Phenyl methacrylate

Endpoint summary

Description of key information

Skin irritation:
Not irritating; OECD guideline 404; GLP compliant; very slight skin reactions, fully reversible within 48 h
Eye irritation: 
Not irritating; OECD guideline 405; GLP compliant; grade 1 redness after 24 h, fully reversible after 48 h 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study. GLP.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 24 April 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

other: New Zealand White (Hsdlf:NZW)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 12 to 20 weeks
- Weight at study initiation: 2.34 to 2.69 kg
- Housing: individually in suspended cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 30 to 70
- Air changes (per hr): min. 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

3 min, 1, 4 h in first animal; 4 h in second animal

Observation period:

1, 24, 48, 72 h

Number of animals:

2

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: patches secured with surgical adhesive tape + wrapped in an elasticated corset

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: after patch removal: 3 min, 1, 4 h in first animal; 4 h in second animal

SCORING SYSTEM: as stipulated in OECD guideline 404 (Draize scale)

On the day before the test each rabbit was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.
One rabbit was initially treated. Three suitable sites were selected on the back of the rabbit. A quantity of 0.5 ml of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton gauze patch. Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset for the duration of the exposure period.
One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Any residual test item was removed by gentle swabbing with cotton wool soaked in distilled water.
After consideration of the skin reactions produced in the first animal, an additional animal was treated with 0.5 ml of test item. One patch was applied to the back of the rabbit and was allowed to remain in contact with the skin for a period of four hours.
Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation.

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No edema observed

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No irritation observed

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No edema observed

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

3 min exposure:
very slight erythema was noted at the treated skin site immediately and 1 h after patch removal

1 h exposure:
very slight erythema was noted at the treated skin site immediately and 1 h after patch removal

4 h exposure:
very slight erythema was noted at one treated site immediately after patch removal, at both treated sites 1 h after patch removal and at one treated site at the 24 h observation; all effects were fully reversible within 48 h

No corrosive effects were noted.

Other effects:

Both animals showed the expected body weight gains during the study period.

 

Skin reaction	Animal 1
	score after 0/1/24/48/72 h
3 min exposure
Erythema/eschar (max. score 4)	1/1/0/0/0
Edema (max. score 4)	0/0/0/0/0
1 h exposure
Eeythema/eschar (max. score 4)	1/1/0/0/0
Edema (max. score 4)	0/0/0/0/0

 

 

Skin reaction	Animal 1	Animal 2
	score after 0/1/24/48/72 h	score after 0/1/24/48/72 h
4 h exposure
Erytheme/eschar (max score 4)	1/1/1/0/0	0/1/0/0/0
Edema (max. score 4)	0/0/0/0/0	0/0/0/0/0

 

 

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)

Conclusions:

PHMA is not irritating to rabbit skin.

Executive summary:

In a primary dermal irritation study according to OECD guideline 404, adopted 24 April 2002, 2 male 12 to 20 weeks old New Zealand white rabbits were dermally exposed to 0.5 mL of PHMA (99.6% a.i.) for 4 h to 2.5 cm x 2.5 cm body surface area. In one of the animals additional patches were applied, which were removed after 3 min and 1 h. Animals then were observed for 3 days. Irritation was scored by the Draize method (OECD guideline 404).

3 min and 1 h semi-occluded applications of the test item to the intact skin of one rabbit produced very slight erythema (grade 1) immediately and 1 h after patch removal.

After 4 h exposure very slight erythema (grade 1) was noted at one treated site immediately after patch removal, at both treated sites 1 h after patch removal and at one treated site at the 24 h observation. All effects were fully reversible within 48 h.

No corrosive effects were noted.

PHMA was not irritating in this dermal irritation study.

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:

2012-08-20 to 2012-09-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study. GLP.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 24 April 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

other: New Zealand White (Hsdlf:NZW)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: 12 to 20 weeks
- Weight at study initiation: 2.38 to 2.89 kg
- Housing: individually in suspended cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 30 to 70
- Air changes (per hr): min. 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated left eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

eyes were not rinsed after application

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

2

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: light source from a standard ophthalmoscope

Initially, a single rabbit was treated. After consideration of the ocular responses produced in the first treated animal, a second animal was treated.

Irritation parameter:

chemosis score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No corneal or iridial effects were noted during the study.
Moderate conjunctival irritation was noted in both animals one hour after treatment (grade 2 conjunctival redness, grade 1 chemosis), minimal conjunctival irritation (grade 1 redness) at the 24 h observation. No irritating effects were observed after 48 h.

Other effects:

Both animals showed the expected body weight gains during the study.

Eye reaction	Animal 1	Animal 2
	Score after 1/24/48/72 h	Score after 1/24/48/72 h
Cornea, opacity (max. score 4)	0/0/0/0	0/0/0/0
Iris (max. score 2)	0/0/0/0	0/0/0/0
Conjunctivae, redness (max. score 3)	2/1/0/0	2/1/0/0
Conjunctivae, chemosis (max score 4)	1/0/0/0	1/0/0/0
Conjunctivae, discharge (max. score 3)	2/1/0/0	1/0/0/0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)

Conclusions:

PHMA is not irritating to the rabbit eye.

