Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009-12-01 to 2009-12-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the appropriate OECD guideline and it was compliant with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd
- Age at study initiation: 8-12 wk
- Weight at study initiation: 215-257 g
- Housing: 3/solid bottomed polycarbonate cages with stainless steel mesh lid
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 40-70
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: 4 groups of 3 animals treated starting December 1, 4, 9 and 14 (2009). In-life dates for the first group were from: 2009-12-01 to 2009-12-15. The final group were necropsied on 2009-12-28.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
purified
Details on oral exposure:
VEHICLE
purified water

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

Doses:
300, 2000 mg/kg bw
No. of animals per sex per dose:
2 groups of 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for mortality twice daily; clinical observations at unspecified frequent intervals during dosing day then twice daily until day 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
None stated

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths during the study.
Clinical signs:
Clinical signs of reaction to treatment following administration of 2000 mg/kg bw comprised flat posture, underactivity, reduced body tone, unsteadiness, hunched posture, elevated gait, reduced body temperature, shallow and fast respiration, piloerection and salivation. Signs were first noted within a few minutes of dose administration and had gradually resolved by the start of Day 2. Piloerection was noted for 3 animals at the start of Day 2 and had resolved by the afternoon check.
No signs were observed for any animal treated at 300 mg/kg bw.
Body weight:
Low bodyweight gains were noted between Days 8-15 for one female receiving 300 mg/kg bw and two females receiving 2000 mg/kg bw. All other animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
A small (atrophy) stomach was seen in one animal dosed at 300 mg/kg bw at study termination. No treatment related abnormalities were noted in the remaining animals at the macroscopic examination at study termination on Day 15.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A reliable study conducted in compliance with a standard guideline and in accordance with GLP, found the LD50 to be greater than 2000 mg/kg bw in female rats.