Registration Dossier

Acute Toxicity:Oral

Based on the available results and applying the weight of evidence approach the acute oral LD50 value can be considered to be greater than 2000 mg/kg. Hence, the test chemical can be classified under the category “Not Classified” as per CLP Regulation

Acute Toxicity: Inhalation

The study doesnot need to be conducted due to the low vapor pressure of the chemical and its exposure as aerosols, dusts, mists or vapors of inhalable size during manufacture/use is highly unlikely.The estimated vapour pressure for the test chemical was 0.093 Pa or 0.0007 mmHg at 25 deg C, also the primary route of exposure oral. Hence, exposure via inhalation route is highly unlikely.

Acute Toxicity: Dermal

Based on the available results and applying the weight of evidence approach, the acute dermal LD50 for the test chemical can be considered to be greater than 2000 mg/kg. Hence, the test chemical can be classified under the category "Not Classified" as per CLP Regulation

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:

Weight of evidemce approach based on various test chemicals

Justification for type of information:

Weight of evidemce approach based on 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: Weight of evidemce approach based on various test chemicals

Principles of method if other than guideline:

Weight of evidemce approach based on various test chemicals

GLP compliance:

not specified

Test type:

other: Weight of evidemce approach based on various test chemicals

Limit test:

no

Species:

rat

Strain:

other: 2. Sprague Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2. 2000, 2510, 3160, 3980 and 5010 mg/kg
3. 2300 mg/kg

No. of animals per sex per dose:

2. 5 rats/ dose group

Control animals:

not specified

Details on study design:

2. - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on day 1 and day 14
- Necropsy of survivors performed: yes/no:No data available
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:No data available

Preliminary study:

no data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 350 mg/kg bw

Based on:

test mat.

Mortality:

50% mortality was observed

Clinical signs:

other: no data available

Gross pathology:

no data available

Other findings:

no data available

Interpretation of results:

other: Not Classified

Conclusions:

Based on the available results and applying the weight of evidence approach the acute oral LD50 value can be considered to be greater than 2000 mg/kg. Hence, the test chemical can be classified under the category “Not Classified” as per CLP Regulation

Executive summary:

Various studies were reviewed to determine the acute oral toxicity of the test chemical. These include in vivo experimental studies performed on rats for the test chemical. These results are mentioned below:

An acute toxicity study of the test chemical was carried out in male and female Sprague Dawley rats to determine its LD50. 5 male and female rats were dosed with 2000, 2510, 3160, 3980 and 5010 mg/kg of the test chemical orally via gavage. The treated rats were observed for mortality and other effects till 14 days. The LD50 values were considered to be (with 95% confidence limits) 2350 (2060-2620) mg/kg in males and in females when SpragueDawleyrats were treated with the test chemical orally.

This result is supported by other acute toxicity study of the test chemical was carried out on female rats. 50% mortality was observed at dose 2300mg/kg bw. Damage to the liver and kidneys was also noted in treated female rats. Hence, the LD 50 value was considered to be 2300mg/kg bw when female rats were treated with the test chemical orally.

Based on the available results and applying the weight of evidence approach the acute oral LD50 value can be considered to be greater than 2000 mg/kg. Hence, the test chemical can be classified under the category “Not Classified” as per CLP Regulation.

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 350 mg/kg bw

Quality of whole database:

Klimisch Rating 4

Reference

Endpoint:: acute toxicity: inhalation
Data waiving:: study scientifically not necessary / other information available
Justification for data waiving:: the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Quality of whole database:

waiver

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:

Weight of evidence approach based on various test chemicals

Justification for type of information:

Weight of evidence approach based on 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: Weight of evidence approach based on various test chemicals

Principles of method if other than guideline:

Weight of evidence approach based on various test chemicals

GLP compliance:

not specified

Test type:

other: Weight of evidence approach based on various test chemicals

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Type of coverage:

other: 2. occlusive; 3. not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

2. TEST SITE
- Area of exposure: shaved (abraded and intact) back skin
- % coverage:
- Type of wrap if used: covered under occlusive conditions (gauze pad, rubber dam and several wrappings of Elastoplast)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: The test chemical was removed with a wet towel. pst exposure observation time 14 days
3. TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.03 mol/kg

Duration of exposure:

2. 24 hours
3. not specified

Doses:

2. 2000 mg/kg
3. 5000 mg/kg

No. of animals per sex per dose:

2. 2 rabbits

Control animals:

not specified

Details on study design:

2. - Duration of observation period following administration: 14 days (or other?)
: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes/no
: yes
- Clinical signs including body weight : yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: death and surviving animals were necropsied.

Statistics:

2. LD50 value was calculated according tzo the method of Weil (1952).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

2. No death occurred at 2000 mg/kg

Clinical signs:

other: 2. 1 animal suffered from diarrhea; all others were unremarkable

Gross pathology:

2. At necropsy, there were no remarkable findings in males whereas females showed dark red mottled lungs

Other findings:

2. skin reactions:
abraded skin:
-----male:
no erythema, no edema no atonia no desquamation, no fissuring and no
eschar formation
------female:
erythema: score: 1 from d3-13; d14 score 0
edema: score: 1 from d3-13; d14 score 0
atonia: score 1 from d6-8, score 2 from d9-10, score 1 d11-13; d14 score 0
Fissuring: score 1 from d5-7; score 2 d8-13; score 1 d14
Eschar formation from d9 onwards and from d11 exfoliation
intact skin:
-----male
Erythema from d10-14 score 1
edema from d4-14 score 1
atonia from d5-8 score 1; d9-12 score 2; d13-14 score 1
Desquamation from d13-14 score 1
Fissuring from d5-13 score 2; d14 score 1
Eschr formation fron d 9 onwards and exfoliation at d 14
-----female
no erythema
edema: from d4-9 score 1
atonia: from d7-9 score 1; d9-14 score 0
Desquamation: from d10-14 score 1
Fissuring: at d 5 score 2; d 6-11 score 1; from d 12 score 0
no eschar formation and no exfoliation

