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Diss Factsheets

Administrative data

Endpoint:
eye irritation, other
Remarks:
eye irritation : in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-12-03 to 2009-11-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline compliantGLP compliant

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
as at 2002
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
as at 2004
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
Reaction mass of (3-hydroxy-2-pentylcyclopentyl)acetic acid and sodium (3-hydroxy-2-pentylcyclopentyl)acetate
EC Number:
932-898-3
IUPAC Name:
Reaction mass of (3-hydroxy-2-pentylcyclopentyl)acetic acid and sodium (3-hydroxy-2-pentylcyclopentyl)acetate
Details on test material:
- Name of test material (as cited in study report): R0034833C
- Physical state: slightly yellow liquid
- Analytical purity: 30.26%
- Composition of test material, percentage of components:
R0034833A (sodium salt form) content, expressed as acid form: 25.76%
R00348338 (acid form) content: 4.5%
NaCl content: 1.6%
Water content: 45.6%
Dipropylene glycol content: 19.0%
Dried extract: 34.0%
Active content: 30.26%
pH: 7.0
Majority diastereoisomers ratio: 57/43
Other diastereoisnmers and isomers content: 9.3%
ER2423 content Not Detected < 0.02%
ER2425 content Not Detected < 0.02%
Inter-molecular esters content Not Detected < 0,01%
intro-molecular esters content 0.08%
ER2410 content 0.8%
Methanol content Not Detected < 1000 ppm

Results consistent with ID LIMB 2% 12631

- Purity test date: 2008-08-01
- Lot/batch No.: R0034833C 027 P 001
- Expiration date of the lot/batch: June 2009
- Stability under test conditions: not reported
- Storage condition of test material: at +4°C and 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: Grimaud Frères Sélection S.A.S., La Corbière, Roussay, France- Age at study initiation: 2 to 4 months- Weight at study initiation: 2.9 ± 0.3 kg- Housing: individually in Pajon cages (50 cm x 57 cm x 75 cm)- Diet (e.g. ad libitum): ad libitum, Control Ref.: 110 pelleted diet (SAFE, Augy, France)- Water (e.g. ad libitum): ad libitum, drinking water filtered by a FG Millipore membrane (0.22 micron)- Acclimation period: at least 5 dENVIRONMENTAL CONDITIONS- Temperature (°C): 18 ± 3- Humidity (%): 30 to 70- Air changes (per hr): ca. 12- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
other: two paralled experiments: unchanged and with purified water (prepared at CIT by reverse osmosis) as vehicle
Controls:
no
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.1 mL in both experiments- Concentration (if solution): - experiment 1: undiluted test item as described under "Details on test materials" - experiment 2: 10 % (w/w) of the test item as described under "Details on test materials"VEHICLE- Amount(s) applied (volume or weight with unit): ca. 0.9 mL- Concentration (if solution): 10 % (w/w) of the test item in the vehicle- Purity: purified water (prepared at CIT by reverse osmosis)
Duration of treatment / exposure:
single treatment, instilled into the conjunctival sac of the left eye after gently pulling the lower lid away from the eyeball
Observation period (in vivo):
1 hour, 24, 48 and 72 hours after administration of the test item, study ended on day 4 in the absence of persistent ocular reactions
Number of animals or in vitro replicates:
- experiment 1: 1 animal- experiment 2: 3 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE- Washing (if done): noSCORING SYSTEM:Draize Score SystemConjunctival lesions and dischargeChemosis (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. 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......................................................................................................................3Discharge. 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...............................3Iris lesions. normal .....................................................................................................................................0. markedly deepened rugae, congestion, swelling, moderate circum-cornealhyperemia, or injection, any of these or combination of any thereof, iris stillreacting to light (sluggish reaction is positive) ........................................................................1. no reaction to light, haemorrhage, gross destruction (any or all of these) ...............................2Corneal lesionsDegree 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...........................................................4Area 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. ...........................................................................4Any other lesions observed were noted.TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: 750
Time point:
other: mean of 24 and 48 h post treatment
Score:
3
Max. score:
4
Reversibility:
other: animal sacrificed for humane reasons on d 4
Irritation parameter:
chemosis score
Basis:
animal: 750
Time point:
other: mean of 24 and 48 h post treatment
Score:
2.5
Max. score:
4
Reversibility:
other: animal sacrificed for humane reasons on d 4
Irritation parameter:
conjunctivae score
Basis:
animal: 750
Time point:
other: mean of 24 and 48 h post treatment
Score:
2
Max. score:
3
Reversibility:
other: animal sacrificed for humane reasons on d 4
Irritation parameter:
iris score
Basis:
animal: 750
Time point:
other: mean of 24 and 48 h post treatment
Score:
1
Max. score:
2
Reversibility:
other: animal sacrificed for humane reasons on d 4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of animals no. 711, 712 and 736
Time point:
other: mean score of 1h, 24, 48 h and 72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of animals no. 711, 712 and 736
Time point:
other: mean score of 1h, 24, 48 h and 72 h
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of animals no. 711, 712 and 736
Time point:
other: mean score of 1h, 24, 48 h and 72 h
Score:
0
Max. score:
3
Irritation parameter:
iris score
Basis:
mean
Remarks:
of animals no. 711, 712 and 736
Time point:
other: mean score of 1h, 24, 48 h and 72 h
Score:
0
Max. score:
2
Irritant / corrosive response data:
Undiluted test item (one animal)- a marked then moderate chemosis (grade 3 then 2) and a moderate redness of the conjunctiva (grade 2)from day 1 until day 3- a clear discharge (grade 2 then grade 1) and an iritis (grade 1) on days 2 and 3- moderate then marked opacity of the cornea (grade 2 then 3), which covered the whole area of the cornea, from day 1 until day 3According to the severe reactions observed, this animal was sacrificed on day 3 for ethicalreasons.Test item at the concentration of 10%- a slight chemosis (grade 1) in all the animals on day 1- a slight redness of the conjunctiva (grade 1) in 2/3 animals on day 1, persiting in one of them on day 2. - a clear discharge in 1/3 animals on day 2Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.0 forchemosis, 0.0, 0.3 and 0.0 for redness of the conjunctiva, 0.0, 0.0 and 0.0 for iris lesions and 0.0,0.0 and 0.0 for corneal opacity.For details see Table 1.

