Registration Dossier

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 6160 mg/kg bw. The study concluded that LD50 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 0.0412 mm Hg. 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 studies concluded that LD50 value is >5000 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.

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 for cross-reference:

read-across source

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 3 acute oral toxicity studies as - WoE 2, WoE 3 and WoE 4.
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

Specific details on test material used for the study:

- Name of test material: Isolongifolene
- IUPAC name: (2S)-1,3,4,5,6,7-hexahydro-1,1,5,5-tetramethyl-2H-2,4a-methanonaphthalene
- Molecular formula: C15H24
- Molecular weight: 204.3546 g/mole
- Smiles :CC1(C)CCC=C2C(C)(C)[C@H]3CC[C@@]12C3
- Inchl: 1S/C15H24/c1-13(2)8-5-6-12-14(3,4)11-7-9-15(12,13)10-11/h6,11H,5,7-10H2,1-4H3/t11-,15-/m0/s1
- Substance type: Organic
- Physical state: Liquid (colorless)

Species:

rat

Strain:

other: 1. Osborne-Mendel 2. not specified 3. Osborne-Mendel

Sex:

male/female

Details on test animals or test system and environmental conditions:

1. Details on test animal
TEST ANIMALS
- Age at study initiation: young and adult rats
- Fasting period before study: approximately 18 hr
- Diet (e.g. ad libitum):diet was provided ad libitum
- Water (e.g. ad libitum): water was provided ad libitum
2. not specified
3. Details on test animal
TEST ANIMALS
- Age at study initiation: young and adult rats
- Fasting period before study: approximately 18 hr
- Diet (e.g. ad libitum):diet was provided ad libitum
- Water (e.g. ad libitum): water was provided ad libitum

Route of administration:

other: 1. oral: gavage 2. oral: unspecified 3. oral: gavage

Vehicle:

other: 1. unchanged (no vehicle) 2. unchanged (no vehicle) 3. unchanged (no vehicle)

Details on oral exposure:

1. not specified
2. not specified
3. No data available

Doses:

1. 6160 mg/kg bw
2. 4400 mg/kg bw
3. 2480 mg/kg bw

No. of animals per sex per dose:

1. Groups of 10 males and 10 females
2. not specified
3. groups of 10 males and 10 females

Control animals:

not specified

Details on study design:

1. Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: All animals were maintained under close observation for recording toxic signs and time of death.
- Other examinations performed: clinical signs
2. not specified
3. Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: All animals were maintained under close observation for recording toxic signs and time of death.
- Other examinations performed: clinical signs

Statistics:

1. LD50'S were computed by the method of Litchfield & Wilcoxon (1949).
2. not specified
3. LD50'S were computed by the method of Litchfield & Wilcoxon (1949).

Preliminary study:

1. not specified
2. not specified
3. No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

6 160 mg/kg bw

Based on:

test mat.

95% CL:

4 400 - 8 630

Remarks on result:

other: 50% mortality was observed

Sex:

not specified

Dose descriptor:

LD50

Effect level:

4 400 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 480 mg/kg bw

Based on:

test mat.

95% CL:

2 100 - 2 930

Remarks on result:

other: 50% mortality was observed

Mortality:

1. Death time was observed from 4 hours to 9 days
2. 50% mortality was observed at 4400 mg/kg bw
3. Death time was observed from 2 hours to 4 days.

Clinical signs:

1. Clinical signs like Depression, scrawny appearance, porphyrin-like deposit around eyes and nose for a week after treatment were observed.
2. not specified
3. Clinical signs like Depression, coma on high doses,scrawny appearance for 3-4 days. All animals recovered within 7 days.

Body weight:

1. not specified
2. not specified
3. No data available

Gross pathology:

1. not specified
2. not specified
3. No data available

Other findings:

1. not specified
2. not specified
3. No data available

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 performed in group of 10 male and female Osborne-Mendel rats using test chemical. Death time was observed from 4 hours to 9 days. Clinical signs like Depression, scrawny appearance, porphyrin-like deposit around eyes and nose for a week after treatment were observed. Hence, LD50 value was considered to be 6160 mg/kg bw (95% confidence limits: 4400-8630 mg/kg bw), when groups of 10 male and female Osborne-Mendel rats were treated with the given test chemical orally via gavage.

2. Acute oral toxicity study of the given test chemical was conducted in rats at the concentration of 4400 mg/kg bw. 50% mortality was observed at 4400 mg/kg bw. Therefore, LD50 value was considered to be 4400 mg/kg bw, when rats were treated with test chemical via oral route.

3. Acute oral toxicity study was performed in group of 10 male and female Osborne-Mendel rats using test chemical. Death time was observed from 2 hours to 4 days. Clinical signs like Depression, coma on high doses, scrawny appearance for 3-4 days. All animals recovered within 7 days. Hence, LD50 value was considered to be 2480 mg/kg bw (95% confidence limits: 2100-2930 mg/kg bw), when groups of 10 male and female Osborne-Mendel rats were treated with the given test chemical orally via gavage.

