Registration Dossier

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:
key study
Study period:
1983-05-04 to 1983-06-03
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions: Purity of test substance not reported

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A skin sensitization test according to OECD 406 has already excisted since 1983 and is sufficient for evaluation of the skin sensitisation potential of the test substance.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Isophorone diisocyanate of Hüls AG, purity not reported

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS: 
- Strain: Dunkin-Hartley, Pirbright White, Hoe: DHPK (SPF - LAC.) /Boe.
- Sex: no data
- Source: Lippische Versuchstierzucht Hagemann, Extertal (Germany)
- Weight at study initiation: mean 350 g
- Controls: 20 animals, concurrent vehicle - Housing conditions: room temperature: 21°C (+/- 2°C); humidity: 45-55%; light: 12h/day, diet: ssniff G (Ssniff, soest); water ad libitum

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: Paraffin oil (DAB 6)
Concentration / amount:
1st application: Induction 10 % intracutaneous
2nd application: Induction undiluted occlusive epicutaneous
3rd application: Challenge undiluted occlusive epicutaneous
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Paraffin oil (DAB 6)
Concentration / amount:
1st application: Induction 10 % intracutaneous
2nd application: Induction undiluted occlusive epicutaneous
3rd application: Challenge undiluted occlusive epicutaneous
No. of animals per dose:
20 test / 20 control
Details on study design:
ADMINISTRATION/EXPOSURE 
- Induction schedule:    
Day 0: Injection   
- Injection details: pairwise injections of 0.05 ml each on shoulders:  
2 x test substance 10 % in vehicle    (control: vehicle)   
2 x test substance 10 % in 50:50 mixture of Freund's Complete Adjuvant (FCA) / oleum arachidis   (control: vehicle instead of test substance)   
2 x FCA / distilled water (50:50)   (control: FCA undiluted) - Days 7-9: 48 hours closed patch treatment of injection sites (0.5 ml;  control: vehicle)
- Challenge schedule:    
Days 21-22: 24 hour closed patch treatment with test substance (left  flank) / vehicle (right flank)   
Days 22-23: Readings at patch removal and 24 hours later
- Concentrations used for challenge: 100 % (0.5 ml)
- Rechallenge: no - Positive control: none
EXAMINATIONS
- Grading system:   
0 = no skin reaction   
0.5 = slight and spotted erythema   
1 = slight and regular, or moderate and spotted erythema   
2 = moderate erythema    
3 = severe erythema or edema
- Pilot study: range finding (skin irritation)   Test substance undiluted; 75 %; 50 % in vehicle tested in 2 animals per  concentration   
Single dermal treatment with 0.5 ml, probably (not reported) 24 hour  occlusive patch  
Observation period 4 days after test substance administration
Challenge controls:
Treatment: vehicle
Positive control substance(s):
no

Results and discussion

Positive control results:
no positive control

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
undiluted
No. with + reactions:
17
Total no. in group:
20
Clinical observations:
RESULTS OF PILOT STUDY: no irritation at any concentration
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: undiluted. No with. + reactions: 17.0. Total no. in groups: 20.0. Clinical observations: RESULTS OF PILOT STUDY: no irritation at any concentration .
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
RESULTS OF PILOT STUDY: no irritation at any concentration
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: RESULTS OF PILOT STUDY: no irritation at any concentration .
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
undiluted
No. with + reactions:
16
Total no. in group:
20
Clinical observations:
RESULTS OF PILOT STUDY: no irritation at any concentration
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: undiluted. No with. + reactions: 16.0. Total no. in groups: 20.0. Clinical observations: RESULTS OF PILOT STUDY: no irritation at any concentration .
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
RESULTS OF PILOT STUDY: no irritation at any concentration
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: RESULTS OF PILOT STUDY: no irritation at any concentration .

Applicant's summary and conclusion

Conclusions:
Under the conditions of this guinea pig maximization test, the test item 3-Isocyanatomethyl-3,3,3-trimetylcyclohexylisocyanate exhibited the potential to produce dermal sensitization in guinea pigs
Executive summary:

In the Guinea pig maximization test performed within this study, after intradermal and epicutaneous inductions 17(16) of 20 guinea pigs showed positive response 24 hours (48 hours) after epicutaneous challenge with undiluted test substance. In a preliminary study no irritating dermal reactions were observed at any concentration used in this study. This results characterizes the test substance as a dermal sensitizer under the conditions of this study.