Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From January 15 to February 10, 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
Adopted 8th February 2002
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 August 19, 2008/ signed on March 04, 2009)
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Remarks:
paste / solid block
Details on test material:
- Physical state: solid, pale yellow to yellow block, or pasty
- Stability under test conditions: no data
- Storage condition of test material: in the dark, preferably at about 4-10°C and under nitrogen.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 187-219 g
- Fasting period before study: Animals were fasted for overnight period before test item administration 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 (2014 Teklad Global Rodent diet supplied by Harlan Teklad, Bicester, 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: January 15, 2009 To: February 10, 2009

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Justification for choice of vehicle: Test material was not dissolved/suspended in distilled water, therefore arachis oil was selected as vehicle.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION:
- Test material was freshly prepared, as required, as a suspension in arachis oil BP.
Doses:
- Sighting study: 300 and 2000 mg/kg bw
- Main study: 300 mg/kg bw
No. of animals per sex per dose:
- Sighting study: 1 female/dose
- Main study: 5 females/dose (One animal from sighting study and 4 additional animals)
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. Body weight of each animal was recorded on Day 0 (the day of dosing) and on Days 7 and 14 or at death.
- Necropsy of survivors performed: Yes; on completion of the observation period, animals were killed by cervical dislocation and subjected to gross necropsy.
Statistics:
None

Results and discussion

Preliminary study:
- There were no deaths or clinical signs of toxicity at a dose level of 300 mg/kg bw.
- Animal treated at a dose level of 2000 mg/kg bw was killed in extremis approximately 2 h after dosing.
- Signs of systemic toxicity noted in animal treated with 2000 mg/kg bw were hunched posture, ataxia, lethargy, pilo-erection, decreased respiratory rate, laboured respiration and hypothermia. The animal was comatose approximately 2 h after dosing.
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 300 - < 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: One animal was found dead at 2000 mg/kg bw
Mortality:
- No mortality was observed at a dose level of 300 mg/kg bw.
Clinical signs:
- No signs of systemic toxicity were noted during the observation period at 300 mg/kg bw.
Body weight:
- All animals showed expected gains in bodyweight over the 14 day study period at 300 mg/kg bw.
Gross pathology:
- No abnormalities were noted at necropsy.
Other findings:
None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the test conditions, the oral LD50 for the registered substance is 300 < Oral LD50 ≤2000 mg/kg bw in female rats, therefore the test material is classified as ‘Category 4’ according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS. Based on narcotic effects observed at the dose level of 2000 mg/kg bw, the test material is classified as a specific target organ toxicant after single exposure, H336: May cause drowsiness or dizziness according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute oral toxicity study performed according to OECD Guideline No. 420 and in compliance with GLP, female Wistar (HsdRccHan®™:WIST™) rats were administered a single oral dose of test material by gavage.

Following a sighting study using one animal at a dose level of 300 and 2000 mg/kg bw, additional four animals were administered a single oral dose of test item at 300 mg/kg bw (main study). Animals were then observed for mortality, clinical signs and bodyweight development for 14 days and at the end of the study the surviving animals were subjected to macroscopic examination.

The animal treated at a dose level of 2000 mg/kg bw was killed in extremis approximately two hours after dosing. Signs of systemic toxicity noted in animal treated with 2000 mg/kg bw were hunched posture, ataxia, lethargy, pilo-erection, decreased respiratory rate, laboured respiration and hypothermia. Animal was comatose approximately two hours after dosing.

No mortality or clinical signs were observed at 300 mg/kg bw. All animals showed expected gains in bodyweight over the 14 day study period. No abnormalities were noted at necropsy.

300 < Rat Oral LD50 (females) ≤2000 mg/kg bw

Under the test conditions, the test material is classified as ‘Category 4’ according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS. Based on narcotic effects observed at the dose level of 2000 mg/kg bw, the test material is classified as a specific target organ toxicant after single exposure, H336: May cause drowsiness or dizziness according to the 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.