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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 1300 mg/kg bw. The study concluded that LD50 is between 300-2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical can be classified in “Category 4” 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 1.24E-008 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 1300 mg/kg bw. The study concluded that LD50 value is between 1000-2000 mg/kg bw, for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical can be classified in “Category 4” 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:
calculation (if not (Q)SAR)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
Data is from Danish QSAR.
Qualifier:
according to guideline
Guideline:
other: Predicted data
Principles of method if other than guideline:
Prediction is done by using Danish QSAR
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
not specified
Doses:
1300 mg/kg bw
No. of animals per sex per dose:
not specified
Control animals:
not specified
Details on study design:
not specified
Statistics:
not specified
Preliminary study:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
1 300 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality observed
Mortality:
not specified
Clinical signs:
not specified
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
LD50 was estimated to be 1300 mg/kg bw, when rats were treated with the given test chemical via oral route.
Executive summary:

Based on the QSAR prediction done using the Danish (Q)SAR Database, the acute oral toxicity was estimated for the given test chemical. The LD50 was estimated to be 1300 mg/kg bw with Reliability Index 0.61 (0.5-0.75 = moderate prediction quality), when rats were treated with the given test chemical via oral route.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 300 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from prediction report.

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 for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
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. white rats 2. not specified
Sex:
male
Details on test animals or test system and environmental conditions:
1. not specified
2. TEST ANIMALS
- Age at study initiation: Adult rats
- Weight at study initiation: At the time of dosing the animals weighed between 200 and 270 g.
- Acclimation period: Rats were acclimatized for 5 days before dosing.
Type of coverage:
other: 1. Dermal 2. occlusive
Vehicle:
other: 1. Aqueous solution 2. distilled water
Details on dermal exposure:
1. TEST SITE
- Area of exposure: Shaved skin of the stomach
- % coverage: 4 cm2 in area
2. TEST SITE
- Area of exposure: The sample was spread over as large an area of the trunk
- % coverage: Appropriate amounts of test substances were weighed and applied on a body weight basis
- Type of wrap if used: The area was secured with double-layered gauze bandaging tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): all coverings were removed and any remaining test material was wiped off.
- Time after start of exposure:24-hr

TEST MATERIAL
- For solids, paste formed: yes
Duration of exposure:
1. 4-day exposure
2. 24-hr
Doses:
1. Range of 1224-1647 mg/kg
2. Range of 960-1750 mg/kg
No. of animals per sex per dose:
1. not specified
2. five animals per group
Control animals:
not specified
Details on study design:
1. - Other examinations performed: Animals were observed for clinical signs.
2. - Necropsy of survivors performed: yes
- Other examinations performed: Animals were observed for clinical signs, body weight changes.
Statistics:
1. Calculation of the mean lethal dose (LD50) was carried out by the probit analysis method of Litchfield and Wilcoxon.
2. LD50 value was calculated by the moving average method of Thompson (1947).
Preliminary study:
1. not specified
2. Preliminary range finding study was performed.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
1 420 mg/kg bw
Based on:
test mat.
95% CL:
1 224 - 1 647
Remarks on result:
other: 50% mortality was observed
Sex:
male
Dose descriptor:
LD50
Effect level:
1 300 mg/kg bw
Based on:
test mat.
95% CL:
960 - 1 750
Remarks on result:
other: 50% mortality was observed
Mortality:
1. 50% mortality was observed at 1420 mg/kg bw.
2. 50% mortality was observed at 1300 mg/kg bw.
Clinical signs:
1. Behavioral changes were observed such as, somnolence (general depressed activity) and hemorrhage was observed.
2. Topical administration caused localized effects, including erythema, edema, desquamation, necrosis, and scab formation; generalized toxic symptoms included sluggishness and reddish nasal and ocular discharges were observed.
Body weight:
1. not specified
2. Body weight gains of animals subjected to test chemical was within normal limits.
Gross pathology:
1. not specified
2. Gross necropsy did not reveal any significant changes related to the test compound.
Other findings:
1. not specified
2. not specified
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
According to CLP regulation, the test chemical can be classified in "Category 4" for acute dermal toxicity, as the LD50 value is between 1000-2000 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. Acute Dermal toxicity study of the given test chemical was conducted in white rats at the concentration range of 1224-1647 mg/kg bw. The given test chemical was applied as aqueous solutions to the shaved skin of the stomach of white rats 4 cm2 in area with a 4-day exposure. Animals were observed for clinical signs. Calculation of the mean lethal dose (LD50) was carried out by the probit analysis method of Litchfield and Wilcoxon. 50% mortality was observed at 1420 mg/kg bw. Behavioural changes were observed such as, somnolence (general depressed activity) and haemorrhage was observed. Hence, LD50 value was considered to be 1420 mg/kg bw, with 95% confidence limit of 1224-1647 mg/kg bw, when white rats were treated with the given test chemical by dermal application.

