(3Z)-hex-3-en-1-yl 2-methylprop-2-en-1-yl ether

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 13 December 2000 and 27 December 200

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with OECD guidelines and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

the relative humidity recorded in the animal room was sometimes outside of the target ranges specified in the protocol.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

yes

Remarks:

the relative humidity recorded in the animal room was sometimes outside of the target ranges specified in the protocol.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

other: colorless liquid

Details on test material:

Storage conditions: at room temperature and protected from light
Purity: 98.91 %

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals
Species, strain: rat, Sprague-Dawley ICO: OFA-SD (lOPS Caw).
Reason for this choice: rodent species generally accepted by regulatory authorities for this type of study.
Breeder: Charles River (lffa Credo, 69210 L'Arbresle, France).
Number and sex: one group of ten animals (five males and five females).
Age/weight: on the day of treatment, the animals were approximately 6 weeks old, and had a mean body weight ± standard deviation of 170 ± 11 g for the males and 132 ± 3 g for the females.
Females were nulliparous and non pregnant.
Acclimation: at least 5 days before the beginning of the study.
Identification: individually by earnotches.

Environmental conditions
During the acclimation period and throughout the study, the conditions in the animal room were set as follows:
temperature: 21 ± 2°C
relative humidity: 30 to 70%
light/dark cycle: 12 h / 12 h
ventilation: approximately 12 cycles/hour of filtered, non-recycled air.
The temperature and relative humidity were under continuous control and recording. The records were checked daily and filed. In addition to these daily checks, the housing conditions and corresponding instrumentation and equipment are verified and calibrated at regular intervals.
The animals were housed in polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm). Each cage contained one to seven animals of the same sex during the acclimation period and five rats of the same sex during the treatment period.
Each cage contained dust-free sawdust (SIC SA, 94142 Alfortville, France).
Sawdust is analysed by the supplier for composition and contaminant levels.

Food and water
All the animals had free access to A04 C pelleted diet (UAR, 91360 Villemoisson-sur-Orge, France), except as noted in "2.3.1 Fasting of the animals".
Each batch of food is analysed by the supplier for composition and contaminant levels.
Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum.
Bacteriological and chemical analyses of water are performed regularly by external laboratories. These analyses include the detection of possible contaminants (pesticides, heavy metals and nitrosamines ).
No contaminants were known to have been present in the diet, drinking water or bedding material at levels which may be expected to have interfered with or prejudiced the outcome of the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test substance was administered undiluted, taking into consideration its specific gravity (0.8180 g/ml).
The administration was performed in a single dose by oral route using a metal gavage tube fitted to a 1 ml plastic syringe (0.01 ml graduations).
The volume administered to each animal was adjusted according to body weight determined on the day of treatment.

Doses:

As the test substance was anticipated to be non-toxic at 2000 mglkg, a limit test was performed by administering 2000 mg/kg of the test substance to one group of ten animals (five males and five females).

No. of animals per sex per dose:

five males and five females

Control animals:

no

Details on study design:

Fasting of the animals
The animals were fasted for an overnight period of approximately 18 hours before dosing, but had free access to water.
Food was given back approximately 4 hours after administration of the test substance.

Administration of the test substance
As the test substance was anticipated to be non-toxic at 2000 mg/kg, a limit test was performed by administering 2000 mg/kg of the test substance to one group of ten animals (five males and five females).
The test substance was administered undiluted, taking into consideration its specific gravity (0.8180 g/ml).
The administration was performed in a single dose by oral route using a metal gavage tube fitted to a 1 ml plastic syringe (0.01 ml graduations).
The volume administered to each animal was adjusted according to body weight determined on the day of treatment

CLINICAL EXAMINATIONS
Clinical signs and mortality
The animals were observed frequently during the hours following administration of the test substance, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day until day 15.
Type, time of onset and duration of clinical signs were recorded for each animal individually.
Time of death was recorded individually, in terms of the number of hours or days after dosing.

Body weight
The animals were weighed individually just before administration of the test substance on day 1 and then on days 8 and 15.
The body weight gain of the treated animals was compared to that of CIT control animals with a similar initial body weight.

PATHOLOGY
Sacrifice
On day 15, all animals were killed by carbon dioxide asphyxiation.
Macroscopic necropsy examination
All study animals were subjected to a macroscopic examination as soon as possible after death.
After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed.

Preservation of tissues
No organ samples were taken.
Microscopic examination
No microscopic examination was performed.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 95% confidence limits cannot be derived due to the absence of mortality.

Mortality:

There were no deaths.

Clinical signs:

Sedation and piloerection were observed in 4/5 males and 5/5 females, on day 1 only .
Recovery was complete on day 2 .
No other clinical signs were noted during the study .

Body weight:

The body weight gain of the treated animals was similar to that of CIT historical control animals .

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Oral LD50 of the test substance is higher than 2000 mg/kg in rats Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions, the oral LD50 of the test substance Vivaldie is higher than 2000 mg/kg in rats .

Executive summary:

The acute oral toxicity of the test substance Vivaldie was evaluated in rats according to OECD (No. 401, 24th February 1987) and EC (92/69/EEC, B. l , 31st July 1992) guidelines. The test substance was administered by oral route (gavage) to one group of ten fasted SpragueDawley rats (five males and five females). The test substance was administered undiluted at the dose of 2000 mg/kg, taking into consideration that its specific gravity was 0.8180 g/ml. No deaths were observed during the study. Sedation and piloerection were observed in 4/5 males and 5/5 females, on day 1 only. Recovery was complete on day 2. No other clinical signs were noted during the study. The overall body weight gain of the animals was not affected by treatment with the test substance. No apparent abnormalities were observed at necropsy in any animal. Under the experimental conditions of this study, the oral LD50 of the test substance Vivaldie is higher than 2000 mg/kg in rats.