Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
other: Japan MAFF 8147
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Laromer LR 8887
- Physical state: Clear yellowish liquid
- Content of active ingredient: 78.1g/100g by H-NMR spectroscopy
- Purity test date: 2011-11-03
- Lot/batch No.: 110009P040
- Expiration date of the lot/batch: no data
- Stability under test conditions: guaranteed by sponsor
- Storage condition of test material: room temperature in the dark
- Other: density: 1.096g/ml (determined by Bioassay)

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: app. 10 weeks
- Weight at study initiation: 170 - 190g
- Fasting period before study: 16h (water available ad lib.)
- Housing: single in Macrolon type III cages
- Diet (e.g. ad libitum): VRF1(P); SDS Special diets services, 67122 Altrip, Germany ad lib.
- Water (e.g. ad libitum): tap water ad lib.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12h/12h

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.82mL/kg b.w.
Doses:
2000mg/kg
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: several times on the day of administration, daily thereafter on workdays
- Frequency of weighing: before administration and weekly thereafter, additionally at the day of death of the animal that died on study day 1
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 1 of 6 animals died
Mortality:
one female died on day one
Clinical signs:
One animal did not show any clinical signs.
Impaired general state, dyspnoea and piloerection were observed in two animals at hour 4 and 5. Ataxia was observed in these animals at hour 5. Either of them was found dead on study day 1.
Beginning with hour 1 or 2, impaired general state, dyspnoea and piloerection was noted until hour 5 in three animals. In one of these animals these clinical signs persisted until study day 3, while ataxia was noted in this animal at hour 5 only.
Body weight:
The mean body weight of the test groups increased throughout the study period within the normal range with the exception of one female of the first administration group, which showed reduction of body weight during the first post-exposure week, but gained adequately weight during the second post-exposure week.
Gross pathology:
There were no macroscopic pathological findings in the five females sacrificed at the end of the observation period.
In the animal that died on study day 1 the following findings were observed at necropsy:
stomach filled with liquid content, extensive bleeding in the glandular stomach; partly black discolored spleen (one-third), red discoloration of content in small intestine, red discolored small intestine and congestion in the kidneys.

Applicant's summary and conclusion

Interpretation of results:
relatively harmless
Remarks:
Migrated information
Conclusions:
The acute oral LD50 in rats was found to be greater than 2000mg/kg b.w. in female rats.
Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class method, 2000 mg/kg bw of the undiluted test item were administered to two test groups of three fasted Wistar rats by gavage. The following test item-related clinical observations were recorded during the course of the study:

· One out of six animals died

· Impaired general state

· Dyspnoea

· Piloerection

· Ataxia

· The mean body weight of the animals increased within the normal range throughout the study period with the exception of one female of the first administration group, which showed reduction of body weight during the first post-exposure week, but gained adequately weight during the second postexposure week.

The following macroscopic pathological findings were recorded in the animal that died:

· Stomach: filled with liquid content

· Glandular stomach: extensive bleeding

· Spleen: black discoloration in one-third

· Small intestine: red discoloration

· Content of the small intestine: red discoloration

· Kidneys: congestion

· There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period (5 females).