Interpretation of results:

other: not classified

Conclusions:

Based on the available results and applying the weight of evidence approach, the acute dermal LD50 for the test chemical can be considered to be greater than 2000 mg/kg. Hence, the test chemical can be classified under the category "Not Classified" as per CLP Regulation

Executive summary:

Various studies were reviewed to determine the acute dermal toxicity of the test chemical. These include in vivo experimental studies performed on rats for the test chemical. These results are mentioned below:

Astudy was performed to determine the acute dermal LD50 of the test chemical. 2000 mg/kg bw undiluted test chemical was applied to shaved (abraded and intact) areas of the back of each of 2 New Zealand White rabbits/sex und covered under occlusive conditions (gauze pad, rubber dam and several wrappings of Elastoplast) for 24 hours. Afterwards the restrainer and wrappings were removed and the test chemical was removed with a wet towel. pst exposure observation time 14 days, death and surviving animals were necropsied. LD50 value was calculated according tzo the method of Weil (1952). No death occured throughout the observation period. At necropsy, there were no remarkable findings in males whereas females showed dark red mottled lungs.Hence, the acute dermal LD50 can be considered to be greater than 2000 mg/kg when the test chemical was applied to the skin of New Zealand White rabbits.

This result is supported by another study performed to determine the acute dermal toxicityof the test chemical. Rabbits were dermally applied 0.03 mol/kg i.e approximately 5000 mg/kg of the test chemical and observed for effects.The acute dermal LD50 of the test chemical was considered to be 5000 mg/kg (0.03 mol/kg) in rabbits.

Based on the available results and applying the weight of evidence approach, the acute dermal LD50 for the test chemical can be considered to be greater than 2000 mg/kg. Hence, the test chemical can be classified under the category "Not Classified" as per CLP Regulation

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch Rating 4

Acute Toxicity:Oral

Various studies were reviewed to determine the acute oral toxicity of the test chemical. These include in vivo experimental studies performed on rats for the test chemical. These results are mentioned below:

An acute toxicity study of the test chemical was carried out in male and female Sprague Dawley rats to determine its LD50. 5 male and female rats were dosed with 2000, 2510, 3160, 3980 and 5010 mg/kg of the test chemical orally via gavage. The treated rats were observed for mortality and other effects till 14 days. The LD50 values were considered to be (with 95% confidence limits) 2350 (2060-2620) mg/kg in males and in females when SpragueDawleyrats were treated with the test chemical orally.

This result is supported by other acute toxicity study of the test chemical was carried out on female rats. 50% mortality was observed at dose 2300mg/kg bw. Damage to the liver and kidneys was also noted in treated female rats. Hence, the LD 50 value was considered to be 2300mg/kg bw when female rats were treated with the test chemical orally.

Based on the available results and applying the weight of evidence approach the acute oral LD50 value can be considered to be greater than 2000 mg/kg. Hence, the test chemical can be classified under the category “Not Classified” as per CLP Regulation.

Acute Toxicity: Inhalation

The study doesnot need to be conducted due to the low vapor pressure of the chemical and its exposure as aerosols, dusts, mists or vapors of inhalable size during manufacture/use is highly unlikely.The estimated vapour pressure for the test chemical was 0.093 Pa or 0.0007 mmHg at 25 deg C, also the primary route of exposure oral. Hence, exposure via inhalation route is highly unlikely.

Acute Toxicity: Dermal

Various studies were reviewed to determine the acute dermal toxicity of the test chemical. These include in vivo experimental studies performed on rats for the test chemical. These results are mentioned below:

Astudy was performed to determine the acute dermal LD50 of the test chemical. 2000 mg/kg bw undiluted test chemical was applied to shaved (abraded and intact) areas of the back of each of 2 New Zealand White rabbits/sex und covered under occlusive conditions (gauze pad, rubber dam and several wrappings of Elastoplast) for 24 hours. Afterwards the restrainer and wrappings were removed and the test chemical was removed with a wet towel. pst exposure observation time 14 days, death and surviving animals were necropsied. LD50 value was calculated according tzo the method of Weil (1952). No death occured throughout the observation period. At necropsy, there were no remarkable findings in males whereas females showed dark red mottled lungs.Hence, the acute dermal LD50 can be considered to be greater than 2000 mg/kg when the test chemical was applied to the skin of New Zealand White rabbits.

This result is supported by another study performed to determine the acute dermal toxicityof the test chemical. Rabbits were dermally applied 0.03 mol/kg i.e approximately 5000 mg/kg of the test chemical and observed for effects.The acute dermal LD50 of the test chemical was considered to be 5000 mg/kg (0.03 mol/kg) in rabbits.

Based on the available results and applying the weight of evidence approach, the acute dermal LD50 for the test chemical can be considered to be greater than 2000 mg/kg. Hence, the test chemical can be classified under the category "Not Classified" as per CLP Regulation

Based on the available results, the test chemical can be considered to be comparatively non-toxic when exposed via oral, dermal or inhalation route of exposure and classified under the category "Not Classified" as per CLP Regulation