2-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-5-(3-((2-ethylhexyl)oxy)-2-hydroxypropoxy)phenol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

24 Feb 1987

Deviations:

yes

Remarks:

The rabbits used in the study were slightly lighter and younger than proposed

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

31 Jul 1992

Deviations:

yes

Remarks:

The rabbits used in the study were slightly lighter and younger than proposed

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4500 (Acute Eye Irritation)

Version / remarks:

1 Jul 1993

Deviations:

yes

Remarks:

The rabbits used in the study were slightly lighter and younger than proposed

Principles of method if other than guideline:

The rabbits used in the study were slightly lighter and younger than proposed in the protocol

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-5-(3-((2-ethylhexyl)oxy)-2-hydroxypropoxy)phenol

EC Number:

419-740-4

EC Name:

2-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-5-(3-((2-ethylhexyl)oxy)-2-hydroxypropoxy)phenol

Cas Number:

137658-79-8

Molecular formula:

C36 H45 N3 O4

IUPAC Name:

2-[4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl]-5-{3-[(2-ethylhexyl)oxy]-2-hydroxypropoxy}phenol

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: Z2651-01
- Expiration date of the lot/batch: Feb 1997
- Purity: ˃ 95%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature (ca. 20°C) away from sunlight
- Stability under test conditions: stable at storage conditions

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test article was applied as delivered by the sponsor, with the exception that it was ground in a mortar and pestle before administration.

OTHER SPECIFICS:
- pH: not assessed (insoluble)
- Description: yellowish solid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Remarks:

CRL:KBL(NZW)BR

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Stolzenseeweg 32-36 0-88353 Kisslegg
- Age at study initiation: 11-12 weeks
- Weight at start of acclimatization: 1,9 kg
- Weight at start of treatment: male: 2.2kg female: 2.0-2.1 kg
- Identification: By unique cage number and corresponding ear number
- Housing: Individually in stainless steel cages with an automatic cleaning system, equipped with feed hoppers, drinking water bowls and wood for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Kliba 341, Batch 89/95 rabbit maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst), ad libitum.
- Water (e.g. ad libitum): Community tap water from Itingen, ad libitum.
- Acclimation period: Five days under laboratory test conditions after health examination. Only animals without any visual signs of illness were used for the study, May 11 - 15, 1995

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23 °C
- Humidity (%): humidity between 40-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light (approx. 100 Lux) / 12 hours dark (light period between 6.00 a.m. to 6.00 p.m.), music during the light period.

IN-LIFE DATES:
Treatment May 16, 1995
Observation May 16 -19, 1995
Termination May 19, 1995

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

yes, concurrent no treatment

Amount / concentration applied:

0.1 g / animal (left eye only)

Observation period (in vivo):

72h

Number of animals or in vitro replicates:

1 male, 2 female

Details on study design:

The eyes of the animals were examined for intactness once, one day prior to test article administration. Only those animals with no signs of ocular injury or irritation were used on the test.
On test day 1, 0.1 g of the test article (undiluted) was placed in the conjunctival sac of the left eye of each animal 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 article. The right eye remained untreated and served as the reference control.

SCORING SYSTEM:
EVALUATION OF EYE REACTIONS
CORNEAL IRRITATION
Opacity: degree of density (densest area used for assessment)
No ulceration or opacity 0
Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details of iris clearly visible 1
Easily discernible translucent area, details of iris slightly obscured 2
Nacrous area, no details of iris visible, size of pupil barely discernible 3
Opaque cornea, iris not discernible through the opacity 4

IRIDIC IRRITATION
Normal 0
Markedly deepened rugae, congestion, swelling, moderate circumcomeal hyperemia, or injection, any of these or combination thereof, iris still reacting to light (sluggish reaction is positive) 1
No reaction to light, hemorrhage, gross destruction (any or al 1 of these) 2

CONJUNCTIVAL IRRITATION
Redness (refers to palpebral and bulbar conjunctivae, excluding cornea and iris).
Blood vessels normal 0
Some blood vessels definitely hyperemic (injected) 1
Diffuse, crimson color, individual vessels not easily discernible 2
Diffuse beefy red 3

Chemosis: lids and/or nictitating membranes
No swelling 0
Any swelling above normal (includes nictitating membranes) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids more than half closed 4

The maximum scores are:
Cornea 4
Iris 2
Conjunctival Redness 3
Conjunctival Chemosis : 4

Maximum attainable score 13

TOOL USED TO ASSESS SCORE: Eye examinations were made with a Varta Cliptrix diagnostic-lamp (A. Riegger, Basel / Switzerland).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48 and 72h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 24h

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48 and 72h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 24h

Irritant / corrosive response data:

VIABILITY / MORTALITY AND CLINICAL SIGNS
No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.

IRRITATION
The test substance showed a primary irritation score of: 0.67, when applied to the conjunctival sac of the rabbit eye.

COLORATION
No staining of the cornea, sclera or conjunctivae by the test article was observed.

CORROSION
No corrosion of the cornea was observed at any of the reading times.

BODY WEIGHTS
The body weight of the animals was within the normal range of variability.

Any other information on results incl. tables

Table 1: Results Eye irritation / Eye corrosion: Mean values of the scores for each type of lesion, calculated for each animal separately

	Mean values 24 – 72 hours
Animal No.	Cornea Opacity	Iris	Conjunctivae
			Redness	Chemosis
34, male	0	0	0	0
35, female	0	0	0.67	0.67
36. female	0	0	0.33	0.33

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results and according to classification criteria of EEC Commission Directive 93/21/EEC (April 27, 1993), the test article is classified as "not irritating" to the rabbit eye.

Executive summary:

The primary irritation potential of the test article was investigated by instillation of 0.1 g into one eye of each of three young adult New Zealand rabbits. The treated eyes were not rinsed after application. Scoring of irritation effects were performed 1, 24, 48 and 72 hours after test article application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion. The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 hours and then dividing the resulting total by the number of figures. It was found to be 0.67 (max. 13), when applied to the conjunctival sac of the rabbit eye. No staining of the cornea, sclera or conjunctivae of the treated eyes by the test article was observed. No corrosion was observed at any of the measuring intervals.