Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 November 2008 and 11 December 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in compliance with agreed protocols with no deviations from standard test guidelines and/or minor methodological deficiences which do not affect the quality of the relevant results

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:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Dark red powder
Batch Number MB-1-A
Storage room temperature in dark

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: 142-176 g
- Fasting period before study: Overnight fast immediately before dosing
- Housing: Groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): Free access to 2014 Teklad Global Rodent diet
- Water (e.g. ad libitum): Free access to mains drinking water
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 dark:12 light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
2000 mg/kg was chosen dose: 2000 mg/kg dose level, 200 mg/mL concentration, 10 mL/kg dose volume.
Animals were dosed once by gavage using a metal cannula attached to a graduated syringe.
Volume administered to each animal was calculated according to fasted bodyweight at time of dosing.

MAXIMUM DOSE VOLUME APPLIED:
10mL/kg

DOSAGE PREPARATION (if unusual):
For the purpose of the study the test material was freshly prepared, as required, as a solution in distilled water.

Determination by analysis of the concentration, homogeneity and stability of the test material preparations was not appropriate because it was not specified in the Study Plan and is not a requirement of the Test Guideline.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
Using available information on the toxicity of the test material, 2000 mg/kg was chosen as the starting dose. In the absence of toxicity at a dose level of 2000 mg/kg, an additional group of animals was treated in the same manner. A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5f
Control animals:
no
Details on study design:
- 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:
Using available information on the toxicity of the test material, 2000 mg/kg was chosen as the starting dose. 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 deatjs
Clinical signs:
No signs of systemic toxicity were noted. Red stained faeces was noted in all animals during the study.
Body weight:
All animals showed expected gains in bodyweight over the observation period
Gross pathology:
No abnormalities were noted at necropsy.

Any other information on results incl. tables

The acute oral median lethal dose (LD50) of test material in female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information No signs of toxicity Criteria used for interpretation of results: EU
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: 0959/0236) the test material was determined to have an LD50 of greater than 2000 mg/kg bodyweight. There were no deaths. No signs of systemic toxicity were noted. Red stained faeces was noted in all animals during the study. All animals showed expected gains in bodyweight over the observation period. There were no abnormalities noted at necropsy.

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 AcuteToxicity (Oral) ofCommissionDirective2004/73/EC.