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Description of key information

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:
January - March 2019
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Animals
Species: Rat (Rattus norvegicus)
Strain: RccHan: WIST
Age/weight at dosing: 9 to 11 weeks, weight (g) minimum: 179.9, Maximum 207.3
Source: Animal Breeding facility, Jai Research Foundation.
total number of animals used: Nine females
Female rats were nulliparous and non-pregnant.

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 throught 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.
Projec proposal for the experimentation was approved by the "institutional Animal Ethics Committee (LAEC)", JRF.

Acclimatisations period: 7 to 14 days
Caging: Polypropylene rat cages covered with stainless steel grid top were used. Autoclaved clean rice husk was used as the bedding material. Wooden blocks were provided as enrichment material.
Water bottle: Each cage was supplied with a polypropylene water bottle with a stainless steel nozzle.
Housing: Maximum 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.

Animal identification: Each rat was uniquely numbered on the tail using a tattoo machine on day 1 of acclimatisation. Appropiate labels were attached to the cages indicating the study number, sutdy code, test item code, set number, sex, dose, type of study, cage number and animal number.

Feed and water: The reats werwe provided with feed (with the exception of vovernight fasting prior to dosing and three hours post-dosing) and water, ad libitum. The quality of feed and water is regularly monitored at Jai Research Foundation. There were no known contaminatns in the feed and water at levels that would have interfered with the experimental results obatined.
Feed: Teklad certified global high fiber rat/mice feed maufactured by Envigo, USA.
Water: UV sterilized water filtered through reverse osmosis water filtration system.

Environmental conditions:
Animal room: DCR 208, department of toxicology
Temperature: 20 to 23ºC
Relative Humidity 57 to 66%
Air changes: Minimum 15 air changes/hour
Photoperiod: The photoperiod was 12 hours artificial light and 12 hours darkness, light hours being 06:00 h - 18:00 h (photoperiod was maintained through automatic timer).
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
As the test item was found to be viscous the test item was slightly heated and was filled in the syringe and air bubble was removed. The same was brougth to room temeprature and then the amount to be dosed was adjusted. Individual dose volume was adjusted according to body weight, dose level and density (1050 mg/mL information provided by the sponsor via TIDS). All rats were dosed by oral gavage (day 0) using a metal cannula attached to a BD 1 mL disposable syringe which was graduated up to 1 mL. Rats were fasted overnight prior to dosing until three hours post -dosing.
Doses:
300 mg/kg, 2000 mg/kg
No. of animals per sex per dose:
3 female rats were dosed at 300 mg/kg (set I)
3 female rats were dosed at 300mg/kg (set II)
3 female rats were dosed at 2000 mg/kg (set III)
Control animals:
no
Details on study design:
As no information was available, the first set (set I) of three female rats were given a single dose of 300 mg/kg. No mortality was observed at this dose level, soa a second set (set II) of three female rats were treated at same dose level of 300 mg/kg. One mortality was observed at this dose level, so third set (set III) of three female rats were treated at higher dose level of 2000mg/kg. All rats were found dead at this dose level, hence the endpoint was achieved and fuerther testing was not required.
Preliminary study:
As no information was available, the first set (set I) of three female rats were given a single dose of 300 mg/kg. No mortality was observed at this dose level, soa a second set (set II) of three female rats were treated at same dose level of 300 mg/kg. One mortality was observed at this dose level, so third set (set III) of three female rats were treated at higher dose level of 2000mg/kg. All rats were found dead at this dose level, hence the endpoint was achieved and fuerther testing was not required
Key result
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
ca. 500 mg/kg bw
Based on:
test mat.
Mortality:
300 mg/kg 1/6 rats were found dead
2000 mg/kg 3/3 (all) rats were found dead
Clinical signs:
clinical signs are lethargy and piloerection. Observed in one out of six rats treated at 300mg/kg, while lethargy was observed in all rats treated at 2000 mg/kg.
Body weight:
Normal gain in body weight was observed in all surviving rats.
Gross pathology:
No abnormalities were found in any of the rats.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
According to the found DL50 (cut-off value) of 500 mg/kg, the substance classifies as category 4.
Executive summary:

EXECUTIVE SUMMARY: In an acute oral toxicity study, fasted Wistar rats (3 female rats/set) (9 to 11 weeks) were given a single oral dose of POLIOL MB 600 at 300 (for set I and II) and 2000 (for set III) mg/kg 


body weight and all surviving rats were observed for a period of 14 days. 


 

One out of six rats was found dead treated with 300 mg POLIOL MB 600/kg body weight. All rats were found dead treated with 2000 mg POLIOL MB 600/kg body weight. 


