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Description of key information

Acute toxicity:Oral

The acute oral median lethal dose (LD50) of test chemical in male/female sprague-dawley rat was determined to be 8440-9710 mg/kg of body weight. LD50 value indicates that the test chemical does not exhibits acute toxicity by the oral route.

Acute Toxicity:Inhalation

The particle size distribution of the test substance was found to vary in the size of 53-500 µm, so the potential for the generation of inhalable forms is low.Moreover the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur, and therefore acute toxicity by inhalation route was considered to be waived.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Experimental study performed using standard test guideline
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Acute oral toxicity study of test chemical was performed on Rats(Male/female)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
Test animals :Spraque-Dawley rats (male/female), SPF breed : WIGA, Sulzfeld, FR G

Body weight : 77/13 0
Mean weight for
- male animals : 298 g
- female animals : 215 g

Diet : The animals were offered Herilan MRH-Kraftfutter, supplied by H . EGGERSMANN, Rinteln/Weser, FRG, and water ad libitum . Diet withdrawn 16 hours before beginning of study .

Form of application : The product was administered once by gavage as a 50% solution in aqua dest . in doses of 5620, 6810, 8250 and 10000 mg/kg .
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
No details available
Route of administration:
oral: drinking water
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
the product was administered once by gavage as a 50% solution in aqua dest . in doses of 5620, 6810, 8250 and 10000 mg/kg .
Doses:
5620 mg/kg
6810 mg/kg
8250 mg/kg
and 10000 mg/kg
No. of animals per sex per dose:
10 males
10 female
Control animals:
not specified
Details on study design:
Not specified
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
8 980 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no other details available
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
9 140 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no other details available
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
8 820 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no other details available
Mortality:
50% death was observed in male and female rats
Clinical signs:
Not specified
Body weight:
Not specified
Gross pathology:
Not specified
Other findings:
Not specified
Interpretation of results:
other: Not classified
Conclusions:
The acute oral median lethal dose (LD50) of test chemical in male/female sprague-dawley rat was determined to be 8440-9710 mg/kg of body weight. LD50 value indicates that the test chemical does not exhibits acute toxicity by the oral route.
Executive summary:

The acute oral toxicity of test chemical was performed in Sprague-Dawley rats . For this purpose, the product was administered once by gavage as a 50% solution in aqua dest . in doses of 5620, 6810, 8250 and 10000 mg/kg .

The median lethal dose (LD 50) after 14 days was observed to be 8980 (8440 - 9710) mg/kg in male and female rats.In male animals LD50 value was observed to be 9140 (8350 - 10510) mg/kg whereas in female animals ,8820 (7960 - 10090) mg/kg.

From the above study it is concluded that test chemical does not exhibits acute toxicity by the oral route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
8 980 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from study report

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Quality of whole database:
Waiver

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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
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 3 acute dermal toxicity studies as- WoE 2, WoE 3 and WoE 4
Acute dermal 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:
other: 2.Rat, 3.Rabbit,4.Rabbit
Strain:
other: 2.Sprague-Dawley,3.Not specified,4.Not specified
Sex:
male/female
Details on test animals and environmental conditions:
2. TEST ANIMALS
- Source:
2. National Institute of Biosciences, Pune.
3.Not specified
4.Not specified
- Females (if applicable) nulliparous and non-pregnant: No data available
- Age at study initiation:
2.Young adult male and female rats aged between 8 – 12 weeks were used.
3.Not specified
4.Not specified
- Weight at study initiation:
2.The weight range of approximately 217.8 to 251.8 grams at initiation of dosing.
3.Not specified
4.Not specified

Body weights at the start :
Male
Mean : 246.46 g (= 100 %)
Minimum : 238.5 g (- 3.23 %)
Maximum : 251.8 g (+ 2.17 %)
Total No. of animals : 5
Female
Mean : 221.36 g (= 100 %)
Minimum : 217.8 g (- 1.61 %)
Maximum : 224.3 g (+ 1.33 %)
Total No. of animals : 5

3.Not specified
4.Not specified

- Identification:
2.Each rat was individually identified by the cage number.
3.Not specified
4.Not specified
- Fasting period before study: No data available
- Housing:
2.The rats were individually housed in polycarbonate cages with paddy husk as bedding.
3.Not specified
4.Not specified
- Diet (e.g. ad libitum):
2.Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
3.Not specified
4.Not specified
- Water (e.g. ad libitum):
2.Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
3.Not specified
4.Not specified
- Acclimation period:
2. 5 days.
3.Not specified
4.Not specified

2.ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 to 22.3 degree centigrade.
- Humidity (%): 54.8% to 58.8%.
- Air changes (per hr): Ten to fifteen air changes per hour.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.

3.ENVIRONMENTAL CONDITIONS-Not specified
4.ENVIRONMENTAL CONDITIONS-Not specified

IN-LIFE DATES: 18-07-2017 to 02-08-2017


Type of coverage:
other: 2.Semiocclusive 3.Not specified,4.Not specified
Vehicle:
not specified
Details on dermal exposure:
2.TEST SITE
- Area of exposure: Trunk (dorsal surface and sides from scapular to pelvic area)
- % coverage: Approximately 10% of the body surface area.
- Type of wrap if used: Porous gauze dressing and non-irritating tape.

