Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 February 2017 - 02 March 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:
December 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
May 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
December 2002
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147
Version / remarks:
November 2000
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Name as cited in report: X-19924
Appearance: thick amber paste
Storage: at room temperature
Specific details on test material used for the study:
- Purity correction factor: 1.138
- Stability at higher temperatures: yes, maximum temperature: 60°C; maximum duration: 30 minutes
- Solubility and stability in vehicle: not indicated

Test animals

Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
female
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 8 weeks old)
- Weight at study initiation: 149 to 158 g
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test item.
- Housing: Group housing of 3 animals per cage in labeled Makrolon cages (MIV type; height 18 cm.), containing sterilized sawdust as bedding material and paper as cage-enrichtment.
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 40-49
- Air changes (per hr): approx 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 14 February 2017 to 02 March 2017

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Remarks:
Specific gravity: 1.036
Details on oral exposure:
VEHICLE
- Concentration in vehicle: not indicated\
- Justification for choice of vehicle: Trial preparations were performed at the Test Facility to select the suitable vehicle and to establish a suitable formulation procedure. There was no information available regarding the solubility or stability in vehicle.
- Specific gravity: 1.036

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg (10 mL/kg) body weight.

DOSAGE PREPARATION: Test item dosing formulations (w/w) were homogenized to visually acceptable levels at appropriate concentrations to meet dose level requirements. In order to obtain homogeneity, the test item (preparations) were heated in a water bath with a maximum temperature of 60ºC for a maximum of 34 minutes. The test item (formulations) were allowed to cool to a temperature of maximally 40ºC prior to dosing. The dosing formulations were kept at room temperature until dosing. The dosing formulations were stirred until and during dosing. Adjustment was made for specific gravity of the vehicle. A factor of 1.138 was used to correct for the purity/composition of the test item.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: maximum recommended dose according to OECD 423.
Doses:
2000 mg/kg (10 mL/kg) body weight
The study was conducted in a stepwise manner with two groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. Based on the results, one additional group was dosed at 2000 mg/kg.

No. of animals per sex per dose:
6 females/dose (2 groups of three females in a stepwise manner)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: twice daily
Body weights: days 1 (pre-administration), 8 and 15
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: No
Statistics:
The LD50 cut-off value was established based on OECD guideline 423. No statistical analysis was performed (the method used is not intended to allow the calculation of a precise LD50 value).

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 occurred.
Clinical signs:
Hunched posture and/or piloerection were noted for all animals on Day 1 only.
Body weight:
The mean body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Any other information on results incl. tables

The results were evaluated according to:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments).

- Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of items and mixtures

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Not classified according to Regulation 1272/2008/EC
Conclusions:
In an acute oral toxicity study with rats, performed according to OECD/EC test guidelines, an LD50 was established to exceed 2000 mg/kg bw. Based on the result obtained in this study, X-19924 does not need to be classified for acute toxicity under GHS and under Regulation 1272/2008/EC.
Executive summary:

The acute oral toxicity study on rats was conducted in accordance to OECD/EC 423 test guidelines. The study was conducted in a stepwise manner with two groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. 6 females/dose (2 groups of three females in a stepwise manner). The mean body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. Based on the results, one additional group was dosed at 2000 mg/kg. An LD50 was established to exceed 2000 mg/kg bw. Based on the result obtained in this study, X-19924 does not need to be classified for acute toxicity under GHS and under Regulation 1272/2008/EC.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.