Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 December 1997 to 23 April 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: bulk
Details on test material:
brown crystalline solid
Specific details on test material used for the study:
brown solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crl:CD ®BR
Sex:
male/female
Details on test animals and environmental conditions:
At the start of the study the males weighed 209 to 218g, and the females 205 to 217g, and were eight to twelve weeks old. After a minimum acclimatisation period of at least five days the animals were selected at random.
The animals were housed in groups of up to five by sex in solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food was allowed throughout the study.
The animal room was maintained at a temperature of 19 to 22*C and relative humidity of 47 to 66%. The rate of air exchange was approximately 15 changes per hour and the lighting was 12 hours light and 12 hours darkness

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
All animals were dosed once only by gavage. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
Prelimary study: All animals were dosed with a dosing volumn of 10mls (50 and 200 mg/ml) corresponding to a final concentration of 500 mg/kg and 2000mg/kg.
Final limit test: All animals were dosed with a dosing volumn of 10mls ( 200 mg/ml) corresponding to a final concentration of 2000mg/kg.
Doses:
Limit test 2000 mg/kg
No. of animals per sex per dose:
5 Male/ 5 Female
Control animals:
no
Details on study design:
Following a preliminary study in which there were no deaths at dose levels of 500 and 2000 mg/kg, a group of ten fasted animals (five males and five females) was given a single oral dose of test material, as a suspension in arachis oil BP at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were then killed and subjected to gross necropsy.
Clinical observations were made 1/2, 1, 2, and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 1, 2, 3, 7 and 14 or at death. At the end of the study the animals were killed by cervical dislocation and subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD 50) of the test material was determined

Results and discussion

Preliminary study:
A preliminary study was performed with 500 and 2000 mg/kg was given in a single oral dose of test material. Clinical observations were made 30mins, 1, 2 and 4hours afer dosing and daily for seven days. Morbidity and mortality checks were made twice daily.
Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality recorded
Clinical signs:
No clinical signs of toxicity were noted during the study
Body weight:
All animals showed expected gains in bodyweight over the 14-day study period
Gross pathology:
No abnormalities were noted at necropsy

Any other information on results incl. tables

Preliminary Study:

There were no deaths. Clinical signs of toxicity noted in the animals treated with 500 mg/kg were pallor of the extremities and hunched posture. No signs of systemic toxicity were noted in animals treated with 2000 mg/kg. Based on this information, a dose level of 2000 mg,/kg bodyweight was selected for the main study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD 50) of the test material in the SpragueDawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight. The test material was considered to have no significant acute toxic risk if swallowed and did not meet the criteria for classification under EC labelling regulations. No symbol or risk phrase are required.