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Administrative data

Description of key information

Skin Irritation: not irritant; OECD Guideline 404, RCC 2001.
Eye Irritation: not irritant; OECD Guideline 405, RCC 2001.

Studies conducted according to GLP.

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:
04.12.2001 - 13.12.2001 (experimental)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted July 17,1992
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
July 31, 1992
Deviations:
not specified
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage Scientifique des Dombes, Chatillon sur Chalaronne / France
- Age at study initiation: 11-12 weeks (males), 10-11 weeks (females)
- Weight at the day of treatment: male: 2305 g; females: 2461 g and 2127 g
- Housing: Individually
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 92/01) provided by Provimi Kliba
AG, Kaiseraugst, Switzerland. Haysticks (QS no. 125/01) provided by Eberle Nafag AG, Gossau, Switzerland.
- Water (e.g. ad libitum): Community tap water from Fuellinsdorf, ad libitum.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Remarks:
The test item was moistened with purified water.
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test item was administered at 0.5 g/animal, the dose specified in the test guidelines for a solid test item.
- Concentration (if solution): The test item was moistened with approximately 0.1 ml purified water before application.

Duration of treatment / exposure:
4 h
Observation period:
Throughout 72 hours after treatment.
Number of animals:
3 (1 male, 2 females)
Details on study design:
TEST SITE
- Area of exposure: one flank
- % coverage: approximately 100 cm² (10 cm x 10 cm).
- Type of wrap if used: On the day of treatment, 0.5 g of the test item 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 (if done): The skin was flushed with lukewarm tap water to clean the application site.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
- The skin reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992 approximately 1, 24, 48 and 72 hours after the removal of the dressing, gauze patch and test item.

OBSERVATIONS:
- Viability/Mortality: Daily from delivery of the animals to the termination of test.
- Clinical signs: Daily from delivery of the animals to the termination of test.
- Body weights: At start of acclimatization, on the day of application and at termination of observation.
- Necropsy: No necropsy was performed in the animals sacrificed at termination of observation.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The test item did not elicit any skin reactions at the application site of any animal at any of the measuring intervals (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.
Other effects:
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
No staining by the test item of the treated skin was observed.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material was determined to be not irritating to rabbit skin under the conditions of the test.
Executive summary:

In this guideline (OECD 404) study conducted with GLP, the test material (EC 438-340-0) was induced mean erythema and edema scores of 0.0 in all test animals (rabbit) across the 24, 48, & 72 hour observation periods. The test material was exposed to the test animals (intact skin, 4 hours) under semi-occlusive conditions. The result of the test is not sufficient to meet the criteria for classification as a skin irritant under the criteria of the EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

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:
04.12.2001 - 13.12.2001 (experimental)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted February 24, 1987
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
July 31, 1992
Deviations:
not specified
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage Scientifique des Dombes, Chatillon sur Chalaronne / France
- Age at study initiation: 11-12 weeks (male), 10-11 weeks (females)
- Weight at the day of treatment: male: 2250 g; females: 2172 g and 2090 g
- Housing: Individually
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 92/01) provided by Provimi Kliba
AG, Kaiseraugst, Switzerland. Haysticks (QS no. 125/01) provided by Eberle Nafag AG, Gossau, Switzerland.
- Water (e.g. ad libitum): Community tap water from Fuellinsdorf, ad libitum.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye remained untreated and served as the reference control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g (per animal)

Duration of treatment / exposure:
single treatment
Observation period (in vivo):
1 to 72 hours
Number of animals or in vitro replicates:
3 (1 male, 2 females)
Details on study design:
TEST ITEM PREPARATION and TREATMENT
- The test item was applied undiluted and handeled in a dark room under red light.
- The test item was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were
then gently held together for about one second to prevent loss of test item.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eyes were not rinsed after instillation.

SCORING SYSTEM:
- The ocular reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992 at approximately 1, 24, 48 and 72 hours after application.

