Hexadecyl 3,5-bis-tert-butyl-4-hydroxybenzoate

Skin irritation / corrosion

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

CYASORB® UV-2908 Light Stabilizer

IUPAC Name:

CYASORB® UV-2908 Light Stabilizer

Details on test material:

- Name of test material (as cited in study report): CYASORB® UV-2908 Light Stabilizer
- Substance type: White to off-white powder
- Physical state: Powder
- Purity: >98%
- Lot/batch No.: WP1022803
- Expiration date of the lot/batch: 18 April 2013
- Storage condition of test material: At room temperature protected from light
- Hygroscopic: No
- Volatile: No
- Reactivity: Reactive to oxygen, moisture and light
- Test substance handling: For oxygen and moisture: no specific handling required
- For light: use amber-coloured glassware or wrap container in aluminium foil
- pH (1% in water, indicative range): 7.2 – 6.7 (determined at WIL Research Europe B.V.)
- Stability in vehicle:
• 50% Ethanol in water Stable for at least 4 hours
- Solubility in vehicle:
• 50% Ethanol in water Not indicated

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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

Test system

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.

Results and discussion

In vivo

Results

Results 1

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

Results 2

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.

Applicant's summary and conclusion

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.