3-Pyridinecarbonitrile, 4-methyl-2,6-bis[(4-methylphenyl)amino]-5-[2-[2-(trifluoromethyl)phenyl]diazenyl]-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-09-25 to 2003-10-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline and GLP-compliant study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

RCC Ltd.

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

444-370-5

EC Name:

-

Cas Number:

669005-94-1

Molecular formula:

C28 H23 F3 N6

IUPAC Name:

4-methyl-2,6-bis[(4-methylphenyl)amino]-5-{2-[2-(trifluoromethyl)phenyl]diazen-1-yl}pyridine-3-carbonitrile

Details on test material:

- Description: Orange solid
- Expiry date: 01-OCT-2005
- Storage conditions: At room temperature (range of 20 ± 3 °C), protected from light.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services; CH-4414 Füllinsdorf / Switzerland
- Age at study initiation: Males: 8 weeks; Females: 12 weeks
- Housing: 5 rats/sex in Macrolon type-4 cages during acclimatisation, individually in Macrolon type-3 cages during treatment and observation.
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet; ad libitum
- Water: Community tap water from Fullinsdorf ad libitum.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): between 30-70 %
- Air changes (per hr): Air-conditioned with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): light cycle of 12 hours light and 12 hours dark

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

polyethylene glycol

Remarks:

300 (PEG 300)

Details on dermal exposure:

TEST SITE
- Area of exposure: 10 % of the total body surface

REMOVAL OF TEST SUBSTANCE
- Twenty-four hours after the application the dressing was removed and the skin was flushed with lukewarm tap water and dried with disposable paper towels.

TEST MATERIAL
- Amount applied: 6 mL/kg bw of a dose formulation containing a test item concentration of approx. 333 mg/mL.

Duration of exposure:

The application period was 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
- Frequency of observations and weighing: On test days 1 (prior to administration), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed:
*Mortality/viability: daily during acclimitization and twice daily during days 1-15.
*Clinical signs: Daily during acclimatization and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. All abnormalities were recorded.

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No systemic or local signs of toxicity were observed during the study period. Orange discoloration produced by the test item on the test site was observed in all animals immediately after removal of the dressing on test day 2 and persisted up to test day

Gross pathology:

No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median lethal dose of test item after single dermal administration to rats of both sexes, observed over a period of 14 days is:
LD0 (rat): greater than 2000 mg/kg body weight.