Concrete of Salvia sclarea L. (Lamiaceae) obtained from leaves, flowers and twigs by apolar hydrocarbon solvent extraction with or without purification by molecular distillation

Endpoint summary

Description of key information

Based on a Read across strategy, the substance is considered to have a DL50 higher than 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

1964

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Rats were treated with test substance by oral gavage and then observed for clinical signs and mortality for two weeks. LD50 was computed by the method of Litchfield & Wilcoxon (1949).

GLP compliance:

no

Remarks:

pre-GLP

Test type:

standard acute method

Specific details on test material used for the study:

No data

Species:

rat

Strain:

Osborne-Mendel

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Fasting period before study: Ca. 18 h prior to treatment
- Diet: Food, ad libitum
- Water, ad libitum

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No data

Doses:

No data

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Duration of observation period following administration: 2 weeks
Frequency of observations and weighing: Frequency not known, all animals were maintained under close observation for recording toxic signs and time of death. Such observation was continued until animals appeared normal or showed weight gain

Statistics:

LD50 with 95 % confidence limits was calculated with use of Litchfield-Wilcoxon's method (1949).

Preliminary study:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 790 mg/kg bw

Based on:

test mat.

95% CL:

> 2 440 - < 3 180

Mortality:

Mortality was observed between 4 and 18 h after test substance administration.

Clinical signs:

Ataxia soon after treatment was observed.

Body weight:

No data

Gross pathology:

No data

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions of this study, the test substance is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS.

Executive summary:

In an acute oral toxicity study, Osborne-Mendel rats were treated with Linalool by oral gavage and then observed for clinical signs and mortality for two weeks. LD50 was computed by the method of Litchfield & Wilcoxon (1949).

Mortality was observed between 4 and 18 h after test substance administration. Ataxia soon after treatment was observed. In this study, the oral LD50 of test substance was 2790 mg/kg bw (95 % Cl: 2440-3180) in rats.

 

Under the experimental conditions of this study, the test substance is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

1964

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Only short abstract available

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

read-across: supporting information

Principles of method if other than guideline:

Rats were treated with test substance by oral gavage and then observed for clinical signs and mortality for two weeks. LD50 was computed by the method of Litchfield & Wilcoxon (1949).

GLP compliance:

no

Remarks:

pre-GLP

Test type:

standard acute method

Specific details on test material used for the study:

No data

Species:

rat

Strain:

Osborne-Mendel

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Fasting period before study: Ca. 18 h prior to treatment
- Diet: Food, ad libitum
- Water, ad libitum

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No data

Doses:

No data

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Duration of observation period following administration: 2 weeks

Statistics:

LD50 with 95 % confidence limits was calculated with use of Litchfield-Wilcoxon's method (1949).

Preliminary study:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

14 550 mg/kg bw

Based on:

test mat.

95% CL:

> 12 300 - < 17 170

Mortality:

Mortality was observed between 4 h and 4 days after test substance administration.

Clinical signs:

Depression soon after treatment, coma and wet posterior region were observed.

Body weight:

No data

Gross pathology:

No data

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions of this study, the test substance is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS.

Executive summary:

In an acute oral toxicity study, Osborne-Mendel rats were treated with Linalyl acetate by oral gavage and then observed for clinical signs and mortality for two weeks. LD50 was computed by the method of Litchfield & Wilcoxon (1949).

Mortality was observed between 4 h and 4 days after test substance administration. Depression soon after treatment, coma and wet posterior region were observed. In this study, the oral LD50 of test substance was 14550 mg/kg bw (95 % Cl: 12300-17170) in rats.

 

Under the experimental conditions of this study, the test substance is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

15 March - 19 April 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

no data about purity and no certificate of analysis of the test substance; no data on bodyweight changes

Justification for type of information:

Sclareol is one of the main constituent of Clary sage concrete (it represents between 40 and 80% of the substance).

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

no data about purity and no certificate of analysis of the test substance; no data on bodyweight changes

Principles of method if other than guideline:

Not applicable

GLP compliance:

no

Remarks:

pre-GLP

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Batch: W1626

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Licensed dealer
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 200-250 g
- Fasting period before study: ca. 18 hours
- Housing: Housed in galvanized cages with indirect bedding, in a temperature controlled room
- Diet: Growth and maintenance ration from a commercial producer, ad libitum
- Water: Ad libitum
- Acclimation period: At least 2 days

ENVIRONMENTAL CONDITIONS
- Photoperiod: 12 hours dark / 12 hours light cycle

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

DOSAGE PREPARATION: Test item was used in 25% gravimetric suspension in corn oil.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Animals were observed for signs of pharmacologic activity and drug toxicity at 1, 3, 6 and 24 hours post-dosage, and at least once daily thereafter for a total of 14 days.
- Necropsy: Non-survivors and animals surviving the 14 day observation period were subjected to gross necropsy, with all findings noted.

Statistics:

No data

Preliminary study:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

Clinical signs including slight depression, and moist and matter hair were noted in all animals within 3 -24 hours after treatment, but all appeared normal after 5 days.

Body weight:

No data

Gross pathology:

Internal organs on superficial examination appeared normal except for a deposit of fibrous tissue in the thoracic cavity in one animal.

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the oral LD50 of the test substance is >5000 mg/kg bw therefore it is not classified according to the Regulation (EC) N° 1272-2008 and according to the GHS.

