2-methylbenzene-1,4-diyl bis{4-[3-(acryloyloxy)propoxy]benzoate}

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

8 JUL 1996 - 25 SEP 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

This study was conducted according to Good Laboratory Practice (GLP) and followed the OECD guideline for testing of Chemicals 405.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

425-560-7

EC Name:

-

Cas Number:

174063-87-7

Molecular formula:

C33H32O10

IUPAC Name:

2-methylbenzene-1,4-diyl bis{4-[3-(acryloyloxy)propoxy]benzoate}

Test material form:

solid: crystalline

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Strain: Albino rabbit, Crl:KBL(NZW)BR, female (f)
- Source: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: about 16 weeks
- Weight at study initiation: 2.84 (2.78 - 2.88) kg
- Housing: They were kept separately in cages type KK 017 (floor area: 75 x 54.5 = 4087 cm2, height: 40 cm; manufacturer: Hulskamp) on metal grids. The paper underneath the cages was changed three times a week. The cages were machine-cleaned before the start of the study.
- Diet (e.g. ad libitum): ad libitum, Altromin Standard Diet TPF(R) 2113, pellets and acidified (The diet is checked periodically according to the specifications of the manufacturer by an independent laboratory, approved by the German government. Analysis includes both qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides, and antibiotics. The analytical results show that the limits set by German regulations for animal feed have been followed.)
- Water (e.g. ad libitum): ad libitum, fully demineralized water
- Acclimation period: more than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21°C
- Humidity (%): 48 to 93
- Air changes (per hr): air-conditioned
- Photoperiod (hrs dark / hrs light): daylight

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

0.1 g test material was instilled into the conjunctival sac of the left eye of each animal by gently pulling the lower lid away from the eyeball to form a cup into which the test material was placed. The right eye remained untreated and served as control. After instillation, the eyelids were closed for about 30 seconds.

Observation period (in vivo):

The rabbits were investigated for eye irritation and for changes in behaviour and general condition 1 hour after treatment, and than after 24, 48, 72 hours and so on daily up to day 8 of the experimental part.

Number of animals or in vitro replicates:

3 female rabbits

Details on study design:

SCORING SYSTEM:

-- Evaluation of eye reactions

- Cornea Scores
A) Opacity-degree of density (area most dense taken for reading)

No ulceration or opacity 0

Scattered or diffuse areas of opacity (other than slight dulling
of normal lustre), 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

B) Area of cornea involved not evaluated (Rating according to the DRAIZE method)

- Iris
A) Normal 0
Markedly deepened rugae, congestion, swelling, moderate
circumcorneal hyperemia, or injection, any of these or combination
of any thereof, iris still reacting to light
(sluggish reaction is positive) 1
No reaction to light, hemorrhage, gross destruction
(any or all of these) 2

- Conjunctivae Scores
A) Redness (refers to palpebral and bulbar conjunctivae,
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

B) Chemosis: lids and/or nictating membranes
No swelling 0
Any swelling above normal (includes nictating 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

C) Discharge (Rating according to the DRAIZE method )
No discharge 0
Any amount different from normal (does not include small
amounts observed in inner canthus of normal animals) 1
Discharge with moistening of the lids and hairs just adjacent to lids 2
Discharge with moistening of the lids and hairs,
and of a considerable area around the eye 3

Mean score of all animals = Mean grading for irritations of cornea, iris, and conjunctivae per time point
Mean score per animal = Mean grading for each animal of irritations of cornea, iris, and conjunctivae (1, 24, 48, and 72 hours after application)
Maximum value = Maximum grading of a sign of irritation within a period

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

After single instillation of 0.1 g test material, into the conjunctival sac of the left eye, no signs of irritation of the cornea and iris were observed. The conjunctivae showed redness (score 1) at the first reading and in one animal also at the second reading. Chemosis (scores 1 and 2) was seen in two animals at the first reading. Later on, no signs of irritation were seen.
The untreated eyes were normal.

Other effects:

No signs of clinical toxicity were detected.

Any other information on results incl. tables

Ocular alterations

After single instillation of 0.1 g test material, into the conjunctival sac of the left eye, no signs of irritation of the cornea and iris were observed. The conjunctivae showed redness (score 1) at the first reading and in one animal also at the second reading. Chemosis (scores 1 and 2) was seen in two animals at the first reading. Later on, no signs of irritation were seen.

Clinical findings

No signs of irritation were observed at the cornea and iris. The conjunctivae showed redness (score 1) on day 1 of the study. Later on no signs of irritation were observed. The untreated eyes were unchanged.

No signs of clinical toxicity were detected.

Mortality

All animals survived the observation period.

Body weight

Body weight development of the treated rabbits was inconspicuous.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

According to the result of the irritation scores, the test material has not to be classified as an eye irritant.

Executive summary:

The registered substance was tested for eye irritation in an Acute Eye Irritation / Corrosion test according to OECD Guideline 405 following GLP.

Purpose
The purpose of this primary eye irritation assay was to provide information on possible health hazards in case of acute eye contact with a test material and serve as a a rational basis for risk assessment to the eye irritating potential of the test item in human.

Study design
The test material was tested for eye irritation potential. 0.1 g of the test material was applied into the conjunctival sac of rabbits. The first examination of the eyes followed 1 hour after instillation. The examinations were performed daily for further 7 days.

Results
No signs of irritation concerning to cornea and iris were observed. The conjunctivae showed redness (score 1), and chemosis (scores 1 and 2) at the first and second readings, maximally. This is a common finding in the case of powder. The untreated eyes were unchanged.

The cumulative mean scores/group for cornea, iris, and conjunctivae were:

Study day (hours)	1 (1)	2 (24)	3 (48)	4 (72)
Cornea	0.0	0.0	0.0	0.0
Iris	0.0	0.0	0.0	0.0
Conjunctivae                     redness                                              chemosis	1.0 1.0	0.3 0.0	0.0 0.0	0.0 0.0

The scores/animal (24, 48, 72 hours) were:

	Mean			Max
Animal No.	14	13	12	14	13	12
Cornea	0.0	0.0	0.0	0	0	0
Iris	0.0	0.0	0.0	0	0	0
Conjunctivae                     redness                                              chemosis	0.3 0.0	0.0 0.0	0.0 0.0	1 0	0 0	0 0

Conclusion
According to the result of the irritation scores, the test material has not to be classified as an eye irritant.