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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Justification for type of information:
Acute oral toxicity has been estimated from a dose selection experiment preceeding an in-vivo Comet assay.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report date:
2005

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The study was performed according to internationally accepted protocol for the in vivo Comet assay (A Hartmann et al, 2003)
GLP compliance:
yes
Test type:
other: In vivo mammalian cell study : DNA damage and/or repair
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
481-170-7
EC Name:
-
Cas Number:
502453-61-4
Molecular formula:
Hill formula: C23H30BrN3O2 CAS formula: C23H30N3O2.Br
IUPAC Name:
dimethyl(3-{[4-(methylamino)-9,10-dioxo-9,10-dihydroanthracen-1-yl]amino}propyl)propylazanium bromide
Details on test material:
- Name of test material (as cited in study report): B119 HC Blue 16
- Molecular formula (if other than submission substance): C23H30N3O2Br
- Molecular weight (if other than submission substance): 460.42
- Smiles notation (if other than submission substance): N/A
- InChl (if other than submission substance): N/A
- Structural formula attached as image file (if other than submission substance): N/A
- Substance type: Active
- Physical state: Solid, dark blue powder

Test animals

Species:
rat
Strain:
other: Wistar Crl:WI BR
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: 6-8 weeks of age
- Weight at study initiation: 152-203 g
- Assigned to test groups randomly: Yes; Animals were randomized according to randomization numbers generated by a computer program created and validated in house.
- Fasting period before study: Food withdrawn prior to weighing at the start of the pilot and main studies, 4-5 hours before the first treatment and were given food again 1 hour after treatment
- Housing: Individually in Makrolon type IIA cages
- Diet (e.g. ad libitum): Fixed- formula feed "Maus/Ratte Haltung (NAFAG 9441), 3883.0.15" for mice and rats, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: At least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5-23.0 °C
- Humidity (%): 41-52%
- Air changes (per hr): 10/hour
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: N/A To: N/A

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Deionised water
Details on oral exposure:
Single administration
Doses:
100, 200, 400, 600, 2000 mg/kg bw
No. of animals per sex per dose:
Three
Control animals:
no
Details on study design:
Range finding study to determine maximum tolerated dose levels preceeding an in-vivo Comet assay.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
> 600 - < 2 000 mg/kg bw
Based on:
test mat.

Any other information on results incl. tables

- Dose range: Initially 2000 mg/kg bw was administered which caused the rats to die shortly after administration so another range finding study was conducted using doses of 100 and 200 mg/kg bw. Since the maximum tolerated dose was not reached another range finding study was conducted at levels of 400 and 600 mg/kg bw.

- Clinical signs of toxicity in test animals: Roughened fur, rapid breathing, twitching at the 100 and 200 dose levels. At the 400 mg/kg dose level, rats were observed with roughened fur, rapid breathing, and discolored feces. At the 600 mg/kg bw dose level, rats were observed with roughened fur, rapid breathing, palmospasms, discolored feaces and langour. Based on these results 600 mg/kg bw was selected as maximum tolerated dose for this test in male rats.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The oral LD50 (rat) was estimated to be in the range of >600-<2000 mg/kg bw.
Executive summary:

In a dose selection experiment preceeding an in-vivo Comet assay three animals receiving 2000 mg/kg bw of the test substance died whereas a dose of 600 mg/kg bw was found to be the maximum tolerated dose. The oral LD50 (rat) was estimated to be in the range of >600-<2000 mg/kg bw.

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