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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
18 July - 02 August 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:
dated 17 December, 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
27 April 2017
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Physical state: clear dark yellow solid
Storage Conditions: room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage JANVIER LABS, France
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8 or 9 weeks
- Weight at study initiation: 194-211 g
- Fasting period before study: Food was removed on Day 1 and then redistributed 4 hours after the test item administration.
- Housing: Animals were housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
- Diet (e.g. ad libitum): Foodstuff (ENVIGO - 2016), ad libitum
- Water (e.g. ad libitum): Drinking water (tap-water from public distribution system), ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25°C
- Humidity: 30-70%
- Air changes: At least 10/hour
- Photoperiod: 12 hours dark / 12 hours light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
DOSAGE PREPARATION:In the first and second step of the study, 2.0082 g and 2.0030 g of the test item were weighed and DMSO (Dimethyl sulfoxide) was added to two 10 mL volumetric flasks. Just before the administration, the preparations were stirred, magnetically during 10 minutes at 50°C and by vortex, to obtain yellow solutions.
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: Clinical observations and mortality were recorded at 30 minutes, 1 hour, 3 hours, 4 hours, and then once daily for 14 days. Animals were weighed on Day 0 (just before administering the test item) and then on Day 2, Day 7 and Day 14.
- Necropsy of survivors performed: Yes; animals were euthanized with sodium pentobarbital on Day 14 and macroscopic observations were noted.
Statistics:
No data

Results and discussion

Preliminary study:
Not applicable
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study.
Clinical signs:
An increase of salivation was noted in the first hours of the test in one animal (1/6). Then a decrease of spontaneous activity, muscles tones and righting reflex was noted 24 hours post dose associated with a noisy breathing. The animal recovered normal activity on day 3. No other signs of systemic toxicity were noted.
Body weight:
The body weight evolution of the animals remained normal throughout the study.
Gross pathology:
The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.
Other findings:
None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the oral LD50 of the test substance is >2000 mg/kg bw in rats. In accordance with OECD Guideline 423, the LD50 cut-off of the test substance may be considered to be >5000 mg/kg bw by oral route in the rat. Therefore it is not classified according to the Regulation (EC) N° 1272-2008 and according to the Globally Harmonised System of classification and labelling of chemicals (GHS). No signal word or hazard statement is required.
Executive summary:

In an acute oral toxicity study performed according to the OECD Guideline 423 and in compliance with GLP, a single dose of 2000 mg/kg bw of the test substance in DMSO was given by oral gavage to a group of 6 female Wistar rats. Animals were then observed for mortality and clinical signs of toxicity for 14 days.

No mortality occurred during the study. An increase of salivation was noted in the first hours of the test in one animal (1/6). Then a decrease of spontaneous activity, muscles tones and righting reflex was noted 24 hours post dose associated with a noisy breathing. The animal recovered normal activity on day 3. No other signs of systemic toxicity were noted. The body weight evolution of the animals remained normal during the study. The macroscopic examination of the animals at the end of the study did not reveal any treatment related changes.

Rat Oral LD50 >2000 mg/kg bw.

Under the test conditions, the oral LD50 of the test substance is >2000 mg/kg bw in rats. In accordance with OECD Guideline 423, the LD50 cut-off of the test substance may be considered to be >5000 mg/kg bw by oral route in the rat. Therefore it is not classified according to the Regulation (EC) N° 1272-2008 and according to the Globally Harmonised System of classification and labelling of chemicals (GHS). No signal word or hazard statement is required.