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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labeling and/or risk assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Remarks:
The study was conducted according to guideline in effect at time of study conduct.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity: 98.5%


Test animals

Species:
rat
Strain:
other: CD strain (remote Sprague-Dawley origin)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: approximately five weeks
- Weight at study initiation: males from 110 - 144 g and for females from 105 - 130 g.
- Fasting period before study: yes
- Housing: The animals were housed in stainless steel grid cages measuring 54 x 33 x 20 cm. The grid floor ensured rapid removal of waste material to undertrays which were cleaned as necessary. Five animals of the same sex were accommodated in each cage, unless reduced by mortality. The cages were suspended in mobile stainless steel racks.
- Diet: A commercially-available complete pelleted rodent diet was fed without restriction, except for the removal of food approximately 18 hours before administration of the test material.
- Water: Animals had free access to tap water supplied in a single bottle per cage and re-filled as required.
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- All rooms were kept at slight positive pressure relative to the outside and each had its own filtered air supply giving approximately 15 complete air changes per hour without re-circulation. A temperature of 18 - 22°C and a relative humidity range of 32 - 48%. were achieved during the study. The relatively low humidity values did not overtly affect the health of the animals. Electric time-switches regulated a lighting cycle of 12 hours of artificial light per day.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: methylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: The test material was prepared at appropriate concentrations in 0.5% w/v methylcellulose in purified water (obtained through the reverse osmosis of tap water).


MAXIMUM DOSE VOLUME APPLIED: volume-dosage of 20 ml/kg

Doses:
202, 254, 320 and 402 mg/kg bodyweight
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Three separate inspections were made during the first hour after dosing and two further inspections during the remainder of Day 1. From Day 2 onwards, the animals were inspected twice daily (morning and afternoon). The type, time of onset and duration of reactions to treatment and the circumstances of any death were recorded
-Frequency of weighing: The bodyweight of each animal was recorded on the day before dosing and on Days 1, 8 and 15. The test was terminated on the morning of Day 15.
- Necropsy of survivors performed: yes
Statistics:
Probit analysis by the method of Finney was used to determine the acute median lethal dosage, 95% confidence interval and slope of the dose response curve of the test material for both sexes. The calculations were performed by the GLIM statistics program using a special macro program developed by Baker.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
334 mg/kg bw
Based on:
test mat.
95% CL:
278 - 390
Sex:
female
Dose descriptor:
LD50
Effect level:
333 mg/kg bw
Based on:
test mat.
95% CL:
271 - 395
Sex:
male/female
Dose descriptor:
LD50
Effect level:
337 mg/kg bw
Based on:
test mat.
95% CL:
306 - 368
Mortality:
No animals died at 202 or 254 mg/kg.
Four males and 1 female died at 320 mg/kg.
Three males and 5 females died at 402 mg/kg
Clinical signs:
Ante mortem signs comprised lethargy, reduced mobility, staggering gait, reddening, muscle tremor, piloerection, salivation and hunched posture.

Signs of reaction in surviving animals were similar to those of the decedents with the addition of irritability, breathing irregularities, ungroomed appearance, diarrhoea, pigmented orbital secretion, pigmented staining of the snout and closed eyes. All the surviving animals were overtly normal by the sixth day.
Body weight:
The surviving animals acheived expected bodyweight gains.
Gross pathology:
Necropsy of the decedents revealed localised yellow, red or brown fur staining, abnormal gastro-intestinal contents and a single observation of dark areas on the glandular mucosa of the stomach. Necropsy of the surviving animals recorded no significant macroscopic lesions.

Any other information on results incl. tables

Mortality data

 

 

Day

Dose mg/kg

Sex

 Mortality: Dead/Alive

 

 

1

2

3

4

14

202

M

0/5

0/5

0/5

0/5

0/5

F

0/5

0/5

0/5

0/5

0/5

254

M

0/5

0/5

0/5

0/5

0/5

F

0/5

0/5

0/5

0/5

0/5

320

M

0/5

4/5

4/5

4/5

4/5

F

0/5

1/5

1/5

1/5

1/5

402

M

0/5

3/5

3/5

3/5

3/5

F

1/5

5/5

5/5

5/5

5/5

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).
Combined sex LD50 = 337 mg/kg.
Executive summary:

The acute oral toxicity of the test substance was investigated in four groups of five male and five female CD rats. The test material was administered at dosages in the range 202 - 402 mg/kg, at a volume-dosage of 20 mL/kg in 0.5% w/v aqueous methylcellulose. Mortality and signs of reaction to treatment were recorded during a subsequent 14-day observation period. The surviving animals were killed on the following day. All animals were subjected to necropsy. No deaths ocurred at the 202 and 254 mg/kg dose. Mortalities were noted at the two higher doses of 320 and 402 mg/kg. All deaths ocurred on the day of dosing or during the first overnight period. The combined LD50 was determined to be 337 mg/kg.