Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-08-27 to 2008-09-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
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 material form:
solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and batch No.of test material: Sponsor and 902/695838/D/2/1

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: approximately 4°C in the dark
- Solubility and stability of the test substance in the solvent/vehicle: Suspension could be achieved in arachis oil BP tot the desired dosing concentrations

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Suspended in arachis BP oil at a concentration of 300 mg test ingredient/kg bodyweight and 2000 mg test ingredient /kg bodyweight

FORM AS APPLIED IN THE TEST
Suspended in arachis BP oil at a concentration of 300 mg test ingredient/kg bodyweight and 2000 mg test ingredient/kg bodyweight

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: by Harlan UK Limited, Bicester, Oxon, UK
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: +- 20% of 169 g
- Fasting period before study: Overnight fast before dosing and for three to four hours after dosing
- Housing: Groups of three in suspended solid-floor polypropylene cages furnished with woodflake
- Diet (e.g. ad libitum): 2014 Teklad Global Rodent diet ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: >5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Remarks:
BP
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg test ingredient / ml vehicle and 200 mg test ingredient / ml vehicle
- Amount of vehicle (if gavage): 10 ml dose / kg bodyweight
- Justification for choice of vehicle: Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL dose / kg bodyweight
Doses:
1
No. of animals per sex per dose:
3 for the preliminary study
3 for the main test
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observedSigns of systemic toxicity noted in animals treated at a dose level of 300 or 2000 mg/kg were
hunched posture, lethargy, ataxia, pilo-erection and decreased respiratory rate. Additional
observations noted in one animal treated at a dose level of 300 mg/kg were increased
lachrymation, hypothermia and loss of righting reflex. No signs of systemic toxicity were noted
in three animals treated at a dose level of 300 mg/kg. 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for up to fourteen days.
- Necropsy of survivors performed: yes
- Other examinations performed: gross pathological examination and clinical signes were observed

Results and discussion

Preliminary study:
The preliminary study had no deaths at a dosage level of 300 mg test ingredient / kg bodyweight.
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 500 mg/kg bw
Based on:
test mat.
Mortality:
All animals treated at a dose level of 2000 mg/kg were found dead one day after dosing. One animal treated at a dose level of 300 mg/kg was killed in extremis one day after dosing.
Clinical signs:
Signs of systemic toxicity noted in animals treated at a dose level of 300 or 2000 mg/kg were hunched posture, lethargy, ataxia, pilo-erection and decreased respiratory rate. Additional observations noted in one animal treated at a dose level of 300 mg/kg were increased lachrymation, hypothermia and loss of righting reflex. No signs of systemic toxicity were noted in three animals treated at a dose level of 300 mg/kg.
Body weight:
The surviving animals showed expected gains in bodyvveight over the study period.
Gross pathology:
Abnormalities noted at necropsy of animals that died or were killed in extremis during the study were abnormally red lungs, dark liver or patchy pallor of the liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The test substance was classified as a category 4 oral toxin based on GHS criteria.