Yellow PE 3260

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996-07-23-1996-08-27

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

1

Reference substance name:

bis[2-hydroxy-N,N-bis(2-hydroxyethyl)ethanaminium] 7-{[4-(4-{[2-(cyanoamino)-4-hydroxy-6-oxo-1,6-dihydropyrimidin-5-yl]diazenyl}benzamido)-3-methoxyphenyl]diazenyl}naphthalene-1,3-disulfonate

Cas Number:

115811-45-5

Molecular formula:

C29H19N9O10S2.2C6H16NO3

IUPAC Name:

bis[2-hydroxy-N,N-bis(2-hydroxyethyl)ethanaminium] 7-{[4-(4-{[2-(cyanoamino)-4-hydroxy-6-oxo-1,6-dihydropyrimidin-5-yl]diazenyl}benzamido)-3-methoxyphenyl]diazenyl}naphthalene-1,3-disulfonate

Test material form:

solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL Biological Research Laboratories Ltd., Wölferstr. 4, 4414 Füllinsdorf / Switzerland
- Age at study initiation: 8-11 weeks
- Weight at study initiation: females: 202-221g; males: 215-251g
- Housing: during acclimatization in groups of 5 animals in Makrolon type-4 cages with standard softwood bedding, during treatment and opbservation individually in Makrolon type-3 cages with standard softwood bedding
- Diet (e.g. ad libitum): pelleted standard Kliba 343 rat maintainance diet ad libitum
- Water (e.g. ad libitum): Itingen community tap water ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 40-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1996-07-30 To: 1996-08-13

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: bi-distilled water

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: approximately 10%
- Type of wrap if used: semi-occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4.0 mL/kg bw
- Concentration (if solution): 500 g/L
- Constant volume or concentration used: yes
- For solids, paste formed: no, substance is well soluble in water

Duration of exposure:

24 h

Doses:

limit dose of 2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations: Four times during test day 1 and once daily during days 2-15.
- Frequency of observations and weighing: On test days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes

Statistics:

The LOGIT-Model for determination of LD50 could not be used as no deaths occurred.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the observation period.

Clinical signs:

other: Yellow discoloration of the skin at the application site was evident in all animals after the removal of the dressing on test day 2 and persisted until study termination.

Gross pathology:

No macroscopic organ findings were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 (rat) after single dermal application is greater than 2000 mg/kg.

Executive summary:

The acute dermal toxicity of the substance was determined according to OECD Guidelines for Testing of Chemicals, Section 4, Number 402 "Acute Dermal Toxicity", adopted February 24, 1987 and Directive 92/69/EEC, 6.3. "Acute Toxicity-Dermal", July 31, 1992.

A group of five male and 5 female Wistar rats was treated with the substance at 2000 mg/kg by demal application. The test article was suspended in water at a concentration of 0.2 g/m1 and administered at a volume of 4 ml/kg. Four times during day 1 and once daily during days 2-15 the animals were examined for clinical signs. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 before administration and on days 8 and 15. All animals were necropsied and examined macroscopically.

No deaths occurred during the study period. Yellow discoloration of the skin at the application site was evident in all animals after the removal of the dressing on test day 2 and persisted until the study termination. The body weight of the animals was within the physiological range of variability known for rats of this strain and age. The slight loss of body weight in one female animal (no. 8) during the first observation week was considered to be a consequence of the semi-occlusive dressing used during treatment. Commonly female animals prove to be more sensitive in relation to the effects on body weight caused by semi-occlusive dressing than male. No macroscopic organ findings were observed at necropsy.

The mean lethal dose of the substance after single dermal administration to rats of both sexes, observed over a period of 14 days, could not be estimated. It can therefore be concluded that the LD50 is greater than 2000 mg/kg.