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

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

repeated dose toxicity: inhalation

Remarks:

other: inhalation during developmental toxicity study (GD 6-15)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Developmental toxicity study comparable to guideline study (OECD Guideline 414) with sufficient documentation, well documented;

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Developmental toxicity evaluation of inhaled citral in Spraque-Dawley rats.

Author:

Gaworksi C.L., Vollmuth T.A., York R.G., Heck J.D., Aranyi C.

Year:

1992

Bibliographic source:

Fd Chem. Toxic. 30, 269-275

Materials and methods

Principles of method if other than guideline:

Mortalities, clinical signs of intoxication, body weight gains and gross lesions were investigated as signs of maternal toxicity during a developmental toxicity study.

GLP compliance:

not specified

Limit test:

no

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
- Lot/batch No.: 9966
- Analytical purity: 90%
- Impurities (identity and concentrations): not identified
- Composition of test material, percentage of components: approx. 90% purity representing a commercial product
- Isomers composition: 35% neral, 55% geranial

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

see Section 7.8.2

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: nitrogen

Remarks on MMAD:

MMAD / GSD: 4.2 µm / 1.9

Details on inhalation exposure:

see Section 7.8.2

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

see Section 7.8.2

Duration of treatment / exposure:

from gestation day 6 - 15

Frequency of treatment:

daily, 6 h/d

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
10, 34, 68 ppm
Basis:
other: nominal conc. corresponding to 63, 215 and 430 mg/m3 (=MW*ppm/24.1*1000); MW=152,2 g/mol

Doses / concentrations 2

Remarks:

Doses / Concentrations:
10.2 +- 0.9, 34.4 +- 4.1 ppm citral as vapour
Basis:
analytical conc.

Doses / concentrations 3

Remarks:

Doses / Concentrations:
68 ppm: composed of 30.7 +- 4.2 ppm as aerosol and 37.0 +- 14.1 ppm as vapour
Basis:
analytical conc.

No. of animals per sex per dose:

25

Control animals:

yes, sham-exposed

Details on study design:

- Dose selection rationale: highest selected to produce maternally toxic effects

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice a day

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice a day

BODY WEIGHT: Yes
- Time schedule for examinations: days 0, 2 4, 6, 8 (exposure days), 12, 16, 20 (post-exposure period)

FOOD CONSUMPTION: No data

WATER CONSUMPTION: No data

OPHTHALMOSCOPIC EXAMINATION: No /

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

Statistics:

Maternal body weights and body-weight gains were analysed by a one-way analysis of variance (ANOVA), followed by a Dunnett's when applicable ( Steel and Torrie, 1960).

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
68 ppm: moribund condition of 1/25 animals (killed on gestation day 17); ocular opacity, difficulty in breathing during the exposure phase of the study indicating stress of severe respiratory tract irritation; normal breathing returned in most of affected animals by gestation day 20; other frequently observed clinical signs: nasal discharge, salivation, redness around eyes, discolored facial fur, scrubby hair coat

BODY WEIGHT AND WEIGHT GAIN
68 ppm:
- Body weight loss during exposure period from gestation day (GD) 6 to 15; after exposure period body weight gain was comparable to other groups;
- overall mean body weight (GD 20) significantly decreased
- Body weight gain (GD0-20) decreased by 39% compared to controls.


Evaluation: In the 68 ppm dose group, significant signs of maternal toxicity as mortality, decreased body weight gain and clinical signs of toxicity were attributable to the stress produced by severe respiratory tract irritation. Weight loss on the third day of exposure was followed by constantly decreased body weight throughout the exposure. However, after completion of the exposure period recovery of body weight and clinical signs of toxicity occurred. At 10 and 34 ppm, findings were incidental and not siginficantly different from control animals.

Effect levels

1

Dose descriptor:

NOAEC

Effect level:

34 ppm

Sex:

female

Basis for effect level:

other: corresponds to 215 mg/m3

2

Dose descriptor:

LOAEC

Effect level:

68 ppm

Sex:

female

Basis for effect level:

other: severe respiratory tract irritation with reduced body weight gain and clinical signs as secondary effects in pregant rats; corresponds to 430 mg/m3

Target system / organ toxicity

Critical effects observed:

not specified