Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03 June 2009 to 19 June 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant to OECD 423 and GLP 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 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name: Thiazol Blau

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (Europe) Laboratories Inc. Toxi Coop Ltd., 1103 Budapest, Cserkesz u. 90.
- Age at study initiation: 7-8 weeks old
- Weight at study initiation: 187 g to 203 g
- Fasting period before study: over night until 3 hours post treatment
- Housing: Group caging (3 animals/cage)
- Diet: ssniff® SM R/M-Z+H ad libitum
- Water: tap water ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 03 June 2009 To: 17 June 2009

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: solubiltity in vehicle
- Lot/batch no. (if required): 1421464
- Expiry Date: September 2010



CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: test item was considered to have low toxicity based on experience with similar compounds
Doses:
2000 mg/kg
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Clinical signs: 30 minutes, 1, 2, 3, 4 and 6 hours after dosing on Day 0 and daily for 14 days thereafter
- Body weight: Days -1, 0 (shortly before the treatment), 3, 7 and 14
- Necropsy of survivors performed: yes
Statistics:
NA

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no deaths occurred
Clinical signs:
There were no adverse treatment-related clinical signs noted following treatment or during the 14-day observation period. On the day of administration, black faeces were observed in all rats. This is most likely due to a staining effect of the test item.
Body weight:
no adverse effects
Gross pathology:
no findings

Any other information on results incl. tables

Mortality

Treatment group:

1

2

Dose (mg/kg bw):

2000

2000

Number of animals treated:

3

3

Mortality:

0/3

0/3

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the conditions of this study, the acute oral median lethal dose (LD50) of the test item was above 2000 mg/kg bw in female CRL:(WI) BR rats.
Thiazol Blau was ranked into Category 5 of the Globally Harmonized Classification System.
Executive summary:

The single-dose oral toxicity study of THIAZOL BLAU was performed according to the acute toxic class method (OECD 423, OPPTS 870.1100 and Commission Regulation (EC) No 440/2008, B.1 tris (L 142, 30 May 2008)) in CRL:(WI) BR rats.

The study was performed at a dose level of 2000 mg/kg body weight (bw). Two groups of three female CRL:(WI)BR Wistar rats (7 to 8 weeks of age) were treated with a solution of THIAZOL BLAU in Polyethylene-glycol (PEG) 400 at 2000 mg/kg bw by oral gavage (Groups 1 and 2).

Initially, three females (Group 1) were treated at 2000 mg/kg bw. As no mortality occurred in this dose group within 24 hours after dosing, a confirmatory treatment according to OECD 423 was performed on 3 further females at the same dose level (2000 mg/kg bw). Rats were maintained without compound administration for a 2-week observation period after the day of dosing. As no mortality was observed in the second dose group, no further treatment was needed.

A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. THIAZOL BLAU was administered at a concentration of 200 mg/mL (Groups 1 and 2) prepared in PEG400 with a treatment volume of 10 mL/kg bw.

Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Food was made available again 3 hours after the treatment. Bodyweight was measured on Days -1, 0, 3 and 7 and before necropsy. Gross necropsy was performed on all animals (Day 14).

Mortality

THIAZOL BLAU did not cause mortality at 2000 mg/kg bw.

Clinical observations

Coloured faeces were recorded in all treated animals on the day of administration. No clinical signs were observed during the 14 day observation period.

Bodyweight and Bodyweight gain

Bodyweight gains of THIAZOL BLAU treated animals during the study showed no indication of a test item-related effect.

Macroscopic Findings

A single oral gavage of Thiazol Blau to the CRL:(WI)BR rat at a dose level of 2000 mg/kg bw, followed by a 14 day observation period, was not associated with any test item-related macroscopic findings.

 

Under the conditions of this study, the acute oral median lethal dose (LD50) of the test item THIAZOL BLAU was greater than 2000 mg/kg bw in female CRL:(WI)BR rats.

THIAZOL BLAU was ranked into Category 5 of the Globally Harmonized Classification System.