Registration Dossier

Administrative data

Description of key information

Non skin irritating

Eye irritation potential is still under investigation

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 June 12th to July 02nd, 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted April 24, 2002
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage Scientifique des Dombes F-01400 Chatillon sur Chalaronne / France.
- Age at study initiation: 22-23 weeks old male; 9-10 and 20-21 weeks old females.
- Housing: individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks 4646 were provided for gnawing.
- Diet: pelleted standard Provimi Kliba 3418 rabbit maintenance diet, ad libitum (batch no.28103) 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. Four days before treatment, one 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 again clipped; 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.

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 *C
- Humidity: 30-70 %
- Air changes: approximately 10-15 air changes per hour.
- Photoperiod: the animals were provided with an automatically controlled light cycle of 12 hours light and 12 hours dark.
- Other: music was played during the daytime light period.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 g (per animal) of test item was weighed as delivered by the sponsor and then moistened with approximately 0.1 ml of purified water before application.
The pH of the test item was measured before the study initiation date. A formulation of 1 % in water was prepared. The pH was found to be 5 to 6.
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
1 male and 2 females
Details on study design:
TEST SITE
- Area of exposure: 0.5 g of test item was placed on a surgical gauze patch (ca. 4 cm x 4 cm). The gauze patch was applied to the intact skin of the clipped area.
- Type of wrap if used: 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 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.
- Time after start of exposure: 4 hours

OBSERVATIONS
- 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.

OBSERVATION TIME POINTS
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, as well as 7, 10 and 14 days after the removal of the dressing, gauze patch and test item.

SCORING SYSTEM
Grading of Skin Reactions
ERYTHEMA AND ESCHAR FORMATION
No erythema 0
Very slight erythema 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) or eschar formation (injuries in depth preventing erythema) reading 4

OEDEMA FORMATION
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (edges raised approximately 1 mm) 3
Severe oedema (raised more than 1 mm and extending beyond the area of exposure) 4
Irritation parameter:
erythema score
Basis:
animal: 3/3
Time point:
24/48/72 h
Score:
< 2.3
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal: 3/3
Time point:
24/48/72 h
Score:
< 2.3
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
With the exception of the yellow staining, 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.

COLORATION
Slight yellow staining produced by the test item of the treated skin was observed in all animal from the 1-hour reading up to 10 days after treatment. Slight yellow staining was still present in two animals at the 14 day examination, the end of the observation period.

CORROSION
Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.
Other effects:
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. One animal (no. 69) slightly lost body weight (1.4 %) between the treatment start and the end of the study. The body weilnt loss was considered to be incidental and treatment unrelated.

Individual reactions

Animal Reaction After
1 hr 24 hrs 48 hrs 72 hrs 7 days 10 days 14 days
67 M Erythema 0 0 0 0 0 0 0
68 F Erythema 0 0 0 0 0 0 0
69 F Erythema 0 0 0 0 0 0 0
67 M Oedema 0 0 0 0 0 0 0
68 F Oedema 0 0 0 0 0 0 0
69 F Oedema 0 0 0 0 0 0 0
Interpretation of results:
other: not classified, according to the CLP Regulation (EC) No 1272/2008
Conclusions:
Not irritating
Executive summary:

The primary skin irritation potential of the substance was investigated according to OECD test guideline no. 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 durition of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours, as well as 7, 10 and 14 days after removal of the dressing.

With the exception of the yellow staining the test item did not elicit any skin reactions at the application sitä 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 test item caused yellow staining of the treated skin in all animals. This effect was not reversible and was still evident in two animals 14 days after treatment, the end of the observation period for all animals. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no other clinical signs of test item related effects were observed.

Conclusion

Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 06, 2001), with the exception of the yellow staining which persisted in two animals throughout the observation period, test item is considered to be "not irritating" to rabbit skin.

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

Additional information

SKIN IRRITATION

The primary skin irritation potential of the Fluorescent Brightener 367 was investigated according to OECD test guideline no. 404. The test item was applied by topical semi-occlusive application of 0.5 g to the intact skin of three New Zealand White rabbits. The durition of treatment was four hours.

With the exception of the yellow staining the test item did not elicit any skin reactions at the application sitä 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 test item caused yellow staining of the treated skin in all animals. This effect was not reversible and was still evident in two animals 14 days after treatment, the end of the observation period for all animals. However, no corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no other clinical signs of test item related effects were observed.

Justification for classification or non-classification

According to the CLP Regulation (EC) No 1272/2008, 3.2 Skin corrosion/irritation section, skin irritation means the production of reversible damage to the skin following the application of a test substance for up to 4 hours.

In the study conducted with Fluorescent Brightener 367, the mean values from gradings at 24, 48 and 72 hours after patch removal were lower than 2.3 in all animals, for both erythema/eschar and oedema reactions.

According to the CLP Regulation (EC) No 1272/2008, serious eye damage means the production of tissue damage in the eye, or serious physical decay of vision, following application of a test substance, which is not fully reversible within 21 days of application.

The eye irritation potential of the substance is still under investigation; thus, a conclusion from the classification point of view will be updated as soon as experiment(s) will be ended.

In conclusion, the substance does not meet the criteria to be classified for the skin irritation, according to the CLP Regulation (EC) No 1272/2008.