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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:
key study
Study period:
1983-09-19 - 1983-10-14
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions: no positive control group (not required by 1981 version of guideline)

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)
Version / remarks:
1981
Deviations:
no
GLP compliance:
no
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Isophorone diamine of Hüls AG, purity >= 99.7 %

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS: 
- Strain: Dunkin-Hartley (Bor: DHPW)
- Source: Winkelmann, Borchen (Germany)
- Weight at study initiation: 363 g (mean)
- Diet: ad libitum, special diet for guinea pigs, SSniff G 4 (Ssniff, Soest, Germany)
- Water: ad libitum, tab water
- Acclimation period: 5-8 days
ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 1 °C
- Humidity: 60 +/- 5 %
- Photoperiod: 12 hours artificial light, 12 hours dark

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
other: intracutaneous (1st) and occlusive epicutaneous (2nd)
Vehicle:
other: 10 % ethanol
Concentration / amount:
1st application: Induction 0.1 % intracutaneous
2nd application: Induction 7.5 % occlusive epicutaneous
3rd application: Challenge occlusive epicutaneous
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: 10 % ethanol
Concentration / amount:
1st application: Induction 0.1 % intracutaneous
2nd application: Induction 7.5 % occlusive epicutaneous
3rd application: Challenge occlusive epicutaneous
No. of animals per dose:
9 (10) control group, 1 animal died after 1 week, cause of death is unkwon
20 test group
Details on study design:
- Induction schedule: injection followed 1 week later by patch treatment (0.3 ml) for 48 hours;
- Injection details: 0.1 ml each at 6 positions on shoulders:
2 x Freund's Complete Adjuvant
2 x test substance in 10 % ethanol
2 x Freund's Complete Adjuvant / 0.2 % test substance (1:1)
simultaneous and symmetrical application of each solution
controls: 10 % ethanol instead of test substance
- Challenge schedule: 2 weeks after end of induction patch treatment for 24 hours
- Concentrations used for challenge: 2.5 and 5 %; readings 24, 48, and 72 hours after removal of patch
- Rechallenge: no
EXAMINATIONS
- Grading system: possible scores 0 / 1 / 2 / 3
- Pilot study: dose range finding study
Challenge controls:
9 (10) animals, 1 animal died after 1 week, cause of death is unkwon
vehicle treatment
Positive control substance(s):
no

Results and discussion

Positive control results:
not applicable

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
2.5 %
No. with + reactions:
7
Total no. in group:
20
Clinical observations:
see section "Remarks on results including tables and figures"
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 2.5 %. No with. + reactions: 7.0. Total no. in groups: 20.0. Clinical observations: see section "Remarks on results including tables and figures".
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
2.5 %
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
see section "Remarks on results including tables and figures"
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 2.5 %. No with. + reactions: 5.0. Total no. in groups: 20.0. Clinical observations: see section "Remarks on results including tables and figures".
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
2.5%
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
see section "Remarks on results including tables and figures"
Remarks on result:
other: Reading:
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
2.5% test substance used for challenge
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
see section "Remarks on results including tables and figures"
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 2.5% test substance used for challenge. No with. + reactions: 0.0. Total no. in groups: 9.0. Clinical observations: see section "Remarks on results including tables and figures".
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
2.5% test substance used for challenge
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
see section "Remarks on results including tables and figures"
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 2.5% test substance used for challenge. No with. + reactions: 0.0. Total no. in groups: 9.0. Clinical observations: see section "Remarks on results including tables and figures".
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
2.5% test substance used for challenge
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
see section "Remarks on results including tables and figures"
Remarks on result:
other: see Remark
Remarks:
Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 2.5% test substance used for challenge. No with. + reactions: 0.0. Total no. in groups: 9.0. Clinical observations: see section "Remarks on results including tables and figures".
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5 %
No. with + reactions:
18
Total no. in group:
20
Clinical observations:
see section "Remarks on results including tables and figures"
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5 %. No with. + reactions: 18.0. Total no. in groups: 20.0. Clinical observations: see section "Remarks on results including tables and figures".
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5 %
No. with + reactions:
15
Total no. in group:
20
Clinical observations:
see section "Remarks on results including tables and figures"
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5 %. No with. + reactions: 15.0. Total no. in groups: 20.0. Clinical observations: see section "Remarks on results including tables and figures".
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
5 %
No. with + reactions:
10
Total no. in group:
20
Clinical observations:
see section "Remarks on results including tables and figures"
Remarks on result:
other: Reading:
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5% test substance used for challenge
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
see section "Remarks on results including tables and figures"
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 5% test substance used for challenge. No with. + reactions: 0.0. Total no. in groups: 9.0. Clinical observations: see section "Remarks on results including tables and figures".
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5% test substance used for challenge
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
see section "Remarks on results including tables and figures"
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5% test substance used for challenge. No with. + reactions: 0.0. Total no. in groups: 9.0. Clinical observations: see section "Remarks on results including tables and figures".
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
5% test substance used for challenge
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
see section "Remarks on results including tables and figures"
Remarks on result:
other: see Remark
Remarks:
Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 5% test substance used for challenge. No with. + reactions: 0.0. Total no. in groups: 9.0. Clinical observations: see section "Remarks on results including tables and figures".

Any other information on results incl. tables

  
Clinical signs:
Local effects:
- 24 hours after intracutaneous applications, animals mainly from the test substance treated group displayed poorly healing necrotic
inflammations. - After the induction patch treatment for 48 hours, the animals treated with the test substance had bleeding and matter discharging inflammations at the places of injections leading to thick crusts. - In general after removal of the patch, severe inflammation and itching were observed,causing particularly the animals treated with test substance to scratch their skins open in the area of injection. - after challenge scale formation and desiccation of skin was observed during the observation period on some animals

Applicant's summary and conclusion

Conclusions:
Isophorone diamine has to be considered to be sensitizing to the skin of guinea pigs under the conditions of the study.
Executive summary:

The skin sensitizing properties of isophorone diamine were determined in a guinea pig maximation test according to OECD TG 406 (positive controls not required by 1981 guideline version). Twenty female guinea pigs were intradermally injected with isophorone diamine at 0.1 % in 10% ethanol and one week later epidermally exposed to a 7.5 % concentration of test substance for 48 hours (occlusive). Ten control animals were similary treated, but with vehicle alone. Two weeks after the epidermal application all animals were challegend with 2.5 % and 5 % test substance and with vehicle (24 hours occlusive). At challenge concentration of 2.5 % 7/20 animals showed a sensitization 24 hours after the patch test, 5/20 animals 48 hours after the test and 2/20 72 hours after the test. At challenge concentration 5 % 18/20 animals showed a sensitization 24 hours after the patch test, 15/20 animals 48 hours after the patch test and still 10/20 72 hours after the test. No animal of the control group showed any positive reaction. Therefore Isophorone diamine has to be considered to be sensitizing to the skin of guinea pigs under the conditions of the study.