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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
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.3. To address toxicological endpoints as part 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:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
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): not 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:
other: "Kleinrusse" Chbb: HM
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Karl Thomae GmbH, Biberach
- Age at study initiation: young adult
- Weight at study initiation: 2286 g (males), 2156 g (females)
- 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: female animals were acclimatised for four days, male animals were maintained at the laboratory for about 2 months

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

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: aqueous suspension with 2% carboxymethyl cellulose and 0.5% Cremophor
Details on dermal exposure:
TEST SITE
- Area of exposure: back and on the sides
- % coverage: about 10% of skin surface area
- Type of wrap if used: application area was covered by gauze and polyethylene foil that was fixed with Leukosilk strips; the whole area was then wrapped with an elastic bandange (Acrylastik Kompressionsbinde) with acrylate adhesive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed-off with water
- Time after start of exposure: after removal of cover following 24 hours after application

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): between 8.4 and 9.5 g of the preparation containing the test substance at a level of 50% was applied to the skin of the animals by brushing the preparation onto the skin
VEHICLE
- Amount(s) applied (volume or weight with unit): the substance was applied as an aqueous solution containing 2% carboxymethylcellulose and 0.5% Cremophor
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 females, 5 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Directly and 1, 2, 3, 4 and 6 hours after application, then twice daily
- Frequency of weighing: animals were weighed one hour before application and 1, 7 and 14 days after application
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: skin reaction
Statistics:
not applicable

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Slightly reduced activity during the first six hours after application; slightly reduced body temperature in three females and one male during first six hours after application
Body weight:
Slight body weight reduction after application
Gross pathology:
No findings were reported.
Other findings:
Skin reactions: Slight reddening of skin after application (erythema score of 1 according to Draize); clear signs of erythema in all animals after removal of coverage; signs of erythema were reversible within 5 days, but scaling was observed until test day 12

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 value in an acute dermal toxicity study with rabbits was LD50 > 2000 mg/kg bw and the substance is not classified for acute dermal toxicity according to the CLP regulation.
Executive summary:

The acute toxicity of the substance Cyclohexyl salicylate was studied under GLP in accordance with the EU Method B.3. Five female and five male young adult rabbits of the strain "Kleinrusse" were used in the test. Females and males had body weights of 2156 g and 2286 g, respectively. The substance was applied to the shave skin of the back and on the sides (application area about 10% of the total skin surface area) in form of a preparation, which was an aqueous suspension containing 50% of the test substance, 2% carboxymethylcellulose and 0.5% Cremophor. The preparation was brushed onto the skin and animals were then exposed to the material under occlusion for 24 hours. After this exposure period, the coverage was removed and remaining test substance was washed-off with water. None of the animals died after application or during the 14-day observation period. A slight body weight reduction was observed after application. Animals exhibited signs of skin irritation (erythema persisted for up to 5 days, scaling occurred and persisted until test day 12). No clinical signs were observed after patch removal. No pathological findings were made at necropsy following the 14-day observation period. The acute dermal toxicity study resulted in a LD50 value > 2000 mg/kg bw.