Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
May 26, 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The test was conducted by means of Read Across approach. The reliability of the source study report is 1. Further information was attached at section 13

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
A LLNA study has not been conducted because adequate data from guinea pig Maximisation test study are already available

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright-White
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HARLAN WINKELMANN Gartenstr. 27, D-33178 Borchen, SPF breeding colony
- Females (if applicable) nulliparous and non-pregnant: not specified
- Weight at study initiation: mean = 364 g
- Housing: macrolon cages (type 4) on soft wood granulate in groups of 5 animals
- Diet (e.g. ad libitum): ssniff® Ms-H (V2233), ad libitum
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
- Acclimation period: at Ieast 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 50 ± 20 %
- Photoperiod (hrs dark / hrs light): 12 hours light daily
- Animai identification: fur marking with KMnO4 and cage numbering

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
100 % of test substance moistened with 0.8 mi deionized water
Day(s)/duration:
Day 1 to 15
Challenge
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
100 % of test substance moistened with 0.8 ml deionized water
Day(s)/duration:
day 29
No. of animals per dose:
20 in the test group
10 in the control group
3 in the primary non-irritant concentration test group
Details on study design:
RANGE FINDING TESTS:
In a dermal-occlusive test for primary skin irritation, each of the following test concen-trations was administered to the flank of two guinea pigs:
100.0 % Telon-Gelb GW Micro 20.0 % in deionized water 4.0 % in deionized water
The hair on the flank of the animals was removed mechanically. 0.5 g of the test substance preparation was administered to a 2 x 2 cm cellulose patch, which was fixed to the flank and covered occlusively for 6 hours with a bandage and film. 24 hours after removal of the patches, the treated skin areas were examined for erythema and oedema according to the scale of the EEC-Guideline B.6.

MAIN STUDY
A. INDUCTION EXPOSURE
Day 1 to 15
During this test phase, the following procedures were carried out once a week. For the dermal treatments, 100 % Telon-Gelb GW Micro moistened with 0.8 ml deionized water was administered in evenly over a 2 x 2 cm cellulose patch, which was fixed to the front part of the left flank of the 20 animals of the treatment group and then covered with an occlusive polyethylene film and a bandage (Fixomull). The 10 contrai animals were treated analogously with 0.5 ml of the vehicle. After an exposure period of 6 hours the occlusive bandage was removed and the flank skin washed. Clinical signs and irritant effects emerging during the sensitization phase were recorded.

Days 16 to 28
No further animai treatment.
Animals under observation (weekends excepted).


B. CHALLENGE EXPOSURE
Day 29
Challenge treatment. This took piace under identical conditions for control and treated animals alike. The hair of the previously untreated right flank was removed mechanically. Challenge treatment was performed with 100 % Telon-Gelb GW Micro moistened with 0.8 ml deionized water. 0.5 g of the test concentration was administered to a 2 x 2 cm cellulose patch, which was placed on the hind part of the right flank and covered with an occlusive bandage.
Positive control substance(s):
yes
Remarks:
alpha-hexyl cinnamic aldehyde

Results and discussion

Positive control results:
Based on the results of this study alpha-hexyl cinnamic aldehyde may cause sensitization by skin contact. The test system used in this study proved to be suitable for the determination of dermal sensitizer.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100 % of test substance
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100 % of test substance
No. with + reactions:
0
Total no. in group:
20

Any other information on results incl. tables

Determination of the primary non-irritant concentration

The skin surface of the animals was discolored light yellow but no signs of irritation occurred after administration of the different test concentrations.

Based on these resuits, 100 % of test substance was selected for the sensitization treatments.

Body weight gains and clinical signs

The body weight gains of the animais were not impaired. The treated animals showed no clinical signs of intoxication throughout the study.

Irritations during the sensitization phase

The skin surface of the animals was discolored light yellow in the treatment group during the sensitization phase. The animais of the control group showed no signs of irritation.

Dermal challenge treatment

The skin surface of the animals was discolored tight yellow in the control and the treatment group 24 and 48 hours after removal of the occlusive bandage.

Applicant's summary and conclusion

Interpretation of results:
other: CLP criteria not met
Conclusions:
Not skin sensitizer
Executive summary:

Method

Testing for the sensitizing properties of the tested substance was performed in female guinea pigs according to the method of BUEHLER (OECD guideline 406).

Dermal induction was performed using 100 % of the test substance moistened with 0.8 ml of deionized water. The control group was exposed to deionized water only. Challenge treatment was carried out with 100 % of test substance moistened with 0.8 ml of deionized water.

The validity of the test system is confirmed by the periodically conducted positive contral test using alpha-hexyl cinnamic aldehyde for the BUEHLER test.

Results

Under the conditions of the present study, none of twenty animais of the treatment group showed a positive skin response after the challenge procedure. Thus, the percentage of animals reacting positive is below the threshold of 15 %.

Based on the results of this study the test substance showed no evidence for sensitizing properties.