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Description of key information

Acute oral toxicity: 

The acute oral toxicity dose (LD50) was considered based on different studies conducted on rats for the given test chemical. The LD50 value is >5000 mg/kg bw. The study concluded that the LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
experimental data from various test chemicals
Justification for type of information:
Data is summarized based on the available information from various test chemicals.
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
WoE report is based on 2 acute oral toxicity studies as- WoE 2 and WoE 3.
Acute oral toxicity test was carried out to study the effects of the test chemicals on rodents.
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Species:
rat
Strain:
other: 2. not specified 3. Wistar
Sex:
female
Details on test animals and environmental conditions:
2. not specified
3. TEST ANIMALS
- Source: Geniron Biolabs Pvt. Ltd. Bengaluru
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 10 to 12 weeks
- Weight at study initiation: 176.24 g to 215.59 g
- Identification:By rat accession number. Identification of individual rats was by cage card and turmeric colour body markings. The rat accession number was allotted during the course of the study. The temporary body marking during acclimatization period was done with crystal violet.
- Fasting period before study: rats were fasted for approximately 16 to 18 hours
- Housing:Rats were housed individually in standard polysulfone cages (Size: L 425 x B 266 x H 185 mm), with stainless steel top grill
- Diet (e.g. ad libitum): Hypro Rat & Mice pellet feed, ad libitum
- Water (e.g. ad libitum): Deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier, Mumbai, ad libitum
- Acclimation period: The animals were acclimatized six days for G1-FTS, eight days for G1-STS, thirteen days for G2-FTS before treatment and and fifteen days for G2-STS.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 24°C
- Humidity (%): 65 to 67 %
- Air changes (per hr): air conditioned with adequate fresh air supply (between 13.1 and 13.2 air changes/hour).
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark cycle.

IN-LIFE DATES: From: 27 June 2018 To: 26 July 2018
Route of administration:
other: 2. oral: unspecified 3. oral: gavage
Vehicle:
other: 2. unchanged (no vehicle) 3. Milli-Q water
Details on oral exposure:
2. not specified
3. VEHICLE
- Concentration in vehicle: 300 & 2000 mg/kg body weight.
- Amount of vehicle (if gavage):dose volume was 30 & 200 mg/ml body weight
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bodyweight
Doses:
2. 5000 mg/kg bw
3. G1 (FTS) - 300 mg/kg
G1 (STS) - 300 mg/kg
G2 (FTS) - 2000 mg/kg
No. of animals per sex per dose:
2. not specified
3. G1 (FTS) - 300 mg/kg - 3
G1 (STS) - 300 mg/kg - 3
G2 (FTS) - 2000 mg/kg - 3
G2 (STS) - 2000 mg/kg - 3
Control animals:
not specified
Details on study design:
2. not specified
3. - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Clinical signs and pre-terminal deaths:At each step, the animals were observed five times on test day 1 (day of administration) i.e. at 30 minutes and four times at hourly intervals and once daily during days 2 to 15 post administration. Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern. Attention was directed to the observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma and all observed clinical signs were recorded.
- Body weights:The body weights were recorded on test day 1 (pre-administration), day 8 (7 days post administration) and day 15 (14 days post administration).
- Necropsy of survivors performed: yes, the rats surviving to the end of the observation period were euthanised by using isoflurane anaesthesia and subjected to detailed necropsy.
- Other examinations performed:Gross pathological findings were recorded and reported. Microscopic examination was not carried out as no gross pathological changes were observed.
Statistics:
2. not specified
3. not specified
Preliminary study:
2. not specified
3. not specified
Sex:
not specified
Dose descriptor:
LD50
Remarks:
2
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No Mortality was observed
Sex:
female
Dose descriptor:
LD50
Remarks:
3
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Mortality:
2. No Mortality was observed in treated rats at 5000 mg/kg bw.
3. G1 - [300 mg/kg body weight - Treatment (FTS and STS)]: There were no pre-terminal deaths.
G2 - [2000 mg/kg body weight - Treatment (FTS and STS)]: There were no pre-terminal deaths.
Clinical signs:
2. not specified
3. G1 - [300 mg/kg body weight - Treatment (FTS and STS)]: There were no clinical sings.
G2 - [2000 mg/kg body weight - Treatment (FTS and STS)]: There were no clinical signs observed in any of the rats.
Body weight:
2. not specified
3. G1 - [300 mg/kg body weight - Treatment (FTS and STS)]: The body weights of all the rats increased throughout the observation period.
G2 - [2000 mg/kg body weight - Treatment (FTS and STS)]: The body weights of all the rats increased throughout the observation period.
Gross pathology:
2. not specified
3. There were no gross pathological changes at necropsy.
Other findings:
2. not specified
3. not specified
Interpretation of results:
other: Not classified
Conclusions:
The test chemical cannot be classified for acute oral toxicity, as the LD50 value is >5000 mg/kg bw according to CLP regulation.
Executive summary:

