7,17,28,38-tetraazatridecacyclo[24.16.2.2²,⁵.1⁸,¹².1²⁹,³³.0³,²².0⁴,¹⁹.0⁶,¹⁷.0²³,⁴³.0²⁷,³⁸.0⁴⁰,⁴⁴.0¹⁶,⁴⁶.0³⁷,⁴⁵]octatetraconta-1(42),2(48),3,5(47),6,8,10,12(46),13,15,19,21,23,25,27,29(45),30,32,34,36,40,43-docosaene-18,39-dione; 7,17,28,38-tetraazatridecacyclo[24.16.2.2²,⁵.1⁸,¹².1²⁹,³³.0³,²².0⁴,¹⁹.0⁶,¹⁷.0²³,⁴³.0²⁸,³⁹.0⁴⁰,⁴⁴.0¹⁶,⁴⁶.0³⁷,⁴⁵]octatetraconta-1(42),2(48),3,5(47),6,8,10,12(46),13,15,19,21,23,25,29,31,33,35,37(45),38,40,43-docosaene-18,27-dione

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Aug. 23, 2005 - Sep. 14, 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Reference 2

Reference Type:

other: Amendment

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted April 24, 2002

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Test material form:

solid: nanoform, no surface treatment

Details on test material:

- State of aggregation: solid, powder
- Particle size distribution (TEM): 29.1 nm (D50)
- Mass median aerodynamic diameter (MMAD): not specified
- Geometric standard deviation (GSD): not specified
- Shape of particles: plate
- Surface area of particles: 89 m²/g
- Crystal structure: crystalline
- Coating: no
- Surface properties: not applicable
- Density: 1566 kg/m³ at 20°C
- Moisture content: refer to IUCLID chapter 1
- Residual solvent: refer to IUCLID chapter 1
- Activation: not applicable
- Stabilisation: not applicable

Specific details on test material used for the study:

- Physical state: Powder / black
- Storage condition of test material: Room temperature
- Analytical purity: 99.9%
- Expiration date of the lot/batch: unlimited at room temperature

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Remarks:

A 1077 INRA (SPF)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Centre Lago S.A., 01540 Vonnas, France
- Age at study initiation: 2 - 3 months
- Weight at study initiation: 2.23 kg - 2.34 kg
- Housing: Individually in stainless steel wire mesh cages with grating, floor area: 3000 cm2
- Diet (e.g. ad libitum): Kliba-Labordiät (Kaninchen & Meerschweinchenhaltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g/animal per day)
- Water: Tap water ad libitum
- Acclimation period: At least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70%
- Air changes (per hr): Fully air-conditioned rooms with a central air-conditioning system
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: Aug. 17, 2005 (arrival of the animals) To: Sep. 01, 2005 (Day of last observation)

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated left eye

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL bulk volume (about 16 mg of the comminuted test substance)

Duration of treatment / exposure:

1 h

Observation period (in vivo):

9 days

Number of animals or in vitro replicates:

3 animals (2 males, 1 female animal)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): About 1 hour after application of the solid test substance the treated eye of the animal(s) was rinsed with 3 to 6 mL of hand warm tap water for 1 to 2 minutes using a syringe with a blunt probe.
- Time after start of exposure: 1 h

SCORING SYSTEM: according to OECD 405

TOOL USED TO ASSESS SCORE: Daylight tubes "Lumilux" (L 58W/860 PLUS ECO 25X1, Osram, Germany)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: Two animals showed injected scleral vessels in a circumscribed area (reversible within 24 - 48 h)

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Irritant / corrosive response data:

Slight to moderate conjunctival redness, slight conjunctival chemosis and slight discharge were observed in the animals up to 24 hours after application.

Two animals showed injected scleral vessels in a circumscribed area.

The ocular reactions were reversible in all animals within 48 hours after application.

The average score (24 to 72 hours) for irritation was calculated to be 0.0 for corneal opacity, iris and chemosis and 0.3 for conjunctival redness.

Any other information on results incl. tables

		Cornea		Iris	Conjunctiva
Animal	Reading	Opacity	Area involved		Redness	Chemosis	Discharge	Additional findings
1	1 hr	0	0	0	2	1	1
2	1 hr	0	0	0	1	0	0	Scleral vesseis injected, circumscribed area
3	1 hr	0	0	0	2	0	0	Scleral vesseis injected, circumscribed area
1	24 hrs	0	0	0	1	0	0
2	24 hrs	0	0	0	1	0	0	Scleral vesseis injected, circumscribed area
3	24 hrs	0	0	0	1	0	0
1	48 hrs	0	0	0	0	0	0
2	48 hrs	0	0	0	0	0	0
3	48 hrs	0	0	0	0	0	0
1	72 hrs	0	0	0	0	0	0
2	72 hrs	0	0	0	0	0	0
3	72 hrs	0	0	0	0	0	0
mean animal 1	24 - 72 hrs	0		0	0.3	0
mean animal 2	24 - 72 hrs	0		0	0.3	0
mean animal 3	24 - 72 hrs	0		0	0.3	0
mean 1 - 3	24/48/72 h	0.0		0.0	0.3	0.0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Considering the described ocular reactions as well as the average score for irritation, the test article does not show an eye irritation potential under the test conditions chosen.

Executive summary:

The test article's potential to cause damage to the conjunctiva, iris or cornea was assessed by a single ocular application of 0.1 mL bulk volume (about 16 mg) of the test substance to one eye of three White New Zealand rabbits (stepwise procedure starting with one animal and supplementing two additional animals). The study was performed according to OECD test guideline 405 and in compliance with GLP. About 1 hour after application the eye was rinsed with tap water. The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application. Slight to moderate conjunctival redness, slight conjunctival chemosis and slight discharge were observed in the animals up to 24 hours after application. Two animals showed injected scleral vessels in a circumscribed area. The ocular reactions were reversible in all animals within 48 hours after application. The average score (24 to 72 hours) for irritation was calculated to be 0.0 for corneal opacity, iris and chemosis and 0.3 for conjunctival redness. In conclusion, considering the described ocular reactions as well as the average score for irritation, the test article is considered to be not irritating under the test conditions chosen.