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Description of key information

Acute oral toxicity: A primary oral toxicity study (Beerens-Heijnen, 2010) was available which is key study. This study showed that the oral LD50 value of test substance is established to exceed 2000 mg/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
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
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
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).
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
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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
1 (reliable without restriction)

Additional information

Acute oral toxicity:

A primary oral toxicity study was conducted according to OECD 423 using rat (Beerens-Heijnen, 2010). Key study.

This study showed that the oral LD50 value of test substance is established to exceed 2000 mg/kg body weight.


Justification for selection of acute toxicity – oral endpoint
This study was conducted according to OECD 423 under GLP.

Justification for classification or non-classification

Oral LD50 = >2,000 mg/kg (actual value >2,000 mg/kg) Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.1.1 the substance is not classified for the acute toxicity endpoint.