Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-08-06 till 2008-08-29
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of the test material (as cited in the study report: FAT 40842/A TE
- Substance type: coloring dye
- Physical state: solid, dark bluish green powder
- Analytical purity: 96%
- Lot/batch No.: Blau DRI 2098 Op 1/07
- Expiration date of the lot/batch: June 30, 2014
- Storage condition of test material: at room temperature at about 20 ºC

Test animals

Species:
rat
Strain:
other: WIST (SPF)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd Laboratory Animal Services Wölferstrasse 4 4414 Füllinsdorf / Switzerland
- Age at study initiation: 11 weeks
- Weight at study initiation: 181.5g - 194.9g
- Housing: in groups of three
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimatization: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.
- Fasting period before study: fasted for approximately 18½ to 20½ hours (access to water was permitted). Food was provided again approximately 3 hours after dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): relative humidity between 30-70 % (values above 70 % during cleaning process possible)
- Air changes (per hr): Air-conditioned with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark
- music during the daytime light period

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20% (w/w)
- Amount of vehicle (if gavage):
- Justification for choice of vehicle:The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date.
- Lot/batch no. (if required): Polyethylene glycol 300 (PEG 300); Lot number: 1349048; FLUKA Chemie GmbH, CH-9471 Buchs


MAXIMUM DOSE VOLUME APPLIED: a single dose of the test item by oral gavage administration at 2000 mg/kg body weight (Vehicle: 10mL/kg body weight)


DOSAGE PREPARATION (if unusual): The dose formulations were made shortly before each dosing occasion using a magnetic stirrer and a spatula as homogenizers. The test item was reduced into a fine powder using a mortar and a pestle. Thereafter, the pulverized test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle was added (weight:volume). Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: experience with similar compounds
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
6 females, in groups of three
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- weighing: On test days 1 (prior to administration), 8 and 15
- Mortality / Viability Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15
- Clinical Signs Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: yes. All animals were killed at the end of the observation period by carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. No organs or tissues were retained.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Statistics:
no statistical analysis was used

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: CL not applicable
Mortality:
No deaths occurred during the study.



Clinical signs:
All animals showed green stained faeces at the 5-hour reading up to test day 2 or from test day 2 to 4. Otherwise, no clinical signs were noted.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.

Any other information on results incl. tables

Body Weights (gram)

Dose (kg/kg)

Sex

Animal

Day 1 (treatment)

Day 8

Day 15

Group 1

F

F

F

1

194.9

218.9

233.0

2

188.7

201.9

204.0

3

186.3

195.1

207.3

Mean

189.9

205.3

214.7

St.Dev.

4.5

12.3

15.9

N

3

3

3

Group 2

F

F

F

4

181.5

206.1

212.8

5

183.2

210.3 4

222.

6

185.7

213.0

222.5

Mean

183.5

209.8

219.2

St.Dev.

2.1

3.4

5.6

N

3

3

3

Individual Findings

Dose mg/kg bw

Ani-malNo.

Sex

Signs

Test days

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

0.5*

1*

2*

3*

5*

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

2000

1

F

No clinical signs

 

 

Green stainedfeces

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

2

F

No clinical signs

 

 

Green stainedfeces

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

3

F

No clinical signs

 

 

Green stainedfeces

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

2000

4

F

No clinical signs

 

 

 

Green stainedfeces

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

5

F

No clinical signs

 

 

 

Green stainedfeces

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

6

F

No clinical signs

 

 

 

Green stainedfeces

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Key:√ noted

 

* Examinations were performed within the first 30 minutes and 1, 2, 3 and 5 hours after  treatment.

No clinical signs were evident in any animal during the acclimatization period.

Macroscopic Findings

Dose

mg/kg

Animal

No.

Sex

Mode of

death

Findings

2000

1

F

S

No macroscopic findings

2

F

S

No macroscopic findings

3

F

S

No macroscopic findings

2000

4

F

S

No macroscopic findings

5

F

S

No macroscopic findings

6

F

S

No macroscopic findings

S: scheduled necrospsy

 

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose of FAT 40842/A TE after single oral administration to female rats, observed over a period of 14 days is:
LD50 (female rat): greater than 2000 mg/kg body weight
Executive summary:

Two groups, each of three female HanRcc:WIST (SPF) rats, were treated with FAT 40842/A TE by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (PEG 300) at a concentration of 0.2 g/mL and administered at a dosing volume of 10 mL/kg.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study period.

All animals showed green stained faeces at the 5-hour reading up to test day 2 or from test day 2 to 4. Otherwise, no clinical signs were noted.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were recorded at necropsy.

The median lethal dose of FAT 40842/A TE after single oral administration to female rats, observed over a period of 14 days is: LD50 (female rat): greater than 2000 mg/kg body weight

Categories Display