 

Clinical signs lethargy and piloerection were observed in one out of six rats treated with 300 mg POLIOL MB 600/kg body weight while lethargy was observed in all rats treated with 2000 mg POLIOL MB 600/kg body 


weight. 


 

Normal gain in the body weight was observed in all surviving rats. 


 

External and internal examination of found dead and terminally sacrificed rats did not reveal any abnormality. 


 

The acute oral median lethal dose (LD50 cut-off value) of POLIOL MB 600 in Wistar rats was found to be 500 


mg/kg body weight. 


 

Based on results of this study, an indication of the classification for POLIOL MB 600 is as mentioned below: 


 

Globally Harmonized System of Classification and 


Labelling of Chemicals (GHS 2017) 



Category 


4 


Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
500 mg/kg bw

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March to April 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Species:
rat
Strain:
Brown Norway
Sex:
female
Details on test animals or test system 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.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test item was held in contact with the skin using porous gauze dressing (not more than 8 ply) and a non-irritating tape (Medi tape 330, hypo-allergenic surgical tape) throughout the 24 h exposure period to prevent any loss of the test item and also to ensure that the rats did not lick or ingest it. At the end of the exposure period (24 h), the residual test item was removed using cotton soaked in RO water (freshly collected).
Duration of exposure:
24 h
Doses:
200, 1000 and 2000 mg/kg bw
No. of animals per sex per dose:
5 females
Control animals:
no
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No morbidity and mortality was observed in any rat treated with 200, 1000 and 2000 mg POLIOL MB 600/kg body weight.
Clinical signs:
Erythema, oedema, and scale were observed at the site of the test item application in rat treated with POLIOL MB 600.
Very slight erythema (score of 1) and very slight oedema (score of 1) were observed, at the site of the test item application in rat treated with POLIOL MB 600 post patch removal
Body weight:
Changes in body weight were considered within the expected range for this strain and age of rats and not influenced by the treatment with POLIOL MB 600/kg body weight.
Gross pathology:
External
External examination of terminally sacrificed rats treated at 200 mg POLIOL MB 600/kg body weight did not reveal any abnormality while scales formation was observed in rats treated at 1000 and 2000 mg POLIOL MB 600/kg body weight.
Internal
Visceral examination of terminally sacrificed rats did not reveal any abnormality.
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Based on results of this study, an indication of the classification for POLIOL MB 600 is as mentioned below:
Globally Harmonized System of Classification and
Labelling of Chemicals (GHS): Category 5 or Unclassified
As per Globally Harmonized System of Classification and Labelling of Chemicals (GHS 2017), if test item is classified under Category 5 or Unclassified it indicate that the LD50 is found to be greater than 2000 mg/kg body weight.
Executive summary:

In this acute dermal toxicity study, five female Wistar rats (three rat for the range finding study dosed at 200, 1000, and 2000 mg/kg body weight and additional two rats for the main study, sequentially dosed at 2000 mg/kg body weight) were dermally exposed toPOLIOL MB 600for 24 h.

Based on individual body weights, the required undiluted volume (0.05 to 0.47 mL) ofPOLIOL MB 600using density 1050 mg/mL, was applied over the clipped dorsolateral thoracic surface of the skin (approximately7 cm × 5 cm body surface area).

Initially one rat was tested for a period of 24 h.Based on observations at 24 h post patch removal, additional four rats were tested sequentially. At the end of the 24 h exposure period, the residual test item was removed with a piece of cotton, soaked in RO water.Skin reactions of each rat were observed at an interval of 24, 48, and 72 h post patch removal.Rats were observed for a period of 14 days.

Erythema, oedema, and scale were observed at the site of the test item application in rat treated with POLIOL MB 600.

There was no treatment-related mortality or change in the body weight recorded.

External examination of terminally sacrificed rats treated at200 mg POLIOL MB 600/kg body weightdid not reveal any abnormality while scales formation was observed in rats treated at 1000 and2000 mg POLIOL MB 600/kg body weight. Internal examination of terminally sacrificed rats did not reveal any abnormality.

Very slight erythema (score of 1) and very slight oedema (score of 1) were observed, at the site of the test item application in rat treated with POLIOL MB 600 post patch removal.

Based on results of this study, an indication of the classificationforthePOLIOL MB 600isas mentioned below:

Globally Harmonized System of Classification and Labelling of Chemicals (GHS)                                            :          Category 5 or Unclassified

As per the Globally Harmonized System of Classification and Labelling of Chemicals (GHS 2017), if a test item is classified under Category 5 or Unclassified it indicate that the LD50is found to be greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Justification for classification or non-classification