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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16-29 May 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant OECD404 guideline study without significant deviations

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
2-ethylhexyl salicylate
EC Number:
204-263-4
EC Name:
2-ethylhexyl salicylate
Cas Number:
118-60-5
Molecular formula:
C15H22O3
IUPAC Name:
2-ethylhexyl 2-hydroxybenzoate
Test material form:
other: colourless liquid
Details on test material:
. batch number: 06 037 01
. CAS Number: 118-60-5
. description: colorless liquid
. container: one glass ask
. date ofreceipt: 22 March 2006
. storage conditions: at room temperature
. purity: 99.8%
. expiry date: 06 February 2008.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Sex, species, strain: male New Zealand White rabbits.
Breeder: Grimaud freres selection S.A.S., La Corbiere, Roussay, France.
Number: three animals were used, as recommended by the international guidelines.
Age/weight: on the day of treatment, the animals were 2 to 4 months old and had a mean body
weight istandard deviation of2.6 i0.1 kg.
Acclimation: at least 5 days before the beginning ofthe study.
Identication: individual metal ear tag.
The conditions in the animal room were set as follows:
. temperature: 18 ± 3° C
. relative humidity: 30 to 70%
. light/dark cycle: 12 h/12 h
. ventilation: approximately 12 cycles/hour ofltered, non-recycled air.
The temperature and relative humidity were under continuous control and recording. The records were checked daily and led. In addition to these daily checks, the housing conditions and corresponding instrumentation and equipment were veried and calibrated at regular intervals.
The animals were housed individually in Pajon cages (50 cm x 57 cm x 75 cm).
Each cage was equipped with a food container and a water bottle.
During the study, the animals had free access to 110C pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France). Food was analyzed regularly by the supplier for composition and contaminant levels. Drinking water ltered by a FG Millipore membrane (0.22 micron) was provided ad libitum. Bacteriological and chemical analyses ofwater are performed regularly by external laboratories. These analyses include the detection of possible contaminants (pesticides, heavy metals and nitrosamines). No contaminants were known to have been present in the diet or drinking water at levels which may be expected to have interfered with or prejudiced the outcome ofthe study.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated skin served as control.
Amount / concentration applied:
Doses of 0.5 mL of the undiluted test item were placed on a dry gauze, which was then applied to an area of approximately 6 cm2 of the anterior left ank (application for 3 minutes), the anterior right ank (application for l hour) or the posterior right ank (application for 4 hours) of the animals. The gauze pad was held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.
The untreated skin served as control. No residual test item was observed on removal ofthe dressing.
Duration of treatment / exposure:
3 minutes on anterior left ank, 1 hour on anterior right ank and 4 hours on posterior right ank
Observation period:
The skin was examined approximately 1 hour, 24, 48 and 72 hours after removal of the dressing. Since there were persistent irritation reactions (dryness) at 72 hours in animal No. 697 (anterior left ank), the observation period was extended up to their complete reversibility (Le. day 14).
Number of animals:
3 male animlas
Details on study design:
Criteria for irritation
A substance or a preparation is considered to be irritating to the skin if, when it is applied to healthy intact animal skin for up to 4 hours, significant inammation is caused and which persists for 24 hours or more after the end of the exposure period.
Criteria for corrosion
A substance or a preparation is considered to be corrosive if, when it is applied to healthy intact animal skin, it produces full thickness destruction of skin tissue on at least one animal during the test for skin irritation, or if the result can be predicted (for example: from strongly acid or alkaline reactions).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of three animals
Time point:
other: 24 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 4 hours exposure
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of three animals
Time point:
other: 48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 4 hours exposure
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of three animals
Time point:
other: 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 4 hours exposure
Irritation parameter:
edema score
Basis:
mean
Remarks:
of three animals
Time point:
other: 24 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 4 hours exposure
Irritation parameter:
edema score
Basis:
mean
Remarks:
of three animals
Time point:
other: 48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 4 hours exposure
Irritation parameter:
edema score
Basis:
mean
Remarks:
of three animals
Time point:
other: 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 4 hours exposure
Irritant / corrosive response data:
A well defined erythema (grade 2) was noted 1 h after removal of patches but reversed to grade 0 within 24 hours in 2 animals and within 48 hours in one animal.
Other effects:
Following 3 minutes exposure dryness of the skin was noted from day 4 up to day 13.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under these experimental conditions, the test item SALICYLATE D'OCTYLE was slightly irritant when applied topically to rabbits. A classification according to CLP/DSD however is not required.
Executive summary:

In this study 3 animals were exposed topically to 2-ethylhexyl salicylate over a period of 3 minutes, 1 hour and 4 hours respectively. One hour following removal of the patches slight erythrema were noted at the sites exposed to 3 minutes and 1 hour wereas the erythema were well-defined (grade 2) where exposed for 4 hours. However, all erythema fully reversed within 24 hours and onyl in one animal following 48 hours. No Edema were recorded in any of the animals at any time. Dryness of skin was noted in one animal following 3 minutes exposure but this fully reversed within 14 days. Thus, the test item was considered non-irritant following the CLP (Regualtion EC No 1272/2008) classification system