Registration Dossier

Administrative data

Description of key information

The test substance was found to be not irritating or corrosive to the skin and 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Remarks:
RCC Ltd, CH-4452 Itingen, Switzerland
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories France, BP 0109, F-69592 L'Arbresle
- Age at treatment: 13 weeks (male), 11 weeks (females)
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no. 38/04, Provimi Kliba AG) were provided for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 93/04) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water: Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

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

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.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
no
Amount / concentration applied:
0.5 g test substance moistened with approximately 0.5 mL purified water.
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
1 male, 2 females
Details on study design:
TREATMENT
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. Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test. On the day of treatment, 0.5 g of FAT 40821/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. The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.

OBSERVATIONS
Viability/Mortality: Daily from acclimatization of the animals to the termination of test.
Clinical signs: Daily from acclimatization of the animals to the termination of test.
Body weights: At start of acclimatization, on the day of application and at termination of observation.

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, as well as 7 days after the removal of the dressing, gauze patch and test item. To allow further examination of the test sites all animals were re-clipped on completion of the 48- and 72-hour examination. If evident, corrosive or staining properties of the test item were described and recorded.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 hour
Score:
1.67
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours
Score:
0.67
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 and 72 hours
Score:
0.33
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 7 days
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours and 7 days
Score:
0
Max. score:
4
Irritant / corrosive response data:
- Very slight to well-defined erythema were observed in all animals one hour after treatment and very slight erythema persisted up to 24- or 72-hour examinations in two animals, respectively. Very slight swelling (oedema) was noted in all animals one hour after treatment. No abnormal findings were observed on the treated skin of any animal 7 days after treatment, the end of the observation period.
- Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.
Other effects:
- Slight black staining produced by the test item of the treated skin was observed in all animals at the observations performed 1 and 24 hours after treatment and persisted up to the 48-hour examination in two of these animals.
- No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
- The body weights of all rabbits were considered to be within the normal range of variability.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Test substance is considered to be not irritating or corrosive to the rabbit skin.
Executive summary:

In a GLP compliant skin irritation study, performed according to OECD guideline 404, the test substance (moistened, 0.5 g) was applied, semi-occlusive, to the skin of three New Zealand White rabbits for 4 hours. After 4 hours, the dressing was removed and the skin was flushed with lukewarm tap water and observations were made for an additional 7 days. The test substance showed an edema score of 0 during the whole observation period. An erythema score of 1.67 and 0.67 was observed after 1 and 24 hours, respectively. An erythema score of 0.33 was observed after 48 and 72 hours. Erythema was fully reverisble within 7 days. Slight black staining was observed in all animals up to 48 hours. No corrosive effects were noted. Also no other clinical signs of test item related effects were observed. Under the conditions of this experiment, the test substance was found to be not irritating or corrosive.

.
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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Remarks:
RCC Ltd, CH-4452 Itingen, Switzerland
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories France, BP 0109, F-69592 L'Arbresle
- Age at treatment: 11-12 weeks (male), 10-12 weeks (females)
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no. 74/04, Provimi Kliba AG) were provided for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 2/05) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water: Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

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

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.
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
17 days
Observation period (in vivo):
up to 17 days
Number of animals or in vitro replicates:
1 male, 2 females
Details on study design:
TREATMENT:
The eyes of the animals were examined one day prior to test item administration. Animals with overt signs of ocular injury or irritation which may have interfered with the interpretation of the results were not used in the test. On the day of treatment, 0.1 g of FAT 40821/A 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. The right eye remained untreated and served as the reference control. The treated eyes were not rinsed after instillation.

OBSERVATIONS:
Viability/Mortality: Daily from acclimatization of the animals to the termination of test.
Clinical signs: Daily from acclimatization of the animals to the termination of test.
Body weights: At start of acclimatization, on the day of application and at termination of observation.

SCORING SYSTEM:
The ocular reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 2004/73/EC, April 29, 2004 at approximately 1, 24, 48 and 72 hours, as well as 7, 10, 14, and 17 days after instillation. Additionally, ocular discharge, reddening of the sclerea and staining of conjunctivae, sclerea and cornea by the test item was assessed.

