Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 January 2010 to 02 February 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guidelineopen allclose all
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:
Date of GLP inspection: Date of Signature on GLP certificate:
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Description : clear colourless viscous liquid
Batch number : MW9F23A901
Date received : 05 November 2009
Expiry date : 15 June 2010
Storage conditions: approximately 4°C in the dark 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:
At the start of the study the animals were eight to twelve weeks of age.

- Weight at study initiation:
The bodyweight variation did not exceed ± 20% of the initial/mean bodyweight of any previously dosed animal(s).

- Fasting period before study:
overnight fast immediately before dosing

- Housing:
The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes.

- Diet (e.g. ad libitum):
(2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed ad libitum throughout the study.

- Water (e.g. ad libitum):free access to mains drinking water

- Acclimation period: acclimatisation period of at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C):
19 to 25°C

- Humidity (%):
30 to 70%

- Air changes (per hr):
The rate of air exchange was at least fifteen changes per hour.

- Photoperiod (hrs dark / hrs light):
lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.


IN-LIFE DATES: From: Day 1 To: Day 14

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:

VEHICLE
- Concentration in vehicle:
For the purpose of the study the test material was freshly prepared, as required, as a solution in arachis oil BP to give a dose level of 300mg/kg and 2000mg/kg bodyweight.

- Amount of vehicle (if gavage):
Not stated

- Justification for choice of vehicle:
Arachis oil was the prefered vehicle as the test material did not dissolve/suspend in distilled water.

- Lot/batch no. (if required):
Not stated

- Purity:
Not stated



CLASS METHOD (if applicable)

- Rationale for the selection of the starting dose:
In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose.
Doses:
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 arachis oil BP, at a dose level of 2000 mg/kg bodyweight.
No. of animals per sex per dose:
1 female at 2000 mg/kg and 300mg/kg
4 females at 2000 mg/kg
Control animals:
no
Details on study design:
EXAMPLE:
- Duration of observation period following administration:
14 days

- Frequency of observations and weighing:
Clinical observations were made ½, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.

- Necropsy of survivors performed:
Yes

- Other examinations performed:
Clinical signs, body weight.

Results and discussion

Preliminary study:
A sighting test at a dose level of 300 mg/kg was performed.
Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 mg/kg bw
Remarks on result:
other: Not reported
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: Not reported
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity. Pale faeces were noted in one animal.
Body weight:
All animals showed expected gains in bodyweight.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
- Organ weights:
Not recorded

- Histopathology:
Not recorded

- Potential target organs:
Not recorded

- Other observations:
None

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information: 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 bodyweight (Globally Harmonised Classification System
Conclusions:
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 bodyweight (Globally Harmonised Classification System- Unclassified).
Executive summary:

Introduction. The study was performed to assess the acute oral toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of the following:

§        OECD Guidelines for Testing of Chemicals No 420 “Acute Oral Toxicity - Fixed Dose Method” (2001)

§        Method B1 bis Acute Toxicity (Oral) of CommissionRegulation (EC) No. 440/2008

Method. 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 arachis oil BP, at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity. Pale faeces were noted in one animal.

Bodyweight. All animals showed expected gains in bodyweight.

Necropsy. No abnormalities were noted at necropsy.

Conclusion. The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000mg/kg bodyweight (Globally Harmonised Classification System-Unclassified).