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

Eye irritation

Administrative data

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.

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 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye 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

Test animals / tissue source

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

Test system

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.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

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

Results 4

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.

Applicant's summary and conclusion

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.