Reaction products of 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane with maleic anhydride and methacrylic acid

Eye irritation

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 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 Nousan, Notification No 8147, November 2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane with maleic anhydride and methacrylic acid

EC Number:

701-427-1

Cas Number:

36425-16-8

Molecular formula:

Not applicable: UVCB

IUPAC Name:

Reaction products of 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane with maleic anhydride and methacrylic acid

Details on test material:

- Name of test material (as cited in study report):Substance 3, NLP 500-090-6 (old name of Ec 701-427-1)
- 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: Varies

SCORING SYSTEM:
CORNEAL IRRITATION
Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity (may include slight dulling of normal luster) ............................................ 0
Scattered or diffuse areas of opacity, details of iris clearly visible ................................................. 1
Easily discernible translucent area, details of iris slightly obscured ............................................... 2
Nacreous area, no details of iris visible, size of pupil barely discernible ........................................ 3
Opaque cornea, iris not discernible through the opacity .............................................................. 4
Area of cornea involved:
No ulceration or opacity ................................................................................................................ 0
One quarter or less but not zero .................................................................................................. 1
Greater than one quarter, but less than half ................................................................................. 2
Greater than half, but less than three quarters ............................................................................. 3
Greater than three quarters, up to whole area .............................................................................. 4
IRIS
Normal ....................................................................................................................................... 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, 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 all of these) ....................................... 2
CONJUNCTIVAL IRRITATION
Redness (refers to palpebrae and sclera, excluding cornea and iris):
Blood vessels normal .................................................................................................................. 0
Some blood vessels definitely hyperaemic (injected) .................................................................... 1
Diffuse, crimson color, individual vessels not easily discernible .................................................... 2
Diffuse beefy red .......................................................................................................................... 3
Chemosis (refers to 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
Discharge:
No discharge (may include small amounts observed in inner canthus of normal animals) ........... 0
Any amount different from normal and/or lacrimation ................................................................... 1
Discharge with moistening of the lids and hairs just adjacent to lids ............................................. 2
Discharge with moistening of the lids and hairs (considerable area around the eye) ................... 3

TOOL USED TO ASSESS SCORE: Ophthalmic examination lamp

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

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

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)
16^1	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:

GHS criteria not met

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.