TOOL USED TO ASSESS SCORE:
Eye examinations were made with a Varta Cliptrix diagnostic-lamp (Roth AG, CH-4153 Reinach/Switzerland).
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1
Score:
0.33
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hours and 7, 10, 14, 17 days
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours and 7, 10, 14, 17 days
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1 hour
Score:
2
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 hours
Score:
1.33
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 48 and 72 hours
Score:
1
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 7, 10, 14, 17 days
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1 hour
Score:
1.67
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 hours
Score:
0.33
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 48, 72 hours and 7, 10, 14, 17 days
Score:
0
Max. score:
4
Irritant / corrosive response data:
- Very slight corneal opacity affecting the whole area which was attributed to marked black staining caused by the test item was noted in one animal one hour after treatment. No abnormal findings were observed in the cornea of the remaining two animals and in the iris of any animal at any of the measurement intervals. Moderate reddening of the conjunctivae was noted in two animals at the 1-hour reading whereas the remaining animal was not assessable due to the staining produced by the test item and the opacity produced by the staining at the same reading time. Slight to moderate reddening of the conjunctivae was noted in all animals at the 24-hour examination and persisted as slight reddening of the comjunctivae up to the 72-hour reading. Slight to marked swelling (chemosis) of the conjunctivae with half-closed lids was observed in the three animals one hour after instillation and persisted as slight swelling in one animal until the 24-hour reading. Moderate reddening of the sclerea was present in two animals at the 1-hour reading whereas the remaining animal was not assessable due to the swelling produced by the test item. Slight to moderate reddening of the sclerea was noted in all animals at the 24-hour examination and persisted as slight reddening of the sclerea in one animal until the 48-hour reading and in the other animal up to the 72-hour reading. Slight to moderate ocular discharge was observed in all animals one hour after treatment and persisted as slight ocular discharge in one animal until the 24-hour examination. No abnormal findings were observed in the treated eye of any animal 7 days after treatment.
- No corrosion of the cornea was observed at any of the reading times.
Other effects:
- Slight to marked black staining produced by the test item was noted in all animals at the 1-hour reading and persisted as slight black staining in two animals up to test day 14. Black remnants of the test item were observed in the eye or conjunctival sac of two animals one hour after treatment.
- No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred. One animal screamed after the application.
- The body weights of all rabbits were considered to be within the normal range of variability.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is considered to be not irritating or corrosive to the rabbit eye.
Executive summary:

In a GLP compliant eye irritation study, performed according to OECD guideline 405, test substance (0.1 g) was placed in the conjunctional sac of the left eye of 3 New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours, as well as 7, 10, 14, and 17 days after test item instillation. The test substance showed a mean cornea score of 0.33 after 1 hour and 0 at the other time points (24 -72 hours, 7 -17 days). The conjunctivae score was 2 and 1.33 after 1 and 24 hours, respectively. After 48 and 72 hours, a score of 1 was observed and a score of 0 was present at the other time points (7 - 17 days). The chemosis score was 1.67 after 1 hour, 0.33 after 24 hours and 0 at the other time points (48, 72 hours and 7 - 17 days). The iris score was 0 during the whole observation period. No corrosion of the cornea was observed at any of the measuring intervals. Under the conditions of this experiment, the test substance was found to be not irritating or corrosive.

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 GLP compliant skin irritation study, performed according to OECD guideline 404, the test substance (moistened, 0.5 g) was applied, semi-occlusive, to the skin of three New Zealand White rabbits for 4 hours (RCC 2005). After 4 hours, the dressing was removed and the skin was flushed with lukewarm tap water and observations were made for an additional 7 days. The test substance showed a mean cornea score of 0.33 after 1 hour and 0 at the other time points (24 -72 hours, 7 -17 days). The conjunctivae score was 2 and 1.33 after 1 and 24 hours, respectively. After 48 and 72 hours, a score of 1 was observed and a score of 0 was present at the other time points (7 - 17 days). The chemosis score was 1.67 after 1 hour, 0.33 after 24 hours and 0 at the other time points (48, 72 hours and 7 - 17 days). The iris score was 0 during the whole observation period. No corrosion of the cornea was observed at any of the measuring intervals. Under the conditions of this experiment, the test substance was found to be not irritating or corrosive.

Eye irritation:

In a GLP compliant eye irritation study, performed according to OECD guideline 405, test substance (0.1g) was placed in the conjunctional sac of the left eye of 3 New Zealand White rabbits (RCC 2005). Scoring of irritation effects was performedapproximately 1, 24, 48 and 72 hours, as well as 7, 10, 14, and 17 days after test iteminstillation.The test substance showed a mean cornea score of 0.33 after 1 hour and 0 at the other time points (7 -14 days). The conjunctivae score was 2 and 1.33 after 1 and 24 hours, respectively. After 48 and 72 hours, a score of 1 was observed and a score of 0 was present at the other time points. The chemosis score was 1.67 after 1 hour, 0.33 after 24 hours and 0 at the other time points. The iris score was 0 during the whole observation period. No corrosion of the cornea was observed at any of the measuring intervals. Under the conditions of this experiment, the test substance was found to be not irritating or corrosive.


Justification for selection of skin irritation / corrosion endpoint:
Only study available.

Justification for selection of eye irritation endpoint:
Only study available.

Justification for classification or non-classification

Based on the findings in the skin and eye irritation study the test substance does not need to be classified according to the Directive 67/548/EEC and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.