In different studies, the given test chemical has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for the given test chemical. The studies are summarized as below -

 

Acute oral toxicity study was conducted using test chemical in rats at the concentration of 5000 mg/kg bw. Animals were observed for mortality. No Mortality was observed at dose 5000 mg/kg bw. Hence, LD50 value was considered to be >5000 mg/kg bw, when rats were treated with test chemical via oral route.

 

The above study is supported with the data available in study report for the given test chemical. The acute oral toxicity study was conducted to assess the toxicological profile as per OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) in Wistar rats. The dose formulation was prepared by using Milli-Q water and administered as a single oral gavage to overnight fasted (16 to 18 hours) three female rats (G1-FTS) at the dose of 300 mg/kg body weight. There were no clinical signs of toxicity and pre-terminal deaths observed. As all the rats survived at this step, the test was confirmed with three additional female animals with the same dose of 300 mg/kg body weight (G1-STS). There were no clinical signs of toxicity and pre-terminal deaths observed at this step. Based on the scheme - Annex 2c of the guideline OECD 423, the test was repeated at the dose of 2000 mg/kg  body weight (G2-FTS). There were no clinical signs of toxicity observed. Hence, the test was confirmed with three additional female rats at the same dose of 2000 mg/kg body weight (G2-STS) as per the scheme - Annex 2c of the guideline OECD 423. There were no clinical signs of toxicity and pre-terminal deaths observed at this confirmatory test. Hence, the further dosing was stopped. The rats were observed for mortality and clinical signs for 14 days post treatment. Body weights were recorded prior to dosing on day 1 and again on days 8 and 15. Gross necropsy was performed for all the rats at termination. The body weight growth of all rats was unaffected by the test item. There were no gross pathological changes at necropsy, hence histopathology was not performed. Based on the results of the present study, the LD50 value for the given test chemical is considered to be >2000 mg/kg. The test item is “not classified (> 2000 mg/kg)” as per the criteria of CLP.

  

Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from handbook or collection of data.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity:

In different studies, the given test chemical has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for the given test chemical. The studies are summarized as below -

 

Acute oral toxicity study was conducted using test chemical in rats at the concentration of 5000 mg/kg bw. Animals were observed for mortality. No Mortality was observed at dose 5000 mg/kg bw. Hence, LD50 value was considered to be >5000 mg/kg bw, when rats were treated with test chemical via oral route.

 

The above study is supported with the data available in study report for the given test chemical. The acute oral toxicity study was conducted to assess the toxicological profile as per OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) in Wistar rats. The dose formulation was prepared by using Milli-Q water and administered as a single oral gavage to overnight fasted (16 to 18 hours) three female rats (G1-FTS) at the dose of 300 mg/kg body weight. There were no clinical signs of toxicity and pre-terminal deaths observed. As all the rats survived at this step, the test was confirmed with three additional female animals with the same dose of 300 mg/kg body weight (G1-STS). There were no clinical signs of toxicity and pre-terminal deaths observed at this step. Based on the scheme - Annex 2c of the guideline OECD 423, the test was repeated at the dose of 2000 mg/kg body weight (G2-FTS). There were no clinical signs of toxicity observed. Hence, the test was confirmed with three additional female rats at the same dose of 2000 mg/kg body weight (G2-STS) as per the scheme - Annex 2c of the guideline OECD 423. There were no clinical signs of toxicity and pre-terminal deaths observed at this confirmatory test. Hence, the further dosing was stopped. The rats were observed for mortality and clinical signs for 14 days post treatment. Body weights were recorded prior to dosing on day 1 and again on days 8 and 15. Gross necropsy was performed for all the rats at termination. The body weight growth of all rats was unaffected by the test item. There were no gross pathological changes at necropsy, hence histopathology was not performed. Based on the results of the present study, the LD50 value for the given test chemical is considered to be >2000 mg/kg. The test item is “not classified (> 2000 mg/kg)” as per the criteria of CLP.

  

Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral toxicity.

 

Justification for classification or non-classification

Based on the above studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral toxicity.