Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 27, 1990 to March 13, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline test with GLP, detailed information

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

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: liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Animals and Animal Husbandry
Five male and five female Sprague-Dawley strain rats were supplied by Bantin & Kingman Ltd., Grimston, Aldborough, Hull, U.K. At the start of the study the males weighed 216 - 227 g, and the females 200 - 213 g and were approximately eight to ten weeks old. After a minimum acclimatisation period of five days the animals were selected at random and given a unique number within the study by ear punching and a number written on a cage card.
The animals were housed in solid-floor polypropylene cages with sawdust bedding and allowed free access to mains drinking water and food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.) throughout the study.

Animals and Animal Husbandry (contd)
The animal room was maintained at a temperature of 21 - 23 °C and relative humidity of 39 - 50%. On one occasion the relative humidity was outside the upper limit specified in the protocol (40%). This did not affect the purpose or integrity of the study. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours light and 12 hours darkness.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
 A group of ten animals (five males and five females), was given a single, 24-hour, semi-occluded dermal application of the test material to intact skin, at a dose level of 5000 mg/kg bodyweight. The appropriate amount of the undiluted test material, as received, was applied uniformly to an area of shorn skin approximating to 10% of the total body surface area using a graduated syringe. A piece of surgical gauze measuring 7 cm x 4 cm was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage (HYPERTIE). The bandage was further secured with a piece of BLENDERM wrapped around each end.
Shortly after dosing the dressings were checked. After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material.
Duration of exposure:
24 hours
Doses:
5000 mg/kg
No. of animals per sex per dose:
5
Control animals:
yes, concurrent no treatment
Details on study design:
Approximately twentyfour hours prior to the commencement of the test the back and flanks of each animal were clipped free of hair using veterinary clippers to expose a skin area of approximately 5 cm x 4 cm.
A single group of animals was treated.
Observations
All animals were observed for overt signs of toxicity and death 1 and 4 hours after dosing and subsequently at least once daily for fourteen days.
Individual bodyweights were recorded on the day of treatment (day 0) and on days seven and fourteen.
All animals were subjected to a gross necropsy examination for any macroscopic abnormalities. No tissues were retained.

Statistics:
no data

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No adverse effects were observed in test article treated rats.
Mortality:
There were no deaths.
Clinical signs:
No evidence of systemic toxicity or dermal irritation was noted during the study.
Body weight:
Two females showed slight bodyweight loss during the first week. All other animals showed expected gain in bodyweight during the study period.
Gross pathology:
No abnormalities were noted at necropsy of animals killed at the end of the study.
Other findings:
no data

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 (dermal, rat, 24h): > 5000 mg/kg
Executive summary:

This study was performed to assess the acute dermal toxicity of test article with the method described in the OECD Guidelines for Testing of Chemicals (1981) No. 402 "Acute Dermal Toxicity".A group of tenrats (five malesand five females), was given a single, 24-hour, semi-occluded dermal application of the test material tointact skin, at a dose level of 5000 mg/kg bodyweight.  There were no deaths. No evidence of systemic toxicity or dermal irritation was noted during the study. Two females showed slight bodyweight loss during the first week. All other animals showed expected gain in bodyweight during the study period. No abnormalities were noted at necropsy of animals killed at the end of the study.

Therefore, based on the results of this study, the acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was considered to be greater than 5000 mg/kg body­weight.