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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 test chemical. The LD50 value is >5000 mg/kg bw. The study 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.

Acute Inhalation Toxicity:

The acute inhalation toxicity study need not be conducted because exposure to humans via inhalation route is not likely taking into account due to the low vapour pressure of the test chemical, which is reported to be 2.19E-19 Pa. Thus, exposure to inhalable dust, mist and vapour of the chemical is highly unlikely. Therefore this study is considered for waiver. 

Acute Dermal toxicity:

The acute dermal toxicity dose (LD50) was considered based on different studies conducted on rats for the test chemical. The LD50 value is >2000 mg/kg bw, for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute dermal 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: 1. Carworth Farm Strain E SPF 2. not specified
Sex:
male/female
Details on test animals and environmental conditions:
1. TEST ANIMALS
- Fasting period before study:18 hours
- Diet (e.g. ad libitum): Spillers Small Laboratory Animal Diet was given to animal
2. not specified
Route of administration:
other: 1. oral: gavage 2. oral: unspecified
Vehicle:
other: 1. water 2. not specified
Details on oral exposure:
1. VEHICLE
- Concentration in vehicle:5000 mg/kg
- Justification for choice of vehicle: Test substance was soluble in water
2. not specified
Doses:
1. 5000 mg/kg
2. 5000 mg/kg bw
No. of animals per sex per dose:
1. Total: 10 animals
5000 mg/kg :5 males and 5 females
2. not specified
Control animals:
not specified
Details on study design:
1. - Duration of observation period following administration: 14 days
- Necropsy of survivors performed: no
- Other examinations performed: Clinical signs
2. not specified
Statistics:
1. Litchfield & Wilcoxon (1949)
2. not specified
Preliminary study:
1. not specified
2. not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Mortality:
1. No mortality was observed in treated rats at 5000 mg/kg bw.
2. No mortality was observed at dose 5000 mg/kg bw
Clinical signs:
1. In clinical signs examination, a substantial amount of coloured material was excreted in the faeces.
2. not specified
Body weight:
1. not specified
2. not specified
Gross pathology:
1. not specified
2. not specified
Other findings:
1. not specified
2. not specified
Interpretation of results:
other: Not classified
Conclusions:
According to CLP regulation, the test chemical cannot be classified for acute oral toxicity, as the LD50 value is >2000 mg/kg bw.
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 test chemical. The studies are summarized as below –

1. Acute oral toxicity study was done in group of 5 male and female Carworth Farm Strain E SPF rats using test material. No mortality was observed at dose 5000 mg/kg bw. In clinical signs examination, substantial amounts of coloured material were excreted in the faeces. Hence, LD50 value was considered to be >5000 mg/kg bw, when rats were treated with test chemical orally.

2. In an acute oral toxicity study, rats were treated with test chemical in the concentration of 5000 mg/kg bw orally. No mortality observed in treated rats at 5000 mg/kg bw. Therefore, LD50 was considered to be >5000 mg/kg bw, when rats were treated with test chemical orally.

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 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 journal.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
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
Qualifier:
according to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
WoE report is based on 2 acute dermal toxicity studies as- WoE 2 and WoE 3.
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:
rat
Strain:
other: 1. Wistar 2. Tif: RAIf
Sex:
male/female
Details on test animals and environmental conditions:
1. TEST ANIMALS
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: 200±20g
- Fasting period before study: Animals were fasted overnight prior to test
- Housing: The animals were then housed individually in cages with a collar around the neck in order to avoid the ingestion of the test compound.
- Diet (e.g. ad libitum): food was offered three hours after dosing.
- Acclimation period:The healthy wistar albino rats selected for study acclimatized to standard laboratory condition for period of one week under close Veterinary supervision.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature between 22-25°C
- Humidity (%): relative humidity 40-60%
- Air changes (per hr): Air conditioned rooms with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.
2. TEST ANIMALS
- Source: in-house bred
- Age at study initiation:
- Weight at study initiation: 247-274 g for males (mean 261 g) and 211-244 g for females (mean 231 g)
Type of coverage:
other: 1. open 2. semiocclusive
Vehicle:
other: 1. unchanged (no vehicle) 2. CMC in 0.1% (w/v) aqueous polysorbate 80
Details on dermal exposure:
1. TEST SITE
- Area of exposure: The test substance was applied uniformly over an exposed area of skin.
- Type of wrap if used: The test compound was held in contact with the skin with an impervious dressing secured in place with an adhesive tape.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressing was removed and the site of application was cleaned with lukewarm water wiping the test compound.
- Time after start of exposure:24 hours
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test compound was applied at the dose level of 2000 mg/kg b.w.t as such (as the compound was in liquid form).TEST SITE
- Area of exposure: back skin of total body surface area
- % coverage: Approximate 10 percent
- Type of wrap if used: The test compound was held in contact with the skin with an impervious dressing secured in place with an adhesive tape.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressing was removed and the site of application was cleaned with lukewarm water wiping the test compound.
- Time after start of exposure:24 hours
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test compound was applied at the dose level of 2000 mg/kg b.w.t as such (as the compound was in liquid form).
2. TEST SITE
- Area of exposure: Skin
- % coverage: 10% of body surface

