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Registration Dossier
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EC number: 264-727-7 | CAS number: 64194-22-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
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- Endpoint summary
- Stability
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- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
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- Toxicological Summary
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- Acute Toxicity
- Irritation / corrosion
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- Additional toxicological data

Endpoint summary
Administrative data
Description of key information
Two in vitro studies (Valin 2013) are available to evaluate the skin irritation potential of 3-methyl-1,5-pentanediyl diacrylate : The in vitro irritation test is positive and the in vitro corrosion test is negative; Therefore 3-methyl-1,5-pentanediyl diacrylate is considered to be a skin irritating.
An in vivo eye irritation study is available on rabbits: 3-methyl-1,5-pentanediyl diacrylate is considered to be an eye irritating.
Moreover respiratory irritation was observed in the acute toxicity by inhalation.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 15 April 2013 - 29 April 2013
- 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:
- yes
- Remarks:
- see below
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guideline 439 (In vitro dermal irritation)
- Deviations:
- no
- Principles of method if other than guideline:
- The study was performed in accordance with study plan with the following deviations from the agreed study plan:
. § Test for direct MTT reduction with the test item: due to a typing error in the study plan, the volume of MTT solution used for the negative control in the preliminary test for direct MTT reduction which is specified in the study plan is incorrect. Indeed, the volume of MTT solution used in this study was 2 mL (as described in CiToxLAB’s SOP) instead of 2.2 mL. This deviation was considered not to have compromised the validity or integrity of the study, - GLP compliance:
- yes (incl. QA statement)
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- other: reconstructed human epidermis
- Details on animal used as source of test system:
- EpiskinTM Model Kit (0.38 cm2 tissues) supplied by SkinEthic Laboratories, Lyon, France.
Medium and Incubation T°C: 37°C
Dates of experimental phase: from 23 April 2013 to 29 April 2013 - Vehicle:
- unchanged (no vehicle)
- Details on test system:
- REMOVAL OF TEST SUBSTANCE
- Rinsing: at the end of the treatment period, each tissue was removed from the well of the treatment plate, and rinsed with D-PBS. Rinsing was achieved by gently filling and emptying several times each tissue with D-PBS to gently remove any residual test or control items. Excess D-PBS was removed by blotting the bottom of the tissue culture insert with absorbent paper.
The rinsed tissues were transferred to the second column of 3 wells containing 2 mL of maintenance medium in each well and the plates were incubated at +37°C, 5% CO2 in a humidified incubator for 42 (± 1) hours.
POSITIVE CONTROL
Sodium Dodecyl Sulphate (SDS) at a 5% (w/v) aqueous solution.
NEGATIVE CONTROL
Name: Dulbecco’s Phosphate-Buffered Saline (D-PBS).
SCORING SYSTEM:
- Optical density (OD) was measured at 570 nm:
Relative mean viability (%) = 100 x mean cOD(test item) / mean cOD(negative control)
where:
- mean cOD Negative Control = mean ODNC – mean ODblank
- mean cOD Test Item = mean ODTI – mean ODblank
Interpretation: see below - Control samples:
- yes, concurrent no treatment
- yes, concurrent positive control
- Amount/concentration applied:
- Amount applied per tissue: 10 ± 2 µL
- Duration of treatment / exposure:
- Exposure period of 15 minutes, followed by a 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, after a 3-hour MTT incubation
- Number of replicates:
- Triplicate for each tested substance (test item, negative control, positive control).
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 15 minute exposure (treated)
- Value:
- 6
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- Preliminary tests
In the preliminary tests, the test item was found not to have direct MTT reducing properties or a 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 a 42-hour recovery period, the relative mean viability of the tissues treated with the test item was 6% with a standard deviation of 1%. As the mean viability was < 50% after the MTT reduction, the results met the criteria for an in vitro classification as irritant (R38) to skin. - Interpretation of results:
- Category 2 (irritant) based on GHS criteria
- Conclusions:
- Under the experimental conditions of this study, the test item is considered to be irritant to skin.
- Executive summary:
The objective of this study was to evaluate the skin irritation potential of the test item using the EpiskinTMreconstructed 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’s 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 topically applied on triplicate tissues and incubated at room temperature for 15 (± 1) minutes. At the end of the treatment period, each tissue was rinsed with D-PBS and incubated for 42 (± 1) hours at, 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
Preliminary tests
In the preliminary tests, the test item was found not to have direct MTT reducing properties or a 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 a 42-hour recovery period, the relative mean viability of the tissues treated with the test item was 6% with a standard deviation of 1%. As the mean viability was < 50% after the MTT reduction, the results met the criteria for an in vitro classification as irritant (R38) to skin.