2. Acute Dermal toxicity study of the given test chemical was conducted in group of 5 male rats at the concentration range of 960-1750 mg/kg bw. Preliminary range finding study was performed. 24 hours before dosing the entire trunk area of each rat was clipped free of hair. Appropriate amounts of test substances were weighed and applied on a body weight basis by moistening the sample with distilled water to form a paste. The sample was spread over as large an area of the trunk as possible and secured with double-layered gauze bandaging tape. After a 24-hr exposure period, all coverings were removed and any remaining test material was wiped off. Necropsy of survivors performed. Animals were observed for clinical signs, body weight changes.LD50 value was calculated by the moving average method of Thompson (1947). 50% mortality was observed at 1300 mg/kg bw. Topical administration caused localized effects, including erythema, edema, desquamation, necrosis, and scab formation; generalized toxic symptoms included sluggishness and reddish nasal and ocular discharges were observed. Body weight gains of animals subjected to test chemical was within normal limits. Gross necropsy did not reveal any significant changes related to the test compound. Hence, LD50 value was considered to be 1300 mg/kg bw, with 95% confidence limit of 960-1750 mg/kg bw, when group of 5 male rats were treated with test chemical by dermal application occlusively for 24-hr.

Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value is between 1000-2000 mg/kg bw, for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical can be classified in “Category 4” for acute oral toxicity.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 300 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from authoritative database.

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. Based on the QSAR prediction done using the Danish (Q)SAR Database, the acute oral toxicity was estimated for the given test chemical. The LD50 was estimated to be 1300 mg/kg bw with Reliability Index 0.61 (0.5-0.75 = moderate prediction quality), when rats were treated with the given test chemical via oral route.

2. Acute oral toxicity study was performed using test chemical in male rats at the dose concentration of 1100 mg/kg bw. 50% mortality was observed at dose 1100 mg/kg bw. Hence, LD50 value was considered to be 1100 mg/kg bw, when male rats were treated with test chemical orally.

3. Acute oral toxicity study was performed in rats using test chemical. 50% mortality was observed at dose 1250 mg/kg bw. Hence, LD50 value was considered to be 1250 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 between 300-2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, the given test chemical can be classified in “Category 4” 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 1.24E-008 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. Acute Dermal toxicity study of the given test chemical was conducted in white rats at the concentration range of 1224-1647 mg/kg bw. The given test chemical was applied as aqueous solutions to the shaved skin of the stomach of white rats 4 cm2 in area with a 4-day exposure. Animals were observed for clinical signs. Calculation of the mean lethal dose (LD50) was carried out by the probit analysis method of Litchfield and Wilcoxon. 50% mortality was observed at 1420 mg/kg bw. Behavioural changes were observed such as, somnolence (general depressed activity) and haemorrhage was observed. Hence, LD50 value was considered to be 1420 mg/kg bw, with 95% confidence limit of 1224-1647 mg/kg bw, when white rats were treated with the given test chemical by dermal application.

2. Acute Dermal toxicity study of the given test chemical was conducted in group of 5 male rats at the concentration range of 960-1750 mg/kg bw. Preliminary range finding study was performed. 24 hours before dosing the entire trunk area of each rat was clipped free of hair. Appropriate amounts of test substances were weighed and applied on a body weight basis by moistening the sample with distilled water to form a paste. The sample was spread over as large an area of the trunk as possible and secured with double-layered gauze bandaging tape. After a 24-hr exposure period, all coverings were removed and any remaining test material was wiped off. Necropsy of survivors performed. Animals were observed for clinical signs, body weight changes.LD50 value was calculated by the moving average method of Thompson (1947). 50% mortality was observed at 1300 mg/kg bw. Topical administration caused localized effects, including erythema, edema, desquamation, necrosis, and scab formation; generalized toxic symptoms included sluggishness and reddish nasal and ocular discharges were observed. Body weight gains of animals subjected to test chemical was within normal limits. Gross necropsy did not reveal any significant changes related to the test compound. Hence, LD50 value was considered to be 1300 mg/kg bw, with 95% confidence limit of 960-1750 mg/kg bw, when group of 5 male rats were treated with test chemical by dermal application occlusively for 24-hr.

Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value is between 1000-2000 mg/kg bw, for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical can be classified in “Category 4” 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 between 300-2000 mg/kg bw, for acute oral toxicity and LD50 value is between 1000-2000 mg/kg bw, for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical can be classified in “Category 4” for acute oral and acute dermal toxicity. For acute inhalation toxicity wavier was added so, not possible to classify.