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Diss Factsheets

Administrative data

Description of key information

The test item did not show any signs of sensitising properties in an OECD 406 guinea pig maximisation test.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
In vivo test (maximisation test) was available already.
Species:
guinea pig
Strain:
Dunkin-Hartley
Remarks:
Pirbright-White
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG, Kastengrund, breeding colony, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Weight at study initiation: mean = 334 g (n = 30)
- Housing: in fully air-conditioned rooms in Makrolon cages on soft wood granulate, in groups of 5 animals
- Diet (e.g. ad libitum): Altromin 3112, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 d
- Indication of any skin lesions: none

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 55 +/- 20%
- Air changes (per hr): fully air-conditioned
- Photoperiod (hrs dark / hrs light): 12:12

Identification with cage numbering and fur-marking (KMnO4)
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
2 x 0.1 ml 50% Freund's Adjuvant
2 x 0.1 ml 5% solution of test substance in isotonic saline
2 x 0.1 ml 5% solution of test substance in 50% Freund's adjuvant
Day(s)/duration:
Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
25% / 0.5 mL
Day(s)/duration:
Day 8 for 48 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
25% /0.5 mL
Day(s)/duration:
Day 22 for 24 h
Adequacy of challenge:
highest non-irritant concentration
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
25% / 0.5 mL
Day(s)/duration:
Day 29 for 24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Control group: 10
Treatment group: 20
Details on study design:
RANGE FINDING TESTS:
Intradermal: 0.2, 2, 5% in isotonic saline
Dermal: 1, 5, 25% in isotonic saline

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 intradermal; 1 dermal
- Exposure period: Day 1 and Day 8
- Test groups: 1
- Control group: 1
- Site: neck
- Frequency of applications: single
- Duration: 48 h
- Concentrations: 5% and 25%

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: Day 22 and Day 29
- Exposure period: 24 h
- Test groups: 1
- Control group: 1
- Site: flank
- Concentrations: 25%
- Evaluation (hr after challenge): 24 and 48 h after patch removal

OTHER:
Challenge controls:
yes
Positive control substance(s):
yes
Positive control results:
valid
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
6
Total no. in group:
20
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10

Body weight gains and clinical signs

The treated animals showed no clinical signs of intoxication throughout the study.

The intradermal injections with Freund's Adjuvant (with and without test sub­stance) caused severe erythema and oedema as well as indurations and encrusta­tions. The intradermal injections with the test substance in the vehicle caused very slight erythema and oedema. The intradermal applications of the vehicle alone caused no signs of irritation. Additionally the application sites treated with the test substance in Freund's Adjuvant and in the vehicle were discoloured yellow.

Due to these strong irritation reaction of the skin, 10% sodium dodecylsulfate was not applied at day 7.

After the removal of the patch at day 10, erythema and oedema, indurated, scab­bed and encrusted skin as well as necrosis and open wounds were observed at the sites previously treated with Freund's Adjuvant. The injection sites treated with the test substance in the vehicle and the vehicle alone showed no signs of irritation. Additionally the skin of the animals in the treatment group was discoloured yellow.

The body weight gains of the treated animals were not impaired.

Challenge treatment

48 hours after removal of the patches five animals of the treatment group showed very slight and one animal a well-defined erythema. Additionally the skin of all animals was discoloured yellow-orange. No signs of irritation occurred in the animals of the control group.

Repeated challenge treatment

No signs of irritation were observed 24 and 48 hours after removal of the occlusive bandage in the control group and in the treated group. The skin of the animals was discoloured yellow-orange

Under the conditions of the present study, none of twenty animals of the treatment group showed a positive skin response after the repeated challenge procedure. Therefore, the positive skin reactions after the first challenge procedure cannot be attributed to a sensitizing potential.

Interpretation of results:
GHS criteria not met
Conclusions:
None of the 20 animals in the treatment group showed a positive response after the repeated challenge procedure. The test substance did not show evidence for sensitizing properties.
Executive summary:

Testing for sensitizing properties of the test substance was performed in female Guinea pigs according to the method of MAGNUSSON & KLIGMAN.

Intradermal induction was performed using 5.0 % test substance in isotonic saline. Dermal induction as well as first and second challenge treatment were carried out with 25 % test substance in isotonic saline.

Based on the results of this study there is no evidence for sensitizing properties.

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

Justification for classification or non-classification