Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 December 2012 to 3 January 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

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
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: JMAFF, 12 Nohsan, Notification No. 8147, 2011; including the most recent partial revisions
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid (unspecified)
Details on test material:
- Appearance: red-brown liquid
- Storage conditions: room temperature in the dark
- Stability under storage conditions: stable

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Crl:WI (Han) (outbred, SPF-Quality).
- Age at study initiation: Approximately 10 weeks old.
- Weight at study initiation: 173 to 186 g on the first day of the test. Bodyweight variation did not exceed ± 20 % of the sex mean.
- Fasting period before study: Yes. Animals were deprived of food overnight prior to dosing and until 3 to 4 hours after administration of the test material.
- Housing: Group housing of 3 animals per cage in labelled cages containing sterilised 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): 18 to 24 °C.
- Humidity (%): 40 to 70 %.
- Air changes (per hr): Approximately 15 room air changes/hour.
- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour dark cycle.

IN-LIFE DATES: From: 13 December 2012 To: 3 January 2013

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.247 mL/kg bodyweight.
Specific gravity of the test material was 0.89 at 15.6 °C. Therefore the dose volume was calculated as dose level (g/kg) / specific gravity (g/mL).
Doses:
2000 mg/kg bodyweight
No. of animals per sex per dose:
6 female animals; dosed in two groups of 3.
Control animals:
no
Details on study design:
The test material was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Animals were weighed on day 1 (prior to dosing) and on days 8 and 15.
At periodic intervals on the day of dosing and once daily thereafter clinical signs were noted. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.
- Necropsy of survivors performed: Yes. At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure. Descriptions of all internal macroscopic abnormalities were recorded.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality.
Clinical signs:
Hunched posture was noted in all animals on day 1. Piloerection was also noted on the first day in one animal.
Body weight:
The bodyweight gain shown by the 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:
Rupture of the right and left medial lobe of the liver and watery-clear, dark red contents in the abdominal cavity were noted in one animal at macroscopic post mortem examination.
Macroscopic post mortem examination of the other animals at termination did not reveal any abnormalities.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the oral LD50 of the test material was established to be >2000 mg/kg bodyweight and as such requires no classification in accordance with EU criteria.
Executive summary:

The acute oral toxicity of the test material was investigated in accordance with the standardised guidelines OECD 423, EU Method B.1 tris, EPA OPPTS 870.1100 and JMAFF 12 Nohsan, Notification No. 8147 under GLP conditions.

The undiluted test material was administered by gavage to two groups of three female Wistar rats at a limit dose level of 2000 mg/kg. The animals were observed for 15 days before being subjected to necropsy.

No mortality was seen throughout the study; hunched posture was noted in all animals on day 1 and piloerection was also noted on the first day in one animal. Bodyweight gains were considered to be normal. Rupture of the right and left medial lobe of the liver and watery-clear, dark red contents in the abdominal cavity were noted in one animal at macroscopic post mortem examination. Macroscopic post mortem examination of the other animals at termination did not reveal any abnormalities.

Under the conditions of this study, the oral LD50 of the test material was established to be >2000 mg/kg bodyweight and as such requires no classification in accordance with EU criteria.