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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):Substance 3, NLP 500-090-6- Substance type: Technical product- Physical state: Viscous liquid- Analytical purity: 100%- Composition of test material, percentage of components: - Approximately 57.5% bisGMA, - Approximately 14.5% monomaleic adduct of bisGMA, - Approximately 10% polymeric methacrylates (more Bisphenol-A’s + glycidyl in the chain)- Lot/batch No.:7008043- Expiration date of the lot/batch: 01 June 2011- Stability under test conditions: Stable- Storage condition of test material:In refrigerator (2-8°C) protected from light

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS- Source:Charles River France, L’Arbresle Cedex, France- Age at study initiation:at least 6 weeks old- Weight at study initiation:at least 1.0 kg- Housing: Animals were individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm).- Diet (e.g. ad libitum): Pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) and wooden sticks (Swedish aspen wood, Bioservices, Uden, The Netherlands) were available during the study period- Water (e.g. ad libitum): ad libitum- Acclimation period: At least five days.ENVIRONMENTAL CONDITIONS- Temperature (°C): 21.0 ± 3.0 ºC (actual range: 18.8-19.4 ºC),- Humidity (%):40-70% (actual range: 47-71%)- Air changes (per hr): 15- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL - Amount(s) applied (volume or weight with unit): 0.08 mL
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3 animals of one sex
Details on study design:
REMOVAL OF TEST SUBSTANCE- Washing (if done):Rinsed with tap water- Time after start of exposure: VariesSCORING SYSTEM:CORNEAL IRRITATIONOpacity: degree of density (area most dense taken for reading)No ulceration or opacity (may include slight dulling of normal luster) ............................................ 0Scattered or diffuse areas of opacity, details of iris clearly visible ................................................. 1Easily discernible translucent area, details of iris slightly obscured ............................................... 2Nacreous area, no details of iris visible, size of pupil barely discernible ........................................ 3Opaque cornea, iris not discernible through the opacity .............................................................. 4Area of cornea involved:No ulceration or opacity ................................................................................................................ 0One quarter or less but not zero .................................................................................................. 1Greater than one quarter, but less than half ................................................................................. 2Greater than half, but less than three quarters ............................................................................. 3Greater than three quarters, up to whole area .............................................................................. 4IRISNormal ....................................................................................................................................... 0Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination thereof, iris still reacting to light (sluggish reaction is positive) ....................................................................................................... 1No reaction to light, hemorrhage, gross destruction (any or all of these) ....................................... 2CONJUNCTIVAL IRRITATIONRedness (refers to palpebrae and sclera, excluding cornea and iris):Blood vessels normal .................................................................................................................. 0Some blood vessels definitely hyperaemic (injected) .................................................................... 1Diffuse, crimson color, individual vessels not easily discernible .................................................... 2Diffuse beefy red .......................................................................................................................... 3Chemosis (refers to lids and/or nictitating membranes):No swelling ………………………………………… ........................................................................ 0Any swelling above normal (includes nictitating membranes) ...................................................... 1Obvious swelling with partial eversion of lids ................................................................................ 2Swelling with lids about half closed ............................................................................................. 3Swelling with lids more than half closed ....................................................................................... 4Discharge:No discharge (may include small amounts observed in inner canthus of normal animals) ........... 0Any amount different from normal and/or lacrimation ................................................................... 1Discharge with moistening of the lids and hairs just adjacent to lids ............................................. 2Discharge with moistening of the lids and hairs (considerable area around the eye) ................... 3TOOL USED TO ASSESS SCORE: Ophthalmic examination lamp

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
Cornea opacity
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours
Score:
0.4
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Reversible in 2 animals within 24 hours, and 1 animal within 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Irritant / corrosive response data:
Instillation of approximately 100.4 mg of Substance 3, NLP 500-090-6 (a volume of approximately 0.08 mL) into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness and discharge. The irritation had completely resolved within 24 hours on two animals and within 48 hours in the other animal. 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. Results are presented in Table 1 below.

Any other information on results incl. tables

Table 1. Individual eye irritation scores

Animal

Time after dosing

Cornea

Iris

Conjunctivae

 

Comments

Opacity

(0-4)

Area

(0-4)

Fluor area (%)2

 

Redness

(0-3)

Chemosis

(0-4)

Discharge

(03)

161

1 hour

0

0

-

0

1

0

1

b

24 hours

0

0

0

0

0

0

0

-

48 hours

0

0

-

0

0

0

0

-

72 hours

0

0

-

0

0

0

0

-

18

1 hour

0

0

-

0

2

0

1

c

24 hours

0

0

0

0

1

0

0

-

48 hours

0

0

-

0

0

0

0

-

72 hours

0

0

-

0

0

0

0

c

23

1 hour

0

0

-

0

1

0

1

-

24 hours

0

0

0

0

0

0

0

-

48 hours

0

0

-

0

0

0

0

-

72 hours

0

0

-

0

0

0

0

-

1Sentinel,1Green staining after fluorescein treatment (percentage of total corneal area)

Comments:

b                       Remnants of the test substance in the eye.

c                       Remnants of the test substance on the outside of the eyelids.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Eye irritation of Modified Small Vinyl Ester was tested in a guideline study (OECD 405) in vivo in rabbits. No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein 24 hours after instillation of Modified Small Vinyl Ester revealed no corneal epithelial damage. Redness of the conjunctivae and discharge was observed at one hour after instillation that reversed completely within 24 hours except redness in one aminal that reversed completely within 48 hours. Based on these data, Modified Small Vinyl Ester is not eye irritating.
Executive summary:

Acute eye irritation/corrosion of Modified Small Vinyl Ester was tested in vivo in the rabbit in a the guideline study (OECD 405).

Single samples of approximately 100.4 mg of Modified Small Vinyl Ester (a volume of approximately 0.08 mL) were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours after instillation. Remnants of Modified Small Vinyl Ester were present in the eye of one animal and on the outside of the eyelids in the two other animals on Day 1.

Instillation of Modified Small Vinyl Ester resulted in irritation of the conjunctivae, which consisted of redness and discharge. The irritation had completely resolved within 24 hours on two animals and within 48 hours in the third animal. 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. Based on these results Modified Small Vinyl Ester is not irritating to the eyes.