Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 23, 2017 - November 22, 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

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
Specific details on test material used for the study:
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final preparation of a solid: The test item preparation was made directly before administration. Appropriate amounts of the test item were suspended in the vehicle using a spatula, a mini shaker (Vortex Genie 2®, Scientific Industries Inc, New York, USA), Ultra-Turrax device (Ultra-Turrax T25, IKA®-Werke GmbH & Co. KG, Staufen, Germany) and a magnetic stirrer. The test item preparation was administered within less than 1 hour after preparation. The stability of the test item in the vehicle was not investigated.

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: 164 - 178g
- Fasting period before study: 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): 21.8 - 23.2°C
- Humidity (%): 45.9 - 59.5%
- 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 bw
No. of animals per sex per dose:
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.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
All rats survived the observation period.
Clinical signs:
No clinical signs of toxicity were observed.
Body weight:
One rat showed a decrease of body weight on day 2 of the experimental phase. The body weight development of all other rats 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 bw in 3 female rats and continued with further 3 females treated with 2000 mg/kg bw.

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 during the course of this study.

No clinical signs of toxicity were observed.

One rat showed a decrease of body weight on day 2 of the experimental phase. The body weight development of all other rats was inconspicuous throughout the study.

The gross pathological examination revealed no organ alterations.

Conclusion

The test item has no acute toxic potential under the conditions of the present study, and 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:
The test item has no acute toxic potential under the conditions of the present study, and 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. The test item has no acute toxic potential under the conditions of the present study, and the LD50value is higher than 2000 mg/kg after single oral administration in female rats.