, 48, and 72 hours after administration
- Concentrations used for challenge: 25 %
- Positive control: 1-chloro-2,4-dinitrobenzene (not concurrent)
EXAMINATIONS
- Grading system: as usual for skin irritation, 0-8 scores possible
- Pilot study: determination of slightly and not skin irritating  concentrations   
dermal concentrations: 1; 5; 10; 25 % w/w   4 animals each with 4 different concentrations at different sites   
6 hour occlusive patch test   
assessment of dermal reactions at patch removal plus 24 and 48 hours  after administration
Challenge controls:
Vehicle alone on one clipped flank  
Positive control substance(s):
yes
Remarks:
1-chloro-2,4-dinitrobenzene (not concurrent)

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

RESULTS OF PILOT STUDY: None of the applied test substance concentrations  caused primary skin irritation.
RESULTS OF TEST
- Sensitization reaction: No signs of skin irritation were observed in  the application areas of test and control animals 24, 48, and 72 

hours  after administration.
- Clinical signs: No treatment related signs of systemic toxicity were  observed.
  1st, 2nd, and 3rd induction: No signs of skin irritation were observed  in the application areas of test and control animals 6 and 24 

hours after  administration.
- Other: No treatment related effects on body weight development were  observed.

Applicant's summary and conclusion

Conclusions:
Under the conditions of this skin sensitisation study according to OECD 406 the test item (51% of cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, caprolactam-blocked and 49% of isophorone diisocyanate, caprolactam-blocked) showed no dermal sensitization in female guinea pigs.
Executive summary:

The skin sensitizing properties of the test item (contains 51% of cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, caprolactam-blocked and 49% of isophorone diisocyanate, caprolactam-blocked) were assessed in a buehler test according to OECD 406. Ten female guinea pigs were treated with three identical inductions on  days 0, 7, and 14 (occlusive epicutaneous) of 25 % test substance. Ten control animals were similary treated, but with vehicle (petrolatum) alone. Two weeks after the induction treatment all animals were challengend with 25 % substance and the vehicle. All the reactions, especially erythema and oedema formation, were assessed 24, 48 and 72 hours after administration of the challenge treatment.

During the test, neither the test animals nor the controls did show any systemic effects related to the substance or impairment of bodyweight gain due to the substance.

Dermal administration in the three induction phases did not leave to any skin irritation on the administration sites of any of the test and control animals.

Challenge treatment did not cause any signs of dermal irritation in any of the treated animals in the test and control groups.

Therefore, under the conditions of this study the test item showed no dermal sensitization in female guinea pigs.