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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study. Only 10 animals in test group and 4 animals in control group.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
Only 10 animals in test group and 4 animals in control group
Principles of method if other than guideline:
Test was performed before actual guideline was established.
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Historical study available for this endpoint so used on animal welfare grounds to avoid further testing

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: aqueous formulation
Details on test material:
- Name of test material (as cited in study report): Solution C/4685
- Physical state: clear yellow liquid
- Analytical purity: 38% active
- Other: container: Glass bottle

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Darley Oaks, Burton-on-Trent, Staffordshire
- Weight at study initiation: average 300-500 g
- Housing: up to groups of 5
- Diet: TR2 with added vitamin C by Pilsbury's Birmingham, ad libitum
- Water: tap water containing 0.01% vitamin C, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Photoperiod (hrs dark / hrs light): 10/14

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Induction: intradermally neat sample and neat sample + FCA (1:1); epicutaneously neat sample
Challenge: epicutaneously 25% and 12.5%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Induction: intradermally neat sample and neat sample + FCA (1:1); epicutaneously neat sample
Challenge: epicutaneously 25% and 12.5%
No. of animals per dose:
10 (controls 4)
Details on study design:
RANGE FINDING TESTS:
A range finder study was performed to determine the maximum non-irritant concentration of the test substance in a separate group of 4 animals. The animals were pretreated with Complete Freund's Adjuvant and received test substance concentrations of 100%, 50%, 25% and 12.5% applied to patches of 2x2 cm of filter paper on a clipped area of 8x5 cm on both flanks, two patches per flank. The patches were occlusively covered and secured by an overlapping impermeable plastic 5 cm Blenderm adhesive tape. This was secured by elastic bandage (5 cm Elastoplast) wound around the torso of the animal and left in position for 48 hours. The results indicated that a 25 % concentration could be used for challenge without causing irritation. For safety reasons the challenge was also carried out with 12.5% of the test substance to ensure the use of a non-irritant concentration.

MAIN STUDY
Three pairs of injections were made on either side of the midline in a clipped 4x6 cm area over the shoulder of the animals for intradermal induction, followed by an epicutaneous application of neat test substance on a 4x2 cm patch of filter paper on the same area seven days later. Occlusive dressing was applied as described for the range-finder test and left in place for 48 hours. Control animals were treated with sterile distilled water instead of the test substance but otherwise received an identical induction treatment with Complete Freund's Adjuvant. Challenge was performed 2 weeks after topical induction application. The test substance was applied to the clipped flank on a 2x2 cm patch of filter paper and secured as for induction application. The patch was left in place for 24 hours. A second patch with a lower concentration was applied to the other flank of the animal.

A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous)
- Exposure period: 48 hours (epicutaneous)
- Test groups: FCA; TS, TS + FCA (1:1)
- Control group: FCA, water, water + FCA (1:1)
- Site: on either side of the midline in an area of 4x6 cm over the shoulder
- Frequency of applications: 7 days
- Duration: 9 days
- Concentrations: test group: 100% neat test substance and 50% test substance in FCA; control group: water and water in FCA

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21
- Exposure period: 24 hours
- Test groups: TS
- Control group: TS
- Site: flank
- Concentrations: 25 and 12.5%, respectively
- Evaluation (hr after challenge): 24 and 48
Challenge controls:
In principle, the challenge exposure of the control group to test substance on their flanks has the function of a challenge control. The preceding treatment of the control group during the induction phase should not have any influence on the challenge reaction in this group.
Positive control substance(s):
no

Results and discussion

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:
10
Clinical observations:
Irritation and exudation of the injection site (induction site) in one animal
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: 10.0. Clinical observations: Irritation and exudation of the injection site (induction site) in one animal.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Irritation and exudation of the injection site (induction site) in one animal
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: 10.0. Clinical observations: Irritation and exudation of the injection site (induction site) in one animal.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
12.5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Irritation and exudation of the injection site (induction site) in one animal
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 12.5%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: Irritation and exudation of the injection site (induction site) in one animal.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
12.5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Irritation and exudation of the injection site (induction site) in one animal
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 12.5%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: Irritation and exudation of the injection site (induction site) in one animal.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
4
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: 4.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
4
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: 4.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
12.5%
No. with + reactions:
0
Total no. in group:
4
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 12.5%. No with. + reactions: 0.0. Total no. in groups: 4.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
12.5%
No. with + reactions:
0
Total no. in group:
4
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 12.5%. No with. + reactions: 0.0. Total no. in groups: 4.0.
Group:
positive control
Remarks on result:
not measured/tested

Any other information on results incl. tables

The test performed according to the method of Magnusson and Kligman was negative for the test substance, no sensitisation reactions were observed.

According to the criteria of the DSD and the CLP criteria the test substance does not have to be classified as skin sensitising.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
EU Directive 67/548/EEC: not classified
Regulation (EC) No 1272/2008: not classified