Any other information on results incl. tables

Table 1: Individual ocular examinations and mean values of the scores recorded for each animal (24, 48 and 72 hours)

Rabbit number

Region of eye

Description of ocular

 

Scores

 

 

Mean irritation

reactions

1h, D1

24h, D2

48h, D3

72h, D4

score (1)

Undiluted test item

750

Conjunctivae

Chemosis

3

3

2

-

(2)

 

 

Redness

2

2

2

-

(2)

 

 

Discharge

E

2

1

-

(2)

 

Iris

 

0

1

1

-

(2)

 

Corneal opacity

Intensity

2

3

3

-

(2)

 

 

Area

2

4

4

-

(2)

 

Other

 

*

*

*

-

 

 

Fluorescein

 

/

U

U

-

 

Test item at the concentration of 10%

711

Conjunctivae

Chemosis

1

0

0

0

0.0

 

 

Redness

1

0

0

0

0.0

 

 

Discharge

E

1

0

0

0.3

 

Iris

 

0

0

0

0

0.0

 

Corneal opacity

Intensity

0

0

0

0

0.0

 

 

Area

0

0

0

0

0.0

 

Other

 

*

*

*

*

 

 

Fluorescein

 

/

U

/

/

 

712

Conjunctivae

Chemosis

1

0

0

0

0.0

 

 

Redness

1

1

0

0

0.3

 

 

Discharge

E

0

0

0

0.0

 

Iris

 

0

0

0

0

0.0

 

Corneal opacity

Intensity

0

0

0

0

0.0

 

 

Area

0

0

0

0

0.0

 

Other

 

*

*

*

*

 

 

Fluorescein

 

/

U

/

/

 

736

Conjunctivae

Chemosis

1

0

0

0

0.0

 

 

Redness

0

0

0

0

0.0

 

 

Discharge

E

0

0

0

0.0

 

Iris

 

0

0

0

0

0.0

 

Corneal opacity

Intensity

0

0

0

0

0.0

 

 

Area

0

0

0

0

0.0

 

Other

 

*

*

*

*

 

 

Fluorescein

 

/

U

/

/

 

(1) mean of scores on days 2, 3 and 4

(2) = not calculable

h = hour

D = day

* = none

U = fluorescein batch No. P756

/ = fluorescein not used

E = scoring masked by residual test item

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
the potential of the test item R0034833C (batch No. R0034833C 027 P 001) at the concentration of 10% in purified water to induce ocular irritation was evaluated in rabbits according to OECD (No. 405, 24th April 2002) and EC (2004/73/EC, part B.5, 29th April 2004) and GLP.Under the experimental conditions of the study, the undiluted test item R0034833C (batch No. R0034833C 027 P 001) caused severe effects in the rabbit eye. The animal had to be killed for humane reasons based on the inflicted effects.Under the experimental conditions of the study, the test item at the concentration of 10% in purified water was well-tolerated when administered by ocular route to rabbits.
Executive summary:

The potential of the test item Mexoryl SBO (termed R0034833C in the study report, batch No. R0034833C 027 P 001) undiluted and at the concentration of 10% in purified water to induce ocular irritation was evaluated in rabbits.

The study was conducted in compliance with the principles of Good Laboratory Practice

Regulations.

The undiluted test item was first administered to a single male New Zealand White rabbit. Since the test item showed severe irritant properties on this first animal, the undiluted test item was not evaluated on other animals.

At the request of the Sponsor, a second assay was performed with the test item at the concentration of 10%. The dosage form was first administered to a single animal. Since the dosage form was not severely irritant on this animal, it was then evaluated simultaneously in two other animals.

A single dose of 0.1 mL of the undiluted test item or test item at the concentration of 10% (w/w) was instilled into the left conjunctival sac. The right eye was not treated and served as control. 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. The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal.

Undiluted test item (one animal):

A marked then moderate chemosis and a moderate redness of the conjunctiva were observed from day 1. A clear discharge and an iritis was noted on days 2 and 3. Moderate then marked opacity of the cornea, which covered the whole area of the cornea, was noted from day 1. According to the severe reactions observed, this animal was sacrificed on day 3 for ethicalreasons.

Test item at the concentration of 10%:

A slight chemosis was noted in all the animals on day 1. A slight redness of the conjunctiva was noted in 2/3 animals on day 1; it persisted in one of them on day 2. A clear discharge was noted in 1/3 animals on day 2. Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.0 for chemosis, 0.0, 0.3 and 0.0 for redness of the conjunctiva, 0.0, 0.0 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for corneal opacity.

Under the experimental conditions of the study, the undiluted test item R0034833C (batch No. R0034833C 027 P 001) caused severe effects in the rabbit eye.

Under the experimental conditions of the study, the test item R0034833C (batch No. R0034833C 027 P 001) at the concentration of 10% in purified water was well-tolerated when administered by ocular route to rabbits.

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