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Diss Factsheets

Administrative data

Description of key information

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:
1981-05-11 to not provided
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted equivalent to a guideline study.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
please refer to "Principles of method"
Principles of method if other than guideline:
The guinea pig maximization test was conducted according to Magnusson, B. and Kligman, A.M. (eds.): Identification of Contact Allergens in Allergic Contact Dermatitis in the Guinea Pig, C.C. Thomas, Illinois, USA; pp. 102-123. This test method was later included into the OECD Guideline 406.
Deviations from the protocol in the report were:
- The protocol states the room will be air-conditioned with the air temperature maintained at 18 °C +/- 3 °C and relative humidity of 60 % (+ 10 %). Temperature range recorded during the study was 16- 22°C. Humidity range recorded during the study was 52- 81 % (air-conditioning unit not functioning correctly).
- Protocol states main tap water containing 0.1 % ascorbic acid will be freely available. During the study tap water containing 0.01 % ascorbic acid was freely available (Error in original protocol, 0.01% is the level of ascorbic acid for this type of study).
- Protocol specifies the use of Whatmans Number 1 filter paper in topical applications. Whatman Number 3 paper was used throughout the study (Whatman Number 1 paper was not available).
- Protocol specifies the challenge application is carried out at a single concentration of the test material. The challenge was conducted using two concentrations of test material (Standard Toxicol Laboratories Procedure, carried out in error for this study).
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Information from in vivo test other than LLNA was already available before LLNA guideline was in place.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: accredited breeder
- Age at study initiation:
- Weight at study initiation: 300-400 g
- Housing: groups of max.. 5 animals
- Diet: ad libitum, TR2 with added vitamin C manufactured and supplied by Pilsbury's Birmingham,
- Water: ad libitum, containing 0.01 % vitamin C

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-22
- Humidity (%): 52-81
- Photoperiod (hrs dark / hrs light): 10/14
Route:
intradermal and epicutaneous
Vehicle:
other: ethanol
Concentration / amount:
Induction Phase: Injection, 50 % concentration of the test material in ethanol, with and without FCA
Induction Phase: Topical Application, 50 % concentration of the test material in ethanol
Challenge Phase: 50 % and 25 % concentrations of the test material in ethanol
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol
Concentration / amount:
Induction Phase: Injection, 50 % concentration of the test material in ethanol, with and without FCA
Induction Phase: Topical Application, 50 % concentration of the test material in ethanol
Challenge Phase: 50 % and 25 % concentrations of the test material in ethanol
No. of animals per dose:
20 test animals and 8 control animals, and 4 animals for the dose finding test
Details on study design:
RANGE FINDING TESTS: Performed in 4 animals pretreated with FCA. Concentrations of 50, 25, 12.5, 6.25 % were used in topical application (occlusive) for 24 h. After 24 h and 48 h sites were scored and maximum non-irritant concentration was selected.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (1 injection, 1 topical application)
- Exposure period: : Injection, 7 days later 48 h exposure to topical application
- Control group: vehicle control group (ethanol) with the same form of applications
- Site: shoulder region, 4*2 cm area
- Frequency of applications: 2 times (1 injection, 1 topical application)
- Duration: 48 h for topical application
- Concentrations: 50 %

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: 14 days after topical induction
- Exposure period: 24 h
- Site: flanks of the animals
- Concentrations: 50 % on one flank, 25 % on the other flank
- Evaluation (hr after challenge): 24 and 48 h after removal
Challenge controls:
One vehicle control group was done.
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
1 animal died during the study
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 19.0. Clinical observations: 1 animal died during the study.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
1 animal died during the study
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 19.0. Clinical observations: 1 animal died during the study.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
1 animal died during the study
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 19.0. Clinical observations: 1 animal died during the study.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
1 animal died during the study
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 19.0. Clinical observations: 1 animal died during the study.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
8
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 8.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
8
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 8.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
8
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 8.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
8
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 8.0.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Key study

The aim of the guniea pig maximization test was to investigate the delayed dermal sensitization of the test substance using female albino Dunkin-Hartley guinea pigs (BASF SE.1981). The study was conducted using a method similar to OECD 406. Four animals were used in a preliminary concentration range finding test, 28 animals were used in the main study (20 test animals and 8 control animals). In the pretest concentrations of 6.25 %, 12.5 %, 25 % and 50 % in ethanol (24-hour occlusive patch) were tested. No clinical signs or mortality were observed and 25 and 50 % concentrations were selected for the main study. For induction test animals were given intradermal injections of a 50 % solution of the test substance in ethanol with and without Freund's Complete Adjuvant. Seven days later, the animals received a topical application of a 50 % solution of the test substance in ethanol (24-hour occlusive patch). The skin was scored at 24 and 48 hours after removal of the patches. The challenge was conducted 14 days after the last induction treatment. Each animal of both the test and control group received topical applications of the test substance in ethanol at concentrations of 25 % and 50 % (24-hour occlusive patches onto previously untreated skin sites). The skin was scored at 24 and 48 hours after removal of the patches. One test animal died during the study. There were no signs of any skin reaction, neither in test animals nor in control animals at all times and concentrations. Therefore there was no evidence suggesting that the test substance acts as a skin sensitizer in the guinea pig.

 

Supporting study

A second guinea pig maximization test was conducted to investigate the dermal sensitization potential of the test substance (BASF SE. 1984). The study was conducted using a method similar to OECD 406. Four animals were used in a preliminary concentration range finding test, 26 animals were used in the main study (10 test animals and 16 control animals). For the induction test animals were given intradermal injections of a 0.1 % solution of the test substance with and without Freund's Complete Adjuvant (vehicle: 6 % ethanol, 20 % polyethylene glycol 400, 0.01 % dodecylbenzene sulphate in physiological saline). Seven days later, the test animals received a topical application of a 10 % solution of the test substance in ethanol (24-hour occlusive patch). The skin was scored at 24 and 48 hours after removal of the patches. A group of 4 control animals was treated intradermally and topically with the corresponding vehicles (treated controls). The remaining control animals remained untreated (untreated controls; 3 groups of 4 animals) during induction. The first challenge was done 13 to 14 days after the last induction treatment. Each animal of the test group, the treated control group and one untreated control group received a topical application of the test substance in ethanol at a concentration of 2.5 % (24-hour occlusive patches onto previously untreated skin sites). One week after the first challenge, a second challenge was conducted, and one week after the second challenge, a third challenge was conducted. At every challenge, a group of 4 previously untreated guinea pigs (untreated controls) was treated in the same way as the test animals. The skin was scored at 24 and 48 hours after removal of the patches. None out of the 10 guinea pigs of the test group were sensitized after 3 challenge treatments. There was evidence of a very slight sensitization reaction in one guinea pig at the second challenge. However, this reaction was not confirmed at the third challenge. There was no evidence suggesting that the test substance acts as a sensitizer in the guinea pig.

 

Conclusion

Both studies were conducted based on the same method, comparable to OECD 406. As one study (BASF SE.1981) used a concentration of 25 and 50 % of the test substance this study was selected as key study, as it represents the worst case and more sensible endpoint. The supporting study (BASF SE.1984) used concentrations of 0.1 and 10 % (induction) and 2.5 % (challenge). Several challenges were performed in the supporting study and the results are in line with the observations from the key study.

Migrated from Short description of key information:

The test substance was not skin sensitising.

Justification for selection of skin sensitisation endpoint:

The study was conducted comparable to a OECD 406 guideline study. The result is supported by a secound study.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Skin sensitisation

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation (EU) No 2015/1221. As a result the substance is considered to be not classified for skin sensitisation.