6-(2-chloro-6-cyano-4-nitrophenylazo)-4-methoxy-3-[N-(methoxycarbonylmethyl)-N-(1-methoxycarbonylethyl)amino]acetanilide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 January 1999 to 10 February 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP methodology followed and OCED guideline 402 used to performed the experiment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

430-500-8

EC Name:

-

Cas Number:

204277-61-2

Molecular formula:

Hill formula: C23 H23 Cl N6 O8 CAS formula: C23 H23 Cl N6 O8

IUPAC Name:

methyl 2-({4-[2-(2-chloro-6-cyano-4-nitrophenyl)diazen-1-yl]-5-acetamido-2-methoxyphenyl}(2-methoxy-2-oxoethyl)amino)propanoate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Identification: FAT 41024/B
Batch number: ARL 83-PP 1/98
Purity: Approx 94%
Colr / Physical form: Balck/Solid
Stability of the testarticle: Stable under storage conditions
Stability of the test article dilution: 24 hours at room temperature
Expiry date: September 04, 2004
Storage conditions: At room temperature away from direct sunlight
Safety precations: Gloves, goggles and face mask.

Test animals

Species:

rat

Strain:

other: HanIbm: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, CH-4414 Switzerland
- Age when treated: 9 weeks (male) and 12 weeks (female)
- Body weight rage when treated: 230.9-246.8 g (male) and 193.5-206.1 g (female)
- Identification: By unique cage number and corresponding color-coded spots on the tail.
- Acclimatization: 7 days under laboratory conditions, after health examination.
- Diet: ad libitum
- Water : ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%):40-70%
- Air changes (per hr):10-15 air changes per hour
- Photoperiod (hrs dark / hrs light):12 hour light and 12 hour dark, music was palyed approximately 8 hours during the light period.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Details on dermal exposure:

TEST SITE
- Area of exposure: Backs of the animals
- % coverage: 10% of the total body surface
- Type of wrap if used: semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
24 hours after the application the dressing was removed and the skin was washed with lukewarm tap water and dried with disposable paper towels.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4.0 ml. The test article was prepared in vehicle PEG 300

Duration of exposure:

24 hours

Doses:

Rats were treated with FAT 41024/B at 2000 mg/kg by dermal application.

No. of animals per sex per dose:

5 males and 5 females.

Control animals:

yes, concurrent vehicle

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Four times during test day 1 and once daily during days 2-15
Body weight: On test day 1 (pre-administartion), 8 and 15.
Clinical signs: Each animal was examined for changing in appearance and behaviour four times during day 1, and once daily during days 2-15. All abnormalities were reccorded.
- Necropsy of survivors performed: yes Necropsy were performed by experineced prosectors. At the end of teh observation period all animals were sacrified by intrperitoneal injection of NARCOREN at a dose of at least 2.0 ml/kg body weight (equivalent to at least 320mg sodium pentobarbitone/kg body weight)
- Other examinations performed: clinical signs, body weight.

Statistics:

No statistical analysis was used as no deaths occured.

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 occured during the study.

Clinical signs:

other: In all animals, residual test article was observed on the treated skin on test day two and persisted in two females until test day 14. No systemic signs of toxicity were observed during the study period.

Gross pathology:

No macroscopic finding were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The median lethal dose of FAT 41024/B after single dermal administartion to rats of both sexes, observed over a period of 14 days, could not be estimated as no deaths occured. LD50 is greater than 2000 mg/kg.

Executive summary:

The purpose of this study was to assess the acute dermal toxicty of FAT 41024/B when administred to rats by a single semi-occlusive dermal application, followed by an observation period of 14 days.

This experiment was performed according to the OECD Guideline 402 (Acute Dermal Toxicity).

A group of five male and five female HanIbm: WIST (SPF) rats was treated with FAT 41024/B at 2000 mg/kg by dermal application. The test article was prepared in vehicle (PEG 300) at a concentration of 0.5 mg/ml and administred at a volume of 4 ml/kg. The animals were examined for clinical signs four times during day 1 and once daily during days 2 -15.

Mortality /Viability were recorded together with clinical signs at the same time intervals.

Body weight were recorded on day 1 prior to administration and on days 8 and 15.

All animals were necropsied and examined macroscopically.

No deaths occured during the study.

In all animals, residual test article was observed on the treated skin on test day two and persisted in two females until test day 14. No systemic signs of toxicity were observed during the study period.

The body weight of the animals was within the range commonly recorded for animals of this strain and age.

No macroscopic findings were observed at necropsy.

The median lethal dose of FAT 41024/B after single dermal administartion to rats of both sexes, observed over a period of 14 days, could not be estimated as no deaths occured. LD50 is greater than 2000 mg/kg.