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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 03 to 28 September 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study run to a method comparable with current guidelines and to GLP

Data source

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

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
2-amino-5-bromopyridin-3-ol
EC Number:
689-734-6
Cas Number:
39903-01-0
Molecular formula:
C5H5BrN2O
IUPAC Name:
2-amino-5-bromopyridin-3-ol
Details on test material:
Batch: CCS-952/STG-02/00109
Purity: 96.2% w/w

Test animals

Species:
rat
Strain:
other: Wistar strain Crl:WI (Han) (outbred, SPF-Quality)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Approx. 8 or 12 weeks old
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available ad libitum.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material and paper as cage-enrichment.
- Diet (e.g. ad libitum): Free access to pelleted rodent diet.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0ºC (actual range: 19.6 – 21.6ºC)
- Humidity (%): A relative humidity of 40-70% (actual range: 42 - 75%)
- Air changes (per hr): Approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 03 September 2010 To: 28 September 2010

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Polyethylene glycol 400 (specific gravity 1.125)
Details on oral exposure:
VEHICLE
- Concentration in vehicle:
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.
- Lot/batch no. (if required):
- Purity:
Doses:
2000 mg/kg (10 mL/kg) body weight
No. of animals per sex per dose:
Each dose group consisted of 3 females. (Two subsequent groups)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15. One animal was weighed at death on Day 1.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes. The animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: LD50 cut off was considered to be 2000 mg/kg bw.
Mortality:
For concentration 2000 mg/kg, 1/3 animal died on Day 1, no deaths at the following days.
Clinical signs:
Hunched posture, piloerection and/or salivation were noted in all surviving animals between Days 1 and 3. Two animals showed lethargy, muscle twitching, spasms, tremor, abnormal posture, uncoordinated movements, quick breathing, flat posture and/or salivation, prior to death on Day 1.
Body weight:
The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
Reddish discoloration of the duodenum and the glandular mucosa of the stomach was found in one animal that died during the study, at macroscopic post mortem examination. Macroscopic post mortem examination of the other animals that died during the study and of the surviving animals at termination did not reveal any abnormalities.
Other findings:
none stated

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of this substance in Wistar rats was established to exceed 2000 mg/kg bodyweight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 2000 mg/kg body weight.