Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-06-04 till 2008-06-27
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:
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
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:
- public name of test material:
Reaction mass of 6,13-dichloro-3,10-bis{[2-({[(2-chloroethyl)sulfonyl]alkanoyl}amino)ethyl]-amino}- polycarboheterocyclo 4,11-disulfonic acid, mono and/or disodium salt and 6,13-dichloro-3-{[2-({[(2-chloroethyl)sulfonyl]alkanoyl}amino) ethyl]amino}-10-[(2-{[4-(ethenylsulfonyl)alkanoyl]amino}ethyl)amino] polycarboheterocyclo -4,11-disulfonic acid, mono and/or di sodium salt
- Physical state: solid, dark blue powder
- Analytical purity: approx. 86.6%
- Lot/batch No.: VER 2108 BOP 02/07
- Expiration date of the lot/batch: November 30, 2012

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd. Laboratory Animal Services
- Age at study initiation: 11 weeks
- Fasting period before study:
- Housing:groups of three
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±3
- Humidity (%): 30-70%
- Air changes (per hr): 10-15/h
- Photoperiod (hrs dark / hrs light): 12h / 12h





Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2000 mg/kg body weight
- Amount of vehicle (if gavage):10 mL/kg body weight
- Justification for choice of vehicle:The vehicle was chosen after a non-GLP solubility trial which was performed before the study
initiation date.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg body weight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:experience with similar substances
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
6 females, in 2 groups of 3 animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
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.
Body Weights On test days 1 (prior to administration), 8 and 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
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: no statistical analysis
Mortality:
No deaths occurred during the study.
Clinical signs:
In three animals blue feces were observed on test day 2. Othewise, no clinical signs were
observed during the course of the study.
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 [in grams]

Dose mg/kg

Animal No.

Sex

Day 1 (treatment)

Day 8

Day 15

2000

1

F

185.8

199.6

211.1

2

F

184.8

207.6

218.4

3

F

186.3

207.2

220.0

2000

4

F

180.2

196.7

205.0

5

F

178.7

197.5

204.2

6

F

182.0

202.8

209.8

Mortality / Clinical Signs

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

Blue feces

2

F

No clinical signs

Blue feces

3

F

No clinical signs

Blue feces

2000

4

F

No clinical signs

5

F

No clinical signs

6

F

No clinical signs

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

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 test material 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
The substance is not classified
Executive summary:

Two groups, each of three female HanRcc:WIST (SPF) rats, were treated with test material by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (purified water) 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.

In three animals blue feces were observed on test day 2. Otherwise, no clinical signs were observed during the course of the study.

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 test material 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