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test substance was removed by using lukewarm water.
- Time after start of exposure: 24 hours
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): ca. 4 ml
VEHICLE
- Concentration (if solution): 0.5% (w/v)
Duration of exposure:
1. 24 hours
2. 24 hours
Doses:
1. No. of dose group : Two Group-I: 2000 mg/kg b.wt (limit test); Group-II: 2000 mg/kg b.wt (confirmatory test)
2. 2000 mg/kg bw
No. of animals per sex per dose:
1. 10 (5male & 5 female)
2. Total = 10
Control animals:
not specified
Details on study design:
1. - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The treated animals were observed for clinical signs of intoxication and mortality at different time interval for a period of 14 days. The body weight of each rat was observed on day 0 (pre treatment), 7th and 14th (post treatment).
- Necropsy of survivors performed: yes. The necropsy was performed on all animals which was died during the study or were sacrificed at termination of the study.
2. - Necropsy of survivors performed: yes
- Other examinations performed: Animals were observed for mortality, clinical signs and body weight changes.
Statistics:
1. not specified
2. not specified
Preliminary study:
1. not specified
2. not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Mortality:
1. No mortality was recorded in treated rats after administration of test compound at the dose level of 2000 mg/kg b.wt. throughout observation period of 14 days.
2. No mortality was observed at 2000 mg/kg bw.
Clinical signs:
1. No any clinical sign of toxicity throughout the observation period of 14 days were observed in treated rat.
2. Piloerection and hunched posture were observed and animals recovered within 2 days.
Body weight:
1. The body weight of each animal recorded on day 0, 7th and 14th showed normal increase and there was no significant increase or decrease in weight was recorded.
2. No treatment-related effects were observed.
Gross pathology:
1. NECROPSY FINDING
EXTERNAL
i.Skin- Skin and hair coat was observed wet.
ii.All external orifices- Normal
B. INTERNAL
i. Subcutaneous- No changes were observed.
ii. Superficial and deep lymph nodes- No change in mesenteric lymph node.
ABDOMINAL CAVITY
i.Opening and general examination- In the abdominal cavity all the organs were present in normal position.
ii.Spleen- No changes were recorded.
iii.Digestive system- No gross changes were observed in stomach and intestine.
iv.Liver and biliary ducts- No gross pathological changes were observed
v.Excretory system- No gross pathological changes were observed.
vi.Adrenal- Observed normal.
vii.Male/female genital organs – Showed normal colour, consistency and no inflammatory changes.
2. THORACIC CAVITY
i.Opening and general examination- Thoracic cavity was found to be normal without any fluid, mucous or blood etc.
ii.Lungs- No changes were recorded.
iii.Heart- No changes were observed in color and consistency. Heart found normal.
iv.Thyroid- Normal in shape, size and surface.
3. CRANIAL CAVITY
i.Brain- Normal in shape and size.
2. No treatment-related effects were observed.
Other findings:
1. not specified
2. 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 –

1. The acute dermal toxicity study was conducted as per OECD Guideline 402 (standard acute method) in Wistar rats. Ten healthy wistar albino rats of both sex (ranging b.wt 200±20 gm) selected for study after acclimatization. Approximate 10 percent back skin of total body surface area was prepared 24 hrs prior to application of test compound. The test compound was applied at the dose level of 2000 mg/kg b.w.t as such (as the compound was in liquid form) dermally for each animal. The treated animals were observed for clinical signs of intoxication and mortality at different time interval for a period of 14 days. The body weight of each rat was observed on day 0 (pre treatment), 7th and 14th (post treatment). The necropsy was performed on all animals which was died during the study or were sacrificed at termination of the study. No mortality was recorded in treated rats after administration of test compound at the dose level of 2000 mg/kg b.wt. throughout observation period of 14 days. No any clinical sign of toxicity throughout the observation period of 14 days were observed in treated rat. The body weight of each animal recorded on day 0, 7th and 14th showed normal increase and there was no significant increase or decrease in weight was recorded. No gross pathological changes were observed. Therefore, the LD50 value was considered to be >2000 mg/kg bw, when Wistar male and female rats were treated with test chemical by dermal application.

