Registration Dossier

Administrative data

Description of key information

Key study:- Ianamoto (1999), Acute toxicity oral (OECD 420): LD50 > 2000 mg/kg bw (male/female rats)

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:
28th May to 22nd June 1999 for males, 2nd July to 28th July for females
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted in 1999 in accordance with OECD guideline 420 although not in accordance with GLP. The batch number (807007) and purity (100%) are both noted in the report. A statement of authentication is also provided in the report in lieu of a more formal Quality Assurance procedure. The study is well reported with regards to both the methodology and results. One animal died during the study but no explanation attributing the cause of death is made within the report. There were no abnormalities detected upon necropsy. Due to the lack of observed effects this deviation is not considered to affect the reliability of the study.
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 7 weeks old
- Weight at study initiation: 215-252 g for males and 171-195 g for females
- Fasting period before study: Overnight (18 to 20 hours)
- Housing: Group caged by sex, 2 or 3 animals in each cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 25 days for males, 10 days for females

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 30-70 %
- Air changes (per hr): Approximately 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Route of administration:
oral: gavage
Vehicle:
soya oil
Details on oral exposure:
VEHICLE
- Amount of vehicle: 1 mL/100 g bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 males and 5 females dosed with the test material
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: The animals were observed at least once daily, the animals were weighed prior to dosing and on days 7 and 15
- Necropsy of survivors performed: Yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occcurred in the males dosed with the test material. One female was found dead on day 2.
Clinical signs:
There were no treatment related clinical signs.
Body weight:
All surviving animals showed expected bodyweight gains during test period.
Gross pathology:
There were treatment related necropsy findings. No abnormaltities of the abdominal and thoracic cavities were observed. No abnormalities were observed in animals sacrificed at the end of the study.

Table 1: Results

Sex

Dose (mg/kg)

Number of Rats

Age and Weight (g) at Dosing

Mortality

Male

2000

6

7 weeks old, 215-252 g

0/6

0 (control)

1

0/1

Female

2000

5

7 weeks old, 171-195 g

1/5

0 (control)

1

0/1

Combined

2000

11

7 weeks old, 171-252 g

1/11

0 (control)

2

0/2

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the test, the LD50 of the test material was found to be greater than 2000 mg/kg bw in male and female Wistar rats.
Executive summary:

In a study conducted to OECD 420, the acute oral toxicity of the test material was investigated in male and female Wistar rats using a limit dose of 2000 mg/kg bw. Only one mortatlity was noted during the course of the study, and no treatment related changes were apparent. Under the conditions of the test, the LD50 of the test material was determined to be greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The key study has been assigned a reliability score of 1 in accordance with the criteria of Klimisch (1997) while a supporting study, performed to a methodology similar or equivalent to OECD 401, was assigned a reliability score of 2. Overall, the quality of the database is good.

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

ORAL

In the key study, conducted to OECD 420, the acute oral toxicity of the test material was investigated in male and female Wistar rats using a limit dose of 2000 mg/kg bw. Only one mortality was noted during the course of the study, and no treatment related changes were apparent. Under the conditions of the test, the LD50 of the test material was determined to be greater than 2000 mg/kg bw.

Supporting information is available in the form of a study, conducted to a method that is similar to the now redundant OECD 401 guideline. The test material was dosed using varying volumes by oral gavage. Under the conditions of the test, the test material was found to have a combined LD50 of 5700 mg/kg bw and an LD50 of 5800 and 5600 mg/kg bw in males and females respectively.

Justification for selection of acute toxicity – oral endpoint

The study was conducted in accordance with the standardised guideline OECD 420; although no information relating to the GLP status was provided in the reporting of the study, quality assurances were reported by the laboratory. In line with the criteria for assessing data quality as described in Klimisch (1997), the study was assigned a reliability score of 1, and considered reliable and adequate for assessment.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for acute toxicity by the oral route as no signs of toxicity were noted during the course of the studies.