2-Propenoic acid, polymer with 2,2-bis(hydroxymethyl)-1,3-propanediol, 2-methyloxirane and oxirane

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 07 February 2006 to 01 March 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study (OECD 405)

Data source

Reference

Reference Type:

study report

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)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of (1 mole) Pentaerythritol ethoxylated and propoxylated (4:1) with 2-propenoic acid (4 moles)

EC Number:

604-394-0

Cas Number:

144086-02-2

Molecular formula:

C17H28O12 (C3H6O.C2H4O)n

IUPAC Name:

Reaction products of (1 mole) Pentaerythritol ethoxylated and propoxylated (4:1) with 2-propenoic acid (4 moles)

Constituent 2

Reference substance name:

2,2-bis(hydroxymethyl)-1,3-propanediol, ethoxylated and propoxylated, esters with acrylic acid

IUPAC Name:

2,2-bis(hydroxymethyl)-1,3-propanediol, ethoxylated and propoxylated, esters with acrylic acid

Test material form:

other: liquid

Details on test material:

- Physical state: thick colorless liquid
- Purity: 100%.
- Lot/batch No.: LI2293701VSP
- Storage condition of test material: at room temperature from receipt and protected from light

The pH of the test item undiluted was approximately 4.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Grimaud frères selection S.A.S., La Corbière, Roussay, France
- Age at study initiation: 2-4 months old
- Weight at study initiation: 3.0 ± 0.2 kg.
- Housing:individually in Techniplast (49 cm x 62 cm x 30 cm) or Pajon (50 cm x 57 cm x 75 cm) cages.
- Diet (e.g. ad libitum): free access to 110C pelleted diet
- Water (e.g. ad libitum): Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum
- Acclimation period: 5 days at least

ENVIRONMENTAL CONDITIONS
• temperature: 18 ± 3°C
• relative humidity: 30 to 70%
• light/dark cycle: 12 h/12 h
• ventilation: approximately 12 cycles/hour of filtered, non-recycled air.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eye was not treated and served as control.

Amount / concentration applied:

A single dose of 0.1 mL of the undiluted test item was instilled into the conjunctival sac of the left eye after gently pulling the lower lid away from the eyeball.

Duration of treatment / exposure:

one exposure

Observation period (in vivo):

The eyes were examined approximately 1 hour, 24, 48 and 72 hours after administration of the test item.
Since there were persistent ocular reactions at 72 hours, the observation period was extended up to their complete reversibility (day 15).

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE: no

SCORING SYSTEM:
Conjunctival reactions, iritis and corneal opacification were evaluated daily for each animal.
For the evaluation of corneal opacification (presence or absence, affected area), the eyes were examined under a UV lamp after instillation of one or two drops of 0.5% sodium fluorescein solution (a clear fluorescence is visible in the areas of opacification). This evaluation was performed on day 2 and repeated thereafter whenever necessary.

Ocular reactions were scored according to the following numerical scale:
Conjunctival lesions and discharge
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
Redness (refers to palpebral and bulbar conjunctivae, cornea and iris)
. blood vessels normal ................................................................................................................0
. a number of blood vessels definitely hyperemic (injected)......................................................1
. diffuse, crimson colour, individual vessels not easily discernible ...........................................2
. diffuse, beefy red......................................................................................................................3
Discharge
. absence of discharge ................................................................................................................0
. slight discharge (does not include small amounts normally found in
inner canthus) ...........................................................................................................................1
. discharge with moistening of lids and hairs adjacent to lids....................................................2
. discharge with moistening of lids and hairs on wide area around the eye...............................3
Iris lesions
. normal .....................................................................................................................................0
. markedly deepened rugae, congestion, swelling, moderate circum-corneal
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, haemorrhage, gross destruction (any or all of these) ...............................2

Corneal lesions
Degree of opacity (area most dense taken for reading)
. no ulceration or opacity............................................................................................................0
. scattered or diffuse areas of opacity (other than slight dulling or normal lustre),
details of iris clearly visible .....................................................................................................1
. easily discernible translucent area, details of iris slightly obscured ........................................2
. nacreous areas, no details of iris visible, size of pupil barely discernible ...............................3
. opaque cornea, iris not discernible through the opacity...........................................................4
Area of opacity
. one quarter (or less) but not zero..............................................................................................1
. greater than one quarter but less than a half.............................................................................2
. greater than one half but less than three quarters.....................................................................3
. greater than three quarters up to whole area. ...........................................................................4
Any other lesions observed were noted.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