3.Not specified
4.Not specified

2.REMOVAL OF TEST SUBSTANCE
- Washing (if done): Distilled water was used to remove residual test item.
3.Not specified
4.Not specified

2. TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: No data available
- For solids, paste formed: No data available

3.Not specified
4.Not specified

VEHICLE
- Amount(s) applied (volume or weight with unit): No data available
- Concentration (if solution): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available
Duration of exposure:
2 .24 hr
3.Not specified
4.Not specified
Doses:
2.A single dose of 2000 mg of the test item per kilogram of body weight was administered to ten rats (five males and five females).
3.Not specified
4.Not specified
No. of animals per sex per dose:
2. 10 (5/sex).
3.Not specified
4. 3 rabbits
Control animals:
not specified
Details on study design:
2.Study design
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: Yes
- Other examinations performed:
Clinical Observations and General Appearance:
Animals were observed for clinical signs, mortality, until sacrifice.
Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time.
The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.

Evaluation of Dermal Reaction:
Dermal reaction was observed daily for study period of 14 days.

Body weights:
Individual animal body weights were recorded pre-test (prior to administration of the test item), day 7 and at termination on day 14.

Gross Pathology:
Necropsy was performed on animals surviving at the end of the study. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique (day 15).

Histopathology:
No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.


3.Study design :Not specified
4.Study design :Not specified
Statistics:
Not specified
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
not specified
Remarks on result:
other: No other details observed
Mortality:
2.Sex : Male
Group I -
Animal treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.

Sex : Female
Group I -
Animal treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days

3.No mortality was observed
4.No mortality was observed
Clinical signs:
2.Sex : Male
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.

Sex : Female
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.

3.Not specified
4.Not specified
Body weight:
2.Sex : Male
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 8.14% and 16.70% respectively.

Sex : Female
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 4.74% and 9.61% respectively.
3.Not specified
4.Not specified

Gross pathology:
2.Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group
3.Not specified
4.Not specified
Other findings:
2.- Other observations:
Evaluation of Dermal Reaction
Sex : Male
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.

Sex : Female
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
3.Not specified
4.Not specified
Interpretation of results:
other: Not classified
Conclusions:
According to CLP regulation, the test chemical cannot be classified for acute dermal toxicity, as the LD50 value is >2000 mg/kg bw.
Executive summary:

In different studies, the given test chemical has been investigated for acute dermal 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 test chemical. The studies are summarized as below –

The study now reported was designed and conducted to determine the acute dermal toxicity profile of test chemical in Sprague Dawley rats.

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days.   

Animals exhibited normal body weight gain through the study period of 14 days.

Gross pathological examination did not reveal any abnormalities attributable to the treatment. 

It was concluded that the acute dermal median lethal dose (LD50) of test chemical, when administered to male and female Sprague Dawley rats was found to be greater than 2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that test chemical does not classify as an acute dermal toxicant.

 The above study is supported with another study conducted on rabbit The test chemical was applied onto the skin of rabbits.

The acute dermal LD50 for test chemical was determined to be greater than 5000mg/kg.

Based on value the chemical was not classified as per CLP regulations.

 The above study further supported with another study conducted on rabbits, The animals were treated with test chemical. No mortality was observed in treated rabbits. Therefore, LD50 was considered to be > 5000 mg/kg bw when rabbits were treated with test chemical dermally.

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

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Data is Klimisch 1 and from experimental study report.

Additional information

Acute toxicity:Oral Route

The acute oral toxicity of test chemical was performed in Sprague-Dawley rats . For this purpose, the product was administered once by gavage as a 50% solution in aqua dest . in doses of 5620, 6810, 8250 and 10000 mg/kg .

The median lethal dose (LD 50) after 14 days was observed to be8980 (8440 - 9710) mg/kgin male and female rats.Inmale animals LD50 value was observed to be 9140 (8350 - 10510) mg/kgwhereas infemale animals ,8820 (7960 - 10090) mg/kg.

From the above study it is concluded that test chemicaldoes not exhibits acute toxicity by the oral route.

The study is supported by an acute oral toxicity of test chemical was performed in NMRI mice . For this purpose, the product was administered once by gavage as a 50% solution in distilled water in doses of 10000 mg/kg once by gavage.

No death was observed at a dose of 10000 mg/kg bw in male and female mice,hence LD50 value was considered to be >10000 mg/kg bw

From the above studies it is concluded that test chemical does not exhibits acute toxicity by the oral route.

Acute Toxicity:Inhalation

The particle size distribution of the test substance was found to vary in the size of 53-500 µm, so the potential for the generation of inhalable forms is low.Moreover the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur, and therefore acute toxicity by inhalation route was considered to be waived.

Acute toxicity:Dermal

In different studies, the given test chemical has been investigated for acute dermal 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 structurally similar read across chemicals.The studies are summarized as below:

The study now reported was designed and conducted to determine the acute dermal toxicity profile of test chemical in Sprague Dawley rats.

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days.   

Animals exhibited normal body weight gain through the study period of 14 days.

Gross pathological examination did not reveal any abnormalities attributable to the treatment. 

It was concluded that the acute dermal median lethal dose (LD50) of test chemical, when administered to male and female Sprague Dawley rats was found to be greater than 2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that test chemical does not classify as an acute dermal toxicant.

 The above study is supported with another study conducted on rabbit The test chemical was applied onto the skin of rabbits.

The acute dermal LD50 for test chemical was determined to be greater than 5000mg/kg.

Based on value the chemical was not classified as per CLP regulations.

 The above study further supported with another study conducted on rabbits, The animals were treated with test chemical. No mortality was observed in treated rabbits. Therefore, LD50 was considered to be > 5000 mg/kg bw when rabbits were treated with test chemical dermally.

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

Justification for classification or non-classification

Based upon the studies reviewed it can be concluded that, the test chemicalis not expected to show acute toxicity effect by the oral, inhalation and dermal route and thus will not be considered for further classification.