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:

no adverse effect observed

Dose descriptor:

LD50

Value:

6 160 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from peer-reviewed journal.

Reference

Endpoint:: acute toxicity: inhalation
Data waiving:: other justification
Justification for data waiving:: other:

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:

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

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 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

Specific details on test material used for the study:

- Name of test material: Isolongifolene
- IUPAC name: (2S)-1,3,4,5,6,7-hexahydro-1,1,5,5-tetramethyl-2H-2,4a-methanonaphthalene
- Molecular formula: C15H24
- Molecular weight: 204.3546 g/mole
- Smiles :CC1(C)CCC=C2C(C)(C)[C@H]3CC[C@@]12C3
- Inchl: 1S/C15H24/c1-13(2)8-5-6-12-14(3,4)11-7-9-15(12,13)10-11/h6,11H,5,7-10H2,1-4H3/t11-,15-/m0/s1
- Substance type: Organic
- Physical state: Liquid (colorless)

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

1. not specified
2. not specified
3. not specified

Type of coverage:

other: Dermal

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

1. not specified
2. not specified
3. not specified

Duration of exposure:

1. not specified
2. not specified
3. not specified

Doses:

1. 5000 mg/kg bw
2. 5000 mg/kg
3. 5000 mg/kg bw

No. of animals per sex per dose:

1. not specified
2. not specified
3. not specified

Control animals:

not specified

Details on study design:

1. not specified
2. not specified
3. not specified

Statistics:

1. not specified
2. not specified
3. not specified

Preliminary study:

1. not specified
2. not specified
3. not specified

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 at 5000 mg/kg bw.
2. No mortality was observed at 5000 mg/kg bw.
3. No mortality was observed at 5000 mg/kg bw.

Clinical signs:

1. not specified
2. not specified
3. not specified

Body weight:

1. not specified
2. not specified
3. not specified

Gross pathology:

1. not specified
2. not specified
3. not specified

Other findings:

1. not specified
2. not specified
3. 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. Acute Dermal toxicity study of the given test chemical was conducted in rabbits at the concentration of 5000 mg/kg bw. No mortality was observed at 5000 mg/kg bw. Therefore, LD50 value was considered to be >5000 mg/kg bw, when rabbits were treated with test chemical by dermal application.

2. Acute Dermal toxicity study of the given test chemical was conducted in rabbits at the concentration of 5000 mg/kg bw. No mortality was observed in treated rabbits at 5000 mg/kg bw. Therefore, LD50 was considered to be >5000 mg/kg bw, when rabbits were treated with the given test chemical by dermal application.

3. Acute Dermal toxicity study of the given test chemical was conducted in rabbits at the concentration of 5000 mg/kg bw. No mortality was observed at 5000 mg/kg bw. Therefore, LD50 value was considered to be >5000 mg/kg bw, when rabbits were treated with test chemical by dermal application.

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:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from publication.

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 performed in group of 10 male and female Osborne-Mendel rats using test chemical. Death time was observed from 4 hours to 9 days. Clinical signs like Depression, scrawny appearance, porphyrin-like deposit around eyes and nose for a week after treatment were observed. Hence, LD50 value was considered to be 6160 mg/kg bw (95% confidence limits: 4400-8630 mg/kg bw), when groups of 10 male and female Osborne-Mendel rats were treated with the given test chemical orally via gavage.

2. Acute oral toxicity study of the given test chemical was conducted in rats at the concentration of 4400 mg/kg bw. 50% mortality was observed at 4400 mg/kg bw. Therefore, LD50 value was considered to be 4400 mg/kg bw, when rats were treated with test chemical via oral route.

3. Acute oral toxicity study was performed in group of 10 male and female Osborne-Mendel rats using test chemical. Death time was observed from 2 hours to 4 days. Clinical signs like Depression, coma on high doses, scrawny appearance for 3-4 days. All animals recovered within 7 days. Hence, LD50 value was considered to be 2480 mg/kg bw (95% confidence limits: 2100-2930 mg/kg bw), when groups of 10 male and female Osborne-Mendel rats were treated with the given test chemical orally via gavage.

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 0.0412 mm Hg. 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 rabbits at the concentration of 5000 mg/kg bw. No mortality was observed at 5000 mg/kg bw. Therefore, LD50 value was considered to be >5000 mg/kg bw, when rabbits were treated with test chemical by dermal application.

2. Acute Dermal toxicity study of the given test chemical was conducted in rabbits at the concentration of 5000 mg/kg bw. No mortality was observed in treated rabbits at 5000 mg/kg bw. Therefore, LD50 was considered to be >5000 mg/kg bw, when rabbits were treated with the given test chemical by dermal application.

3. Acute Dermal toxicity study of the given test chemical was conducted in rabbits at the concentration of 5000 mg/kg bw. No mortality was observed at 5000 mg/kg bw. Therefore, LD50 value was considered to be >5000 mg/kg bw, when rabbits were treated with test chemical by dermal application.

Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value is >5000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute dermal toxicity.

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.