1-Propanaminium, 3-[[9,10-dihydro-4-(methylamino)-9,10-dioxo-1-anthracenyl]amino]-N,N-dimethyl-N-propyl-, bromide (1:1)

Acute Toxicity: oral

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

Test material information

Constituent 1

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- Fasting period before study: Food withdrawn prior to weighing at the start of the pilot and main studies, 4-5 hours before the first treatment and were given food again 1 hour after treatment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.