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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:
key study
Study period:
25 September - 10 October 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP compliant

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)
Version / remarks:
dated 17 December, 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
dated 30 May 2008
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Certificate of Compliance with Good Laboratory Practices according to Directives 2004/9/CE and 2004/10/CE, Groupe Interministeriel des Produits Chimiques, Republique Francaise, Certificat n°: 2017/33, dated 27 April 2017
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: received from sponsor on 04 September 2018, batch No. 05347/MA
- Expiration date of the lot/batch: June 2022

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature, darkness
- Solubility and stability of the test substance in the solvent/vehicle: test item was used as supplied

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 (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks
- Weight at study initiation: 185 - 219g, mean: 201.3g ± 11.4g
- Fasting period before study: yes, food was removed the day before treatment and redistributed 4 hours after test item administration
- Housing: housed by groups of three in solid-bottomed clear polycarbonate cages with stainless steel mesh lid, each cage containing sawdust bedding wich was changed at least 2 times a week
- Diet: Teklad Global 16% Protein Rodent Diet from ENVIGO (2016) ad libitum
- Water: tap-water from public distribution system ad libitum; microbiological and chemical analyses of the water carried out once every six months by Bureau Veritas - Eurofins (France)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25 September 2018 To: 10 October 2018

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.13 ml/kg bw (corresponding to 2 g/kg bw according to the calculated density)

CLASS METHOD
- Rationale for the selection of the starting dose: No information was available regarding a possible systemic toxicity, the first test dose was chosen to be 2000 mg/kg bw.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
yes
Remarks:
A control study with distilled water (3 animals used), identified No. TAO423-2018-004, was performed in the laboratory to assess the comportment of the strain of rat used and to give additional historical data.
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations of behavioural or toxic effects on the major physiological functions and of mortality; weighing on Day 0 (just before administration of the test item), then on Days 2, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: body weight changes were calculated

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50 cut-off
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study.
Clinical signs:
No clinical signs related to the administration of the test item were observed during the study.
Body weight:
The bodyweight evolution of the animals remained normal during the study.
Gross pathology:
The macroscopic examination of the animals at the end of the study revealed a red spot on corpus in one animal (1/6).

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 OECD 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.
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 study was performed according to the official method as defined in the OECD Test Guideline No. 423 dated December 17th, 2001, and in compliance with the principles of the Good Laboratory Practice (GLP).

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 red spot on corpus in one animal (1/6).

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