6,13-dichloro-3,10-bis-{2-[4-fluoro-6-(2-sulfo-phenylamino)-1,3,5-triazin-2-ylamino]-propylamino}-benzo[5,6][1,4]oxazino[2,3-.b.]phenoxazine-4,11-disulphonic acid, lithium, sodium salt.

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:

other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

6,13-dichloro-3,10-bis-{2-[4-fluoro-6-(2-sulfo-phenylamino)-1,3,5-triazin-2-ylamino]-propylamino}-benzo[5,6][1,4]oxazino[2,3-.b.]phenoxazine-4,11-disulphonic acid, lithium, sodium salt.

EC Number:

418-000-8

EC Name:

6,13-dichloro-3,10-bis-{2-[4-fluoro-6-(2-sulfo-phenylamino)-1,3,5-triazin-2-ylamino]-propylamino}-benzo[5,6][1,4]oxazino[2,3-.b.]phenoxazine-4,11-disulphonic acid, lithium, sodium salt.

Cas Number:

163062-28-0

Molecular formula:

CAS formula: C42 H34 Cl2F2 N14 O14 S4 .xLi. xNa

IUPAC Name:

dilithium(1+) disodium 6,13-dichloro-3,10-bis({[2-({4-fluoro-6-[(2-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)propyl]amino})-5,12-dioxa-7,14-diazapentacene-4,11-disulfonate

Details on test material:

- Name of test material (as cited in study report): FAT 40529/A
- Lot/batch No.: P 1/95
- Storage: Ambient conditions

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Italia, Calco Como ltaly
- Age at study initiation: 5 to 6 weeks
- Weight at study initiation: 126 - 150g
- Fasting period before study: Overnight
- Housing: Group of five of one sex in clear polycarbonate cages measuring 59x20x39 cm with a stainless steel mesh lid and floor. Each cage tray held absorbent material which was inspected daily and changed as necessary.
- Diet (e.g. ad libitum): Commercially available laboratory rodent diet (Altromin MT, A. Rieper S.p.A., Bolzano, Italy) ad libitum
- Water (e.g. ad libitum): Drinking water supplied to each cage via a water bottle, ad libitum
- Acclimation period: Seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 45-65
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5%

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: throughout the study all animals were checked twice daily for mortality. All animals were weighed at allocation to the study (day -1), immediately prior to dosing (Day 1) and at weekly intervals thereafter (Days 8 and 15). Animals were observed for clinical signs immediately upon dosing, approximately one, two and four hours after dosing and daily thereafter for a total of fourteen days.
- Necropsy of survivors performed: AII animaIs were killed by carbon dioxide narcosis on terminatlon of the defined post-dose observation perlod. Animals were subjected to a gross examination for external abnormalities. The cranial, thoracic and abdominal cavities were opened to allow examination of their contents and larger organs were sectioned. The stomach and representitive sections of the gastrointestinal tract were opened for examinatlon of the mucosal surfaces.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured.

Clinical signs:

other: No significant clinical signs were observed following dosing. Mucoid and blue stained faeces were observed in the litter tray under the cages of animals of both sexes. This was apparent approximately four hours after dosing and was no longer present from

Gross pathology:

No abnormalities were noted on necropsy examination of animals on termination of the study. Findings were limited to blue staining on the tail of all female animals. This staining would have arisen from the coloured test substance but was not a symptom of toxicity or intolerance.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the observations the toxicity of the test substance was estimated to be greater than 2000 mg/kg bw.

Executive summary:

In a GLP compliant oral toxicity study, performed according to OECD guideline 401, Sprague-Dawley rats (5/sex/) were administered the test substance (2000 mg/kg bw) by oral gavage followed by a 14-day observation period. Mortality did not occur. No significant clinical signs were observed and necropsy did not reveal any significant abnormality. Based on these observations, the acute oral toxicity of the test substance in rats of both sexes observed for a period of 14 days was greater than 2000 mg/kg bw.