Registration Dossier

Administrative data

Description of key information

Based on two skin sensitisation tests (Hüls AG, 1991 and RTC, 2000) with substances containing 50 - 60 % cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, caprolactam-blocked no indications for a sensitization potential were observed.

Assessment of the test substance concerning respiratory sensitisation is not possible because no data are available for this toxicological endpoint.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

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.
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.
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
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
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)
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.

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.

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.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2000-03-15 to 2000-05-27
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The test substance tested here is a mixture of the substance to be registered with a similar substance at a ratio of approx. 60:40 %. The similar substance is based on hexamethylene diisocyanate instead of 3-isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1992)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
(1992)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A skin sensitization test according to OECD 406 has already excisted since 2000 and is sufficient for evaluation of the skin sensitisation potential of the test substance.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS: 
- Strain: Dunkin-Hartley
- Source: Harlan Netherlands, Horst (NL)
- Sex: female
- Age: 4-5 weeks at arrival + approx. 2 weeks for acclimatization and  pilot study
- Weight at study initiation: 519.6 +/- 59.4 g (mean test); 503.8 +/-  21.8 g (mean control)
- Identification: temporary markings following arrival
- Controls: 10 females
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days
- Temperature (°C): 20 °C to 24° C
- Humidity (%): 45 % - 65 %
- Air changes (per hr): 15 times
- Illumination: 12 hours dark/ 12 hours light
Route:
intradermal and epicutaneous
Vehicle:
other: corn oil (pilot study + induction) / petrolatum (challenge)
Concentration / amount:
1st application: Induction 0.5 % intracutaneous
2nd application: Induction 50 % occlusive epicutaneous
3rd application: Challenge 20 % occlusive epicutaneous
Route:
epicutaneous, occlusive
Vehicle:
other: corn oil (pilot study + induction) / petrolatum (challenge)
Concentration / amount:
1st application: Induction 0.5 % intracutaneous
2nd application: Induction 50 % occlusive epicutaneous
3rd application: Challenge 20 % occlusive epicutaneous
No. of animals per dose:
20 test
10 control
Details on study design:
ADMINISTRATION/EXPOSURE 
- Preparation of test substance for induction: Mixing with vehicle
- Induction schedule:   
 Day 1: Injections   
Day 2: Draize scoring for erythema and eschar formation 24 hours after  injection   
Day 7: Clipping of hair in injection sites and treatment with 0.5 ml of  10 % sodium laurylsulfate in petrolatum   
Day 8: 48 hours occlusive patch with 0.4 ml of 50 % test substance  (controls: vehicle) on injection sites   
Days 10-11: Removal of patch and residual test substance, approx. 24  hours later assessment for dermal reaction
- Injection details: 0.1 ml each at 6 positions in clipped scapular  region:   
2 x Freund's Complete Adjuvant (FCA) emulsified with sterile water  (50:50)   
2 x test substance 0.5 % in vehicle   
2 x test substance 0.5 % in 50:50 emulsion of FCA with sterile water  
pairwise and symmetrical administration of each solution / suspension   
controls: vehicle instead of test substance
- Challenge schedule:    
Day 22: 24 hours occlusive patches (each 0.2 ml) on clipped flanks with    
20 % test substance (right) and     
vehicle alone (left)   
Days 24 and 25: Assessment for challenge reaction 24 and 48 hours after  patch removal; first assessment preceded by close clipping of hair 3  
hours in advance
- Rechallenge: no
- Positive control: mercaptobenzothiazole, performed Sept. 1999 and May  2000
EXAMINATIONS
- Grading system:   
0 = no visible change   
1 = discrete or patchy erythema   
2 = moderate and confluent erythema   
3 = intense erythema and swelling   
Test animals with skin reaction not observed in the control = sensitized   
Evaluation according to EU Directives for classification and labelling:  Positive if >= 30 % sensitized
- Pilot study: Range finding  
 A) Intracutaneous: Two animals were each treated with 0.1 ml injections  of 10 %, 5 % (both impossible due to the physical properties of the test  
substance, omitted), 2 %, 1 %, 0.5 %, and 0.1 % test substance in vehicle  in the clipped scapular region. Draize scoring for erythema and eschar 
formation six days later.    
B) Epicutaneous: Five animals were each treated initially with two  injections of 0.1 ml FCA emulsion with sterile water (50:50) in the  clipped scapular  region. Seven days later the flanks were clipped and 0.2  ml test substance preparation per flank was applied in 24 hour occlusive  patches. 
Concentrations of 75 %, 50 %, 20 %, 10 %, and 5 % were thus each  applied in duplicate. Skin reaction was assessed 24 and 48 hours after  patch 
removal using the grading system shown above.
Challenge controls:
Vehicle alone on one clipped flank   
Positive control substance(s):
yes
Remarks:
Positive control: mercaptobenzothiazole, performed Sept. 1999 and May  2000
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
20 %
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: 20 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
20 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 20 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
20 %
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: 20 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
20 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 20 %. No with. + reactions: 0.0. Total no. in groups: 20.0.

