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Administrative data

Description of key information

Acute toxicity: oral: LD50 > 5000 mg/kg bw (OECD 420 in rats, K, rel.1)

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:
05 September to 05 December 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted according to OECD Guideline 420 without deviation.
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
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance Programme (inspected on July 05, 2016/ signed on October 28, 2016)
Test type:
fixed dose procedure
Limit test:
no
Specific details on test material used for the study:
- Storage conditions: At room temperature, protected from moisture (Dry area, unopened containers, optimum temp. 11-25 °C / 52-77 °F)
Species:
rat
Strain:
Wistar
Remarks:
RccHan™:WIST
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS (UK) Ltd.
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: ca. 8-12 weeks
- Weight at study initiation: 150-164 g.
- Fasting period before study: overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing.
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: 2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK, ad libitum
- Water: drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Animal room: The rate of air exchange was at least fifteen changes per hour. The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Photoperiod: 12 h dark / 12 h light
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: Arachis oil BP was used after a solubility trial.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The test substance was formulated at concentrations of 30 and 200 mg/mL in the vehicle.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
1 female at 300 mg/kg bw
5 females at 2000 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations:
Mortality: Cages of rats were checked at least twice daily for any mortalities.
Clinical signs: Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for 14 days.
- Frequency of weighing: Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: 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:
None
Preliminary study:
Not applicable
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality was observed
Mortality:
There were no deaths during the study.
Clinical signs:
No signs of systemic toxicity were noted during the observation period for any animals receiving 300 or 2000 mg/kg bw.
Body weight:
All animals showed expected gains in body weight over the observation period.
Gross pathology:
All animals were killed at Day 14. No abnormalities were noted at necropsy.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of the test substance in female Wistar strain rat is estimated to be greater than 2000 mg/kg bw.
Under the test conditions, and according to the OECD TG 420 criteria, the LD50 cut-off value is considered to be greater than 5000 mg/kg bw, therefore it is not classified according to Regulation EC No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute oral toxicity study performed according to OECD Guideline 420 and in compliance with GLP, following a sighting test at dose levels of 300 mg/kg body weight and 2000 mg/kg body weight, a further group of four fasted females Wistar rats was given a single oral dose of test item, as a solution in DMSO, at a dose level of 2000 mg/kg body weight. Animals were then observed for mortality, clinical signs and body weights for 14 days and were all sacrificed for macroscopic examination.

 

There were no deaths and no clinical signs during the study. All animals showed expected gains in body weight. No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 14.

Oral LD50 (female) > 2000 mg/kg bw

Under the test conditions, and according to the OECD TG 420 criteria, the LD50 cut-off value is considered to be greater than 5000 mg/kg bw, therefore it is not classified according to Regulation EC No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The key study is GLP-compliant and of high quality (Klimisch score = 1)

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Not required at a REACH Annex VII level

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Not required at a REACH Annex VII level

Additional information

Acute toxicity: oral

In an acute oral toxicity study performed according to OECD Guideline 420 and in compliance with GLP, following a sighting test at dose levels of 300 mg/kg body weight and 2000 mg/kg body weight, a further group of four fasted females Wistar rats was given a single oral dose of test item, as a solution in DMSO, at a dose level of 2000 mg/kg body weight. Animals were then observed for mortality, clinical signs and body weights for 14 days and were all sacrificed for macroscopic examination.

There were no deaths and no clinical signs during the study. All animals showed expected gains in body weight. No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 14.

Oral LD50 (female) > 2000 mg/kg bw

Under the test conditions, and according to the OECD TG 420 criteria, the LD50 cut-off value is considered to be greater than 5000 mg/kg bw.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Acute toxicity via Oral route:

Based on the available data, the substance is not classified according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS as the oral LD50 is higher than 5000 mg/kg bw.

Acute toxicity via Dermal route:

No data was available.

Acute toxicity (Inhalation):

No data was available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 and to the GHS as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to the Regulation (EC) No. 1272/2008 and to the GHS are not met since narcotic effects were not observed in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Dermal):

No data was available.

Specific target organ toxicity: single exposure (Inhalation):

No data was available.

Based on its physical state (solid - partly melted at 40°C, but very viscous), the substance is not classified for aspiration hazard according to CLP Regulation and GHS.