Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2018-02-28 to 2018-03-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

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 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage JANVIER LABS (53940 Le Genest St Isle – France)

- Females nulliparous and non-pregnant: yes

- Age at study initiation: 8 weeks old.

- Weight at study initiation: 193 - 216 g

- Fasting period before study: day -1 and until 4 hours after the test item administration.

- Housing:
* 3 animals per cage
* solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
* Cage containing sawdust bedding, changed at least 2 times a week.
* Conventional air conditioned animal husbandry.


- Diet : ad libitum
- Water: ad libitum
- Acclimation period: at least five days

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

IN-LIFE DATES:

Step 1
From: 2018-02-28 To: 2018-03-14
Step 2
From: 2018-03-01 To: 2018-03-15

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
VEHICLE
- Concentration in vehicle:
* First step: 2.0043 g of test item was added to a 10 mL volumetric flask.
* Second step: 2.0077 g of test item was added to a 10 mL volumetric flask.
- Amount of vehicle (if gavage): 10 ml/kg of bw
- Justification for choice of vehicle: Dimethyl sulfoxide (DMSO) was chosen as it produced the most suitable formulation at the requested concentration.
Doses:
Steps 1 and 2: 2000 mg/kg bw
No. of animals per sex per dose:
3 females rat per step
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
* Frequency of observation : The first day : at 30 min, 1h, 3h, 4h, 24h, then daily.
* Weighing on D0 (prior administration), D2, D7 and D14.

- Necropsy of survivors performed: yes. Animals were euthanized with sodium pentobarbital
Only those organs likely to be modified in cases of acute toxicity were examined. No organ was removed and preserved in view to microscopic examinations.

- Other examinations performed: clinical signs, body weight,organ weights, histopathology.
- Macroscopic examinations at the end of the study (after euthanisia) with the examination of organs likely to be modified in cases of acute toxicity (i.e. oesophagus, stomach, the entire digestif tract, spleen, liver, thymus, trachea, lungs, heart, kidneys, urinary bladder, ovaries, uterus, treatment area,adrenals, pancreas).

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality observed during the study
Clinical signs:
No clinical signs observed during the study.
Body weight:
The body weight evolution of the animals remained normal during the study.
Other findings:
* thinning of forestomach: 3/6 animals
* green spots on the corpus: 2/6 animals

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the test item is higher than 2000 mg/kg body weight.

In accordance with the O.E.C.D. Test Guideline No. 423, the LD50 cut-off of the test item may be considered as 5000 mg/kg body weight by oral route in the rat.

The test item does not have to be classified in accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures. No signal word or hazard statement is required.
Executive summary:

The test item was administered to a group of 6 female Sprague Dawley rats at the dose of 2000 mg/kg body weight.

The experimental protocol was established according to the official method as defined in the O.E.C.D. Test Guideline No. 423 dated December 17th, 2001 and the test method B.1tris of the Council regulation No. 440/2008 dated May 30th, 2008.

No mortality occurred during the study.

No clinical signs related to the administration of the test item were observed during the study.

The body weight evolution of the animals remained normal during the study.

The macroscopic examination of the animals at the end of the study revealed a thinning of forestomach (3/6) and green spots on the corpus (2/6). No other changes were observed.

In conclusion, the LD50 of the test item is higher than 2000 mg/kg body weight.

In accordance with the O.E.C.D. Test Guideline No. 423, the LD50 cut-off of the test item may be considered as 5000 mg/kg body weight by oral route in the rat.

The test item does not have to be classified in accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures.

No signal word or hazard statement is required.