Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted in GLP compliance and in accordance with OECD Guideline No 420. Identity is not completely clear, therefor reliability 2
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

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:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid
Details on test material:
batch: 08Z359

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laberateries UK Limited, Bicester, Oxon, UK.
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: 160 - 182 g
- Fasting period before study: overnight
- Housing: in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/ml, 5 mg/ml, 0,5 mg/ml
- Amount of vehicle (if gavage): 10 ml /kg


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: ln the absence of data regarding the oral toxicity of the test material, 300 mg/kg was
chosen as the starting dose.
Doses:
300 mg/kg, 50 mg/kg, 5 mg/kg
No. of animals per sex per dose:
300 mg/kg: 1 female
50 mg/kg: 1 female
5 mg/kg: 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical Observations: 0,5, 1, 2, and 4 hours after dosing.Morbidity and mortality checks were made twice daily.
Individual bodyweights: Day 0 (the day of dosing) and on Days 7 and 14 or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: yes

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 5 - <= 50 mg/kg bw
Based on:
test mat.
Mortality:
5 mg/kg: no deaths
50 mg/kg: The animal was found dead approximately five and a half hours after dosing
300 mg/kg: The animal was found dead thirty minutes after dosing.The animal was found dead thirty minutes after dosing.
Clinical signs:
5 mg/kg: No signs of systemic toxicity were noted du ring the observation period
50 mg/kg: Signs of systemic toxicity noted were hunched posture, occasional body tremors, increased salivation and pilo-erection.
300 mg/kg: No signs of systemic toxicity were noted du ring the observation period
Body weight:
5 mg/kg: All animals showed expected gains in bodyweight over the observation period
50 mg/kg: -
300 mg/kg: -
Gross pathology:
5 mg/kg: No abnormalities were noted at necropsy.
50 mg/kg: Abnormalities noted at necropsy were abnormally red lungs, dark liver, dark kidneys and slight haemorrhage of the non-glandular region of the stomach.
300 mg/kg: No abnormalities were noted at necropsy

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category II
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median Iethal dose (LD50) of the test material in the female Wistar strain
rat was estimated to be in the range of 5 - 50 mg/kg bodyweight (Globally Harmonised
Classification System- Category 2).