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Description of key information

Key Study (Mihara, 1988)

Under the conditions of this study, it was estimated that the LD50 value of the test material is greater than 2.0 g/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 June 1988 to 12 September 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted to sound scientific principles with a sufficient level of detail to assess the quality of the submitted data.
Reference:
Composition 0
Qualifier:
no guideline followed
Principles of method if other than guideline:
The acute toxicity of the test material carried out in mice by oral administration.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
mouse
Strain:
ICR
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 5 weeks old
- Weight at study initiation: 25.5 to 29.2 g
- Fasting period before study: Animals were fasted for approximately 8 hours before administration. Feeding resumed 2 hours after administration.
- Housing: Animals were kept in cages made from polyethylene with 10 animals per cage.
- Diet: ad libitum
- Water: Animals had free access to water through feed-water bottles.
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 23 ± 3 °C
- Humidity: 55 ± 15 %
- Air changes: All-fresh ventilation of 12 cycles per hour
- Photoperiod: 12 hours, from 7 A.M. to 7 P.M.; between 200 and 500 lx

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
TEST MATERIAL ADMINISTRATION:
- The test material was prepared as a 5.0 % suspension using olive oil. (Equivalent to 2.0 g/kg, by administrating 0.4 mL per 10 g of body weight.)
The test material was orally administered to the animals at a dosage of 2.0 g/kg. This route was selected because it is the one with the highest risk of accidental exposure, and also because it is potentially the route causing maximum exposure inside living bodies.

Oral administration of a volume of 40 mL per 1 kg of body weight was carried out. Olive oil, which was used as a vehicle, was administered to the control group in a similar manner.

The test material was administered once.
Doses:
Dosage: 2.0 g.kg
Dosage volume: 40 mL per 1 kg of body weight
No. of animals per sex per dose:
Only male animals were used.
Group 1: Olive oil was administered to 10 animals at a dosage volue of 40 mL/kg. (negative control)
Group 2: Test material was administered to 10 animals at a dosage of 2.0 g/kg and a dosage volume of 40 mL/kg.
Control animals:
yes
Details on study design:
Dates were counted based on Day 1 being the day that administration was carried out.
From Day 1 until Day 15, observations were carried out once a day as to whether any of the animals died.

OBSERVATION OF CLINICAL SIGNS:
On Day 1, observation of acute toxicity symptoms was carried out immediately after administration up until approximately 2 hours after administration. In addition, observation was carried out twice (once in the morning, once in the afternoon) on Day 2. From Day 3 to Day 15, observation of the number of surviving animals and general conditions was carried out once a day.

MEASUREMENT OF BODY WEIGHT:
The body weight of all remaining animals was measured on Days 1, 2, 8, and 15 using an electric scale (Shimadzu EB-2800, Shimadzu Corporation).
Statistics:
The body weights were compared to those of the animals in the control group based on Student’s t-test.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed throughout the study.
Clinical signs:
6 hours after administration, eyelid closure in 2 animals, soft stools in 2 animals, and diarrhoea in 5 animals were observed, but the animals recovered on Day 2. Moistness around the root of the tail was also observed in all of the animals in the control group, but the animals recovered on Day 2.
Body weight:
There were no differences observed between the control group and the group that was administered the test material.
Gross pathology:
There were no abnormalities observed in any of the animals.
Interpretation of results:
practically nontoxic
Conclusions:
Under the conditions of this study, it was estimated that the LD50 value of the test material is greater than 2.0 g/kg body weight.
Executive summary:

The acute oral toxicity of the test material was investigated in a study to sound scientific principles with a sufficient level of detail to assess the quality of the submitted data.

During the study, 20 male mice were put into 2 groups of 10. Group 1 was administered with olive oil (the vehicle) and group 2 was administered with the test material at a dosage of 2.0 g/kg and a dosage volume of 40 mL/kg.

The body weight of all remaining animals was measured on Days 1, 2, 8, and 15 using an electric scale. On Day 1, observation of acute toxicity symptoms was carried out immediately after administration up until approximately 2 hours after administration. In addition, observation was carried out twice (once in the morning, once in the afternoon) on Day 2. From Day 3 to Day 15, observation of the number of surviving animals and general conditions was carried out once a day.

Throughout the study, no deaths were observed. Observations were also made on clinical signs and 6 hours after administration, eyelid closure in 2 animals, soft stools in 2 animals, and diarrhea in 5 animals were observed, but the animals recovered on Day 2. Moistness around the root of the tail was also observed in all of the animals in the control group, but the animals recovered on Day 2.

Under the conditions of the study, it was estimated that the LD50 value of the test material is greater than 2.0 g/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Key Study (Mihara, 1988)

Under the conditions of this study, it was estimated that the LD50 value of the test material is greater than 2.0 g/kg body weight.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to acute toxicity via the oral route as the LD50 is greater than 2000 mg/kg.