5,9-dimethyldec-4-enal

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10-12-2015 to 28-01-2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

Information as to the availability of the in vivo study is provided in 'attached justification'.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

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: June 2015; signature: September 2015

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(4E)-5,9-dimethyldec-4-enal; (4Z)-5,9-dimethyldec-4-enal

EC Number:

943-495-7

Cas Number:

689-65-6

Molecular formula:

C12H22O

IUPAC Name:

(4E)-5,9-dimethyldec-4-enal; (4Z)-5,9-dimethyldec-4-enal

Test material form:

liquid

Details on test material:

- Physical state: Liquid
- Storage condition of test material: Approximately 4 °C, in the dark
- Other: clear colourless

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Recognised supplier
- Age at study initiation: 8 - 12 weeks.
- Weight at study initiation: 177 - 195 g (300 mg/kg including sighting test; sentinel); 190 - 211 g (2000 mg/kg sighting test; sentinel); The weight variation did not exceed ±20% of the mean weight during the 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.
- 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.

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: From: To: 2015-12-10 to 2016-01-28

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

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. Singuarly and in the absence of mortality or evident toxicity a further group of 4 was tested in the appropriate dose level.

Doses:

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

No. of animals per sex per dose:

1 (sighting study) and 4 (main study) as applicable; total 5 per dose - based on guideline specified sequential testing strategy

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:

2000 mg/kg bw (sentinel and follow-on test): No mortality in sentinel; 2 mortalities in definitive test
300 mg/kg bw (sentinel and definitive test): No mortality

Clinical signs:

other: 2000 mg/kg bw (sentinel): Appeared normal throughout the study ; (follow-on test): hunched posture, tiptoe gait, pilo erection, decreased respiratory rate, labored respiration, emaciation, lethargy, pallor of the extremities and hypothermia. Surviving ani

Gross pathology:

2000 mg/kg bw (sentinel and follow-on test): Abnormalities noted at necropsy in animals subject to mortality: dark liver, dark kidneys, haemorrhage and epithelial sloughing of the gastric mucosa and haemorrhage and epithelial sloughing of the non glandular epithelium of the stomach. All surivors gave no abnormalities at necropsy.
300 mg/kg bw (sentinel and definitive test): No abnormalities were noted at necropsy.

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 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 material following a single oral administration in the female Wistar strain rat by the fixed dose method. The test substance was administered by oral gavage in an initial sighting study at 2000 mg/kg bw. No mortality and no significant toxicity was observed. A further group of four fasted females was given a single oral dose of test item at a dose level of 2000 mg/kg body weight. Two mortalities were observed. Abnormalities noted at a dose level of 2000 mg/kg, within mortality related necropsy were: dark liver, dark kidneys, haemorrhage and epithelial sloughing of the gastric mucosa and haemorrhage and epithelial sloughing of the non glandular epithelium of the stomach. No abnormalities were observed in surviving animals. Due to mortality at a dose level of 2000 mg/kg, a further sighting test was performed at a dose level of 300 mg/kg. This was then followed by a further group of four fasted females at a dose level of 300 mg/kg body weight. There was no mortality, systemic toxicity or abnormal findings at necropsy and all animals gained body weight. 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 rat. The test substance was classified as Acute Oral Toxicity: Category 4 according to Regulation (EC) 1272/2008.