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Administrative data

Description of key information

Test substance is considered to be a skin sensitiser.

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:
24 November 1992 to 03 February 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Data from a reliable in vivo test conducted before the enforcement of Commission Regulation (EU) 640/2012 of 06 July 2012 amending, for the purpose of its adaptation to technical progress, Regulation (EC) No 440/2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) are available.
Specific details on test material used for the study:
Identification: FAT 40138/D (Cibacron yellow F-4G)
Description: powder, yellow
Batch Number: 275605.26
Purity / Formulation: 79 %
Storage Conditions: At room temperature
Species:
guinea pig
Strain:
other: Pirbright White Strain (Tif: DHP)
Sex:
male/female
Details on test animals and environmental conditions:
Source: CIBA-GEIGY Limited, Animal Production, 4332 Stein / Switzerland

The test was performed on 10 male and 10 female guinea pigs in the test group and 5 males and 5 females in the control group, respectively, initially weighing between 305 to 399 g. The animals were housed individually in Macrolon cages (Type 3), assigned to the different groups by means of random numbers generated by the random number generator, identified by individual ear tags, kept at a constant room temperature of 22±3 °C, at a relative humidity of 30 to 70 % and a 12 hours light cycle day. The animals received ad libitum standard guinea pig pellets - NAFAG No. 845, Gossau SG and fresh water. All batches of the diet are assayed for nutritive ingredients and contamination level by the manufacturer. Analytical results are available at the animal supply office. The drinking water quality fulfilled the critical parameters in the specifications of the "Schweizerisches Lebensmittelbuch" (Edition 1972). The results of the routine chemical examination of water at source (Grundwasserfassung Stein) as conducted periodically by the water authority (Baudepartement des Kantons Aargau, Abteilung Gewaesserschutz) are available to CIBA-GEIGY Limited, as well as the results of inhouse chemical analysis by the analytical laboratories of the Pharmaceutical Division, CIBA-GEIGY Limited.
Route:
intradermal
Vehicle:
other: in Freund's complete adjuvant and physiological saline (1:1)
Concentration / amount:
5 % / 0.1 ml
Day(s)/duration:
Week 1
Adequacy of induction:
highest technically applicable concentration used
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
50 %
Day(s)/duration:
Week 2
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
10 %
Day(s)/duration:
Week 5
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
The test was performed on 10 male and 10 female guinea pigs in the test group and 5 males and 5 females in the control group, respectively,
Details on study design:
RANGE FINDING TESTS:
The following concentrations of FAT 40138/D have been examined on separate animals for the determination of the maximum subirritant concentration: 1, 5, 10, 20, 30, and 50 % in vaseline.
Erythema reactions were observed with 20, 30, and 50 % FAT 40138/D in vaseline.

MAIN STUDY
A. INDUCTION EXPOSURE - INTRADERMAL
- No. of exposures: 1
- Exposure period: Intradermal injection
- Test groups: 1
- Control group: 1
- Site: shaved neck
- Frequency of applications: once
- Duration: -
- Concentrations: 5 %

A. INDUCTION EXPOSURE - EPIDERMAL
- No. of exposures: 1
- Exposure period: 48 hours
- Test groups: 1
- Control group: 1
- Site: neck
- Frequency of applications: once
- Duration: -
- Concentrations: 50 %

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Week 5
- Exposure period: 24 hours
- Test groups: 1
- Control group: 1
- Site: flank
- Concentrations: 10 %
- Evaluation (hr after challenge): 24
Positive control substance(s):
yes
Remarks:
Potassiumdichroinate in a separate study "Test No. 920024"
Positive control results:
1) In the study with Potassium dichroinate, 90 % of the animals were positive at 24 and 48 hours after treatment with a non-irritant test substance concentration of 1 % in vaseline.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
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:
negative control
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
1 % in Vaseline
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Remarks:
Potassium dichroinate
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
1 % in Vaseline
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Remarks:
Potassium dichroinate

Under the experimental conditions employed, 100 % of the animals of the test group showed skin reactions (erythema and edema) 24 and 48 hours after removing the dressings.

Interpretation of results:
GHS criteria not met
Conclusions:
FAT 40138/D was considered to be a skin sensitiser.
Executive summary:

The sensitisation potential of FAT 40138/D was evaluated in a study conducted according to the Guinea Pig Maximisation test described in OECD Guideline 406 and EU Method B.6, in compliance with GLP. Five Guinea Pigs per sex were used in the control group and 10 per sex were used in the test group. Intradermal and epidermal inductions were carried out in week 1 and week 2 at 5 and 50 % test concentrations, respectively. The test and control guinea-pigs were challenged in week 5 with the epidermal application. The test concentration used for challenge was 10 %. Approximately 24 and 48 hours after the removal of the dressing the application sites were assessed for erythema and oedema using the numerical scoring system according to Draize. Under the experimental conditions employed, 100% of the animals of the test group showed skin reactions (erythema and edema) 24 and 48 hours after removing the dressings. Hence, based on the study findings FAT 40138/D is considered to be a skin sensitiser.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Two studies are available for assessment of skin sensitisation potential of FAT 40138. In a key study, the sensitisation potential of FAT 40138/D was evaluated in a study conducted according to the Guinea Pig Maximisation test described in OECD Guideline 406 and EU Method B.6, in compliance with GLP. Five Guinea Pigs per sex were used in the control group and 10 per sex were used in the test group. Intradermal and epidermal inductions were carried out in week 1 and week 2 at 5 and 50 % test concentrations, respectively. The test and control guinea-pigs were challenged in week 5 with the epidermal application. The test concentration used for challenge was 10 %. Approximately 24 and 48 hours after the removal of the dressing the application sites were assessed for erythema and oedema using the numerical scoring system according to Draize. Under the experimental conditions employed, 100 % of the animals of the test group showed skin reactions (erythema and edema) 24 and 48 hours after removing the dressings. Hence, based on the study findings FAT 40138/D is considered to be a skin sensitiser. In a supporting study, FAT 40138/A was not found to induce sensitisation in guinea pigs. However, the evidence from the recently conducted, GLP-compliant key study cannot be overruled. Hence, FAT 40138 is considered to be a skin sensitiser.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the findings in the skin sensitisation study the test substance should be classified as Skin Sensitiser 1B according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.