Registration Dossier

Administrative data

Description of key information

CYASORB® UV-2908 is not irritating to the skin or 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:
02 - 20 July 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No 8147, April 2011, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: Animals used withihn the study were at least 6 weeks old (8-12 weeks).
- Weight at study initiation: Body weights were at least 1.0 kg ( 1893 - 2581 grams).

- Housing: Animals were housed individually in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad, Italy). Hay and wooden sticks were abailable during the study period.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle.

Deviations from the maximum level of daily mean relative humidity occurred.
Evaluation: Laboratory historical data do not indicate an effect of the deviations.

IN-LIFE DATES: From: 02 to 20 July 2012
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: The test substance was moistened with 0.9 mL watery ethanol (50% v/v).
Controls:
other: Adjacent areas of the untreated skin of each animal served as controls.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 grams

VEHICLE
The test substance was moistened with 0.9 mL of the vehicle.
Duration of treatment / exposure:
Single application.
Observation period:
14 days.
Number of animals:
3 males.
Details on study design:
STUDY DESIGN
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner two weeks later, after considering the degree of skin irritation observed in the first animal.

TEST SUBSTANCE PREPARATION
Since the test substance did not mix with water, the powdery test substance was moistened with watery ethanol (50% v/v) (water: Elix, Millipore S.A.S., Molsheim, France; ethanol: Merck, Darmstadt, Germany), immediately before application, to ensure close contact with the animal's skin.

TEST SITE
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm). .

The test substance was applied to the skin of one flank, using a metalline patch of 2x3 cm.

REMOVAL OF TEST SUBSTANCE
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water.

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to application) and after the final observation. .
- Necropsy: No necropsy was performed according to protocol.
- Irritation:
The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #1, #2, #3
Time point:
24/48/72 h
Score:
> 0 - <= 0.3
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Four hours exposure to 0.5 g of CYASORB® UV-2908 Light Stabilizer resulted in very slight erythema or very slight oedema in the treated skin areas of two rabbits. The skin irritation resolved within 24 or 48 hours after exposure in these animals. The other animal showed no irritation after exposure.

There was no evidence of a corrosive effect on the skin.
Other effects:
Coloration/remnants:
No staining of the treated skin by the test substance was observed and no test substance remnants were seen.

Toxicity/mortality:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Interpretation of results:
GHS criteria not met
Conclusions:
In a skin irritation study with rabbits, performed according to OECD/EC test guidelines, no or limited irritation was observed.

Based on these results CYASORB® UV-2908 Light Stabilizer does not have to be classified and has no obligatory labelling requirement for skin irritation according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.
Executive summary:

Three rabbits were exposed to 0.5 grams of CYASORB® UV-2908 Light Stabilizer, moistened with 50% watery ethanol by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours after exposure.

 

 Exposure to CYASORB® UV-2908 Light Stabilizer resulted in very slight erythema or very slight oedema in the treated skin areas of two rabbits. The skin irritation resolved within 24 or 48 hours after exposure in these animals. The other animal showed no irritation after exposure.

 

No staining of the treated skin by the test substance was observed and no test substance remnants were seen.

 

Based on these results CYASORB® UV-2908 Light Stabilizer does not have to be classified and has no obligatory labelling requirement for skin irritation according to the:

-  Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011),

- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.

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:
09 July - 02 August 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No 8147, April 2011, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: Animals used withihn the study were at least 6 weeks old (8 - 13 weeks).
- Weight at study initiation: Body weights were at least 1.0 kg ( 1755 -2486 grams).
- Housing: Individually housed in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (Global Diet 2030 Harlan Teklad, Italy). Hay and wooden sticks were available during the study period.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS

Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle.

Deviations from the maximum level of daily mean relative humidity occurred.
Evaluation: Laboratory historical data do not indicate an effect of the deviations


IN-LIFE DATES: From: 09 July to 02 August 2012
Vehicle:
unchanged (no vehicle)
Controls:
other: One eye of each animal remained untreated and served as the reference control.
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit):
average, 53.8 mg (range 53.4 – 54.1 mg) (a volume of approximately 0.1 mL)
Duration of treatment / exposure:
Single instillation on Day 1.
Observation period (in vivo):
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance.
Number of animals or in vitro replicates:
3 males
Details on study design:
STUDY DESIGN
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 3 weeks later, after considering the degree of eye irritation observed in the first animal.

