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

Endpoint summary

Description of key information

Based on both studies available (OECD 439 and 404), Glycerol, propoxylated, esters with acrylic acid, reaction products with diethylamine is considered to be slightly irritating on skin but not classified according to the CLP regulation. However the substance is severely irritating to the eyes, according to the in vivo study performed on rabbits (OECD 405). 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 February 2015 - 23 March 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder: CEGAV, Argenvilliers, France
- Age at study initiation: at the beginning of the study, the animals were 2 to 4 months old
- Mean body weight at study initiation: 2623 g ± 196.2 g
- 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 treatment.

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 (7:00 - 19:00)

IN-LIFE DATES: 10 March 2015 to 23 March 2015.

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL/flank.

Duration of treatment / exposure:

3 min, 1 h, 4 h.

Observation period:

1, 24, 48 and 72 h after removal of the dressing; if relevant, daily until reversibility of reactions

Number of animals:

Three males.

Details on study design:

TEST SITE
- Area of exposure: two or four areas of skin (3.5 cm x 5 cm) on the right and left anterior and/or posterior flanks of animals
- Coverage: 6 cm2
- Type of wrap if used: gauze pad held in place by a non-irritation semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: using a dry cotton pad
- Time after start of exposure: at removal of each dressing (see Duration of exposure).

SCORING SYSTEM:

- Erythema and eschar formation:
0 no erythema
1 very slight erythema (barely perceptible)
2 well-defined erythema
3 moderate to severe erythema
4 severe erythema (beet redness) to slight eschar formation (injuries in depth)

- Edema formation:
0 no edema
1 very slight edema (barely perceptible)
2 slight edema (edges of area well-defined by definite raising)
3 moderate edema (raised approximately 1 millimeter)
4 severe edema (raised more than 1 millimeter and extending beyond area of exposure)

- Any other lesions were noted

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24, 48, 72 h (mean)

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: Day 4

Remarks on result:

other: 72 h

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24, 48, 72 h (mean)

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24, 48, 72 h (mean )

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24, 48, 72 h (mean)

Score:

1

Max. score:

1

Reversibility:

fully reversible within: Day 7

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24, 48, 72 h (mean)

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24, 48, 72 h (mean )

Score:

0

Max. score:

0

Irritant / corrosive response data:

After a 4-hour exposure (three animals), a very slight erythema was noted in 1/3 animals on Days 2 and 3 and in the two other animals from Day 1 to Day 3 or 6. Dryness of the skin was recorded in 2/3 animals from Day 2 or 3 until Day 6.
 
Mean scores calculated for each animal over 24, 48 and 72 hours were as follows:
.            erythema: 0.7, 0.7, 1.0; showing slight irritating properties but no significant inflammation,
.            edema: 0.0, 0.0, 0.0; showing no inflammation.

Other effects:

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

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions of this study, the test item was non-irritant when applied topically to rabbits.

Executive summary:

The objective of this study was to evaluate the potential corrosive and irritant properties of the test item following dermal application on rabbits.

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

 

Methods

The test item was first applied for periods of 3 minutes, 1 hour and 4 hours to a single male New Zealand White rabbit.

After the 4-hour application, since the mean value from grading at 24, 48 and 72 hours after patch removal was < 2.3 for erythema and for edema, the test item was applied on the skin of two otheranimalsfor 4 hours.

A dosage-volume of 0.5 mL/flank was used.

The test item was placed on a gauze pad, which was then applied to a skin area of approximately 6 cm². The gauze pad was held in place by a non-irritation semi-occlusive dressing and a restraining bandage. After required period of contact with the skin, the dressing was removed.

Each animal was observed once a day for mortality and clinical signs. For each exposure period, cutaneous reactions were evaluated approximately 1, 24, 48 and 72 hours after removal of the dressingand then daily until the reversibility of cutaneous reactions. The mean values of the scores for erythema and edema were calculated for each animal. Body weight was recorded on the day of treatment and at the end of the evaluation of cutaneous 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 were noted in any animals.

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

After a 4-hour exposure (three animals), a very slight erythema was noted in 1/3 animals on Days 2 and 3 and in the two other animals from Day 1 to Day 3 or 6.

