Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-12-02 to 2011-01-19
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Cross-reference
Reason / purpose:
reference to other study

Data source

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

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): L181
- Substance type: inorganic
- Physical state: solid
- Analytical purity: presumably > 99.9 %
- Lot/batch No.: VS 503G/10
- Expiration date of the lot/batch: not applicable
- Stability under test conditions: stable
- Storage condition of test material: room temperature
- Other:

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 9 - 10 weeks
- Weight at study initiation: animals 1 - 3: 158 - 165 g; animals 4 - 6: 176 - 182 g
- Fasting period before study: 16 - 19 h. Access to water was permitted.
- Housing: Full barrier in an air-conditioned room
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: animals 1 - 3: 12 days; animals 4 - 6: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/3 °C
- Humidity (%): 55 +/- 10 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: animals 1 - 3: 2010-12-02; animals 4 - 6: 2010-12-09 To: animals 1 - 3: 2011-12-28; animals 4 - 6: 2011-01-04

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
cotton seed oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.4 g/mL
- Amount of vehicle (if gavage): 5 mL
- Justification for choice of vehicle: non-toxic characteristics
- Lot/batch no. (if required): Sigma, lot no. MKBB7604, expiry date 2011-03-01

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight
Doses:
2000 mg/kg body weight
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 and weighing: daily observation; weighing on days 1 (prior to the administration), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: no

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality observed
Clinical signs:
Prior to the administration a detailed clinical observation was made of all animals.
A careful clinical observation was made several times on the day of dosing; at least once during the first 30 minutes and with special attention during the first 4 hours post-dose. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period.

Clinical signs were not observed during the whole observation period.
Body weight:
Absolute body weights in g and body weight grain in %

day 1 day 8 day 15 % day 1-15
animal 1 158 172 183 16
animal 2 163 178 191 17
animal 3 165 185 190 15
animal 4 182 193 201 10
animal 5 176 198 203 15
animal 6 177 206 222 25
Gross pathology:
With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 value of L181 via the oral route was > 2000 mg/kg body weight.
Executive summary:

The oral toxicity of L181 was examined in a GLP guideline study according to OECD 423.

Under the conditions of the study, a single oral application to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality.

The median dose level of L181 after a single oral administration to female rats, observed over a period of 14 days is:

LD50 cut-off (rat): unclassified