Ethyl salicylate

Endpoint summary

Description of key information

Not sensiting in a closed epicutaneous test and in human maximization test.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

(not referenced in the publication)

Deviations:

yes

Remarks:

see ´principles of method if other than guideline´

Principles of method if other than guideline:

Relevant deviations from OECD TG 406:
- 10 animals used i.s.o. 20 as prescribed for non-sensitizing substances
- Inducton concentraton = 30% = highest non-irritant conc. i.s.o. conc. that exerts mild to moderate irritation
- Multple inductons: 6 times over 2 weeks, i.s.o. single induction

Limited information on results, only tabulated outcome per substance, no individual findings available.

GLP compliance:

not specified

Type of study:

other: closed epicutaneous test

Justification for non-LLNA method:

The REACH Annex VII information requirements were revised in 2016 to endorse a battery of in vitro assays for skin sensitisation. The in vivo closed epicutaneous test was conducted prior to the validation and regulatory acceptance of alternative methods.

Species:

guinea pig

Strain:

Hartley

Sex:

female

Details on test animals and environmental conditions:

Test animals:
Female albino Hartley guinea pigs (Shizuoka Agricultural Cooperative Association for Laboratory Animals), 300 – 350 g body weight

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

30%

Day(s)/duration:

48 H, 3 times a week for 2 weeks

Adequacy of induction:

other: maximum non-irritative concentration

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

1%

Day(s)/duration:

48 h

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

10 – 20 guinea pigs per group

Details on study design:

Preparation of the test animals:
Both flanks are clipped using an electric clipper and shaved using an electric shaver
The nape area of 2.5 cm quartet is clipped and shaved

Application of the test material (induction):
- 20 mg of test material (base material: white petrolatum) at 6 concentrations (30 – 0.1%) is smeared to Finn Chamber (EpitestFinn Chamber on Scanpol Tape) and placed on both flanks
- Two strips of adhesive tape, approximate 5 cm width and approximate 40cm length, are wrapped around the animal completely covering the Finn chamber
- A Reston foam pad, approximate 1.5 cm width, 6 cm length and 1cm thickness, is placed over the Finn chambers
- Reston foam pad is fixed with a strip of adhesive tape, approximate 7.5 cm width and approximate 40 cm length, and then Reston foam pad is fixed again with two strips of adhesive tape, approximate 5 cm width and approximate 40 cm length
- Closed application is continued for 48 hours, and irritation response is judged at 1, 24 and 48 hours after removal of test material.
- Above procedures are repeated totally 6 times, 3 times per week (on Monday, Wednesday and Friday) for 2 weeks.

Application of the test material (challenge):
- After 2-week withdrawal period, closed application of test material is performed on both flanks at several concentrations below the irritation concentration for 2 days for challenging similarly as in irritation test
- Approximate 50 mg of the test material at the minimum irritation concentration or maximum non-irritation concentration is spread homogeneously on the cloth of patch plaster and then the patch is applied on the nape
- Adhesive tape, approximate 2.5 cm width and approximate 30cm length, is wrapped around the nape to secure the patch plaster
- Approximate 2.0 cm quartet Reston foam pad is placed on the patch plaster
- Reston foam pad is fixed with a single strip of adhesive tape, approximate 2.5 cm width and approximate 30 cm length

Challenge controls:

not specified

Positive control substance(s):

not specified

Positive control results:

not applicable

Key result

Reading:

other: summary

Hours after challenge:

48

Group:

test chemical

Dose level:

30% (induction) / 1% (challenge)

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

not specified

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

In the present Closed Epicutaneous Test (CET) the test substance was not sensitizing

Executive summary:

A Closed Epicutaneous Test (CET) was performed on 10 to 20 female guinea pigs to determine the sensitizing potential of the test substance in petrolatum.

The test was not performed according to a guideline but resembles the OECD TG 406 and it was not performed according to GLP.

The method description is rather detailed, with some details missing. The information on the results is limited and no individual findings are available.

In the induction phase of the Closed Epicutaneous Test. (CET), the test material was applied occluded for 48 hours at the highest non-irritative concentration (30%) on the shaved nape and this procedure is repeated three times per week for two weeks.

FoIlowing a two-week rest period, the test material is applied at the maximum non-irritative concentration (1%) under occlusion for 48 hours on the flanks for chaIlenge.

This resulted in no indication of sensitization (rate: 0/10).

In the present Closed Epicutaneous Test (CET) the test substance was not sensitizing

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

For this endpoint one guinea pig test and one human maximization test is available.

A Closed Epicutaneous Test (CET)

A Closed Epicutaneous Test (CET) was performed on 10 to 20 female guinea pigs to determine the sensitizing potential of the test substance in petrolatum.

The test was not performed according to a guideline but resembles the OECD TG 406 and it was not performed according to GLP.

The method description is rather detailed, with some details missing. The information on the results is limited and no individual findings are available.

In the induction phase of the Closed Epicutaneous Test. (CET), the test material was applied occluded for 48 hours at the highest non-irritative concentration (30%) on the shaved nape and this procedure is repeated three times per week for two weeks. FoIlowing a two-week rest period, the test material is applied at the maximum non-irritative concentration (1%) under occlusion for 48 hours on the flanks for chaIlenge.

This resulted in no indication of sensitization (rate: 0/10).

Human maximization test

The cutaneous sensitization potential of the test item has been assessed using a maximization test in human, which was developed by Klingman and modified by Klingman and Epstein. 25 subjects received 12% (induction and challenge phase). The test material indicated no potential for dermal irritation or allergic sensitization.

Conclusion:

The test substance indicates no sensitizing potential.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The available data on skin sensitisation do not indicate a sensitizing potential, thus the test item is not classified according to regulation 1272/2008.