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Registration Dossier
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EC number: 223-861-6 | CAS number: 4098-71-9
Skin sensitisation
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:
- 1 983
- Report date:
- 1983
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- 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 substance name:
- 3-isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate
- EC Number:
- 223-861-6
- EC Name:
- 3-isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate
- Cas Number:
- 4098-71-9
- Molecular formula:
- C12H18N2O2
- IUPAC Name:
- 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethylcyclohexane
- Details on test material:
- Isophorone diisocyanate of Hüls AG, purity not reported
Constituent 1
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
- 2 Animals per cage in Makrolon III cages
- Sniff Bedding from fir-, spruce-, pine wood, dried; cleared from dust and sterilised
- diet: ssniff G (Ssniff, soest)
- water ad libitum
- Acclimation period: approx. 7 days
ENVIRONMENTAL CONDITIONS:
- room temperature: 21°C (+/- 2°C)
- humidity: 45-55%
- light: 12h/day
Study design: in vivo (non-LLNA)
Inductionopen allclose all
- Route:
- intradermal and epicutaneous
- Vehicle:
- other: Paraffin oil (DAB 6)
- Route:
- intradermal
- Concentration / amount:
- 1st application: Induction 10 % intracutaneous in paraffin
10 % intracutaneous in FCA which was diluted 1:1 with Oleum rachaidis prior to mixing with the test item
control group 1:1 FCA in aqua dest
paraffin - Adequacy of induction:
- not specified
- Route:
- epicutaneous, occlusive
- Vehicle:
- unchanged (no vehicle)
- Concentration / amount:
2nd application: Induction undiluted occlusive epicutaneous
Challengeopen allclose all
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: Paraffin oil (DAB 6)
- No.:
- #3
- Route:
- epicutaneous, occlusive
- Vehicle:
- unchanged (no vehicle)
- Concentration / amount:
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 (paraffin) (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 and test item
- 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 chemical
- 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 chemical
- 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 .
- Group:
- positive control
- Remarks on result:
- other: no positive control tested in this study
- Remarks:
- validation tests not reported
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:
The clear liquid test item 3 -isocyanatomethyl-3,5,5 -trimethylcyclohexyl isocyanate; IPDI ( CAS# 4098 -71 -9 / EC# 223 -861 -6) was tested in a Guinea pig maximization test (Magnussen and Kligmann) according to OECD 406 for its sensitizing properties.
20 Dunkin-Hartley, Pirbright White guinea pigs with a mean body weight of 350 g were used in this study for both, for the test item group as well as for the control group. Prior to the main study a pilot range finding study in order to assess skin irritation by the test item was conducted. The test item was tested undiluted; 75 % and 50 % in the vehicle paraffin in 2 animals per concentration.
The induction was conducted on day 0 intradermal and after 7 days epicutane:
Day 0: Pairwise injections of 0.05 ml each on shoulders:
- 2 x test substance 10 % in vehicle (paraffin) (control: vehicle)
- 2 x test substance 10 % in 50:50 mixture of FCA / oleum arachidis
(control: vehicle instead of test substance)
- 2 x FCA / distilled water (50:50) (control: FCA undiluted)
Day 7: 48 hours closed patch treatment of injection sites (0.5 ml undiluted test item; control: vehicle)
The challenge was conducted after 21 -22 days for 24 hour by closed patch treatment of the undiluted the test item (0.5 mL; left flank) / vehicle (right flank) and readings were conducted at patch removal and 24 hours later.
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
The test item showed no indication of primary irritation in the range finding study in concentrations up to 100%.
24 hours after the challenge, 17 out of 20 animals were positive having an overall mean score of 1.15 (max.3). After 48 hours 16 out of 20 animals were positive having an overall mean score of 0.85 (max.3). 24 and 48 hours after the challenge 19 out of 20 animals showed a positive reaction. In the control group 0 out of 20 animals were positive at 24 and at 48 hours after the challenge.
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. These results characterize the test substance as a dermal sensitizer under the conditions of this study.
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