Benzenesulfonic acid, 2-[2-[5-(aminocarbonyl)-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridinyl]diazenyl]-4-[[4-chloro-6-[[4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]-, sodium salt (1:2)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 April 1993 to 29 April 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to EU & OECD test guidance in compliance with GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 2

Qualifier:

according 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

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 species: Winstar rat
Strain: Hoe:WISKf(SPF71)
Source: HOECHST AG, Kastengrund, SPF breeding colony
Body Weight at start of study: males: x = 280g (=100%)
s = ± 4g
x min = 204g (-1.9%)
x max = 213g (+2.4%)
n = 5
females: x = 190g (=100%)
s = ± 6g
x min = 184g (-3.2%)
x max = 200g (+5.3%)
n = 5
Age at start of study: males: approx. 7 weeks
females: approx. 8 weeks
Randomisation: Randomisation schemes 6358/92 and 639/93
Animal maintenance: In fully air-conditioned rooms in Makrolon cages (Type 3) on soft wood granulate one animal per cage
Room temperature: 22 ± 3⁰C
Relative humidity: 55 ± 20%
Lighting time: 12 hours daily
Acclimatisation: not necessary (breeding at identical conditions)
Food: Altromin 1324 rat diet (Altromin GmbH. Lage/Lippe), ad libitum
Water: Tap water in plastic bottles, ad libitum
Animal identification: cage numbering

Administration / exposure

Type of coverage:

occlusive

Vehicle:

physiological saline

Details on dermal exposure:

0.5 g Reaktiv-Gelb F-66 923 FW was moistened with 0.7 ml isotonic saline.

Before dermal treatment the fur was mechanically removed from the dorsal skin of the animals over an area of approximatly 30 cm2.

The appropriate amount of the test substance was moistened on an aluminium foil (6x8 cm) and distributed as uniformly as possible. Together with the foil the test substance was applied to the shaved and intact dorsal skin. The foil was held in place with an elastic plaster bandage fixed around the animal's body (Fixomull, and Elastoplast, 8 cm in width, both manufactured by Beiersdorf).
At the end of the dermal exposure period of 24 hours the bandage was removed and the treated skin area washed with warm water in order to remove any unabsorbed remnants of the test substance.

Duration of exposure:

24 h

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

Five male and five female rats received the pasted test compound

Control animals:

no

Details on study design:

The observation period after the dermal application lasted for 14 days. Symptoms and lethality were recorded twice every day (in the morning and in the afternoon), on weekends and holidays only once. Animals found dead were dissected as soon as possible and examined for macroscopically visible changes. During the observation period the animals were weighed weekly. At the end of the observation period surviving animals were killed by carbon dioxide asphyxiation, dissected and examined for macroscopically visible changes.

Statistics:

No 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:

One male animal was found dead at day 5 of the study.

Clinical signs:

other: No symptoms were observed after application of 2000 mg/kg body weight.

Gross pathology:

The animals killed at the end of the observation period showed no macroscopically visible changes.

Other findings:

From the first day p.a. up to the end of the study the skin surface of the animals was discoloured yellow.
Dark disolouration of the liver, plethora of the lung, blood in the urinary bladder and clear liquid in the abdominal cavity was observed at necropsy in the animal found dead.

Any other information on results incl. tables

CLINICAL OBSERVATIONS TIME TO RESPONSE PRINT

[ABSOLUTE TIME AFTER START DATE]

 

GROUP: 1

DOSE LEVEL: 2000            DOSE UNIT: MG/KG       SEX: BOTH

Day Number	1	2	3	4	5	6	7	8	9	10	11	12	13	14
No. of Animals Dosed	10	10	10	10	10	10	10	10	10	10	10	10	10	10
No. of Animals Survived	10	10	10	10	9	9	9	9	9	9	9	9	9	0
No Abnormalities Detected	10	10	10	10	9	9	9	9	9	9	9	9	9	9
Skin Discolouration Large:Text	-	10	10	10	9	3	3	3	3	3	3	3	3	3
Skin Discolouration Small: Text	-	-	-	-	-	6	6	6	6	6	6	6	6	6
Found Dead	-	-	-	-	1	-	-	-	-	-	-	-	-	-
Killed at End of Study	-	-	-	-	-	-	-	-	-	-	-	-	-	9
Dissection: No. Macroscopic Findings	-	-	-	-	-	-	-	-	-	-	-	-	-	9

Text: Skin discoloured yellow

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 > 2000mg/kw body weight

Executive summary:

Testing for acute dermal toxicity provides information on health risks resulting from acute dermal exposure and serves as a basis for classification and labelling. It permits the selection of optimum dose levels for repeated dermal toxicity testing and gives the first indications on the percutaneous resorptive pro­perties of a substance. The Wistar rat has proved to be a suitable species for acute dermal toxicity testing with many different substances.

 

The present study was conducted in compliance with OECD Guidelines for Testing of Chemicals, 402 "Acute Dermal Toxivity", OECD 1987 updated guideline and EEC Guideline B.3, Acute Dermal Toxoicty in Council Directive 84/449/EEC. This study was conducted in compliance with the Principles of Good Labotarory Practice (GLP).

 

Acute dermal toxicity testing of Reaktiv-Gelb F-66 923 FW in the Wistar rat yielded a median lethal dose above 2000 mg/kg b.w. in both male and female animals.

 

No clinical signs were observed after application of 2000 mg/kg body weight.

 

From the first day p.a. up to the end of the study the skin surface of the animals was discoloured yellow.

 

One male animal was found dead on day 5 of the study. Development of body weight was not impaired.

 

Dark disolouration of the liver, plethora of the lung, blood in the urinary bladder and clear liquid in the abdominal cavity was observed at necropsy in the animal found dead.

 

The animals killed at the end of the observation period showed no macroscopically visible changes.

 

The substance is not considered to be harmful by dermal exposure.