Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 17, 2014 - July 7, 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Specific details on test material used for the study:
Designation: Art. 201386
Synonym: B-2O-O5
Batch: EF13004186
Appearance: White solid
Released until: November 30, 2015
Purity (GC): 99.92%
Storage: Tightly closed, dark at room temperature (15 to 25°C)

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final preparation of a solid: Directly before the administration the test item was prepared with aqueous Methocel® K4M Premium solution as the vehicle using a mini shaker (Vortex Genie 2®, Scientific Industries Inc, New York, USA) and an Ultra-Turrax device (Ultra-Turrax T25, IKA®-Werke GmbH & Co. KG, Staufen, Germany). The stability in the vehicle was not investigated. The test item preparation was administered within < 1 hour after preparation.

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: 158 - 180g
- 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): 22.9 - 23.8°C
- Humidity (%): 45.6-59.8%
- 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:
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 signs of toxicity were seen in the 3 male and 3 female rats after treatment with 2000 mg/kg.
Body weight:
The body weight development of the rats was inconspicuous during the study.
Gross pathology:
The gross pathological examination revealed no organ alterations.

Any other information on results incl. tables

Study Design

The objective of this study was to determine the acute toxicity of the test item Art. 201386 (B-2O-O5) in rats after single oral administration of 2000 mg/kg body weight followed by a

2-week observation period. 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 during the course of this study.
No clinical signs of toxicity were observed.

The body weight development was inconspicuous throughout the study.
The gross pathological examination revealed no organ alterations.

Conclusion

Under the conditions of the present study, it is concluded that Art. 201386 (B-2O-O5) 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 Art. 201386 (B-2O-O5) 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 Art. 201386 (B-2O-O5) has no acute toxic potential and that the LD50value is higher than 2000 mg/kg after single oral administration in female rats.