Conclusion
Under the experimental conditions of this study, the test item is considered to be irritant to skin.
According to the results of this study, the classification of the test item should be:
- irritant (R38) (Directive 67/548/EEC) and category 2 (H315) (Regulation (EC) No. 1272/2008).
- Endpoint:
- skin corrosion: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 22 May 2013 - 13 June 2013
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guideline 431 (In vitro human skin corrosion)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: EU Method B.40 bis (In vitro human skin corrosion)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- other: reconstructed human epidermis
- Details on animal used as source of test system:
- Episkin TM Model Kit (0.38 cm2 tissues) supplied by SkinEthic Laboratories, Lyon, France.
Medium and Incubation T°C: 37°C
Dates of experimental phase: from 04 June 2013 to 13 June 2013 - Vehicle:
- unchanged (no vehicle)
- Details on test system:
- REMOVAL OF TEST SUBSTANCE
- Rinsing: For all treated tissues (test item-treated, positive and negative controls), at the end of the designated incubation periods, each tissue insert was removed from the well of the treatment plate, and rinsed with D-PBS.
Rinsing was achieved by gently filling and emptying several times each tissue with D-PBS to gently remove any residual dose formulation.
POSITIVE CONTROL
Name: glacial acetic acid.
The supplier and batch number of the positive control used are documented in the study files.
NEGATIVE CONTROL
Name: 0.9% NaCl.
The supplier and batch number of the negative control used are documented in the study files.
SCORING SYSTEM:
- Optical density (OD) was measured at 570 nm:
Relative mean viability (%) = 100 x mean cOD(test item) / mean cOD(negative control)
where:
- mean cOD Negative Control = mean ODNC – mean ODblank
- mean cOD Test Item = mean ODTI – mean ODblank
Interpretation: see below - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- Amount applied per tissue: 50 µL
- Duration of treatment / exposure:
- For the test item, exposure periods of 3 minutes, 60 and 240 minutes, followed by rinsing.
For the positive and negative controls, exposure period of 240 minutes only, followed by rinsing. - Duration of post-treatment incubation (if applicable):
- MTT-loading after rinsing. Observation of MTT-> formazan transformation by viable cells, after 3-hour MTT incubation.
- Number of replicates:
- Duplicate tissues for each treatment period and tested substance (test item, negative control, positive control)
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 3 minutes exposure (treated)
- Value:
- 102
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 1 hour exposure (treated)
- Value:
- 115
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 4 hours exposure (treated)
- Value:
- 126
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- Preliminary test
As the MTT solution color did not turn blue/purple when compared to the negative control, the test item is presumed not to reduce MTT. As a result, no additional controls were performed on water-killed tissues in parallel to the main test.
Main test
All acceptance criteria for the negative and positive controls were fulfilled, therefore the study was considered to be valid.
At the end of the MTT incubation period, any tissue discoloration was evaluated with the naked eye. A blue discoloration of the test item-treated tissues following the 3 minutes, 1 hour and 4 hours exposure periods was noted. This discoloration was representative of viable tissues.
The relative mean viabilities of the test item-treated tissues were calculated for each time exposure treatment:
- 102% for the 3 minutes exposure,
- 115% for the 1 hour exposure,
- 126% for the 4 hours exposure.
These values being higher than 35%, the criteria for a non corrosive response were reached. - Interpretation of results:
- other: not corrosive
- Conclusions:
- The test item tested in its original form, is considered to be non corrosive to the skin.
- Executive summary:
The objective of this study was to evaluate the skin corrosive potential of the test item using the EpiskinTMreconstructed human epidermis model.
The study design was based upon international guidelines (OECD Guideline No. 431 and Commission Regulation (EC) No. 440/2008, B.40bis). The study was conducted in compliance with CiToxLAB’s standard operating procedures and the principles of Good Laboratory Practice.
Methods
A preliminary test was performed to detect the ability of the test item to interfere with cell viability measurements by directly reducing MTT.
Following the preliminary test, the corrosive potential of the test item was tested in the main assay. The test item, the negative and positive controls were topically applied on duplicate tissues and incubated at room temperature as follows: positive and negative controls for 4 hours (± 5 minutes); test item for 3 minutes (± 5 seconds), 1 hour (± 5 minutes) and 4 hours (± 5 minutes).
