Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January 31, 2013 - June 27, 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

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)
Version / remarks:
adopted on December 17, 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
Council Regulation (EC) No. 440/2008 laying down test methods pursuant to Regulation (EC) No. 1907/2006 of the European Parliament and the council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).
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
Specific details on test material used for the study:
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final preparation of a solid: Directly before the administration the test material was prepared with aqueous Methocel® K4M Premium solution as the vehicle using a Vortex Genie 2 and an Ultra-Turrax device.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at start of study: 9 weeks
- Weight at study initiation: 168 g (range from 162 to 174 g)
- Fasting period before study: approx. 17 hours before until up to 4 hours after treatment
- Housing: separately in type III Makrolon cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 23°C
- Humidity (%): 45 - 57%
- Photoperiod (hrs dark / hrs light): 12 hour light - 12 hour dark regime

IN-LIFE DATES: From: day 1 To: day 15

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Remarks:
Methocel K4M Premium solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 g/L
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: well tolerated and established standard vehicle

Doses:
2000 mg/kg
No. of animals per sex per dose:
2000 mg/kg: 6 (f)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: day 1, 2, 4, 6, 8, 11, 13 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
Standard statistical methods have been applied for data processing.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was seen in rats treated with 2000 mg/kg.
Clinical signs:
No clinical signs of toxicity were seen.
Body weight:
The body weight development was inconspicuous throughout the study.
Gross pathology:
The gross pathological examination revealed no organ alterations.

Any other information on results incl. tables

Objective

The objective of the present study was to identify potential toxic effects of the test item after single oral administration to rats in a stepwise procedure.

Study Design

The study was started with 2000 mg/kg in 3 female rats and continued with further 3 females at 2000 mg/kg.

Mortality and clinical signs were monitored for at least 6 hours after administration and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the observation period, all surviving rats were sacrificed and subjected to a detailed necropsy.

Results

No mortality occurred in the 6 female rats treated with 2000 mg/kg.

The body weight development was inconspicuous throughout the study.

No clinical signs of toxicity were observed.

The gross pathological examination revealed no organ alterations.

Conclusion

Under the conditions of the present study, it is concluded that the test item has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg after single oral administration in female rats.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present study, it is concluded that the test item has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg after single oral administration in female rats.
Executive summary:

This study was performed according to GLP and is fully compliant with OECD TG 423. Under the conditions of the present study, it is concluded that the test item has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg after single oral administration in female rats.