TREATMENT
Animals were treated by instillation of, on average, 53.8 mg (range 53.4 – 54.1 mg) of the test substance (a volume of approximately 0.1 mL) in the conjunctival sac of one of the eyes 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 the test substance. The other eye remained untreated and served as the reference control.

Immediately after the 24-hour observation, a solution of 2% fluorescein (Merck, Darmstadt, Germany) in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage.

After the final observation, the animals were sacrificed by intra-venous injection of Euthasol® 20% (AST Farma BV, Oudewater, The Netherlands).

REMOVAL OF TEST SUBSTANCE
-Washing: No

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to instillation) and after the final observation.
- Necropsy: No necropsy was performed according to protocol.
- Irritation:
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded. The irritation was assessed according to OECD 405.

Where standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an ophthalmic examination lamp. In cases of equivocal results when comparing the treated and untreated eyes, the illustrated guide from the Consumer Product Safety Commission, Washington, D.C. 20207 was used for additional control purposes.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
animal #1, #2, #3
Time point:
24/48/72 h
Score:
> 0 - <= 0.3
Max. score:
3
Reversibility:
fully reversible within: 24 or 48 hours
Remarks on result:
other: 24-48 hrs
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Instillation of approximately 54 mg of CYASORB® UV-2908 Light Stabilizer (a volume of approximately 0.1 mL) into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness and/or discharge. The irritation had completely resolved within 24 hours in one animal and within 48 hours in the other two animals.

No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.

There was no evidence of ocular corrosion.


Other effects:
Colouration/Remnants:
No staining of (peri) ocular tissues by the test substance was observed. Remnants of the test substance were present in the eyes of two animals on Day 1.

Toxicity/Mortality:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Interpretation of results:
GHS criteria not met
Conclusions:
In an eye irritation study with rabbits, performed according to OECD/EC test guidelines, no or limited irritation was observed.

Based on these results, CYASORB® UV-2908 Light Stabilizer does not have to be classified and has no obligatory labelling requirement for eye irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) and Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures.
Executive summary:

Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness and discharge. The irritation had completely resolved within 24 hours in one animal and within 48 hours in the other two animals. No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.

No staining of (peri) ocular tissues by the test substance was observed. Remnants of the test substance were present in the eyes of two animals on Day 1.

Based on these results, CYASORB® UV-2908 Light Stabilizer does not have to be classified and has no obligatory labelling requirement for eye irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) and Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures.

 

 

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

Additional information

Skin:

In a study by WIL Research (2012), three rabbits were exposed to 0.5 grams of CYASORB® UV-2908 Light Stabilizer, moistened with 50% watery ethanol by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours after exposure.

Exposure to CYASORB® UV-2908 Light Stabilizer resulted in very slight erythema or very slight oedema in the treated skin areas of two rabbits. The skin irritation resolved within 24 or 48 hours after exposure in these animals. The other animal showed no irritation after exposure.

No staining of the treated skin by the test substance was observed and no test substance remnants were seen.

Eye:

In a rabbit study (WIL Research 2012) instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness and discharge. The irritation had completely resolved within 24 hours in one animal and within 48 hours in the other two animals.

No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.

No staining of (peri) ocular tissues by the test substance was observed. Remnants of the test substance were present in the eyes of two animals on Day 1.

This result is supported by an eye irritation study by HRC (1978) in which at 24 hours 1 out of 6 test animals had a diffuse, deep crimson red appearance of the conjunctivae with individual vessels not easily discernible. At 24 hours the individual conjuctivae score for rabbit #5 was 4 with a mean score of 0.67 for all 6 test animals. The effects at 48 hours were fully reversible.

Justification for classification or non-classification

Skin:

Based on results of the NOTOX (2012) rabbit study, CYASORB® UV-2908 Light Stabilizer does not have to be classified and has no obligatory labelling requirement for skin irritation according to the:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011),

- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.

Eye:

Based on the results of the WIL Research study (2012), CYASORB® UV-2908 Light Stabilizer does not have to be classified and has no obligatory labelling requirement for eye irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) and Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures.