Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 12 April 2007 and 02 May 2007.
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:
2007
Report Date:
2007

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)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sponsor's identification: C-Y9
Description: yellow powder
Lot number: MB-l
Date received: 06 March 2007
Storage conditions: room temperature, in the dark, over silica gel

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Female Sprague-Dawley CD (Crl : CD (SD) IGS BR) strain rats were supplied by Charles River (UK) Ltd, Margate, Kent, UK.
- Age at study initiation: Eight to twelve weeks of age.
- Weight at study initiation: 221 - 226 g
- Fasting period before study: Overnight fast immediately before dosing and for approximately three to four hours after 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): Free access to food (Certified Rat and Mosue Diet)
- Water (e.g. ad libitum): Free access to mains drinking water.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 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: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Distilled water
Details on oral exposure:
VEHICLE
The test material was freshly prepared as a solution in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

DOSAGE PREPARATION): All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the absence of data suggesting the test material was toxic, 2000 mg/kg was chosen as the starting dose.
Doses:
2000 mg/kg
No. of animals per sex per dose:
Preliminary sighting study: 1 (female)
Main study: 4 (female)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Clinical observations were made 1/2, 1, 2, and 4 hours after dosing and subsequently once 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 - 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.

Results and discussion

Preliminary study:
Mortality: No death
Clinical Observations: No signs of systemic toxicity noted.
Bodyweight: Animal showed expected gain in bodyweight over the observation period.
Necropsy: No abnormalities were noted at necropsy.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted.
Body weight:
All animals showed expected gains in bodyweight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LDso) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight
Executive summary:

Introduction.

The study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD 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" (adopted 17 December 2001)

• Method Bl bis Acute Toxicity (Oral) of Commission Directive 2004/73/EC

Method.

Following a sighting test in which there was no mortality at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of test material, as a solution in distilled water, 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.

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 Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight