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

Repeated dose toxicity: dermal

Administrative data

Endpoint:

sub-chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets basic scientific principles, specific focus on prostrate, no further endpoints examined, single dose group only

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Early Stages of the Pathogenesis of Rat Ventral Prostate Hyperplasia / Induced by Citral

Author:

Servadio C, Abramovici A, Sandbank U, Savion M, Rosen M

Year:

1986

Bibliographic source:

Eur. Urol. 12, 195-200

Reference 2

Reference Type:

other: Abstract for scientific meeting

Title:

Further observations on the citral-induced experimental model of benign prostatic hyperplasia (BPH) in the rat

Author:

Servadio C, Abramovici A

Year:

1986

Bibliographic source:

Urol. Res. 14, 172

Materials and methods

Principles of method if other than guideline:

Specific histological examination of prostates for induction of benign hyperplasia

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Citral

EC Number:

226-394-6

EC Name:

Citral

Cas Number:

5392-40-5

IUPAC Name:

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

Cas Number:

106-26-3

Molecular formula:

C10H16O

IUPAC Name:

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

Details on test material:

- Name of test material (as cited in study report): Citral

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 6 weeks
- Weight at study initiation: 150 g
- Fasting period before study: none
- Diet: standard chow pellets ad libitum
- Water: ad libitum
- Special pretreatment: animals from groups II and V were subjected to bilateral surgical orchidectomy 24 hrs prior to start of citral treatment

ENVIRONMENTAL CONDITIONS: climatized environment
- Temperature (°C): not specified
- Humidity (%): not specified
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

open

Vehicle:

other: 70 % ethanol

Details on exposure:

Route of Administration: dermal
TEST SITE
- Area of exposure: shaved skin of the back
- % coverage: no data

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.2 mL of a solution of citral dissolved in 70 % ethanol
- Concentration (if solution): not specified

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

USE OF RESTRAINERS FOR PREVENTING INGESTION: no data

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

10, 20, 30, 60, 90 days (intact rats)
10, 20, 30, 40, 50, 60 days (orchidectomized rats)

Frequency of treatment:

5 d/w

Doses / concentrations

Remarks:

Doses / Concentrations:
150 mg/kg bw/day
Basis:
nominal per unit body weight

No. of animals per sex per dose:

not specified (N=54 in total)

Control animals:

yes, concurrent vehicle

Details on study design:

Study groups:
I: citral treatment, intact rats
II: citral treatment, orchidectomized rats
III: untreated control
IV: vehicle control, intact rats
V: vehicle control, orchidectomized rats

Positive control:

no

Examinations

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, only prostrate
prostrate weight and macroscopic examination

HISTOPATHOLOGY: Yes, only prostrate
microscopic examination

Results and discussion

Results of examinations

Details on results:

GROSS PATHOLOGY
Prostrate weight: progressive increase in citral-treated rats (group I) with duration of treatment visible after 10 days of treatment compared to untreated and vehicle control (III and IV); significant reduction in group II (citral-treated, castrated rats) within 10 days compared to untreated and vehicle control (III and IV); weights after 60 days of treatment: group I: 1.44 +- 0.24 g, III: 0.88 +- 0.10 g, IV: 0.92 +- 0.08 g

Macroscopic examination: enlarged ventral prostrate in group I, atrophic prostrate in group II, both compared to untreated control (III)


HISTOPATHOLOGY: NON-NEOPLASTIC
Group I: definite lesions already after 10 days of treatment, becoming progressively more pronounced with duration of treatment expanding over many lobules at time;
findings after 1 mo: enhanced epithelial hyperplasia, stromal elements less reactive
findings after 3 months: significant proliferation of the acini, cystic dilatation lined by atrophic flat cuboid cells; supporting stroma more prominent than in the normal prostrate, mild chronic inflammatory foci often seen, intraluminal secretion deeply eosinophilic and more viscous

Group II: castration prior to citral administration prevented benign prostratic hyperplasia
No data specified for Group V.

Target system / organ toxicity

Critical effects observed:

not specified