Pentyl salicylate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP study in accordance with EU Method B.4 with acceptable restrictions. To address toxicological endpoints as part of the REACH registration of the REACH registration of Benzyl Salicylate (Target Substance) it is proposed to read-across to Cyclohexyl Salicylate (Source Substance). The use of read-across works within the spirit of REACH and the stated aim of the legislation to reduce animal testing where possible. The Target Substance and Source Substance have been characterised using the categories and databases present in the OECD [Q]SAR Toolbox. From the profiling, it can be seen that the two substances share structural similarities and also ‘mechanistic action’ similarities which are both general and endpoint specific. Therefore read across is justified.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

25485-88-5

EC Number:

607-733-0

IUPAC Name:

25485-88-5

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): Salicylsäurecyclohexylester
- Physical state: colourless, oily liquid
- Analytical purity: 98.5%
- Impurities (identity and concentrations): no reported
- Composition of test material, percentage of components: not reported
- Purity test date: not reported
- Lot/batch No.: S 010
- Expiration date of the lot/batch: not reported

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: H. Fortkamp, Lengerich, Germany
- Age at study initiation: adult
- Weight at study initiation: 4.8 kg
- Housing: individually in rabbit batteries
- Diet (e.g. ad libitum): Altromin rabbit food 2023 ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: about one month

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 21
- Humidity (%): 45 to 50
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): a volume of 0.5 mL neat test substance was applied

Duration of treatment / exposure:

4 hours

Observation period:

15 days reported (total observation period was one month)

Number of animals:

six

Details on study design:

TEST SITE
- Area of exposure: shaved back of animals
- % coverage: not reported
- Type of wrap if used: linen patch that was covered with plastic foil, which was fixed by Acrylastic band

SCORING SYSTEM:
Erythema and eschar
No reddening = 0, slight reddening, barely perceptible = 1, clear reddening = 2, moderate to strong reddening = 3, strong reddening (beet red) up to eschar formation (deep skin layers affected) = 4

Oedema
No oedema = 0, slight swelling, barely perceptible = 1, weak swelling (edge of treated skin area clearly visible, swelling below 1 mm) = 2, clear swelling (swelling of treated skin area about 1 mm) = 3, strong oedema (swelling of more than 1 mm and expansion over the edge of the application area) = 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours after patch removal

Score:

1.67

Max. score:

4

Reversibility:

fully reversible

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours after patch removal

Score:

0

Max. score:

4

Irritant / corrosive response data:

In the course of the observation period, eschar formation on the surface of the treated skin area was seen in the animals, fissured skin was observed in some animals and pigmentation was seen in one animal. These effects were reversible in two animals until day 15 and in all animals until day 30.

Any other information on results incl. tables

To address toxicological endpoints as part of the REACH registration of the REACH registration of Benzyl Salicylate (Target Substance) it is proposed to read-across to Cyclohexyl Salicylate (Source Substance). The use of read-across works within the spirit of REACH and the stated aim of the legislation to reduce animal testing where possible. The Target Substance and Source Substance have been characterised using the categories and databases present in the OECD [Q]SAR Toolbox. From the profiling, it can be seen that the two substances share structural similarities and also ‘mechanistic action’ similarities which are both general and endpoint specific. Therefore read across is justified.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The structural analogue, Cyclohexyl salicylate, was found to be not irritating to the rabbit skin.

Executive summary:

The skin irritation potential of the test substance Cyclohexyl salicylate was studied under GLP in accordance with EU Method B.4. Six male adult rabbits of the New Zealand White strain were each exposed to 0.5 mL of the neat test substance. The substance was applied to the shave skin of the back under occlusion for a period of four hours. Skin reactions were scored after 1, 24, 48 and 72 hours (erythema, eschar and oedema formation). The observation period after patch removal was 15 days (or up to 30 days). The substance was not corrosive to the rabbit skin. The mean erythema score obtained from scores given at 24, 48 and 72 hours was 1.67 and the mean oedema score was 0. Superficial eschar formation and fissured skin were observed from day six after patch removal. These effects were reversible within the observation period of 15 days in two animals and within 30 days in all animals. Based on the results the substance was found to be not irritating to the rabbit skin.