RESULTS OF PILOT STUDY:
  A) Intracutaneous: No response at 0.1 % and 0.5 %, score 1 at 1 % and 2  %.
  B) Epicutaneous: No skin reaction at any concentration tested
RESULTS OF TEST
- Sensitization reaction: Upon challenge, no dermal response to test  substance or vehicle treatment was observed in any test or control 

animal.
- Clinical signs: 
  1st induction: Reaction at injection sites treated with
  - preparations including FCA: Well defined reactions (predominantly 2  scores)
  - 50 % test substance in vehicle: Very slight erythema (1 score)
  - vehicle alone: No skin reaction
  2nd induction: No significant skin reaction in test or control group
Other: Mean body weight increase 93.4 g (test group), 96.7 g (control  group) = no treatment related effect.

Conclusions:
The results obtained in this guinea pig maximisation test according to OECD 406 indicate that the test item (60% of cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, caprolactam-blocked and 40% of copolymer of caprolactam and hexane-1,6-diisocyanate) does not elicit a sensitisation response in the guinea pig, there being no evidence of response at challange following a period of induction exposure to the substance.
Executive summary:

The skin sensitizing properties of the test item (60% of cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, caprolactam-blocked and 40% copolymer of caprolactam and hexane-1,6-diisocyanate) were conducted in a guinea pig maximisation test according to OECD 406.

20 female guinea pigs were intradermally injected with an emulsion of Freund's complete adjuvant and a 0.5 % concentration of the test item (in corn oil) and one week later epidermally exposed to a 50 % concentration of test substance. 10 control animals were similary treated, but with vehicle (corn oil) alone. Two weeks after the epidermal application all animals were challengend with 20 % test substance and the vehicle.

At the challenge with the test item at 20 % concentration no response to the test item was apparent in any animal of either test group or control groups. No reaction to the vehicle alone was observed in any animal of either test or control group. These results indicate that the test item (60% of cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, caprolactam-blocked and 40% of copolymer of caprolactam and hexane-1,6-diisocyanate does not elicit a sensitisation response in the guinea pig, there being no evidence of reaction at challenge following a period of induction exposure of the test substance.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There are two skin sensitization tests according to OECD 406 available (Hüls AG, 1986 and RTC, 2000). In both studies, the test item contains 50 to 60% of cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, caprolactam-blocked and 50% of isophorone diisocyanate, caprolactam-blocked (Hüls AG, 1991) or rather 40% copolymer of caprolactam and hexane-1,6 -diisocyanate (RTC, 2000).

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 in compliance with Good Laboratory Practice regulations (Hüls AG, 1991). 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 similarly treated, but with vehicle (petrolatum) alone. Two weeks after the induction treatment all animals were challenged with 25 % substance and the vehicle. No sensitizing effects were observed in any of the ten test animals.

Furthermore, the skin sensitizing properties of the test item (60% of cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, caprolactam-blocked and 40% copolymer of caprolactam and hexane-1,6-diisocyanate) were conducted in a guinea pig maximisation test according to OECD 406 in compliance with Good Laboratory Practice (RTC, 2000). 20 female guinea pigs were intradermally injected with an emulsion of Freund's complete adjuvant and a 0.5 % concentration of the test item (in corn oil) and one week later epidermally exposed to a 50 % concentration of test substance. 10 control animals were similarly treated, but with vehicle (corn oil) alone. Two weeks after the epidermal application all animals were challenged with 20 % test substance and the vehicle. No sensitizing effects were observed in any animal of either test or control group.

Justification for selection of skin sensitisation endpoint:
There are two skin sensitization tests according to OECD 406 available (Hüls AG, 1986 and RTC, 2000). For both studies the purpose flag "weight of evidence" was chosen, because in both studies the test item contains only approx. 50% of cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, caprolactam-blocked (see discussion below). Both studies are valid with restrictions (Klimisch score 2).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the two available animal studies and according to the criteria of EC Regulation 1272/2008 cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, caprolactam-blocked is not classified as sensitizing to skin.

Classification of the substance concerning respiratory sensitisation is not possible because no data are available for this toxicological endpoint.