Hexasodium 6,13-dichloro-3,10-bis[[2-[[4-chloro-6-[(2,4-disulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]ethyl]amino]triphenodioxazine-4,11-disulphonate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1994

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Structural Analogue 01

IUPAC Name:

Structural Analogue 01

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

See below

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Barriered Animal Breeding Unit, Zeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, UK
- Age at study initiation: young adults
- Weight at study initiation: males 265-328g; females 167-188g
- Housing: single
- Diet: Porton Combined Diet
- Water: automatic supply of water ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23°C
- Humidity (%): 40 to 70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 28. April 1994 To: 13. May 1994

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

The substance was tested as a paste with deionised water.

Duration of exposure:

24 h

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
- Clinical signs: once daily
- Body weight: on day 1, 3, 6, 8 and 15
- Necropsy of survivors performed: yes

Sixteen to thirty-two hours before application of the test sample, the hair was removed with a pair of veterinary clippers from an area, approximately 10cmx 5cm , on the dorso-lumbar region of each animal.

A dose-level of 2000mg/kg was selected.
The appropriate amount was calculated for each animal according to its weight at the time of dosing. The paste, covered by a gauze patch (approximately 4cm x 6cm x 4-ply) was applied to the shorn back of each animal and was kept in contact with the skin for 24 hours using an occlusive dressing. The gauze patch was covered by a patch of plastic film (7.5cm x 5cm) and was held jn position using adhesive bandage (25cm x 5cm). This was secured by twop~ece~ of PVC tape (approximately 2.5cm x 20cm) wrapped around the animal.

At the end of the 24-hour contact period, the dressings were carefully cut, using blunt-tipped scissors, removed and discarded. The skin, at the site
of application, was cleansed free of any residual test sample using clean swabs of absorbent cotton wool soaked in clean warm water and was then
dried gently with clean tissue paper.

The animals were observed for signs of systemic toxicity once between one and four hours after application (only gross abnormalities were noted at
this time as the presence of the dressings may have affected the behaviour and movement of the rats) and then once daily for systemic toxicity and
skin irritation, up to day 15. The animals were weighed immediately before application of the test sample (day I), and at intervals thereafter. At the end of the study, all of the animals were humanely killed by inhalation of halothane vapour followed bJ exsanguination and were subjected to a post mortem examination.

Statistics:

mean and standard deviation of body weight data

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occured.

Clinical signs:

other: None of the animals died. The test sample stained the skin of the application sites of all animals blue which, in some cases, was still present at the end of the study (day 15). The tails of some animals were stained blue. Signs of slight skin irritation

Gross pathology:

The only findings at the post mortem examination were blue staining by the test substance and scabbing of the skin at the application site. There
were no other findings.

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results obtained in this study, the dermal median lethal dose value (LD50) for the male and female rat is greater than 2000 mg/kg bw.

Executive summary:

Acute dermal toxicity testing of structural analogue 01 in the rat yielded a dermal median lethal dose (LD50) above 2000 mg/kg bw in both male and female rats. After administration of 2000 mg/kg bw neither deaths nor clinical signs occurred. Only the surface of the skin was blue discolored to a smaller or larger extend. Development of body weight was not impaired. The animals killed at the end of the observation period showed no macroscopically visible changes.

Based on the results obtained in this study, the dermal median lethal dose value (LD50) for the male and female rat is greater than 2000 mg/kg bw.