3-methyl-1,5-pentanediyl diacrylate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 June 2013 -22 July 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2014

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 (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

3-methyl-1,5-pentanediyl diacrylate

EC Number:

264-727-7

EC Name:

3-methyl-1,5-pentanediyl diacrylate

Cas Number:

64194-22-5

Molecular formula:

C12H18O4

IUPAC Name:

3-methyl-5-(prop-2-enoyloxy)pentyl prop-2-enoate

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: breeder: CEGAV, Argenvilliers, France
- Age at study initiation: 2 to 4 months old at the beginning of the study
- Mean body weight at study initiation: 3730 g and 4240 g
- Fasting period before study: no
- Housing: individually housed in noryl cages
- Diet: 110 pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: 02 July 2013 to 22 July 2013

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated right eye served as a control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL/animal

Duration of treatment / exposure:

Not applicable: single application not followed by rinsing.

Observation period (in vivo):

1, 24, 48 and 72 h after administration of the test item; if relevant, daily until reversibility of reactions

Number of animals or in vitro replicates:

two males

Details on study design:

REMOVAL OF TEST SUBSTANCE: No

SCORING SYSTEM: Draize scale.

- Conjunctival chemosis (lids and/or nictitating membranes):
0 no swelling
1 any swelling above normal (includes nictitating membranes)
2 obvious swelling with partial eversion of lids
3 swelling with lids about half-closed
4 swelling with lids more than half-closed

- Conjunctival redness (palpebral and bulbar conjunctivae, cornea and iris):
0 blood vessels normal
1 a number of blood vessels definitely hyperemic (injected)
2 diffuse, crimson colour, individual vessels not easily discernible
3 diffuse, beefy red

- Iris lesions
0 normal
1 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)
2 no reaction to light, haemorrhage, gross destruction (any or all of these)

- Cornea intensity of opacity (direct examination and, if necessary, with an UV lamp)
0 no ulceration or opacity
1 scattered or diffuse areas of opacity (other than slight dulling or normal lustre), details of iris clearly visible
2 easily discernible translucent area, details of iris slightly obscured
3 nacreous areas, no details of iris visible, size of pupil barely discernible
4 opaque cornea, iris not discernible through the opacity

- Cornea area of opacity (direct examination and, if necessary, with an UV lamp)
1 one quarter (or less) but not zero
2 greater than one quarter but less than a half
3 greater than one half but less than three quarters
4 greater than three quarters up to whole area

- Any other lesions observed were noted

TOOL USED TO ASSESS SCORE: UV lamp after instillation of 0.5% sodium fluorescein solution

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: day 21

Results 2

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: day 12

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: day 10

Results 4

Irritation parameter:

cornea opacity score

Remarks:

(intensity)

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: day 7

Results 5

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: day 14

Results 6

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: day 12

Results 7

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: day 9

Results 8

Irritation parameter:

cornea opacity score

Remarks:

(intensity)

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: day 8

Irritant / corrosive response data:

First animal:
In the left treated eye, moderate chemosis of the conjunctiva was noted on days 1 and 2, becoming marked on day 3 and severe from days 4 to 6. Then, marked chemosis was observed again on days 7 to 9, becoming moderate on day 10 and slight on days 11 up to 20. Moderate redness of the conjunctiva was observed from day 1 to day 9, becoming slight until day 11.
Iris lesions was noted from day 3 and persisted up to day 9.
Moderate corneal opacity was recorded on day 3, becoming marked on day 4 up to day 6.
A moderate alopecia was observed around the eye on days 9 to 19, becoming slight on day 20.
Lacrimation was observed from days 3 to 11, associated with a white thick discharge from days 4 to 6 and neovascularisation from days 5 to 7.

Second animal:
In the left treated eye, moderate chemosis of the conjunctiva was noted on day 1, becoming marked on day 2 up to day 7 and moderate again from days 8 to 10. Then, a slight chemosis persisted up to day 13.
Moderate redness of the conjunctiva was observed on day 1, becoming marked from days 2 to 4 and moderate again from days 5 to 8. Then, a slight redness persisted up to day 11.
Iris lesions were noted on day 2 and persisted up to day 8.
Moderate corneal opacity was recorded on days 2 to 6, becoming slight on day 7. Then it completely disappeared.
A slight alopecia was observed around the eye on days 3 to 12, becoming moderate on days 13 and 14.
Lacrimation was observed on days 3 to 6, associated with a whitish thick discharge from days 4 to 6.
 