TOOL USED TO ASSESS SCORE: Eye examinations were made with a Varta Cliptrix diagnostic-lamp (A. Riegger, Basel / Switzerland).
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Remarks:
male
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Remarks:
female
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Remarks:
female
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
male
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
female
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
female
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
male
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
female
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
female
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
male
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
female
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
female
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Application of the test item to healthy rabbit conjunctivae resulted in a primary irritation score of 0.44.
The eye reactions (mean values from 24 to 72 hours) consisted of grade 0.00 corneal opacity, grade 0.00 iris lesions, grade 0.33 redness of the conjunctivae and grade 0.11 chemosis of the conjunctivae.
No abnormal findings were observed in the iris or cornea of any animal at any of the measuring intervals.
Slight reddening of the conjunctivae was observed in all animals 1 hour after treatment and persisted in one animal up to the 24-hour reading and in another animal up to the 48-hour reading.
Slight swelling of the conjunctivae or swelling with partial eversion of lids was noted in all animals 1 hour after treatment. Slight swelling was still evident in one animal at the 24-hour reading.
Slight to moderate reddening of the sclera was present in all animals at the 1 -hour reading and continued to be observed in one animal up to 24 hours after treatment.
A slight watery discharge was evident in one animal at the 1-hour reading.
No abnormal findings were observed in the treated eye of any animal 72 hours after treatment, the end of the observation period for all animals.
The test item did not induce significant or irreversible damage to the rabbit eye.
Other effects:
No signs of toxicity or ill health were observed in any animals.
No staining of the treated eye by the test item was observed.
Yellow remnants of the test item were present in the eye or conjunctival sac of two animals 1 hour after treatment.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material was determined to be not irritating to rabbit eyes under the conditions of the test.
Executive summary:

In this guideline (OECD 405) study conducted to GLP standards, the test material (EC 438-340-0) did not induce any significant irritation in the rabbit eye at 24/48/72 hours. The test material was exposed to the 3 rabbits with an 6 day observation period. Based upon the results of this study, the test material does not meet the criteria for classification as an eye irritant under the EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin:

In a primary dermal irritation study (OECD 404, RCC 2001), 3 New Zealand White rabbits were exposed to 0.5 mg of the test substance for 4 hours under semi-occlusive conditions. Animals then were observed for 72 hours. Irritation was scored by the method of Draize as described in the OECD guideline 404. The mean scores for the 24, 48 and 72 h reading for erythema and edema were 0.00.

In a second study a gauze patch (approx. 12-16 cm2) bearing 0.5 g of the test article, moistened before application with distilled water, was applied to the flank (OECD 404; Ciba Geigy, 1988). The patches were loosely covered with an aluminum foil and held in place for 4 hours by an adhesive tape. The test item did not elicit any skin reactions at the application site of any animal at any of the measuring intervals. The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.00.

Eye:

An eye irritation test was performed with three New Zealand White rabbits according to OECD 405 (RCC 2001). Eyes were left unwashed after application of 0.1 g of the test substance and the animals were observed 72 h. The eye reactions (mean values from 24 to 72 hours) consisted of grade 0.00 for corneal opacity, grade 0.00 for iris lesions, grade 0.33 for redness of the conjunctivae and grade 0.11 for chemosis of the conjunctivae. No staining of the treated eye by the test item was observed.

 

In a second study 0,1 ml (45 mg) of the test substance was placed into the conjunctival sac of the left eye of each animal (OECD 405; Ciba Geigy, 1988). The right eye remained untreated and served as a control. Slight effects on the iris were noted in all animals 1 hour after treatment and persisted in one animal up to the 24-hour reading. Slight to moderate reddening of the conjunctivae was observed in all animals 1 hour after treatment and persisted in two animal up to the 72-hour reading and in another animal up to the 24-hour reading. Slight to moderate swelling of the conjunctivae was noted in all animals 1 and 24 hours after treatment. Slight swelling was still evident in one animal at the 48-hour reading. The eye reactions observed were reversible until the end of the observation period on day 7. The eye reactions (mean values from 24 to 72 hours) consisted of grade 0.00 for corneal opacity, grade 0.11 for iris lesions, grade 0.88 for redness of the conjunctivae and grade 0.44 for chemosis of the conjunctivae.

 

Respiratory system

No data available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008, as amended for the fifth time in Directive EC 944/2013.