Reaction mass of 5-[(Disubstituted-dihydrocarbopolycyclyl)diazenyl]-6-hydroxy-4-methyl-2-substituted-1-propyl-1,2-dihydropyridine-3-carbonitrile and 1-Butyl-5-[(disubstituted-dihydrocarbopolycyclyl)diazenyl]-6-hydroxy-4-methyl-2-substituted-1,2-dihydropyridine-3-carbonitrile

Skin irritation / corrosion

Some information in this page has been claimed confidential.

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

OECD Guidelines for Testing of Chemicals, Section 4, number 404 "Acute Dermal Irritation /
Corrosion", adopted April 24, 2002.

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

Commission Directive 2004/73/EC, B.4. "Acute Toxicity: Dermal Irritation/Corrosion", April
29, 2004.

Deviations:

no

Principles of method if other than guideline:

Guidelines followed

GLP compliance:

yes (incl. QA statement)

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

solid

Details on test material:

Batch: P2/05 UL
Appearance: light orange crystalline powder
Expiration date: 31.05.2011
Storage: at room temperature

Specific details on test material used for the study:

- Identity: FAT41039/A
- Description: Light orange crystalline powder
- Batch number: P2/05 UL
- Purity / Formulation: content of organic pigments > 99 %; main components: 97 %
- Stability of test item: Stable under storage conditions.
- Expiry date: 31-MAY-2011
- Stability of test item dilution: Stable in PEG 300 for at least 7 days at room temperature.
- Storage conditions: At room temperature (range of 20 ± 5 °C), light protected.
- Safety precautions: Routine hygienic procedures were used to ensure the health and safety of the personnel.

Test animals

Species:

rabbit

Strain:

New Zealand White

Remarks:

SPF

Details on test animals or test system and environmental conditions:

TEST SYSTEM
- Test system: Young Adult New Zealand White Rabbit, SPF
- Rationale: Recognized by the international guidelines as the recommended test system
- Source: Charles River Deutschland GmbH, Stolzenseeweg 32-36, D-88353 Kisslegg / Germany
- Number of animals per test: 3 (Animals of both sexes were used)
- Age at treatment: 12 weeks (male), 12 -13 weeks (females)
- Identification: By unique cage number and corresponding ear number.
- Acclimatization: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

HUSBANDRY
Conditions:
Standard Laboratory Conditions
Air-conditioned with ranges for room temperature 17-23 °C, relative humidity 30-70 % and approximately 10-15 air changes per hour. Room temperature and humidity were monitored continuously and values outside of these ranges may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study and, therefore, these data are not reported but are retained at RCC. The animals were provided with an automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the daytime light period.

Accommodation:
Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no. 35/05, Provimi Kliba AG) were provided for gnawing.

Diet:
Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 34/05) provided by Provimi Kliba AG, CH-4303 Kaiseraugst. Results of analysis for contaminants are archived at RCC Ltd.

Water:
Community tap water from Füllinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Remarks:

Four days before treatment, the left flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The skin of the animals was examined one day before treatment, and regrown fur of all animals was clipped again.

Vehicle:

other: The test substance was moistened with purified water.

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

3

Details on study design:

TEST SITE
On the day of treatment, 0.5 g of FAT 41039/A was placed on a surgical gauze patch (ca.4 cm x 4 cm). This gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
- Washing: the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
1, 24, 48 and 72 h

SCORING SYSTEM:
The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004, approximately 1, 24, 48 and 72 hours
after the removal of the dressing, gauze patch and test item.
If evident, corrosive or staining properties of the test item were described and recorded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.

Other effects:

Orange staining produced by the test item was visible up to 24 hours after treatment in two animals and up to 48 hours after treatment in the third animal.

Any other information on results incl. tables

CORROSION

Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.

VIABILITY/MORTALITY/CLINICAL SIGNS

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

BODY WEIGHTS

The body weights of all rabbits were considered to be within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 41039/A is considered to be "not irritating" to rabbit skin.

Executive summary:

The primary skin irritation potential of FAT 41039/A was investigated according to OECD Guideline 404. The test item was applied by topical semi-occlusive application of 0.5 g to the intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.The application of FAT 41039/A to the skin resulted in no signs of irritation. The test item caused slight orange staining of the treated skin in all animals at the 1- and 24-hour reading and persisted in one animal at the 48-hour reading. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the skin. Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), FAT 41039/A is considered to be "not irritating" to rabbit skin.