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: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.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 402 (Acute Dermal 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 S.p.A., Calco (Como), ltaly
- Age at study initiation: 6 to 8 weeks
- Weight at study initiation: 176 - 200g
- Housing: Individually in polycarbonate cages measuring 59x39x20 cm with a stainless steel mesh lid and floor. Cages were suspended over trays and each tray held an 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

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

The fur was removed from the dorsaI surfaces of the trunk over an area estimated to be at least 10% of the total body surface of each animal. An electric cllpper with suitable blade was used and care was taken to avoid any irritation or damage to the skin.
The next day (Day 1), the amount of supplied test substance to be administered, at a dose level of 2000 mg/kg body weight was calculated for each animal according to body weight. This was mixed to a paste with sterile water and spread evenly over the prepared skin of each animal. The mixing with water and volume of water used was not recorded due to oversight. The dosed site was then covered by a porous gauze dressing, held in place by encircling the trunk of the animal with an elastic adhesive bandage overlying aluminium foil. After a period of twenty four hours, the adhesive bandage and gauze dressings were removed. The treated skin was washed gently with warm water to remove residual test substance.

Duration of exposure:

24 hours

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
- Mortality/viability were measured throughout the study twice daily
- Body weights were measured at allocation of 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 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. Particular attention was paid to the treated site.

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 during the fourteen day observation period following dosing.

Clinical signs:

other: No clinical signs were observed during this post-dose observation period that could be attributed to an effect of the test substance. The only finding was hair loss from the ventral surfaces of one female animal, observed on day 15. Such hair loss may be

Gross pathology:

No abnormalities were found on necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The toxicity of the test substance was estimated to be greater than 2000 mg/kg bw

Executive summary:

In a GLP compliant dermal toxicity study, performed according to OECD guideline 402, Sprague-Dawley rats (5/sex) were administered the test substance (2000 mg/kg bw). The test substance was dissolved in water, applied on the skin and covered with an occlusive dressing for 24 hours. The treated skin was washed after 24 hours and a 14-day observation period followed. No mortality was observed during this period. Also no clinical signs and significant changes in body weight were observed. Furthermore, no abnormalities were found on necropsy. Therefore, the toxicity of the test substance was estimated to be >2000 mg/kg bw.