Dryness of the skin was recorded in 2/3 animals from Day 2 or 3 until Day 6.

 

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

.            erythema: 0.7, 0.7, 1.0; showing slight irritating properties but no significant inflammation,

.            edema: 0.0, 0.0, 0.0; showing no inflammation.

 

Conclusion

Under the experimental conditions of this study, the test item was non-irritant when applied topically to rabbits. Therefore, the test item should not be classified as irritating to skin according to the criteria of CLP Regulation.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 November 2014 -- 08 December 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: EU Method B.46 (In vitro dermal irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: OECD Guideline 439 (In vitro dermal irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test system:

human skin model

Source species:

human

Cell type:

other: reconstructed human epidermis

Cell source:

other: EpiskinTM Model Kit (0.38 cm2 tissues) supplied by SkinEthic Laboratories, Lyon, France.

Control samples:

yes, concurrent vehicle

yes, concurrent positive control

Amount/concentration applied:

Amount applied (volume or weight with unit): 10 µL (+/- 2 µL)

Duration of treatment / exposure:

Exposure period of 15 minutes, followed by rinsing

Duration of post-treatment incubation (if applicable):

MTT-loading after a 42h-incubation period following rinsing. Observation of MTT-> formazan transformation by viable cells.

Number of replicates:

3

Irritation / corrosion parameter:

% tissue viability

Value:

98

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Remarks:

Basis: mean. Time point: 15 min exposure + 42h expression. Reversibility: no data not applicable. Remarks: 100% = control.

Other effects / acceptance of results:

In the preliminary tests, the test item was found not to have direct MTT reducing properties or colouring potential.
Main test: All acceptance criteria for the negative and positive controls were fulfilled. The study was therefore considered to be valid.
Following a 15 minutes exposure and 42 hours of recovery period, the relative mean viability of the tissues treated with the test item was 98 % with a standard deviation of 4%. As the mean viability was > 50% after the MTT reduction, the results met the criteria for a non-irritant response.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions of this study, the test item is considered to be non irritant to skin.

Executive summary:

The objective of this study was to evaluate the skin irritation potential of the test item using the EpiskinTM reconstructed human epidermis model.

The study design was based upon international guidelines (OECD Guideline No. 439 and Commission Regulation (EC) No. 761/2009, B.46). The study was conducted in compliance with CiToxLAB France standard operating procedures and the principles of Good Laboratory Practice.

 

Methods

Preliminary tests were performed to detect the ability of the test item to directly reduce MTT as well as its colouring potential.

Following the preliminary tests, the skin irritation potential of the test item was tested in the main test. The test item and both the negative and positive controls were applied topically on triplicate tissues and incubated at room temperature for 15 minutes. At the end of the treatment period, each tissue was rinsed with D-PBS and incubated for 42 hours at 37°C, 5% CO2 in a humidified incubator. The cell viability was then assessed by means of the colourimetric MTT reduction assay.

Relative viability values were calculated for each tissue and expressed as a percentage of the mean viability of the negative control tissues which was set at 100% (reference viability).

 

Results

 

In the preliminary tests, the test item was found not to have direct MTT reducing properties or colouring potential.

In the main test, all acceptance criteria for the negative and positive controls were fulfilled. The study was therefore considered to be valid.

Following a 15 minutes exposure and 42 hours of recovery period, the relative mean viability of the tissues treated with the test item was 98% with a standard deviation of 4%. As the mean viability was > 50% after the MTT reduction, the results met the criteria for a non-irritant response.

 

Conclusion

Under the experimental conditions of this study, the test item is considered to be non irritant to skin.

According to the results of this study, the classification of the test item should be:

- not classified (Directive 67/548/EEC) and no category (Regulation (EC) No. 1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

SKIN IRRITATION

In vitro skin irritation test (Gerbeix, CIToxLAB, 2015)

The objective of this study was to evaluate the skin irritation potential of the test item using the EpiskinTM reconstructed human epidermis model.

The study design was based upon international guidelines (OECD Guideline No. 439 and Commission Regulation (EC) No. 761/2009, B.46).

Preliminary tests were performed to detect the ability of the test item to directly reduce MTT as well as its colouring potential.

