(R)-3,7-dimethyloct-6-enal

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets basic scientific principles, well documented

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Assessment of estrogenic activity in some common essential oil constituents

Author:

Howes M.-J.R., Houghton P.J., Barlow D.J., Pocock V.J., Milligan S.R.

Year:

2002

Bibliographic source:

J. Pharm. Pharmacol. 54, 1521-1528

Materials and methods

Principles of method if other than guideline:

Uterotrophic assay: uterus weights as indicator of estrogenic action after repeated exposure
Acute assay: vascular permeability of uterus as acute indicator of estrogenic action

GLP compliance:

not specified

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

Citral

EC Number:

226-394-6

EC Name:

Citral

Cas Number:

5392-40-5

Molecular formula:

C10H16O

IUPAC Name:

Reaction mass of (E)-3,7-dimethylocta-2,6-dienal and (Z)-3,7-dimethylocta-2,6-dienal

Constituent 2

Reference substance name:

(Z)-3,7-dimethylocta-2,6-dienal

EC Number:

203-379-2

EC Name:

(Z)-3,7-dimethylocta-2,6-dienal

Details on test material:

- Name of test material (as cited in study report): Citral
- Analytical purity: 95%

Test animals

Species:

mouse

Strain:

Swiss

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: A. Tuck & Son Ltd., Essex, UK
- Age at study initiation: 3 mo
- Weight at study initiation: 25-35 g
- Fasting period before study:
- Diet: ad libitum
- Pretreatment: ovariectomy prerformed under anesthesia at least two weeks before the start of each experiment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +- 1
- Humidity (%): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

dermal

Vehicle:

ethanol

Details on exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): acute assay 100 µl; uterotrophic assay 50 µl
- Concentration (if solution): 1.9 M

VEHICLE
- Justification for use and choice of vehicle (if other than water): ethanol due to solubility

USE OF RESTRAINERS FOR PREVENTING INGESTION: no data

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Acute assay of vascular responses: 4 h
Uterotrophic assay: 3 d

Frequency of treatment:

Acute assay: single
Uterotrophic assay: twice daily

Duration of test:

Acute assay: 4 h
Uterotrophic assay: sacrifice 12 h after last application

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
950 mg/kg bw
Basis:
other: calculated from dermal dose of 100 µl in the acute assay

Doses / concentrations 2

Remarks:

Doses / Concentrations:
950 mg/kg bw/d
Basis:
other: calculated from two daily dermal doses of 50 µl in the uterotrophic assay

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

other: positive control: 17ß-estradiol

Details on study design:

Acute assay of vascular responses:
4 hrs after the dermal application of the test substance, 50 μl 0.5 μCi [ 125 I]-labeled human serum albumin was injected into the jugular vein of mice anesthetised with tribromoethanol. Thirty minutes later, a blood sample was drawn from the suborbital canthal sinus with a heparinized capillary pipette and the animals were killed by cervical dislocation. The uteri and a sample of thigh muscle were removed, briefly washed in saline, and weighed. The radioactivity in the uterus, plasma sample, and muscle was determined. The tissue-specific extravascular albumin volume (EAV) was expressed as a ratio of the [ 125 I] counts per minute per milligram of tissue to [ 125 I] counts per minute per microliter of plasma and used as an index of tissue vascular permeability.

Uterotrophic assay:
12 hrs after the last dermal application, the mice were killed and the uterine horns removed, blotted and weighed.

Statistics:

Analysis of variance

Results and discussion

Any other information on results incl. tables

Table: Uterine weight (12 hrs after last application) and vascular permeability 4 hrs following transdermal application

Treatment	Uterine weight (mg)	Uterine vascular permeability (EAV)	Muscle vascular permeability (EAV)
Citral 950 mg/kg bw/d	12.5 ± 0.88	12.5 ± 4.31	0.95 ±- 0.04
Vehicle control	13.5 ± 0.28	5.96 ± 0.54	1.24 ± 0.04
Positive control 0.3 mM Estradiol	19.0 ± 0.15 *	20.3 ± 1.12 *	0.94 ± 0.03

significant change compared to vehicle control: * p<0.01