Executive summary:

In a primary eye irritation study according to OECD guideline 405 (adopted 24th April 2002), 0.1 mL of PHMA (99.6% a.i.) was instilled into the conjunctival sac of 2 male 12 to 20 weeks old New Zealand White rabbits without washing. Animals then were observed for 3 days.  Irritation was scored by the method of Draize.

No corneal or iridial effects were noted during the study. Moderate conjunctival irritation was noted in both animals one hour after treatment (grade 1 conjunctival redness, grade 1 chemosis), minimal conjunctival irritation (grade 1 redness) at the 24 h observation. No irritating effects were observed after 48 h. 

In this study, PHMA is not irritating to the rabbit eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Reliable (RL=1), relevant and adequate studies are available to assess the skin and eye irritation potential of PHMA:

 

Skin irritation

In a primary dermal irritation study according to OECD guideline 404, adopted 24 April 2002, 2 male 12 to 20 weeks old New Zealand white rabbits were dermally exposed to 0.5 mL of PHMA (99.6% a.i.) for 4 h to 2.5 cm x 2.5 cm body surface area. In one of the animals additional patches were applied, which were removed after 3 min and 1 h. Animals then were observed for 3 days. Irritation was scored by the Draize method (OECD guideline 404).

3 min and 1 h semi-occluded applications of the test item to the intact skin of one rabbit produced very slight erythema (grade 1) immediately and 1 h after patch removal. After 4 h exposure very slight erythema (grade 1) was noted at one treated site immediately after patch removal, at both treated sites 1 h after patch removal and at one treated site at the 24 h observation. All effects were fully reversible within 48 h. No corrosive effects were noted. PHMA was not irritating in this dermal irritation study.

 

Eye irritation

In a primary eye irritation study according to OECD guideline 405 (adopted 24th April 2002), 0.1 mL of PHMA (99.6% a.i.) was instilled into the conjunctival sac of 2 male 12 to 20 weeks old New Zealand White rabbits without washing. Animals then were observed for 3 days.  Irritation was scored by the method of Draize.

No corneal or iridial effects were noted during the study. Moderate conjunctival irritation was noted in both animals one hour after treatment (grade 2 conjunctival redness, grade 1 chemosis), minimal conjunctival irritation (grade 1 redness) at the 24 h observation. No irritating effects were observed after 48 h. In this study, PHMA is not irritating to the rabbit eye.

 

Respiratory irritation

No experimental data on the respiratory irritation of PHMA are available. There is an existing entry in Annex VI of Reg (EC) No 1272/2008; Index Number 607-134-00-4; monoalkyl or monoaryl or monoalkyaryl esters of methacrylic acid with the exception of those specified elsewhere in this Annex, that covers this substance. This entry includes classification as STOT SE 3; H335.

Due to the low volatility of PHMA it is, however, extremely unlikely that PHMA would be an irritant to the respiratory system. PHMA exerts a very low vapour pressure (0.5hPa) and the estimated saturated vapour pressure of <5ppm is 5 times lower than the lowest observed NOEL for a methacrylate ester - chronic NOEL of 25ppm for olfactory damage in the rat due to inhalation of methyl methacrylate, the smallest and most volatile methacrylate ester. Furthermore, as rats are considered more sensitive than humans to the development of olfactory damage by simple esters like PHMA, it is extremely unlikely that PHMA would in practice be irritant to the respiratory system in humans.

Nevertheless as a precautionary measure and In the absence of experimental data to confirm this, PHMA shall be regarded as STOT SE 3, H335.

This classification entry is valid for all specifications entered in Chapter 1.2.

 

There are no data gaps for the endpoint irritation/corrosion. No human information is available for this endpoint. However, there is no reason to believe that these results would not be applicable to humans.

Justification for selection of skin irritation / corrosion endpoint:
OECD guideline study, GLP

Justification for selection of eye irritation endpoint:
OECD guideline study, GLP

Justification for classification or non-classification

PHMA is covered by a generic entry in Annex 6 of Reg (EC) No 1272/2008; Index Number 607-134-00-4; monoalkyl or monoaryl or monoalkyaryl esters of methacrylic acid with the exception of those specified elsewhere in this Annex. This entry indicates classification as Eye Irrit. 2; STOT SE 3; Skin Irrit. 2 is appropriate. Recently completed toxicological studies (see IUCLID5 dataset), indicate that labelling with respect to skin and eye irritation is now obsolete but that labelling for skin sensitisation is necessary. Since no new data are available to contradict the existing Annex 6 entry labelling for STOT SE 3 this remains unchallenged.

Based on the available data, PHMA does not need to be classified for skin or eye irritation, but does require classification for respiratory irritation according to CLP, EU GHS (Regulation (EC) No 1272/2008) and Directive 67/548 EEC.

This classification entry is valid for all specifications entered in Chapter 1.2.