Following the preliminary tests, the skin irritation potential of the test item was tested in the main test. The test item and both the negative and positive controls were applied topically on triplicate tissues and incubated at room temperature for 15 minutes. At the end of the treatment period, each tissue was rinsed with D-PBS and incubated for 42 hours at 37°C,5% CO2 in a humidified incubator. The cell viability was then assessed by means of the colourimetric MTT reduction assay. Relative viability values were calculated for each tissue and expressed as a percentage of the mean viability of the negative control tissues which was set at 100% (reference viability). 

In the preliminary tests, the test item was found not to have direct MTT reducing properties or colouring potential.

In the main test, all acceptance criteria for the negative and positive controls were fulfilled. The study was therefore considered to be valid.

Following a 15 minutes exposure and 42 hours of recovery period, the relative mean viability of the tissues treated with the test item was 98% with a standard deviation of 4%. As the mean viability was > 50% after the MTT reduction, the results met the criteria for a non-irritant response.

Under the experimental conditions of this study, the test item is considered to be non irritant to skin.

However, due to the composition of the test item and based on the irritating potential of on the test item on eye irritation studies, the Registrant decided to perform an in vivo study to evaluation the skin irritating potential of the test item, to be sure that the substance will be not mis-classified.

In vivo skin irritation test (Leclere, CIToxLAB, 2015)

The objective of this study was to evaluate the potential corrosive and irritant properties of the test item following dermal application on rabbits (OECD 404).

The test item was first applied for periods of 3 minutes, 1 hour and 4 hours to a single male New Zealand White rabbit. After the 4-hour application, since the mean value from grading at 24, 48 and 72 hours after patch removal was < 2.3 for erythema and for edema, the test item was applied on the skin of two other animals for 4 hours.

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

After a 4-hour exposure (three animals), a very slight erythema was noted in 1/3 animals on Days 2 and 3 and in the two other animals from Day 1 to Day 3 or 6. Dryness of the skin was recorded in 2/3 animals from Day 2 or 3 until Day 6.

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

.            erythema: 0.7, 0.7, 1.0; showing slight irritating properties but no significant inflammation,

.            edema: 0.0, 0.0, 0.0; showing no inflammation.

In conclusion, under the experimental conditions of this study, the test item was non-irritant when applied topically to rabbits. Therefore, the test item should not be classified as irritating to skin according to the criteria of CLP Regulation.

EYE IRRITATION

BCOP / eye corrosion test (Gerbeix, CIToxLAB, 2015)

The objective of this study was to evaluate the potential irritant and corrosive properties of the test item to the eye. The Bovine Corneal Opacity and Permeability (BCOP) test method can identify chemicals inducing serious eye damage and chemicals not requiring classification for eye irritation or serious eye damage.The design of this study was based on the guideline OECD Guideline 437

All acceptance criteria were fulfilled. The study was therefore considered as valid. The meanIn Vitro Irritancy Score (IVIS) of the test item-treated corneas was: 22. As the test item-induced a mean IVIS > 3 and = 55, the eye hazard potential of the test item could not be predicted. The test item could not be identified as inducing serious eye damage (UN GHS Category 1) or as a test chemical not requiring classification for eye irritation or serious eye damage (UN GHS No Category).

In vivo eye irritation test (Modeste, CIToxLAB, 2015)

The objective of this study was to evaluate the potential eye irritant properties of the test item following a single ocular administration to rabbits (OECD 405). The test item was first administered to a single male New Zealand White rabbit, and then to 2 other animals.

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.

 

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

Justification for classification or non-classification

Skin irritation: No CLP classification is required based on both available studies. In the rabbit study, Glycerol, propoxylated, esters with acrylic acid, reaction products with diethylamine is slightly irritating to skin but the criteria of CLP classification are not fulfilled. No classification as skin irritating is required for this substance according to the Regulation EC no.1272/2008.

Eye irritation: Based on the in vivo study on rabbits (OECD 405), Glycerol, propoxylated, esters with acrylic acid, reaction products with diethylamine should be classified as corrosif to the eye (Eye Dam. 1) according to the Regulation EC no.1272/2008 based on the high score of cornea opacity and the non-reversibility of the effects in one animal after 21 -day of observation.