(opacity)

Basis:

mean

Remarks:

(3 rabbits)

Time point:

other: 24-48-72 hours

Score:

1.1

Max. score:

4

Reversibility:

fully reversible within: 9 days

Remarks on result:

other: Individual scores: 1.3-1.0-1.0

Results 2

Irritation parameter:

conjunctivae score

Remarks:

(chemosis)

Basis:

mean

Remarks:

(3 rabbits)

Time point:

other: 24-48-72 hours

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 15 days

Remarks on result:

other: Individual scores: 3.0-3.0-3.0

Results 3

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

(3 rabbits)

Time point:

other: 24-48-72 hours

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 15 days

Remarks on result:

other: Individual scores: 3.0-3.0-3.0

Results 4

Irritation parameter:

iris score

Basis:

mean

Remarks:

(3 rabbits)

Time point:

other: 24-48-72 hours

Score:

0.8

Max. score:

2

Reversibility:

fully reversible within: 6 days

Remarks on result:

other: Individual scores: 0.3-1.0-1.0

Irritant / corrosive response data:

Slight to severe conjunctival reactions including, slight to marked chemosis (grades 1 to 3), slight to severe redness of the conjunctiva (grades 1 to 3) and clear and/or whitish purulent discharge, were observed in all animals from day 1. Some of these reactions persisted up to day 13 (1/3 animals) or 14 (2/3 animals).
An iritis (grade 1) was noted in all animals on day 2; it persisted up to day 4 (1/3 animals) or 5 (1/3 animals).
A slight or moderate corneal opacity (grade 1 or 2), which sometimes covered the whole area of the eye, was recorded in all animals on day 2; it persisted up to day 6 (1/3 animals) or 8 (2/3 animals).
A neovascularisation was noted in 2/3 animals between day 9 and day 14.
Mean scores calculated for each animal over 24, 48 and 72 hours were 3.0, 3.0 and 3.0 for chemosis, 3.0, 3.0 and 3.0 for redness of the conjunctiva, 0.3, 1.0 and 1.0 for iris lesions and 1.3, 1.0 and 1.0 for corneal opacity.

Other effects:

No reported data in the report.

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under these experimental conditions, 2,2-bis(hydroxymethyl)-1,3-propanediol, ethoxylated and propoxylated, esters with acrylic acid was irritant when administered by ocular route to rabbits.

Executive summary:

2,2-bis(hydroxymethyl)-1,3-propanediol, ethoxylated and propoxylated, esters with acrylic acid was administered to three male New Zealand White rabbit. A single dose of 0.1 mL of the undiluted test item was instilled into the left conjunctival sac. The eyes were not rinsed after administration of the test item. Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration and then daily until reversibility of the ocular reactions.

The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal.

Slight to severe conjunctival reactions (slight to marked chemosis, slight to severe redness of the conjunctiva and clear and/or whitish purulent discharge) were observed in all animals from day 1. Some of these reactions persisted up to day 13 (1/3 animals) or 14 (2/3 animals). An iritis was noted in all animals on day 2; it persisted up to day 4 (1/3 animals) or 5 (1/3 animals).

A slight or moderate corneal opacity, which sometimes covered the whole area of the eye, was recorded in all animals on day 2; it persisted up to day 6 (1/3 animals) or 8 (2/3 animals). A neovascularisation was noted in 2/3 animals between day 9 and day 14.

Mean scores calculated for each animal over 24, 48 and 72 hours were 3.0, 3.0 and 3.0 for chemosis, 3.0, 3.0 and 3.0 for redness of the conjunctiva, 0.3, 1.0 and 1.0 for iris lesions and 1.3, 1.0 and 1.0 for corneal opacity.

Under these experimental conditions, 2,2-bis(hydroxymethyl)-1,3-propanediol, ethoxylated and propoxylated, esters with acrylic acid was irritant when administered by ocular route to rabbits.