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Description of key information

Oral

Under the conditions of this study the acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/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:
12 July 2017 to 02 August 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
2008
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
RccHan™:WIST
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 157 to 186 g
- Fasting period before study: overnight before dosing
- Housing: The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with wood flakes.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25 °C
- Humidity: 30 to 70 %
- Air changes: at least fifteen changes per hour
- Photoperiod: lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.
Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: For the purpose of the study the test material was freshly prepared, as required, as a solution in dimethyl sulfoxide. Dimethyl sulfoxide was used because the test material did not dissolve in distilled water or arachis oil BP.

DOSAGE PREPARATION:
- The test material was formulated within 2 hours of being applied to the test system. It is assumed that the formulation was stable for this duration.

CLASS METHOD
- In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose. A single animal was treated at 300 mg/kg and observed.
Doses:
300 mg/kg for a single animal, increased to 2000 mg/kg in the absence of toxicity.
No. of animals per sex per dose:
One female at 300 mg/kg.
Five females at 2000 mg/kg.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for 14 days. Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays.
- Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes, at the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained
Statistics:
No statistical analysis was performed.
Preliminary study:
The following results were observed for the single female dosed at 300 mg/kg:
- There was no mortality.
- No signs of systemic toxicity were noted during the observation period.
- The animal showed expected gains in body weight over the observation period.
- No abnormalities were noted at necropsy.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
Hunched posture and pilo erection were noted, 4 hours after dosing, in the initial treated animal. There were no signs of systemic toxicity noted in the four additional animals treated at a dose level of 2000 mg/kg
Body weight:
All animals showed expected gains in body weight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
Under the conditions of this study, the acute oral LD50 value in female Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

The acute oral toxicity of the test material was investigated in the Wistar strain rat in accordance with the standardised guidelines OECD 420 and EU Method B1 bis, under GLP conditions.

Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test material, as a solution in dimethyl sulfoxide, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths in the treated animals. Hunched posture and pilo erection were noted, 4 hours after dosing, in the initial animal treated at a dose level of 2000 mg/kg. There were no signs of systemic toxicity noted in the four additional animals treated at a dose level of 2000 mg/kg and the animal treated at a dose level of 300 mg/kg. All animals showed expected gains in body weight and no abnormalities were noted at necropsy.

Under the conditions of this study the acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The available study was conducted in accordance with standardised guidelines and under GLP conditions. The quality of the dataset is therefore high.

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

The acute oral toxicity of the test material was investigated in the Wistar strain rat in accordance with the standardised guidelines OECD 420 and EU Method B1 bis, under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test material, as a solution in dimethyl sulfoxide, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths in the treated animals. Hunched posture and pilo erection were noted, 4 hours after dosing, in the initial animal treated at a dose level of 2000 mg/kg. There were no signs of systemic toxicity noted in the four additional animals treated at a dose level of 2000 mg/kg and the animal treated at a dose level of 300 mg/kg. All animals showed expected gains in body weight and no abnormalities were noted at necropsy.

Under the conditions of this study the acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/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.