At the end of the designated incubation periods, each tissue was rinsed with D-PBS. The cell viability was then assessed by means of the 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
Preliminary test
As the MTT solution color did not turn blue/purple when compared to the negative control, the test item is presumed not to reduce MTT. As a result, no additional controls were performed on water-killed tissues in parallel to the main test.
Main test
All acceptance criteria for the negative and positive controls were fulfilled, therefore the study was considered to be valid.
At the end of the MTT incubation period, any tissue discoloration was evaluated with the naked eye. A blue discoloration of the test item-treated tissues following the 3 minutes, 1 hour and 4 hours exposure periods was noted. This discoloration was representative of viable tissues.
The relative mean viabilities of the test item-treated tissues were calculated for each time exposure treatment:
- 102% for the 3 minutes exposure,
- 115% for the 1 hour exposure,
- 126% for the 4 hours exposure.
These values being higher than 35%, the criteria for a non corrosive response were reached.
Conclusion
Under the experimental conditions of this study, the test item tested in its original form, is considered to be non corrosive to the skin.
According to these results, the classification of the test item is the following:
- non corrosive (Directive 67/548/EEC, ECE/TRANS/215 (Vol. I) and Regulation 1272/2008/EEC).
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Eye irritation
Link to relevant study records
- 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
- 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 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 - 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 - 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
- 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
- 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
- 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
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 3
- Max. score:
- 3
- Reversibility:
- fully reversible within: day 14
- 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
- Irritation parameter:
- iris score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 1
- Reversibility:
- fully reversible within: day 9
- 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. - 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".
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Additional information
In vitro skin corrosion test (Valin 2013):
The objective of this study was to evaluate the skin corrosive potential of the test item using the EpiskinTM reconstructed human epidermis model (OECD 431). Following the preliminary test, the corrosive potential of the test item was tested in the main assay. The test item, the negative and positive controls were topically applied on duplicate tissues and incubated at room temperature as follows: positive and negative controls for 4 hours (± 5 minutes); test item for 3 minutes (± 5 seconds), 1 hour (± 5 minutes) and 4 hours (± 5 minutes). At the end of the designated incubation periods, each tissue was rinsed with D-PBS. The cell viability was then assessed by means of the MTT reduction.
At the end of the MTT incubation period, any tissue discoloration was evaluated with the naked eye. A blue discoloration of the test item-treated tissues following the 3 minutes, 1 hour and 4 hours exposure periods was noted. This discoloration was representative of viable tissues.
The relative mean viabilities of the test item-treated tissues were calculated for each time exposure treatment: 102% for the 3 minutes exposure,115% for the 1 hour exposure, and, 126% for the 4 hours exposure.These values being higher than 35%, the criteria for a non corrosive response were reached.Under the experimental conditions of this study, the test item tested in its original form, is considered to be non corrosive to the skin.
In vitro skin irritation test (Valin 2013):
The objective of this study was to evaluate the skin irritation potential of the test item using the EpiskinTM reconstructed human epidermis model (OECD 439). 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 topically applied on triplicate tissues and incubated at room temperature for 15 (± 1) minutes. At the end of the treatment period, each tissue was rinsed with D-PBS and incubated for 42 (± 1) hours at, 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). Following a 15 minutes exposure and a 42-hour recovery period, the relative mean viability of the tissues treated with the test item was 6% with a standard deviation of 1%. As the mean viability was < 50% after the MTT reduction, the results met the criteria for anin vitroclassification as irritant to skin.Under the experimental conditions of this study, the test item is considered to be irritating to skin.
In vivo eye irritation test (Leclere 2014):
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 (OECD 405).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 rinsed before 24-hour reading.
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.
Under the experimental conditions of this study, the test item was severely irritant when administered by ocular route to rabbits.
Respiratory irritation (acute inhalation study, TNO 2016) :
In the acute study, respiratory irritation was evident in animals exposed to 3 -methyl-1.5 -pentanediyl diacrylate. Indeed, hemarrhagic nasal discharge was observed until day 6 in five out of 6 animals exposed to 1.05 g/m3, and nasal discharge was observed on the day of exposure in 5 out of 6 animals exposed to 5.14 g/m3.
Justification for classification or non-classification
Based on the in vitro and in vivo studies, 3-methyl-1,5-pentanediyl diacrylate is irritating for skin, eyes and respiratory tract according to the Regulation EC n°1272/2008 : Skin Irrit. 2 (H315: Causes skin irritation), Eye Irrit. 2 (H319: Causes serious eye irritation), STOT SE 3 (H335: May cause respiratory irritation).
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