1,5-dimethyl-1-vinylhept-4-enyl acetate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study not conducted according to international guideline, but performed under standardized conditions. No data on whether study was conducted under GLP.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

See attached justification

Reason / purpose for cross-reference:

read-across source

Preliminary study:

Not relevant

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 3.2 mg/L air

Exp. duration:

90 min

Remarks on result:

other: no deaths after exposure to 27 mg linalool in 8.4 litres of air

Mortality:

No data

Clinical signs:

other: The exposure led to a decrease in motility of the mice. The observed motility compared to the motility of the untreated control animals was 32%/96% after 30 minutes inhalation, 8%/85% after 60 minutes inhalation and 0%/71% after 90 minutes inhalation for

Body weight:

No data

Gross pathology:

No data

Other findings:

No data

The concentration of linalool in the blood samples following inhalation was approximately 1, 2.8 and 3 ng/ml after 30 minutes, 60 minutes and 90 minutes of exposure, respectively.

Interpretation of results:

other: causes a decrease in motility in mice

Conclusions:

Linalool caused a decrease in motility in mice in a 90-minute inhalation study. This result was used for read-across to ethyllinalyl acetate.
 

Executive summary:

The influence of linalool on the motility in mice was tested in an inhalation study under standardized conditions. After 30 minutes, 60 minutes and 90 minutes, the motility in the exposed mice was decreased to 32%/96%, 8%/85% and 0%/71% (6 -8 week old mice/6 month old mice) of the motility of untreated control animals. No deaths were reported at the concentration tested (approximately 3.2 mg/l), therefore the LC50 was determined to be >3.2 mg/l. This result was used for read-across to ethyllinalyl acetate.

 

Data source

Reference

Reference Type:

publication

Title:

Aromatherapy: Evidence for Sedative Effects of the Essential Oil of Lavender after Inhalation

Author:

Buchbauer G, Jirovetz L, Jäger W, Dietrich H, Plank C and Karamat E

Year:

1991

Bibliographic source:

Zeitschrift für Naturforschung 46c, 1067-1072

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Mice were exposed to linalool in air under standardized conditions, and the effects on motility was determined.

GLP compliance:

no

Test type:

other: Inhalation study under standardized conditions

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Linalool

EC Number:

201-134-4

EC Name:

Linalool

Cas Number:

78-70-6

Molecular formula:

C10H18O

IUPAC Name:

3,7-dimethylocta-1,6-dien-3-ol

Details on test material:

- Name of test material (as cited in study report): Linalool
- Substance type: fragrance compound
- Obtained from Dragoco-Vienna
No further details provided

Test animals

Species:

mouse

Strain:

Swiss

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: no data- Age at study initiation: 6-8 week and 6 months old- Weight at study initiation: 28.5 g- Housing: in groups of 4 on a bedding of wood shavings in polycarbonate cages (Makrolon, type II)- Diet (e.g. ad libitum): standardized pelleted food T 799 (Tagger, Graz, Austria) ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period: one hour adaptation period was offered to the animals in which no pharmacological treatment occurred.ENVIRONMENTAL CONDITIONS- Temperature (°C): 22 ± 2°C- Humidity (%): 60 ± 10%- Air changes (per hr): 12-15- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Remarks:

the substance was introduced directly into the cage in which the mice were present

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTIONFor the exposure of the animals to the fragrance compounds a small glass tube with a slit measuring 3 mm in width and 5 cm in length was used. The fragrance compounds were injected through a small hole of the cage wall and the rubber plug of the glass tube. Immediately after placing the mice into the cages and the horizontal fixation of the glass tube a transparent plastic seal was fixed at the cage to form an airtight seal. A pumping-evaporating-system as a part of a spirometer system as described by Kovar et al. was used to supply fresh air and to guarantee a steady air flow.One hour adaptation period was offered to the animals in which no pharmacological treatment occurred. The small glass tube was then filled with 1.5 ml of the respective fragrance material which was constantly released by the slit. A steady concentration by constant drug evaporation from glass tubes throughout the experiment was ensured.TEST ATMOSPHERE- Brief description of analytical method used: The mean air concentration of linaloool in the cage was determined by means of capillary GC and GC/MS as follows: The air stream carrying the fragrance compounds was passed through a layer of activated charcoal which afterwards was eluted with carbon disulfide. After evaporation of the solvent the amount of fragrance compounds remaining in the air was determined by measuring the difference between the original amount of fragrance material in the glass tube and the residual amount in the charcoal. VEHICLENot applicable

Analytical verification of test atmosphere concentrations:

yes

Remarks:

To calculate the air concentration of the fragrance compounds in the cage to consider the total drug volume, charcoal tubes were used.

Duration of exposure:

90 min

Concentrations:

27 mg of linalool in approximately 8.4 litres of cage air -> approximately 3.2 mg/l

No. of animals per sex per dose:

4 animals, no data on sex distribution

Control animals:

yes

Details on study design:

- Duration of observation period following administration: no data- Frequency of observations and weighing: no data- Necropsy of survivors performed: no data- Other examinations performed: the motility of the mice was examined.The mice were kept in a light-barrier cage. The light-barrier, 2 cm above the cagefloor, was interrupted due to the motor activity of the animals crossing it and triggered impulses which were evaluated during the experiment.

Statistics:

Statistics were calculated using an Atari 1040 personal computer ("WISTAT" scientific statistic-package program). The significance was determined by Student's "t"-test and F-test, the level of significance chosen for p to reject the null hypothesis was < 0.05.

Results and discussion

Preliminary study:

Not relevant

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 3.2 mg/L air

Exp. duration:

90 min

Remarks on result:

other: no deaths after exposure to 27 mg linalool in 8.4 litres of air

Mortality:

No data

Clinical signs:

other: The exposure led to a decrease in motility of the mice. The observed motility compared to the motility of the untreated control animals was 32%/96% after 30 minutes inhalation, 8%/85% after 60 minutes inhalation and 0%/71% after 90 minutes inhalation for

Body weight:

No data

Gross pathology:

No data

Other findings:

No data

Any other information on results incl. tables

The concentration of linalool in the blood samples following inhalation was approximately 1, 2.8 and 3 ng/ml after 30 minutes, 60 minutes and 90 minutes of exposure, respectively.

Applicant's summary and conclusion

Interpretation of results:

other: causes a decrease in motility in mice

Conclusions:

Linalool caused a decrease in motility in mice in a 90-minute inhalation study.

Executive summary:

The influence of linalool on the motility in mice was tested in an inhalation study under standardized conditions. After 30 minutes, 60 minutes and 90 minutes, the motility in the exposed mice was decreased to 32%/96%, 8%/85% and 0%/71% (6 -8 week old mice/6 month old mice) of the motility of untreated control animals. No deaths were reported at the concentration tested (approximately 3.2 mg/l), therefore the LC50 was determined to be >3.2 mg/l.