Registration Dossier

Administrative data

Description of key information

The acute oral median lethal dose (LD50cut-off value) of the substance in Wistar rats was found to be 5000 mg/kg body weight.

Based on the results of this study, an indication of the classification for the substance is as follows:

Unclassified

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 11, 2018 - October 29, 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
OECD 423
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
The study was undertaken in compliance with the guidelines of the “Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC), USA” and “Guidelines for Laboratory Animals Facility” issued by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), India.
Compliance of these guidelines ensures the humane care of animals used throughout the experiment. It further enhances the well-being of animals which subsequently promotes a quality outcome of the experiment, for the advancement of biological knowledge, relevant to human and animals.
Project proposal for the experimentation was approved by the “Institutional Animal Ethics Committee (IAEC)”, JRF.

Acclimatisation
Acclimatisation Period: 6 to 10 days

Husbandry Practices
Caging: Polypropylene rat cages covered with stainless steel grid top were used. Autoclaved clean rice husk was used as the bedding material. Wooden chew blocks were provided as enrichment material.
Water Bottle: Each cage was supplied with a polypropylene water bottle with a stainless steel nozzle.
Housing: Three rat per cage
Room Sanitation: Daily: 1. Rack was cleaned with cloth, 2. Floor of experimental procedure room was swept, 3. All work tops and the floor were mopped with a disinfectant solution.
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Preparation of Dose Formulation

The test item was insoluble in RO water and 0.5% carboxy methyl cellulose while formed homogeneous suspension in corn oil, so the actual dose formulation was prepared using corn oil as vehicle. Required quantity [300 mg (for set I and II) and 2000 mg (for set III and IV)] were mixed in corn oil and the final volume was made up 10 mL. Gavage solutions were prepared freshly prior to dosing on all the occasions.

Dose Administration

Individual dose volume was adjusted according to body weight and dose level. All rats were dosed by oral gavage (day 0) using a BD 1 mL disposable syringe. Rats were fasted overnight prior to dosing and until three hours post-dosing.
Doses:
The first set (set I) and second set (set II) of female rats was treated a single dose of 300 mg test item/kg body weight. No mortality was observed at this dose level so a third set (set III) of three female rats was administered with higher dose level of 2000 mg of test item/kg body weight. No mortality was observed at this dose level so a fourth set (set IV) of three female rats was administered with same dose level of 2000 mg test item/kg body weight.
No. of animals per sex per dose:
3 female rats per study set for a total of 6 for dose:
300 6
2000 6
Control animals:
no
Details on study design:
As no information was available of test item, the first set (set I) of three female rats was given a single dose of 300 mg test itemkg body weight. No mortality was observed at this dose level so a second set (set II) of three female rats was administered with same dose level of 300 mg testi item/kg body weight. No mortality was observed at this dose level so a third set (set III) of three female rats was administered with higher dose level of 2000 mg test item/kg body weight. No mortality was observed at this dose level so a fourth set (set IV) of three female rats was administered with same dose level of 2000 mg test item/kg body weight. No mortality was observed at this dose level hence the endpoint was achieved and further testing was not required.
Statistics:
Dose (mg/kg body weight) Female rats (mortality/total)
300 0/6
2000 0/6
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No mortality was observed in rats treated with 300 and 2000 mg test itemkg body weight
Clinical signs:
No clinical sign was observed in all the rats treated with 300 and 2000 mgtest item/kg body weight.
Body weight:
Normal gain in body weight was observed in all the rats treated with 300 and 2000 mg test item/kg body weight.
Gross pathology:
External
External examination of terminally sacrificed rats did not reveal any abnormality.

Internal
Visceral examination of terminally sacrificed rats did not reveal any abnormality.
In absence of any pathological lesion in terminally sacrificed rats, it is concluded that the test item did not produce any treatment related effect at the dose level used in the present study.
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
No mortality was observed in rats treated with 300 and 2000 mg test item/kg body weight. The acute oral LD50 (cut-off value) of test item in Wistar rats was found to be 5000 mg/kg body weight.
The acute oral median lethal dose (LD50 cut- off value) of test item in Wistar rats was found to be 5000 mg/kg body weight.
Based on the results of this study, an indication of the classification for the substance is as follows:
Globally Harmonized System of Classification and Labelling of Chemicals (GHS 2017): Category 5 or Unclassified
Executive summary:

In an acute oral toxicity study, four sets of fasted Wistar rats (3 females/set) (9 to 11 weeks) were given a single oral dose of the reaction mass at 300(for set I and II) and 2000 (for set III and IV) mg/kg body weight and all rats were observed for 14 days.

There were no treatment-related mortality, clinical sign and changes in body weight or necropsy findings observed.

The acute oral median lethal dose (LD50cut-off value) of the substanceinWistar rats was found to be 5000 mg/kg body weight.

Based on the results of this study, an indication of the classification for the substance is as follows:

Globally Harmonized System of Classification and Labelling of Chemicals (GHS 2017):          

Category 5 or Unclassified

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Additional information

Justification for classification or non-classification