Executive summary:

In an acute oral toxicity study performed similarly to OECD Guideline 401, a single oral (gavage) dose of 5000 mg/kg bw of the test substance, in 25% gravimetric suspension in corn oil, was given to 5 male and 5 female Wistar rats. Animals were then observed for mortality and clinical signs of toxicity for 14 days; and all were macroscopically necropsied after sacrifice.

No deaths occurred. Clinical signs including slight depression, and moist and matter hair were noted in all animals within 3 -24 hours after treatment, but all appeared normal after 5 days. Internal organs on superficial examination appeared normal except for a deposit of fibrous tissue in the thoracic cavity in one animal.

 

Rat Oral LD50 > 5000 mg/kg bw.

 

Under the test conditions, the oral LD50 of the test substance is >5000 mg/kg bw therefore it is not classified according to the Regulation (EC) N° 1272-2008 and according to the GHS.

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Justification for type of information:

Linalool is one of the main constituents of Clary sage concrete , it represents up to 10% of the composition

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

read-across source

Principles of method if other than guideline:

Rats were treated with test substance by oral gavage and then observed for clinical signs and mortality for two weeks. LD50 was computed by the method of Litchfield & Wilcoxon (1949).

Test type:

standard acute method

Species:

rat

Strain:

Osborne-Mendel

Sex:

male/female

Route of administration:

oral: gavage

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 790 mg/kg bw

Based on:

test mat.

95% CL:

> 2 440 - < 3 180

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions of this study, the test substance is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS.

Executive summary:

In an acute oral toxicity study, Osborne-Mendel rats were treated with Linalool by oral gavage and then observed for clinical signs and mortality for two weeks. LD50 was computed by the method of Litchfield & Wilcoxon (1949).

Mortality was observed between 4 and 18 h after test substance administration. Ataxia soon after treatment was observed. In this study, the oral LD50 of test substance was 2790 mg/kg bw (95 % Cl: 2440-3180) in rats.

 

Under the experimental conditions of this study, the test substance is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS.

Therefore the registered substance is considered to have a DL 50 higher than 2790 mg/kg bw

Reference 5

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Justification for type of information:

Linalyl acetate is one of the main constituent of Clary sage concrete (it represents up to 20 % of the substance).

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

read-across source

Principles of method if other than guideline:

Rats were treated with test substance by oral gavage and then observed for clinical signs and mortality for two weeks. LD50 was computed by the method of Litchfield & Wilcoxon (1949).

GLP compliance:

no

Remarks:

pre-GLP

Test type:

standard acute method

Species:

rat

Strain:

Osborne-Mendel

Sex:

male/female

Route of administration:

oral: gavage

Preliminary study:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

14 550 mg/kg bw

Based on:

test mat.

95% CL:

> 12 300 - < 17 170

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions of this study, the test substance is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS.

Executive summary:

In an acute oral toxicity study, Osborne-Mendel rats were treated with Linalyl acetate by oral gavage and then observed for clinical signs and mortality for two weeks. LD50 was computed by the method of Litchfield & Wilcoxon (1949).

Mortality was observed between 4 h and 4 days after test substance administration. Depression soon after treatment, coma and wet posterior region were observed. In this study, the oral LD50 of test substance was 14550 mg/kg bw (95 % Cl: 12300-17170) in rats.

 

Under the experimental conditions of this study, the test substance is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS.

Therefore the registered substance is considered to have a LD50 higher than 14 550 mg/kg bw.

Reference 6

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Sclareol is one of the main constituent of Clary sage concrete (it represents between 40 and 80% of the substance).

Reason / purpose for cross-reference:

read-across source

GLP compliance:

no

Remarks:

pre-GLP

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the oral LD50 of the test substance is >5000 mg/kg bw therefore it is not classified according to the Regulation (EC) N° 1272-2008 and according to the GHS.

Executive summary:

In an acute oral toxicity study performed similarly to OECD Guideline 401, a single oral (gavage) dose of 5000 mg/kg bw of the test substance, in 25% gravimetric suspension in corn oil, was given to 5 male

and 5 female Wistar rats. Animals were then observed for mortality and clinical signs of toxicity for 14 days; and all were macroscopically necropsied after sacrifice.

No deaths occurred. Clinical signs including slight depression, and moist and matter hair were noted in all animals within 3 -24 hours after treatment, but all appeared normal after 5 days. Internal organs

on superficial examination appeared normal except for a deposit of fibrous tissue in the thoracic cavity in one animal.

Rat Oral LD50 > 5000 mg/kg bw.

Under the test conditions, the oral LD50 of the test substance is >5000 mg/kg bw.

Therefore Clary sage concrete is not classified according to the Regulation (EC) N° 1272-2008 and according to the GHS

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Sclareol is one of the main constituent of Clary sage concrete (it represents between 40 and 80% of the substance), and has a DL50 higher than 5000 mg/kg bw in rats. Linalyl acetate represents up to 20% of the substance and has a DL50 higher than 14 550 mg/kg bw. Linalool, represents up to 10% of the substance and has a DL 50 higher than 2790 mg/kg bw. Therefore the DL50 of the registered substance is considered to be higher than 2000 mg/kg bw.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Acute toxicity via Oral route:

Based on the available data the substance is not classified according to the Regulation (EC) No. 1272/2008 (CLP) and to the Globally Harmonised System of classification and labelling of chemicals (GHS) as the oral LD50 is higher than 2000 mg/kg bw.