Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04 Sept - 04 Oct 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
adopted 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
adopted 2008
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
The Department of Health of the Government of the United Kingdom
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 57033
- Expiration date of the lot/batch: 25 November 2014

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK (RccHanTM:WIST strain)
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 150 - 170 g
- Fasting period before study: over night and 3-4 hours after dosing
- Housing: in groups of up to four in suspended solid floorpolypropylene cages furnished with wood flakes
- Diet: 2014C Teklad Global Rodent Diet supplied by Harlan Laboratories Ltd., ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

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

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: unchanged no vehicle for 2000 mg/kg bw and water for 300 mg/kg bw
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:
sighting study: 2000 and 300 mg/kg bw
main study: 300 mg/kg bw
No. of animals per sex per dose:
sighting study: 1
main study: 4
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0.5, 1, 2 and 4 hours after dosing and daily thereafter, weighing was done on day of dosing and on day 7 and day 14 or at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
300 - 2 000 mg/kg bw
Based on:
test mat.
Mortality:
In the sighting study the one female animal dosed with 2000 mg/kg bw was killed for humane reason one day after dosing, since the occurrence of clinical signs of toxicity exceeded the severity limit. No other animal at 300 mg/kg bw died or was killed due to humane reasons.
Clinical signs:
Clinical signs included hunched posture, lethargy, pilo-erection, ptosis and laboured respiration, blood stained urine was also noted. There were no signs of systemic toxicity in the one animal treated at a dose level of 300 mg/kg.
Body weight:
Surviving animals showed expected gains in bodyweight.
Gross pathology:
Abnormalities noted at necropsy of the animal treated at a dose level of 2000 mg/kg were pale liver, dark spleen, dark kidneys, gaseous distension of the stomach, haemorrhage and pallor of the gastric mucosa and red coloured fluid filled bladder. No abnormalities were noted at necropsy of animals treated at a dose level of 300 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: Cat. 4 H302
DSD: Xn, R22