1,3,4,5-tetrahydroxycyclohexanecarboxylic acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study is not done according to OECD guideline. But it is a well documented study.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Development and Validation of an Alternative Dermal Sensitization Test: The Mouse Ear Swelling Test (MEST).

Author:

Gad, S. C., Dunn, B. J., Dobbs, D. W., Reilly, C. and Walsh, R. D.

Year:

1986

Bibliographic source:

Toxicol Appl Pharmacol. 84(1):93-114

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The ears were measured using an engineer’s micrometre. The test compound in solution was applied to the left ear of each animal (test and control) and the solvent was applied to the right ear. At both 24 and 48 hr after this challenge, the thicknesses of both ears measured. Positive responses were defined on an animal-by-animal basis as cases where the test ear demonstrated at least a 20% greater thickness than the control ear. % ear swelling = test ear thickness / control ear thickness x 100
As a starting point, test groups of 10 mice each and irritation control groups of 5 mice each were used. With 6- to 8-old female mice and DNCB as an allergen, combinations of inductions on Days 0 and 3; 0 and 7; 0,3, and 7; and 0, 1,2, and 3 were compared. A volume of 100 µl of test material solution or mixture was topically applied to a I-in-square central section of the stomach with an Eppendorf pipet. The responsiveness of male and female 6- to 8-week old CF-1 mice was evaluated using oxazolone and TDI with intradermal injections of Freund’s complete adjuvant emulsion (FCA)4 on Day 0 followed by tape stripping and topical application of 100 µl of test material in solvent to the stomach regions on Days 0, I, 2, and 3. On Day 10, 20 µl of test material was applied to one ear (10 µl to each side) while 20 µl of solvent alone was applied to the other.

GLP compliance:

not specified

Type of study:

mouse ear swelling test

Justification for non-LLNA method:

The study provides appropriate data. Therefore, further animal testing is not necessary.

Test material

Test material information

Constituent 1

Reference substance name:

Salicylic acid

EC Number:

200-712-3

EC Name:

Salicylic acid

Cas Number:

69-72-7

IUPAC Name:

salicylic acid

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): salicylic acid

In vivo test system

Test animals

Species:

mouse

Strain:

CF-1

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: 6-8 weeks
- Housing: five per cage in wire-bottom stainless-steel cages and allowed water and feed
- Water (e.g. ad libitum): ad libitum

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

other: Acetone

Induction 2

Concentration / amount:

10 % (Basis for selection of concentration: solubility)

Challenge

Challenge 1

Route:

intradermal

Vehicle:

other: Acetone

Challenge 2

Concentration / amount:

10 % (Basis for selection of concentration: solubility)

No. of animals per dose:

Test group: 10 animals
Control group: 5-10 animals

Details on study design:

RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Day(s) of exposure: 1;2;3
- Test groups: 10 animals 100 µl of test substance in vehicle
- Control group: 5-10 100 µl of vehicle
- Concentrations: 10 %

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 10
- Concentrations: 20 µl of test substance in vehicle or 20 µl of vehicle
- Control group: 20 µl of test substance in vehicle and 20 µl of vehicle
- Site: left and right ear
- Concentrations: 10 %
- Evaluation (hr after challenge): 24 and 48

Positive control substance(s):

no

Results and discussion

In vivo (non-LLNA)

Results

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

20 µl of test substance (10 %) in vehicle or 20 µl of vehicle

No. with + reactions:

0

Total no. in group:

10

Any other information on results incl. tables

Salicylic acid did not induce sensitization in mice in the mouse Ear Swelling Test (MEST). No animal of the test group showed a reaction in the challenge test with 10 % salicylic acid after 24 h. No mice were sensitized.

% swelling = [(test ear thickness) / (control ear thickness)] x 100 = 102%

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Salicylic acid is a not sensitising.

Executive summary:

The contact sensitivity of salicylic acid was experimentally evaluated in mice, using the method of Mouse Ear Swelling Test (MEST). CF-1 female mice, 6 to 8 weeks old were used for these studies. In this study, it is shown that, salicylic acid is not a dermal sensitizer.