Methyl ricinoleate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 march 1999 until 8 April 1999

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

Methyl ricinoleate

EC Number:

205-472-3

EC Name:

Methyl ricinoleate

Cas Number:

141-24-2

Molecular formula:

C19H36O3

IUPAC Name:

methyl ricinoleate

Test material form:

liquid: viscous

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animais
Species, strain: rat, Sprague-Dawley ICO: OFA-SD (IOPS Caw).
Reason for this choice: rodent species generally accepted by regulatory authorities for this type of study.
Breeder: Iffa Crédo, 69210 L'Arbresle, France.
Number and sex: one group of ten animais (five males and five females).
Age/weight: on the day of treatment, the animais were approximately 6 weeks old, and had a mean body weight ± standard deviation of 182 ± 10 g for the males and 141 ± 5 g for the females.
Acclimatization: at least 5 days before the beginning of the study.
Identification of the animais: the animais were identified individually by earmarks or eamotches.

Environmental conditions
During the acclimatization 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 animais were housed in polycarbonate cages (48 cm x 27 cm x 20 cm). Each cage contained one to seven animais of the same sex during the acclimatization period and five rats of the same sex during the treatment period.
Each cage contained dust-free sawdust (SICSA, 94142 Alfortville, France).
Bacteriological and chemical analyses of the sawdust, including the detection of possible contaminants (pesticides, heavy metals), are performed regularly by extemal laboratories.
The results of these analyses are archived at CIT.

Food and water
Ali the animais had free access to A04 C pelleted diet (UAR, 91360 Villemoisson-sur-Orge, France), except as noted in "2.3.1 Fasting of the animais".
Each batch of food was analysed by the supplier for composition and contaminant levels. The diet formula is presented in appendix 2.

Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum. Bacteriological and chemical analyses of the water and diet, including the detection of possible contaminants (pesticides, heavy metals and nitrosamines), are performed regularly by extemal laboratories.
The results of these analyses are archived at CIT.

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:

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 animais (five males and five females).

The test substance was administered undiluted, taking into consideration its specific gravity (0.91 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:

2000 mg/kg/day

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

Clinical signs and mortality :
The animais were observed frequently during the hours following administration of the test substance, for detection of possible treatment-related clinical signs. Thereafter, observation of the animais was made at least once a day until day 15.
Type, time of onset and duration of clinicat signs were reèorded for each animal individually. Time of death was recorded individually, in terms of the number of hours or days after dosing.
Body weight
The animais 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 animais was compared to that of CIT control animais with the same initial body weight.




2.5 NECROPSY

On day 15, ail animais were killed by carbon dioxide asphyxiation and a macroscopic examination was performed.

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.
In case of macroscopic lesions, organ samples were taken and preserved in 10% buffered formalin.


2.6 DATA EVALUATION

Evaluation of the toxicity of the test substance following a single oral administration in rats should include the relationship, if any, between the animais' exposure to the test substance and the incidence and severity of all abnormalities including behavioural and clinical abnormalities, macroscopic lesions, body weight changes, mortality and any other toxic effects.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Mortality:

none

Clinical signs:

none

Body weight:

no effect

Gross pathology:

no finding

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under our experimental conditions, the oral LD0 of the test substance RICINOLEATE DE METHYLE (batch No. 9802001) is equal to or higher than 2000 mg/kg in rats. No signs of toxicity were observed at this dose.

Executive summary:

The acute oral toxicity of the testsubstance RICINOLEATEDEMETHYLE (batch No.9802001) was evaluated in rats according to OECD (No.401,24thFebruary1987) and EC (92/69/EEC,B.l,3lstJuly1992) guidelines.

The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

 

The test substance was administered by oral route (gavage) to one group of ten fasted Sprague­Dawleyrats(fivemalesandfivefemales).

 

The test substance was administered undiluted at the dose of 2000mg/kg, taking into consideration that its specificgravity was 0.91g/ml.

Clinical signs,mortality and bodyweight gain were checked for a period of up to 14days following the single administration of the testsubstance.

 All animais were subjected to necropsy.

 No death occurred at 2000mg/kg.The body weight was not affected by the treatment.

 No apparent abnormalities were observed at necropsy in all animals.

Under our experimental conditions the LD0 is equal or higher than 2000 mg/kg in rats. No signs of toxicity were observed at this dose.