Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25/11/2008 to 11/12/2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in accordance with recognised guideline

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)
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:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
No further information required.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
Female Wistar (HsdRccHan®™:WIST®™) strain rats were supplied by 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 rats weighed between 154-183g at day 0

- Fasting period before study:
With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

- 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):
With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to food (2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study.

- Water (e.g. ad libitum):
With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water was allowed throughout the study.

- Acclimation period:
At least 5 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.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.

MAXIMUM DOSE VOLUME APPLIED:
2000 mg/kg bodyweight

CLASS METHOD:
- Rationale for the selection of the starting dose:
Following a sighting test 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/suspension in distilled water, at a dose level of 2000 mg/kg bodyweight.
Doses:
2000 mg/kg bodyweight
No. of animals per sex per dose:
5 females
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 hours after dosing and subsequently once daily for fourteen days. Morbidity and mortality checks were made twice daily.
- Necropsy of survivors performed: Yes, 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. No abnormalities were detected.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Effects on bodyweights and abnormalities noted at necropsy were also identified. All animals showed expected gains in bodyweight over the observation period.
Statistics:
n/a

Results and discussion

Preliminary study:
1 rat was preliminary dosed at 2000 mg/kg followed by 4 rats to make up a dose group of 5 rats.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted. Black stained faeces and blue stained urine were noted in all animals during the study.
Body weight:
Bodyweights at day 14 were between 183 and 216 g. All animals showed expected gains in bodyweight over the observation period.
Gross pathology:
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. No abnormalities were noted at necropsy.
Other findings:
None reported

Any other information on results incl. tables

There were no deaths and no abnormalities noted at necropsy.

No signs of systemic toxicity were noted. Black stained faeces and blue stained urine were noted in all animals during the study.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
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.
Executive summary:

In an Acute oral toxicity in the rat – fixed dose method study (Harlan project number: 0959/0226) the test material was determined to have an LD50 of greater than 2000 mg/kg bodyweight.

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" (adopted 17 December 2001).

Method B1 bis Acute Toxicity (Oral) of Commission Directive 2004/73/EC.

There were no deaths. No signs of systemic toxicity were noted. Black stained faeces and blue stained urine were noted in all animals during the study. All animals showed expected gains in bodyweight over the observation period. No abnormalities were noted at necropsy.