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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: - Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
May 12, 1981
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright white
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: no data
- Weight at study initiation: 268 - 339 g
- Housing: collective housing up to a maximum of 5 animals per cage (Macrolon type IV)
- Diet: ad libitum, Ssniff-G (Alleindiat für Meerschweinchen), Ssniff'Spezialdiaten GmbH, Soest/Westfalen, Germany
- Water: ad libitum, drinking water as for human consumption
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 +/- 3.5
- Humidity (%): 50 - 85
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): artificial lighting (120 lux) from 7.00 a.m. -7.00 p.m.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: aqua ad injectabilia/petrolatum
Concentration / amount:
Range finding study:
Intradermal injection: 5 %
Dermal application: 25 %

Main study:
Intradermal injection: 5 %
Epicutaneous: 25 % (pretreated with 10 % sodium lauryl sulfat in petrolatum)
Challenge: 25 %
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: aqua ad injectabilia/petrolatum
Concentration / amount:
Range finding study:
Intradermal injection: 5 %
Dermal application: 25 %

Main study:
Intradermal injection: 5 %
Epicutaneous: 25 % (pretreated with 10 % sodium lauryl sulfat in petrolatum)
Challenge: 25 %
No. of animals per dose:
Range finding study: 2 animals
Main study: 20 test, 20 control animals
Details on study design:
RANGE FINDING TESTS:
Intradermal Injection
The test article was diluted with water and Freund's complete adjuvant (FCA; Sigma, Deisenhofen, Germany) to give a final concentration of 5 %. If this concentration produced severe systemic toxicity, local necrosis or ulceration, it was reduced accordingly. Two animals were employed, skin reactions being recorded 48 h after treatment.

Dermal Application
The solid test article was incorporated in petrolatum to provide a final concentration of 25 % (w/v); if this concentration proved immoderately irritating, it was reduced accordingly. A closed patch exposure was effected by means of an occlusive bandage. Two animals were employed for each concentration tested and skin reactions were recorded 48 h post application.

MAIN STUDY
A. INDUCTION EXPOSURE

FIRST STAGE (intradermal injection, day 0)
- an area of 4 x 6 cm over the shoulders was clipped short with electric clippers and cleaned with 70 % (v/v) ethanol. Three pairs of intradermal injections were then made symmetrically in two rows on either side of the spine:
- No. of exposures: 3 pairs
- Test groups:
1. 0.1 ml FCA (diluted 1 : 2 in water)
2. 0.1 ml test article (final concentration: 5 % )
3. 0.1 ml test article emulsified in FCA (final concentration: 5 % )
- Control group:
1. 0.1 ml FCA (diluted 1 : 2 in water)
2. 0.1 ml vehicle (undiluted)
3. 0.1 ml vehicle (diluted 1 : 2 with FCA)
- Site: two rows on either side of the spine

SECOND STAGE (day 7)
- The same area was clipped and cleaned again.
- Because the test article was non-irritating at all tested concentrations, the clipped area was pretreated with 10 % sodium laurylsulfat (SLS) in petrolatum.
- 24 hours later, the test article was spread in a thick layer (to saturation) over a 2 x 4 cm patch (gauze).
- The latter was firmly secured over the previous injection sites by an occlusive dressing for 48 h.
- Concentration: based on the results of the pilot study the test article concentration was 25 %.
- Control animals: received a patch loaded with the vehicle alone.

B. CHALLENGE EXPOSURE (day 21)
- Exposure period: 24 h
- Site: 5 x 5 cm clipped and shaved area on each flank (test article was applied to the left flank and the vehicle to the right)
- Concentrations: 25 %, the maximal non-irritating concentration of the test article
- Dressing: occlusive, if necessary, the skin was cleaned with 70 % ethanol 21 h after removal of the patch.
- Evaluation (hr after challenge): 24 and 48 h


GRADING
- according to Magnusson and Kligman
Challenge controls:
Challenge exposure in control: 25 % of test substance
Positive control substance(s):
yes
Remarks:
2,4 dinitrochlorobenzene

Results and discussion

Positive control results:
The last periodic use of a positive control substance (2,4 dinitrochlorobenzene) with the acceptable level of response in the test animals was performed on April 5, 1990.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no observations
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: 20.0. Clinical observations: no observations.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no observations
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: 20.0. Clinical observations: no observations.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no observations
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: 20.0. Clinical observations: no observations.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no observations
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: 20.0. Clinical observations: no observations.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
In this study, Stearic acid, esters with methyl α-D-glucoside (a.i. 100 %, according to producer information), is not a dermal sensitizer.
Executive summary:

In a dermal sensitization study according to OECD TG 406 with Stearic acid, esters with methyl α-D-glucoside (100 % a.i., according to producer information), Pirbright white guinea pigs were tested using the method of Magnusson and Kligman. Positive control substance was 2,4 dinitrochlorobenzene.

For intradermal induction a concentration of 5 % was used. The test concentration used for dermal induction (25 %) was non-irritating. However, 7 days after first intradermal induction the test site was pretreated with 10 % sodium laurylsulfat in petrolatum in order to create a local irritation. 24 hours later a 25 % dilution of the test substance was applied and covered by occlusive dressing for 48 hours. The same non-irritating test substance concentration (25 %) was used for challenge procedure. 

According to OECD guideline 406 a pretreatment with sodium lauryl sulphate is recommended, if the test substance is not a skin irritant. Thus, it can be assumed that including the pretreatment with the promoter substance sodium lauryl sulphate the induction procedure was sufficient to induce a potential allergic sensitisation reaction and the study is judged as valid.

At challenge no visible changes of the treated skin sites (no erythema and no edema) were observed in test or control animals at any time point.

  

In this study Stearic acid, esters with methyl α-D-glucoside (a.i. 100 %, according to producer information), is not a dermal sensitizer.