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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: Well documented and reported study fully adequate for assessment. The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a recognized contract research organization.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
of 1996
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Rats, Sprague Dawley origin (Hsd: Sprague-Dawley (CD))
- Source: Harlan U.K. Ltd., Bicester, Oxon, England
- Age at study start (day of dosing): 5 to 7 weeks.
- Weight at start (day of dosing): minimum 118 g, maximum 141 g.
- Fasting period: Overnight prior to dosing, until ca. 4 hours post administration.
- Housing: In groups of 3 by sex in metal cages with wire mesh floors.
- Diet: standard rodent diet (Special Diet Services RM1(E) SQC expanded pellet), ad libitum
- Drinking water : drinking water ad libitum
- Acclimation period: min. 5 days before dosing.

Routine analysis of the batch of diet used, water and chew blocks did not provide evidence of contamination that might have prejudiced the study.

ENVIRONMENTAL CONDITIONS

- Temperature (°C): 22 ± 3°C
- Relative Humidity (%): 40 to 70%
- Photoperiod (artificial lighting): 12 hrs day / 12 hrs night

There were no deviations from these ranges, which compromised the quality, integrity or outcome of the study.





Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Remarks:
1% w/v acqueous preparation
Details on oral exposure:
DOSE FORMULATION AND DOSE VOLUME:

- Concentration of test material in vehicle: 200 mg/mL
- Amount (dose volume by gavage): 10 mL/kg bw

Preparation of the test material on the day of dosing.

ACUTE TOXIC CLASS METHOD - Rationale for the selection of the starting dose:
The starting dose was 2000 mg/kg bw., conduction not reported.

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 females
3 males
Control animals:
no
Details on study design:
- Duration of observation period: 14 days after dosing (day 1)
- Frequency of observations and weighing: observation of clinical signs after dosing, at frequent intervals of this day 1, day 2-14 twice daily,
day 15 in the morning;
weighing day 1 (prior to dosing), 8 and 15
- Necropsy performed: yes
- other examinations performed: macroscopic pathology





Statistics:
Not applicable, as there were no deaths and only one dose group.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No deaths at 2000 mg/kg bw
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no deaths at 2000 mg/kg bw
Mortality:
Dose level Mortality
2000 mg/kg 0/3 (f)
2000 mg/kg 0/3 (m)
Clinical signs:
Piloerection and loose faeces were seen in all animals from Day 1; females approximately 1-2 hours post dose, males approximately 3 hours post dose.
Hunched posture in all females from Day 1(from approximately 3 hours post dose).
Recovery of rats, as judged by external appearance and behaviour, was complete in all instances by Day 3.
Body weight:
All animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No abnormalities were revealed at the macroscopic examination at study termination on Day 15.

Applicant's summary and conclusion

Interpretation of results:
other: LD50 > 2000 mg/kg
Conclusions:
No labelling regarding acute oral toxicity according to Regulation (EC) No 1272/2008 is required.