Registration Dossier

Administrative data

Description of key information

Not skin sensitizer.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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:
From Mach 6, 1985 to April 4, 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The reliability of the read-across study was established to be R1. Justification for read-across is detailed at section 13.
Justification for type of information:
Justification for read-across is detailed at section 13.
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An appropriate guinea pig maximisation test was already avaiable, which would not justify conducting an additional LLNA due to animal welfare.
Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Lippische Versuchstierzucht Hagemann GmbH
- Weight at study initiation: 263 - 350 g
- Housing: in groups of 5 per Type IV Makrolon cage
- Diet: Kliba rabbit and guinea pig maintenance diet (341.4 mm); ad libitum.
- Water: tap water (drinking water with about 2g of ascorbic acid in 10 I water twice a week); ad libitum.
- Acclimation period: not less than 6 days before the start of the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24 °C
- Humidity: 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 / 12
Route:
intradermal and epicutaneous
Vehicle:
other: Freund's adjuvant, distilled water
Concentration / amount:
Intradermal induction: 5 %
Epicutaneous induction: 50 %
Epicutaneous challenge: 20 %
Route:
epicutaneous, occlusive
Vehicle:
other: Freund's adjuvant, distilled water
Concentration / amount:
Intradermal induction: 5 %
Epicutaneous induction: 50 %
Epicutaneous challenge: 20 %
No. of animals per dose:
Test group: 20
Each control group: 10
Details on study design:
RANGE FINDING TESTS:
- Administration volume: filter paper strips of 2 x 2 cm edge length were allowed to take effect in the region of the flank under occlusive conditions.
- Exposure time: the test substance was administered for 2 x 24 hours within a period of 96 hours in order to detect unspecific phenomena which are not based on a sensitization reaction but which might displace the irritation threshold.
- Site of administration: region of the flank, in each case in the same place.
- Number of animals: 4 for each test concentration.
- Readings: approximately 24 and 48 hours after the start of administration.

MAIN STUDYA. INDUCTION EXPOSURE: INTRADERMAL INDUCTION
- No. of exposures: 6 intradermal injections, two at a time, for each animal.
- Exposure period: single application.
- Two control groups: the animals received the same injections, but without the test substance and only with the agent which was used for preparing the suspension.
- Site: shoulder region
- Concentrations: 5 %

B. INDUCTION EXPOSURE: EPICUTANEOUS INDUCTION
- Time schedule: one week after intradermal induction
- Exposure: liquid immersed filter paper strips of 2 x 4 cm edge length under occlusive conditions.
- No. of exposures: 1
- Exposure period: 48 h
- Site: shoulder region, in the same area as previously with the intradermal application.
- Concentrations: 50%

C. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: the first dose approximately 14 days after the epicutaneous induction, the second dose one week later.
1st challenge: test group and control group 1 (control group 2 untreated);
2nd challenge: test group and both control groups.
- Exposure: liquid immersed filter paper strips of 2 x 2 cm length under occlusive conditions.
- Exposure period: 24 h
- Site: intact clipped region of the flank.
- Concentrations: 20 %
- Evaluation: approximately 24, 48, 72 hours after the start of administration.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
20%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no effects
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
20%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no effects
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
20%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no effects
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
20%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no effects
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
20%
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
no effects
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
20%
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
no effects
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
20%
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
no effects
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
20%
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
no effects
Reading:
1st reading
Hours after challenge:
24
Group:
other: negative control group 2
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Reading:
2nd reading
Hours after challenge:
48
Group:
other: negative control group 2
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects

1/10 animals of control group 1 died 4 days after intradermal induction.

Interpretation of results:
other: Not classified, according to the CLP Regulation EC 1272/2008
Conclusions:
The test substance did not show any sensitising potential.
Executive summary:

The substance was tested for its sensitizing effect on the skin of the guinea pig in the Maximization Test based on the method of Magnusson and Kligman according to OECD guideline 406. After the challenge application, no cutaneous reactions were observed in the animals of the control and test groups at the 24-hour and 48-hour readings.

Therefore, the test substance did not show any sensitising potential and according to the Regulation EC 1272/2008 (CLP) no classification is warranted.

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

Similar Substance 01 was tested for sensitizing effect on the skin of the guinea pig in the Maximization Test based on the method of Magnusson and Kligman according to OECD guideline 406 (BASF 1988) and the purity was 61.4 %.

After the challenge application, no cutaneous reactions were observed in the animals of the control and test groups at the 24-hour and 48-hour readings.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

According to the CLP Regulation (EC n. 1272/2008) 3.4.1.2 Skin sensitiser means a substance that will lead to an allergic response following skin contact. The experiment conducted in read across clearly shows that the substance is not capable to produce positive reactions after treatment with the highest non-irritant test substance concentration and no toxic symptoms were evident. The test article is considered to be a non sensitizer and no classification is warranted.