Glycerol, propoxylated, esters with acrylic acid, reaction products with diethylamine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 December 2014 -- 10 February 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

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:

Glycerol, propoxylated, esters with acrylic acid, reaction products with diethylamine

EC Number:

500-744-0

EC Name:

Glycerol, propoxylated, esters with acrylic acid, reaction products with diethylamine

Cas Number:

162492-10-6

Molecular formula:

(C3H8O3) (C3H6O)m(C3H2O)n ( C4H11N)o ; m (1-6) ; n (1-3) , o (1-3)

IUPAC Name:

Glycerol, propoxylated, esters with acrylic acid, reaction products with diethylamine

Test material form:

liquid

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 on the day of treatment
- Mean body weight at study initiation: 3053 g (range: 2945 g to 3110 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 7 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): 5 to 15 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: 06 January 2015 to 10 February 2015

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.

Observation period (in vivo):

1, 24, 48 and 72 h; if relevant, daily until reversibility of reactions

Number of animals or in vitro replicates:

Three males.

Details on study design:

REMOVAL OF TEST SUBSTANCE: At 24 hours (before scoring), both eyes of two males were rinsed with sterile isotonic
saline solution (0.9% NaCl).

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

- Discharge:
0 absence of discharge
1 slight discharge (does not include small amounts normally found in inner canthus)
2 discharge with moistening of lids and hairs adjacent to lids
3 discharge with moistening of lids and hairs on wide area around the eye

- 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:

other: 24, 48 and 72 h (mean)

Score:

2

Max. score:

3

Reversibility:

fully reversible within: day 13

Results 2

Irritation parameter:

other: redness score

Basis:

animal #1

Time point:

other: 24, 48 and 72 h (mean)

Score:

3

Max. score:

3

Reversibility:

fully reversible within: day 14

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24, 48 and 72 h (mean)

Score:

1

Max. score:

1

Reversibility:

fully reversible within: day 10

Results 4

Irritation parameter:

cornea opacity score

Remarks:

(intensity)

Basis:

animal #1

Time point:

other: 24, 48 and 72 h (mean)

Score:

3

Max. score:

3

Reversibility:

fully reversible within: day 10

Results 5

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24, 48 and 72 h (mean)

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: day 7

Results 6

Irritation parameter:

other: redness score

Basis:

animal #2

Time point:

other: 24, 48 and 72 h (mean)

Score:

2.7

Max. score:

3

Reversibility:

fully reversible within: day 10

Results 7

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24, 48 and 72 h (mean)

Score:

1

Max. score:

1

Reversibility:

fully reversible within: day 8

Results 8

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24, 48 and 72 h (mean)

Score:

2.7

Max. score:

3

Reversibility:

fully reversible within: day 10

Results 9

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24, 48 and 72 h (mean)

Score:

3

Max. score:

3

Reversibility:

fully reversible within: day 16

Results 10

Irritation parameter:

other: redness score

Basis:

animal #3

Time point:

other: 24, 48 and 72 h (mean)

Score:

3

Max. score:

3

Reversibility:

fully reversible within: day 16

Results 11

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24, 48 and 72 h (mean)

Score:

1

Max. score:

1

Reversibility:

fully reversible within: day 14

Results 12

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24, 48 and 72 h (mean)

Score:

3.7

Max. score:

4

Reversibility:

not fully reversible within: day 22

Irritant / corrosive response data:

In the left treated eye of the first animal, slight to severe conjunctiva lesions were recorded between Day 1 and Day 13, iris lesions were noted from Day 2 up to Day 9 and moderate to marked corneal opacity was seen between Day 2 and Day 9.
Ocular lesions were associated with neovascularisation, lacrimation and whitish deposit from Day 2 until Day 9 at the latest. Myosis was seen on Days 4 to 6 and half-closed eyes on Day 6. Then moderate alopecia, followed by scabs around the treated eye was also recorded from Day 7 until Day 10.
In the left treated eye of the second male, slight to severe conjunctiva lesions were observed between Day 1 and Day 9, accompanied by iris lesions until Day 7 and slight to marked corneal opacity until Day 9. Ocular lesions were associated lacrimation and myosis on Days 2 and 3.
In the left treated eye of the third male, slight to severe conjunctiva lesions were observed between Day 1 and Day 15, with iris lesions until Day 13 and slight to severe corneal opacity until the end of the observation period. Neovascularization, lacrimation, whitish deposit and myosis were also noted between
Day 2 and Day 22.

Mean scores calculated for each animal over 24, 48 and 72 hours were as follows:
. chemosis: 2.0, 1.7 and 3.0,
. redness of the conjunctiva: 3.0, 2.7 and 3.0,
. iris lesions: 1.0, 1.0 and 1.0,
. corneal opacity: 3.0, 2.7 and 3.7.

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 1 (irreversible effects on the eye) 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 eye irritant properties of the test item following a single ocular administration to rabbits.

This study was based on the international guidelines (OECD Guideline No. 405 and Commission Regulation (EC) No. 440/2008 of 30 May 2008, part B.5) and 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 [2-4] for conjunctival edema (chemosis) and for conjunctival redness,[1-1.5]for iris lesions and[3-4]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 [2-4] for conjunctival redness, [1-1.5] for iris lesions and [1-3] for corneal opacity, the test item was administered in the left eye of a third animal.

The test item was administered in the 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 all animals, a local anesthetic was used prior to treatment and the animals were placed under systemic analgesia throughout the study.

Before the 24-hour scoring, both eye of two animals were rinsed with a sterile isotonic saline solution (0.9% NaCl). Each animal was observed at least once a day for mortality and clinical signs. Ocular reactions were recorded approximately 1, 24, 48 and 72 hours after the administration and then daily until the end of the observation period. 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 once a week until 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.

In the left treated eye of the first animal, slight to severe conjunctiva lesions were recorded between Day 1 and Day 13, iris lesions were noted from Day 2 up to Day 9 and moderate to marked corneal opacity was seen between Day 2 and Day 9.

Ocular lesions were associated with neovascularisation, lacrimation and whitish deposit from Day 2 until Day 9 at the latest. Myosis was seen on Days 4 to 6 and half-closed eyes on Day 6. Then moderate alopecia, followed by scabs around the treated eye was also recorded from Day 7 until Day 10.

In the left treated eye of the second male, slight to severe conjunctiva lesions were observed between Day 1 and Day 9, accompanied by iris lesions until Day 7 and slight to marked corneal opacity until Day 9. Ocular lesions were associated lacrimation and myosis on Days 2 an

In the left treated eye of the third male, slight to severe conjunctiva lesions were observed between Day 1 and Day 15, with iris lesions until Day 13 and slight to severe corneal opacity until the end of the observation period. Neovascularization, lacrimation, whitish deposit and myosis were also noted between Day 2 and Day 22.

 

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

- chemosis: 2.0, 1.7 and 3.0,

- redness of the conjunctiva: 3.0, 2.7 and 3.0,

- iris lesions: 1.0, 1.0 and 1.0,

- corneal opacity: 3.0, 2.7 and 3.7.

 

Conclusion

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