2. Acute dermal toxicity study of the given test chemical was performed according to OECD Guide-line 402 "Acute dermal Toxicity" in 10 male and femaleTif: RAIf rats at the test concentration of 2000 mg/kg bw. The given test chemical (purity 99.9%) was dissolved as 0.5% (w/v) CMC (vehicle) in 0.1% (w/v) aqueous polysorbate 80 and applied at a dose volume of 4 ml to 10% of body surface via semi-occlusive application. The test chemical was removed after 24 hours with lukewarm water and animals were observed for mortality, clinical signs and body weight changes. Necropsy of survivors performed. No mortality was observed at 2000 mg/kg bw. Piloerection and hunched posture were observed and animals recovered within 2 days. No treatment-related effects were observed in case of necropsy and body weight. Therefore, the LD50 value was considered to be >2000 mg/kg bw, when 10 male and female Tif: RAIf rats were treated with the given test chemical by dermal application semi-occlusively.

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 2 and from study report.

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 test chemical. The studies are summarized as below –

1. Acute oral toxicity study was done in group of 5 male and female Carworth Farm Strain E SPF rats using test material. No mortality was observed at dose 5000 mg/kg bw. In clinical signs examination, substantial amounts of coloured material were excreted in the faeces. Hence, LD50 value was considered to be >5000 mg/kg bw, when rats were treated with test chemical orally.

2. In an acute oral toxicity study, rats were treated with test chemical in the concentration of 5000 mg/kg bw orally. No mortality observed in treated rats at 5000 mg/kg bw. Therefore, LD50 was considered to be >5000 mg/kg bw, when rats were treated with test chemical orally.

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 oral toxicity.

Acute Inhalation Toxicity:

The acute inhalation toxicity study need not be conducted because exposure to humans via inhalation route is not likely taking into account due to the low vapour pressure of the test chemical, which is reported to be 2.19E-19 Pa. Thus, exposure to inhalable dust, mist and vapour of the chemical is highly unlikely. Therefore this study is considered for waiver. 

Acute Dermal Toxicity:

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 –

1. The acute dermal toxicity study was conducted as per OECD Guideline 402 (standard acute method) in Wistar rats. Ten healthy wistar albino rats of both sex (ranging b.wt 200±20 gm) selected for study after acclimatization. Approximate 10 percent back skin of total body surface area was prepared 24 hrs prior to application of test compound. The test compound was applied at the dose level of 2000 mg/kg b.w.t as such (as the compound was in liquid form) dermally for each animal. The treated animals were observed for clinical signs of intoxication and mortality at different time interval for a period of 14 days. The body weight of each rat was observed on day 0 (pre treatment), 7th and 14th (post treatment). The necropsy was performed on all animals which was died during the study or were sacrificed at termination of the study. No mortality was recorded in treated rats after administration of test compound at the dose level of 2000 mg/kg b.wt. throughout observation period of 14 days. No any clinical sign of toxicity throughout the observation period of 14 days were observed in treated rat. The body weight of each animal recorded on day 0, 7th and 14th showed normal increase and there was no significant increase or decrease in weight was recorded. No gross pathological changes were observed. Therefore, the LD50 value was considered to be >2000 mg/kg bw, when Wistar male and female rats were treated with test chemical by dermal application.

2. Acute dermal toxicity study of the given test chemical was performed according to OECD Guide-line 402 "Acute dermal Toxicity" in 10 male and femaleTif: RAIf rats at the test concentration of 2000 mg/kg bw. The given test chemical (purity 99.9%) was dissolved as 0.5% (w/v) CMC (vehicle) in 0.1% (w/v) aqueous polysorbate 80 and applied at a dose volume of 4 ml to 10% of body surface via semi-occlusive application. The test chemical was removed after 24 hours with lukewarm water and animals were observed for mortality, clinical signs and body weight changes. Necropsy of survivors performed. No mortality was observed at 2000 mg/kg bw. Piloerection and hunched posture were observed and animals recovered within 2 days. No treatment-related effects were observed in case of necropsy and body weight. Therefore, the LD50 value was considered to be >2000 mg/kg bw, when 10 male and female Tif: RAIf rats were treated with the given test chemical by dermal application semi-occlusively.

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 on the above studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral and acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral and acute dermal toxicity. For acute inhalation toxicity wavier was added so, not possible to classify.