3-(4,4-dimethylcyclohex-1-en-1-yl)propanal

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22-07-2009 to 23-12-2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline study performed under GLP. All relevant validity criteria were met.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

inspected: August 2008 ; signature: March 2009

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-(4,4-dimethylcyclohex-1-en-1-yl)propanal

EC Number:

700-339-0

Cas Number:

850997-10-3

Molecular formula:

C11H18O

IUPAC Name:

3-(4,4-dimethylcyclohex-1-en-1-yl)propanal

Test material form:

liquid

Details on test material:

- Physical state: Liquid
- Storage condition of test material: Refrigerator (between 0 and 10ºC under nitrogen)
- Other: colourless

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Strain: HsdRccHan WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable): Not applicable.
- Source: Recognised supplier (documented in the full study report)
- Females (if applicable) nulliparous and non-pregnant: yes
- Rationale for use of males (if applicable): Not applicable.
- Age at study initiation: 8 - 12 weeks.
- Weight at study initiation: 166 - 180 g (300 mg/kg including sighting test; sentinel); 190 g (2000 mg/kg sighting test; sentinel); The weight variation did not exceed ±20% of the mean weight in the definitive test.
- Fasting period before study: Overnight before dosing and three to four hours after dosing.
- Housing: Group housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Historical data: The test laboratory possesses historical control data.
- Diet (e.g. ad libitum): Certified diet from recognised supplier, provided ad libitum (except for fasting period).
- Water (e.g. ad libitum): ad libitum (except for fasting period)
- Acclimation period: At least 5 days.
- Microbiological status when known: No issues reported.
- Method of randomisation in assigning animals to test and control groups : Random allocation.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70%
- Air changes (per hr): > 15 air changes per hour
- Photoperiod: 12 h light / 12 h dark

IN-LIFE DATES: 22-07-2009 to 19-08-2009

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

- Concentration in vehicle: The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level. For the purpose of the 300 mg/kg dose level the test item was freshly prepared, as required, as a solution in arachis oil BP. Arachis oil BP was used because the test item did not dissolve/suspend in distilled water. For the purpose of the 2000 mg/kg dose level, the test item was used as supplied. The 300 mg/kg bw and 2000 mg/kg bw dose levels were treated stepwise. Singularly and in the absence of mortality or evident toxicity a further group of 4 was tested in the appropriate dose level.
The test item was formulated at concentrations of 30 mg/mL or dosed as supplied according to specific gravity of the test item. Formulations were prepared on the day of dosing.
- Amount of vehicle (if gavage): Test Item dose volume was 10 mL/kg (of bodyweight) in Arachis Oil BP (at 300 mg/kg bw) or dosed as supplied at 2.23 mL/kg (at 2000 mg/kg bw)
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed. Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.
- Lot/batch no. (if required): See full study report.
- Purity: BP grade.

MAXIMUM DOSE VOLUME APPLIED: 300 mg/kg bw dose level: 10 mL/kg of test item in vehicle (Arachis Oil BP) ; 2000 mg/kg bw dose level: 2.23 mL/kg of test item as supplied.

DOSAGE PREPARATION (if unusual): Not applicable. The test item was prepared in the vehicle. It was administered to the animals under a volume of 10 mL/kg in Arachis Oil BP (300 mg/kg bw) or 2.23 mL/kg as supplied (2000 mg/kg bw).

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Using the available information regarding the toxicity of the test item, 2000 mg/kg was chosen as the starting dose.

Doses:

300 mg/kg bw (initial sighting test and main study)
2000 mg/kg bw (initial sighting test)

No. of animals per sex per dose:

1 (sighting study) and 4 (main study) as applicable; total 5 per dose (in definitive test).

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 0.5, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

300 mg/kg bw (sentinel and definitive test): No mortality (5/5)
2000 mg/kg bw (sentinel): (1/1) humanely terminated day 1

Clinical signs:

other: 300 mg/kg bw (sentinel and definitive test): Hunched posture (4/5), noisy respiration (1/5 ; at 0.5 hours only). All animals appeared normal one to two days after dosing. No signs of toxicity (in 1/5) were noted. 2000 mg/kg bw (sentinel): hunched posture,

Gross pathology:

300 mg/kg bw (sentinel and definitive test): No abnormalities were noted at necropsy.
2000 mg/kg bw (sentinel): No abnormalities were noted at necropsy.

Other findings:

- Organ weights: Not reported.
- Histopathology: Not reported.
- Potential target organs: Not reported.
- Other observations: Not reported.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the oral LD50 was estimated to be in the range of 300 - 2000 mg/kg bw in female Wistar HsdRccHan WIST strain rats.

Executive summary:

The study was performed according to OECD TG 420 and EU Method B.1 bis Acute Toxicity (Oral) and in accordance with GLP to assess the acute oral toxicity of the test item following a single oral administration in the female Wistar HsdRccHan WIST strain rats by the fixed dose method. The test item was administered by oral gavage in a solution in arachis oil BP in an initial sighting study at 2000 mg/kg bw and following a presence of toxicity then at 300 mg/kg bw. Subsequently, a further group of four fasted females was given a single oral dose of test item, at a dose level of 300 mg/kg body weight. The animal treated at a dose level of 2000 mg/kg was humanely terminated on 1 day after dosing. Clinical signs were noted during the day of dosing in the animal treated at a dose level of 2000 mg/kg. There was no mortality at a dose level of 300 mg/kg. Hunched posture (4/5), noisy respiration (1/5 ; at 0.5 hours only) was observed. All animals appeared normal one to two days after dosing. All animals showed expected gains in bodyweight over the study period at a dose level of 300 mg/kg. No abnormalities were noted at necropsy of the animal treated at a dose level of 2000 mg/kg. No abnormalities were noted at a dose level of 300 mg/kg. Under the conditions of this study, the oral LD50 was estimated to be in the range of 300 - 2000 mg/kg bw in the female Wistar rat.