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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1992
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
study was not designed for determining acute inhalation toxicity.

Data source

Reference
Reference Type:
publication
Title:
Fragrance compounds and essential oils with sedative effects upon inhalation
Author:
Buchbauer G., Jirovetz L., Jager W., Plank C., and Dietrich H.
Year:
1993
Bibliographic source:
Journal of Pharmaceutical Sciences. 1993; Volume 82: 660-664

Materials and methods

GLP compliance:
no
Test type:
fixed concentration procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
5-(2,3-dimethyltricyclo[2.2.1.02,6]hept-3-yl)-2-methylpent-2-en-1-ol, stereoisomer
EC Number:
204-102-8
EC Name:
5-(2,3-dimethyltricyclo[2.2.1.02,6]hept-3-yl)-2-methylpent-2-en-1-ol, stereoisomer
Cas Number:
115-71-9
Molecular formula:
C15H24O
IUPAC Name:
5-(2,3-dimethyltricyclo[2.2.1.0~2,6~]hept-3-yl)-2-methylpent-2-en-1-ol
Constituent 2
Chemical structure
Reference substance name:
[1S-[1α,2α(Z),4α]]-2-methyl-5-(2-methyl-3-methylenebicyclo[2.2.1]hept-2-yl)-2-penten-1-ol
EC Number:
201-027-2
EC Name:
[1S-[1α,2α(Z),4α]]-2-methyl-5-(2-methyl-3-methylenebicyclo[2.2.1]hept-2-yl)-2-penten-1-ol
Cas Number:
77-42-9
Molecular formula:
C15H24O
IUPAC Name:
2-methyl-5-(2-methyl-3-methylenebicyclo[2.2.1]hept-2-yl)pent-2-en-1-ol
Constituent 3
Chemical structure
Reference substance name:
(Z)-5-[(6R)-4,6-dimethyl-6-bicyclo[3.1.1]hept-3-enyl]-2-methylpent-2-en-1-ol
Cas Number:
176777-61-0
Molecular formula:
C15H24O
IUPAC Name:
(Z)-5-[(6R)-4,6-dimethyl-6-bicyclo[3.1.1]hept-3-enyl]-2-methylpent-2-en-1-ol
Constituent 4
Chemical structure
Reference substance name:
(E)-(R)-(+)-5-(2,3-dimethyltricyclo[2.2.1.0^2,6]hept-3-yl)-2-methyl-2-penten-1-ol
Cas Number:
14490-17-6
Molecular formula:
C15H24O
IUPAC Name:
(E)-(R)-(+)-5-(2,3-dimethyltricyclo[2.2.1.0^2,6]hept-3-yl)-2-methyl-2-penten-1-ol
Constituent 5
Chemical structure
Reference substance name:
2-​Hepten-​1-​ol, 2-​methyl-​6-​(4-​methylphenyl)​-​, (2Z)​-
Cas Number:
122442-36-8
Molecular formula:
C15H22O
IUPAC Name:
2-​Hepten-​1-​ol, 2-​methyl-​6-​(4-​methylphenyl)​-​, (2Z)​-
Test material form:
liquid

Test animals

Species:
mouse
Strain:
Swiss
Sex:
female
Details on test animals or test system and environmental conditions:
Female 6 – 8 week- and 6-month-old outbred Swiss mice with mean body weights of 28.5 g were housed in groups of four under standardized conditions (room temperature, 22 ±2 °C; relative humidity, 60 ±10%; light-dark rhythm, 12:12 h; air exchange, 12 - 15 times per hour) an a bedding of wood shavings in polycarbonate cages (Makrolon, type II). Standardized pelleted food T 799 (Tagger, Graz, Austria) and drinking water were provided ad libitum. The experimental procedures and technical characteristics have been described elsewhere (Kovar, K.A., Gropper, B., Friess,D., Ammon, H.P.T.; Planta Med. 1987, 53, 315-318). In addition, 400-µL blood samples were carefully taken 0, 30, 60, and 90 min after inhalation by puncturing the retrobulbar venous plexus. The blood samples were collected in plastic tubes and mixed with 0.050 mL of heparin (5000 IU/mL, Immuno Inc., Austria). Plasma was separated by centrifugation, frozen, and stored at - 20 °C until use.

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
1 h
Concentrations:
The air concentration of the inhaled compound, after placing 3 ml of sandalwood oil in the cage (8.4 L), was in the range of 50 - 180 mg/m3
No. of animals per sex per dose:
no data provided
Control animals:
yes
Details on study design:
This study explored the effects of fragrance compounds on the motility of mice using standardized inhalation procedures, but was not designed to provide an acute toxicity endpoint. In total more than 40 compounds were assessed, amongst them sandalwood oil. Animals were exposed whole body in inhalation chambers untretated and in a second experiment pre-treated with prior caffeine exposure and effects on motility were studies. Blood serum samples were taken and analyzed by GC-FID

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LC0
Effect level:
> 180 mg/m³ air (nominal)
Based on:
test mat.
Exp. duration:
1 h
Mortality:
no mortality was observed
Clinical signs:
other: Sandalwood oil, similar to other fragrance, led to a decrese in motility by 40% compared to controls and 20% compared to mice treated with caffeine
Body weight:
no effects reported
Other findings:
6.0 ng/mL alpha-santanol and 5.1 ng/mL beta-santanol was found in blood serum samples, characterized by GC/MS and GC-FTIR

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Conclusions:
In this inhalation study with 1h exposure, low concentrations were investigated, with the main purpose of investigating th eeffect on motility of mice. However, no mortality was seen throughot the study at concentrations of ~ 180 mg/m3.

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