Mean scores calculated for each animal over 24, 48 and 72 hours were as follows:
- chemosis: 3.0 and 3.0;
- redness of the conjunctiva: 2.0 and 3.0;
- iris lesions: 0.7 and 1.0;
- corneal opacity: 1.7 and 2.0.
 
All these scores were indicative of eye irritation.

Other effects:

No unscheduled deaths occurred during the study and no clinical signs indicative of systemic toxicity were noted in any animals.
The body weight of the animals was unaffected by the test item treatment.

Applicant's summary and conclusion

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Conclusions:

Under the experimental conditions of this study, the test item was severely irritant when administered by ocular route to rabbits.

Executive summary:

The objective of this study was to evaluate the potential irritant properties of the test item for the eye following a single administration to rabbits.

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

 

Methods

 

The test item was first administered to a single male New Zealand White rabbit.

 

As mean value from grading at 24, 48 and 72 hours after instillation was = 2 for conjunctival edema (chemosis) and for conjunctival redness, and = 1 for corneal opacity, the test item was administered in the left eye of a second animal.

 

After administration to the second animal,as mean value from grading at 24, 48 and 72 hours after instillation was = 2 for conjunctival edema (chemosis) and for conjunctival redness, and = 1 for iris lesions and for corneal opacity, no other animal was treated.

 

The test item was administered inthe conjunctival sac of the left eye. The right eye remained untreated and served as control.

A dosage-volume of 0.1 mL/animal was used.

 

For both animals, a local anesthetic was used prior to treatment.

 

The eyes were not rinsedbefore 24-hour reading.

 

Each animal was observed at least once a day for mortality and clinical signs.

Ocular reactions were observed approximately 1, 24, 48 and 72 hours after the administration and then daily until the 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. Body weight was recorded on the day of treatment and at the end of the evaluation of ocular reactions.

On completion of the observation period, the animals were sacrificed then discarded without macroscopic post-mortem examination.

Results

 

No unscheduled deaths occurred during the study and no clinical signs indicative of systemic toxicity were noted in any animals.

The body weight of the animals was unaffected by the test item treatment.

 

First animal:

In the left treated eye, moderate chemosis of the conjunctiva was noted on days 1 and 2, becoming marked on day 3 and severe from days 4 to 6. Then, marked chemosis was observed again on days 7 to 9, becoming moderate on day 10 and slight on days 11 up to 20. Moderate redness of the conjunctiva was observed from day 1 to day 9, becoming slight until day 11.

Iris lesions was noted from day 3 and persisted up to day 9.

Moderate corneal opacity was recorded on day 3, becoming marked on day 4 up to day 6.

A moderate alopecia was observed around the eye on days 9 to 19, becoming slight on day 20.

Lacrimation was observed from days 3 to 11, associated with a white thick discharge from days 4 to 6 and neovascularisation from days 5 to 7.

Second animal:

In the left treated eye, moderate chemosis of the conjunctiva was noted on day 1, becoming marked on day 2 up to day 7 and moderate again from days 8 to 10. Then, a slight chemosis persisted up to day 13.

Moderate redness of the conjunctiva was observed on day 1, becoming marked from days 2 to 4 and moderate again from days 5 to 8. Then, a slight redness persisted up to day 11.

Iris lesions were noted on day 2 and persisted up to day 8.

Moderate corneal opacity was recorded on days 2 to 6, becoming slight on day 7. Then it completely disappeared.

A slight alopecia was observed around the eye on days 3 to 12, becoming moderate on days 13 and 14.

Lacrimation was observed on days 3 to 6, associated with a whitish thick discharge from days 4 to 6.

 

Mean scores calculated for each animal over 24, 48 and 72 hours were as follows:

- chemosis: 3.0 and 3.0;

- redness of the conjunctiva: 2.0 and 3.0;

- iris lesions: 0.7 and 1.0;

- corneal opacity: 1.7 and 2.0.

 

All these scores were indicative of eye irritation.

 

Conclusion

 

Under the experimental conditions of this study, the test item was severely irritant when administered by ocular route to rabbits.

 

According to the criteria of CLP Regulation,the test item should be classified category 2 and assigned the signal word "warning" and the hazard statement "H319: causes serious eye irritation".