Registration Dossier

Administrative data

Description of key information

Acute toxicity: oral: LD50 > 2000 mg/kg bw (OECD 420 in rats; GLP, 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:
From July 01-29, 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted in compliance with OECD Guideline 420 without any deviation.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
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 March 12 to 14, 2014/ signed on May 12, 2014)
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 137-180 g
- Fasting period before study: Animals were fasted for overnight period before dosing and for approximately 3-4 h after dosing.
- Housing: Animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: Food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: 15 changes / h
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From: July 01, 2014 To: July 29, 2014
Route of administration:
oral: gavage
Vehicle:
other: Arachis oil BP for 300 mg/kg bw; no vehicle (unchanged) for 2000 mg/kg bw
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/mL
- Justification for choice of vehicle: Test material at 300 mg/kg bw did not dissolve/suspend in distilled water and therefore solution of test material in arachis oil BP was prepared.

DOSAGE PREPARATION (if unusual): Test material at 2000 mg/kg bw dose level was used as supplied. 300 mg/kg bw dose level was freshly prepared as solution in arachis oil BP. Test material was formulated within 2 h before dosing.

DOSE VOLUME APPLIED: 10 mL/kg bw for 300 mg/kg bw; 2.15 mL/kg bw for 2000 mg/kg bw (specific gravity: 0.933)
Doses:
- Sighting study: 300 and 2000 mg/kg bw
- Main study: 2000 mg/kg bw
No. of animals per sex per dose:
- Sighting study: 1 female/dose
- Main study: 5 females/dose (1 animal included from sighting study)
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 h after dosing and then daily for 14 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; at the end of the observation period, animals were killed by cervical dislocation and subjected to gross necropsy.
Statistics:
None
Preliminary study:
- No mortality or clinical signs were observed at 300 mg/kg bw.
- The animal showed a body weight gain over the observation period that was considered to be within the historical range for this strain.
- No abnormalities were noted at necropsy.
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:
- No mortality was observed at 2000 mg/kg bw.
Clinical signs:
- Hunched posture was noted 4 h after dosing in three animals. No other signs of systemic toxicity noted in two animals.
Body weight:
- Animals showed body weight gains over the observation period that were considered to be within the historical range for this strain.
Gross pathology:
- Epithelial sloughing of the non-glandular epithelium of the stomach was noted at necropsy of one animal. No abnormalities were noted at necropsy of four animals.
Other findings:
None

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Rat Oral LD50 (females) > 2000 mg/kg bw
Executive summary:

In an acute oral toxicity study performed according to OECD Guideline 420 and in compliance with GLP, groups (5 females/dose) of Wistar (RccHan™:WIST) rats were given a single oral (gavage) dose of test material at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination. Sighting study was conducted at the dose levels of 300 and 2000 mg/kg bw (one female/dose) to determine the dose for main study.

In the sighting study, no mortality or clinical signs were observed at 300 mg/kg bw. The animal showed a body weight gain over the observation period that was considered to be within the historical range for this strain. No abnormalities were noted at necropsy. In the main study, no mortality was observed at 2000 mg/kg bw. Hunched posture was noted 4 h after dosing in three animals. There were no other signs of systemic toxicity noted in two animals. Animals showed body weight gains over the observation period and that were considered to be within the historical range for this strain. Epithelial sloughing of the non-glandular epithelium of the stomach was noted at necropsy of one animal. No abnormalities were noted at necropsy of four animals.

 

Rat Oral LD50 (females) > 2000 mg/kg bw

 

Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

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:
2 000 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

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute toxicity: oral

A key study was identified (Harlan, 2014). In this acute oral toxicity study, performed according to OECD Guideline No. 420 and in compliance with GLP, groups (5 females/dose) of Wistar (RccHan™:WIST) rats were given a single oral (gavage) dose of test material at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination. Sighting study was conducted at the dose levels of 300 and 2000 mg/kg bw (one female/dose) to determine the dose for main study.

In the sighting study, no mortality or clinical signs were observed at 300 mg/kg bw. The animal showed a body weight gain over the observation period that was considered to be within the historical range for this strain. No abnormalities were noted at necropsy. In the main study, no mortality was observed at 2000 mg/kg bw. Hunched posture was noted 4 h after dosing in three animals. There were no other signs of systemic toxicity noted in two animals. Animals showed body weight gains over the observation period and that were considered to be within the historical range for this strain. Epithelial sloughing of the non-glandular epithelium of the stomach was noted at necropsy of one animal. No abnormalities were noted at necropsy of four animals.

 

Rat Oral LD50 (females) > 2000 mg/kg bw


Justification for selection of acute toxicity – oral endpoint
Only one study available

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 including ATP6.

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 as the LD50 is greater than 2000 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 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.

Specific target organ toxicity: single exposure (Dermal):

No data was available.

Specific target organ toxicity: single exposure (Inhalation):

No data was available.