Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009-11-23 to 2009-12-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study Minor deviation from the guideline was found, but it had no effect on the study results: - humidity was higher than recommend by the OECD guideline
Cross-reference
Reason / purpose:
reference to same study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 2001-12-17
Deviations:
yes
Remarks:
please refer to the field "Rationale for reliability incl. deficiencies" above
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
, 2008
Deviations:
yes
Remarks:
please refer to the field "Rationale for reliability incl. deficiencies" above
GLP compliance:
yes (incl. certificate)
Remarks:
signed 2008-04-17
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid
Details on test material:
- Physical state: solid/ brown, dark
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age: approx. 10 weeks
- Weight: 172 - 186 g
- Fasting period before study: feed was withdrawn at least 16 hours before administration, but water was available ad libitum.
- Housing: single housing in Makrolon cage, type III; bedding: H 15005-29
- Diet: VRF1(P)
- Water (ad libitum): tap water
- Acclimation period: at least 5 days before the beginning of the experimental phase

ENVIRONMENTAL CONDITIONS
- Temperature: 20 – 24 °C
- Relative humidity: 20 – 80 %
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5 % CMC-solution in doubly distilled water
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: a good homogeneity in water could not be guaranteed.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION:
- test-item preparation was produced for each test group shortly before administration by stirring.
- homogeneity of the test-item preparation during application was provided by stirring.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: starting dose was requested by the sponsor.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: individual body weights shortly before administration (day 0), weekly thereafter and on the last day of
observation. Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals. A check for any dead or moribund animal was made at least once each workday
- Necropsy of survivors performed: yes, necropsy with gross-pathology examination on the last day of the observation period after sacrifice.
Statistics:
not applicable

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No clinical signs were observed during clinical examination.
Body weight:
The mean body weight of the test groups increased throughout the study period within the normal range.
Gross pathology:
There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 (female rats) > 2000 mg/kg bw
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not acutely toxic via the oral route.
Executive summary:

The acute oral toxicity of the substance was investigated according to the OECD guideline 423 (2001). First, three female Wistar rats were dosed with 2000 mg/kg bw of the substance in 0.5 % CMC-solution by gavage. Since no mortalitiy occurred 2000 mg/kg bw was administered to another group of 3 female animals. As no animal died the study was terminated. Overall, no mortality, no clinical signs and no macroscopic pathological findings were noted for the animals at the 2000 mg/kg dose level. Also, the mean body weight of the test groups increased throughout the study period within the normal range. Based on these results the LD50 was considered to be greater than 2000 mg/kg bw for female rats.

According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not acutely toxic via the oral route.