SILATRIZOLE

Endpoint summary

Description of key information

Skin irritation : Key study OECD 404, V1, 1996 : not irritating to the rabbit skin
Eye irritation : Key study, OECD 405, V1, 1996 : not irritating to the rabbit eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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

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

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.

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

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.

None

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 15 November 1996 to 6 March 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted according to OECD Guideline 405 (adopted 1987) without any deviation.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4500 (Acute Eye Irritation)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

16.06.1994

Species:

rabbit

Strain:

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

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River, Stolzenseeweg 32-36, D-88353 Kisslegg
- Age at study initiation: 15 weeks
- Weight at study initiation: male : 3.0 kg bw; females: 2.7-3.1 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

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 15 November 1995 To: 23 November 1995

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.1 g
- The test article was ground in a mill and applied undiluted.

Duration of treatment / exposure:

Eyes of the animals were not rinsed.

Observation period (in vivo):

1, 24, 48 and 72 hours after administration

Number of animals or in vitro replicates:

1 male and 2 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: Grading of ocular lesions as described in OECD test guideline 405.

TOOL USED TO ASSESS SCORE: Eye examinations were made with a Varta Cliptrix diagnostic-lamp (A. Riegger, Basel, Switzerland)

Other: When present, corrosion and /or staining of sclera and cornea by the test article were recorded and reported.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not fully reversible within: 48 h

Irritant / corrosive response data:

The test item showed a primary irritation score of 1.11 when applied to the conjunctival sac of the rabbit eye, with a full reversibility at 72 hours.

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. No staining of the cornea was observed at any of the reading times.

Table 7.3.2/1: Results of eye irritation for each animal at each observation time

Rabbit Nº	Time	Opacity (/4)	Iritis (/2)	Conjunctival redness (/3)	Chemosis (/4)
1	1h	0	0	2	2
	24h	0	0	2	1
	48h	0	0	1	0
	72h	0	0	0	0
2	1h	0	0	2	2
	24h	0	0	2	1
	48h	0	0	1	0
	72h	0	0	0	0
3	1h	0	0	2	2
	24h	0	0	1	0
	48h	0	0	1	0
	72h	0	0	0	0

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, Silatrizole (encoded "G4375") induced slight irritations being reversible within 72 hours. Therefore the test material is not classified as irritant to the eyes according to the Regulation (EC) N° 1272-2008 (CLP) and according to the Directive 67/548/EEC.

Executive summary:

In an eye irritation study conducted according to the OECD Guideline 405 (1987 version) and in compliance with GLP, 3 healthy rabbits of the New Zealand White strain (1 male and 2 females) were exposed to 0.1 g of undiluted test item Silatrizole (encoded "G4375"), previously ground in a mill, in their left eye while the right eye remained untreated and served as control. The treated eye of the animals was left unrinsed. The eyes were examined and the changes in the cornea, iris and conjunctivae (redness and chemosis) were observed at 1, 24, 48 and 72 h.

Slight signs of ocular irritation were observed at 1h, 24h and 48h. All ocular reactions reverted after 72 hours. In this study, Silatrizole is a slight eye irritant in rabbits.

Under the test conditions, Silatrizole is not classified as irritant to the eyes according to the Regulation (EC) N° 1272-2008 (CLP).

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

In a primary skin irritation studyperformed according to OECD Guideline 404 (1992 version) and in compliance with the GLP, three New Zealand White rabbits (1 male and 2 females) were exposed for 4 hours to 0.5 mg of Silatrizole (encoded "G4375"), previously ground in a mill and moistened with bi-distilled water, under a semi-occlusive dressing. 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.

Eye irritation:

In an eye irritation study conducted according to the OECD Guideline 405 (1987 version) and in compliance with GLP, 3 healthy rabbits of the New Zealand White strain (1 male and 2 females) were exposed to 0.1 g of undiluted test item Silatrizole (encoded "G4375"), previously ground in a mill, in their left eye. Slight signs of ocular irritation were observed at 1h, 24h and 48h. All ocular reactions reverted after 72 hours. In this study, Silatrizole is not an eye irritant in rabbits.

Justification for selection of skin irritation / corrosion endpoint:
Only one study available, GLP-compliant and of high quality (Klimisch score = 1)

Justification for selection of eye irritation endpoint:
Only one study available, GLP-compliant and of high quality (Klimisch score = 1)

Justification for classification or non-classification

As the submission substance is expected to be not irritating to the skin, it is not classified for skin irritation according to the Regulation (EC) N° 1272-2008 (CLP).

As the submission substance is expected to be not irritating to the eye, it is not classified for eye irritation according to the Regulation (EC) N° 1272-2008 (CLP).