Registration Dossier

Administrative data

Description of key information

Oral: LD50 > 2000 mg/kg bw and the LD50 cut-off estimated to be > 5000 mg/kg bw, female rat, OECD TG 420, 2018

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:
23-08-2018 to 14-08-2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met.
Justification for type of information:
Information as to the availability of the in vivo study is provided in 'attached justification'.
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
inspected: July 2017 ; signature: November 2017
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Recognised supplier
- Females (if applicable) nulliparous and non-pregnant: Yes.
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 148 g (300 mg/kg including sighting test; sentinel); 154 - 181 g (2000 mg/kg sighting test; sentinel); The weight variation did not exceed ±20% of the mean weight during the test.
- Fasting period before study: Overnight before dosing and three to four hours after dosing.
- Housing: Group housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): Certified diet from recognised supplier, provided ad libitum (except for fasting period).
- Water (e.g. ad libitum): ad libitum (except for fasting period)
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70%
- Air changes (per hr): > 15 air changes per hour
- Photoperiod: 12 h light / 12 h dark

IN-LIFE DATES: 2018-07-23 to 2018-08-14
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level. For the purpose of the 300 mg/kg dose level the test item was freshly prepared, as required, as a solution in arachis oil BP. Arachis oil BP was used because the test item did not dissolve/suspend in distilled water. For the purpose of the 2000 mg/kg dose level, the test item was used as supplied. The 300 mg/kg bw and 2000 mg/kg bw dose levels were treated stepwise. Singularly and in the absence of mortality or evident toxicity a further group of 4 was tested in the appropriate dose level.
The test item was formulated at concentrations of 30 mg/mL or dosed as supplied according to specific gravity of the test item. Formulations were prepared on the day of dosing.
- Amount of vehicle (if gavage): Test Item dose volume was 10 mL/kg (of bodyweight) in Arachis Oil BP or dosed as supplied at 2.20 mL/kg
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed.
- Lot/batch no. (if required): See full study report.
- Purity: BP grade.

MAXIMUM DOSE VOLUME APPLIED: 300 mg/kg bw dose level: 10 mL/kg of test item in vehicle (Arachis Oil BP) ; 2000 mg/kg bw dose level: 2.2 mL/kg of test item as supplied.

DOSAGE PREPARATION (if unusual): Not applicable. The test item was prepared in the vehicle. It was administered to the animals under a volume of 10 mL/kg in Arachis Oil BP (300 mg/kg bw) or 2.20 mL/kg as supplied (2000 mg/kg bw).

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose based on guideline recommendations.
Doses:
300 mg/kg bw (initial sighting test and main study)
2000 mg/kg bw (initial sighting test and main study)
No. of animals per sex per dose:
300 mg/kg bw in Arachis Oil vehicle (starting dose) : 1 (sighting study)
2000 mg/kg bw: 1 (sighting study) and 4 (main study) as applicable; total 5 per dose - based on guideline specified sequential testing strategy
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 0.5, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
300 mg/kg bw: No mortality.
2000 mg/kg bw: No mortality.
Clinical signs:
300 mg/kg bw: No signs of systemic toxicity were noted.
2000 mg/kg bw: Hunched posture was noted in all (5/5) females on day 1 and 2 and appeared normal on day 4.
Body weight:
300 mg/kg bw: Expected bodyweight gains were seen over the study period.
2000 mg/kg bw: Expected bodyweight gains were seen over the study period.
Gross pathology:
300 mg/kg bw: No abnormalities were noted at necropsy.
2000 mg/kg bw: No abnormalities were noted at necropsy.
Other findings:
- Organ weights: Not reported.
- Histopathology: Not reported. No macropathological abnormalities amongst survivors.
- Potential target organs: Not applicable.
- Other observations: Not applicable.
Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the oral LD50 was established to exceed 2000 mg/kg bw in female Wistar rats. Under the conditions of this study, and according to the OECD TG 420 criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.
Executive summary:

The study was performed according to OECD TG 420 and EU Method B.1 bis Acute Toxicity (Oral) under GLP to assess the acute oral toxicity of the test item by the fixed dose method following a single oral administration in the female Wistar strain rat. The test item was administered by oral gavage in an initial sighting study at 300 mg/kg using Arachis Oil BP vehicle. In the absence of significant toxicity the test item was then administered by oral gavage in a further initial sighting at 2000 mg/kg dosed as supplied. Subsequently a further group of four fasted females was given a single oral dose of test item, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study and gross necropsy performed. There was no mortality during the course of the study. No signs of systemic toxicity were noted. Animals showed expected gains in bodyweight over the study period and there were no abnormalities noted at necropsy. Under the conditions of this study the oral LD50 was established to exceed 2000 mg/kg bw in the female Wistar rat. Under the conditions of this study, and according to the OECD TG 420 criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The available information as a whole meets the tonnage driven information requirements of REACH.

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:

Key study : OECD TG 420, 2018 : The study was performed according to OECD TG 420 and EU Method B.1 bis Acute Toxicity (Oral) under GLP to assess the acute oral toxicity of the test item by the fixed dose method following a single oral administration in the female Wistar strain rat. The test item was administered by oral gavage in an initial sighting study at 300 mg/kg using Arachis Oil BP vehicle. In the absence of significant toxicity the test item was then administered by oral gavage in a further initial sighting at 2000 mg/kg dosed as supplied. Subsequently a further group of four fasted females was given a single oral dose of test item, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study and gross necropsy performed. There was no mortality during the course of the study. No signs of systemic toxicity were noted. Animals showed expected gains in bodyweight over the study period and there were no abnormalities noted at necropsy. Under the conditions of this study the oral LD50 was established to exceed 2000 mg/kg bw in the female Wistar rat. Under the conditions of this study, and according to the OECD TG 420 criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.

Justification for classification or non-classification

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity: oral