SILATRIZOLE

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 8 November 1995 to 06 March 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted according to OECD Guideline 404 (adopted 1992) without any deviation.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4470 (Acute Dermal Irritation)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

16.06.1994

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

422-940-4

EC Name:

-

Cas Number:

155633-54-8

Molecular formula:

C24H39N3O3Si3

IUPAC Name:

2-(2H-1,2,3-benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-(2,2,4,6,6-pentamethyl-3,5-dioxa-2,4,6-trisilaheptan-4-yl)propyl]phenol

Test material form:

other: solid

Details on test material:

- Name of test material (as cited in study report): G4375
- Physical state: whitish solid
- Analytical purity: 98% minimum
- Impurities (identity and concentrations): Methanol (<100 ppm) and Isopropanol (<100 ppm)
- Purity test date: certificate of analysis 20/10/1995
- Lot/batch No.: DEF/C 95003/B
- Expiration date of the lot/batch: No data
- Stability under test conditions: Stable under storage condition; Stable in bidistilled water.
- Storage condition of test material: In the original container at room temperature away from direct sunlight.

Test animals

Species:

rabbit

Strain:

other: New Zealand White Rabbit - CRL:KBL(NZW)BR

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Stolzenseeweg 32-36, D-88353 Kisslegg
- Age at study initiation: 13 weeks
- Weight at study initiation: male : 2.3 kg bw; females: 2.2-2.3 kg bw
- Housing: Individually in stainless steel cages with an automatic cleaning system, equipped with feed hoppers, drinking water bowls and wood for gnawing.
- Diet (e.g. ad libitum): Pelleted standar Kliba 341, Batch 91-95 rabbit maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst), available ad libitum.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, available ad libitum.
- Acclimation period: 4 days under test conditions

ENVIRONMENTAL CONDITIONS
Temperature (°C): 20±3°C
- Humidity (%): 40-70 %
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12h dark/ 12h light

IN-LIFE DATES: From: From 8 November 1995 To: 16 November 1995

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

Bi-distilled water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- The test article was ground in a mill and thereafter moistened with bi-distilled water before application.
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:

4 h

Observation period:

1, 24, 48 and 72 hours after removal of the test article

Number of animals:

1 male and 2 females

Details on study design:

TEST SITE
- Area of exposure: approximately 6 cm2 of the intact skin of the dorsal clipped area
- Type of wrap if used: 3.0 cm x 3.0 cm patch of surgical gauze, covered with a semi-occlusive dressing wrapped around the abdomen and anchored with an elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Dressing was removed and the skin was washed with lukewarm tap water.
- Time after start of exposure: 4h

SCORING SYSTEM: Draize scale, as described in OECD test guideline 404.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Neither edema nor erythema was observed during the observation period in the treated areas of all rabbits at 24, 48 and 72 hours.
The test item showed a primary irritation score of 0.00 (max 8.0) when applied to healthy intact rabbit skin.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.
The body weight gain of all animals was within the normal range of variability.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, the test substance Silatrizole (encoded "G4375") is not classified for skin irritation according to the Regulation (EC) N° 1272-2008 (CLP) and according to the Directive 67/548/EEC.

Executive summary:

In a primary dermal irritation study performed according to OECD Guideline 404 (1992 version) and in compliance with GLP, three New Zealand White rabbits (1 male and 2 females) were dermally exposed under a semi-occlusive gauze dressing to 0.5 mg of Silatrizole (encoded "G4375"), previously ground in a mill and moistened with bi-distilled water. The test item was applied to the clipped skin under a gauze patch held in place for 4 hours. Animals were observed at 1, 24, 48 and 72 hours after removal of test substance for signs of erythema and edema.

Neither edema nor erythema was observed during the observation period in the treated areas of all rabbits at 24, 48 and 72 hours. In this study, Silatrizole is not a skin irritant on rabbits.

 

Under the test conditions, the test substance Silatrizole is not classified for skin irritation according to the Regulation (EC) N° 1272-2008 (CLP).

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.