Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 23, 1990 to March 15, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline test with GLP, well documented

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
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
Details on test material:
Chemical name: Benzoic acid, 2-hydroxy-2-ethyl hexyl ester

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Animals and Animal Husbandry
Nine male and nine female Sprague-Dawley strain rats were supplied by Bantin & Kingman Ltd., Aldborough, Hull, U.K. At the start of the main study the males weighed 129 - 148g, and the females 120 - 154g, and were approximately five to eight 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 groups of up to five by sex in solid-floor polypropylene cages with sawdust bedding. With the exception of an overnight fast immediately before dosing and for approximately two hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet No. 1 Special Diet Services Limited, Witham, Essex, U.K.) was allowed 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 - 55%. On one occasion the relative humidity was outside the lower limit specified in the protocol (40%). This did not affect the purpose or integrity of the study. The rate of air exchange was approxi- mately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours light and 12 hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
a single dose: 5000 mg/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
a) Range-finding Study
In order to establish a suitable dose level for the main study groups of two rats (one male and one female) were treated once only at levels of 5000, 3000, 1000 and 500 mg/kg. Animals were observed 1 and 4 hours after dosing and then daily for five days.
Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.
b) Main Study
A group of ten rats (five males and five females) was dosed as follows in order to confirm the findings of the range-finding study.
All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
Animals were observed 1 and 4 hours after dosing and subsequently once daily for 14 days. Deaths and evidence of overt toxicity were recorded at each observation.
Individual bodyweights were recorded on the day of treatment (day 0) and on days 7 and 14 or at death.

Statistics:
no data

Results and discussion

Preliminary study:
No mortality was observed in the range finding study at doses of 500, 1000, 3000 and 5000 mg/kg bw (observation period 5 days). Using the mortaiity data given above the oral LD50 of the test materiai was considered to be greater than 5000 mg/kg bodyweight. This dose level was therefore used for the main study.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No evidence of toxicity related to test article was observed.
Mortality:
There were no deaths.
Clinical signs:
No evidence of systemic toxicity or skin irritation was noted during the study.
Body weight:
No toxicologically significant effects on bodyweight gain were noted 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 (oral, rat): >5000 mg/kg
Executive summary:

This acute study was performed to determine the acute oral median lethal dose (LD50) of the test material, administered undiluted in the Sprague-Dawley strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 401 "Acute Oral Toxicity".  Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of test material preparation at a dose level of 5000 mg/kg bodyweight. There were no deaths. No evidence of systemic toxicity or skin irritation was noted during the study.  No toxicologically significant effects on bodyweight gain were noted during the study period.   No abnormal ties were noted at necropsy of animals killed at the end of the study.

Therefore, the acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat, was found to be greater than 5000 mg/kg bodyweight under the condition of this study.