Reaction products of Glycerin formal and 2-Propenoic acid, 2-methyl-, methyl ester

Endpoint summary

Description of key information

In a read across approach with Tetrahydrofurfuryl methacrylate (THFMA, CAS 2455-24-5), Hydroxyethyl methacrylate  (HEMA, CAS 868-77-9) and

Hydroxypropyl methacrylate (HPMA, CAS 27813-02-1), Glycerolforma methacrylate is not irritating to skin

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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Justification for type of information:

Due to structural similarity, molecular weight and log Pow a read across with Tetrahydrofurfuryl methacrylate is justified

Reason / purpose for cross-reference:

reference to same study

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: no scoring at 48 h

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: no scoring at 48h

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: no scoring at 48h

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not specified

Remarks:

study termination at 72 h, thus, reversibility cannot be evaluated

Remarks on result:

other: no scoring at 48 h

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: no scoring at 48h

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: no scoring at 48 h

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: no scoring at 48 h

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: no scoring at 48h

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: no scoring at 48h

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: no scoring at 48h

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: no scoring at 48h

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: no scoring at 48h

Interpretation of results:

GHS criteria not met

Conclusions:

In a read across approach with THFMA, Hydroxyethyl methacrylate (HEMA, CAS 868-77-9) and Hydroxypropyl methacrylate (HPMA, CAS 27813-02-1) Glycerolformal methacrylte is not irritating to skin.

Executive summary:

THFMA was used additionally to Hydroxyethyl methacrylate  (HEMA, CAS 868-77-9) and Hydroxypropyl methacrylate (HPMA, CAS 27813-02-1) in a read across approach to assess the skin irritation of Glycerolformal methacrylate.

In a primary dermal irritation study similar to US FHSA Federal regulation: 16 CFR 1500.41, 6 rabbits were dermally exposed to 0.5 mL of THFMA (purity ca. 98%) to approximately 2.5 cm² skin area. Two application sites per animal were treated, one site was left intact, the other was abraded. Test sites were covered with an occlusive dressing for 24 hours. Animals were observed for 72 hours. Irritation was scored similar to FHSA Federal guideline 16 CFR 1500.41. This scoring system is similar to OECD guideline 404.

Very slight dermal irritation response was observed in 1/6 animals on intact and abraded skin after 24 and 27 h and in 1/6 animals on intact skin after 24 h. All other animals showed no dermal irritation response.

The observation time did not extend beyond 72 hours, even though a slight skin response was still present at that time in one animal. Therefore, the full reversibility of the effects can not be proved. However skin effects showed clear tendency of reversibility. At study termination, reversibility was complete in 1/2 affected animals. Therefore, a full reversibility seems to be very likely if the observation period had been extended to the period stipulated in the international guidelines.

In this study, THFMA is not a dermal irritant.

 

Study performance does not comply with requirements of the relevant recent EU and OECD guidelines, where a less vigorous application regime with semi-occlusive dressing, an exposure period of 4 hours, treatment of only intact skin is stipulated.

Thus, it can be assumed, that a substance which shows no irritating activity under the application regime of guideline US FHSA Federal regulation: 16 CFR 1500.41 will also be non irritating under the application regimes of the relevant recent EU and OECD guidelines. Therefore the study is adequate for C&L purposes.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.

Justification for type of information:

see attached justification

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: Appraisal of the safety of Chemicals in foods, drugs and cosmetics by staff of the Division of Pharmacology, FDA acc. to Draize

Principles of method if other than guideline:

Method: Appraisal of the safety of chemicals in foods, drugs and cosmetics by the Staff of the Division of Pharmacology, FDA, Hautgiftigkeit nach Draize (1959)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 2.5 kg (average)
- Housing: individual cages
- Diet: rabbit standard diet (Höing 222)
- Water ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 -1 (max. limitation)
- Humidity (%): 50-60
- Photoperiod ( hrs light): 12

Type of coverage:

occlusive

Preparation of test site:

other: shaved, shaved and scarified

Vehicle:

unchanged (no vehicle)

Controls:

other: as a contol 2 areas of the treated animals were also shaved ans scrarified but remained untreated

Amount / concentration applied:

TEST MATERIAL
- Amount applied (volume): 0.5 ml

Duration of treatment / exposure:

24 hour(s)

Observation period:

72 h

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: rubberized cloth

CONTROL.
- as a contol 2 areas of the treated animals were also shaved and scrarified but remained untreated

REMOVAL OF TEST SUBSTANCE
- Washing : no wahing was done


SCORING SYSTEM:
1. Erythema and scars formation
no erythema 0
very slight erythema 1
clear erythema 2
moderate to severe erythema 3
severe erythema (scarlet red) 4
and slightly scars formation

2. Edema formation
no edema 1
very slight edema 2
moderate edema (thickness ca. 1mm) 3
severe edema (thickness more than 4
1mm, large than the edge of the
contact)

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24/72h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

no scoring at 48h

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

no scoring at 48h

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

no scoring at 48h

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

no scoring at 48h

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24/72h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

no scoring at 48h

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

no scoring at 48h

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

no scoring at 48h

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

no scoring at 48h

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

no scoring at 48h

 

Animal Nr.			Scores (24 h)	Scores (72 h)
1	shaved	Erythema and scras formation	0	0
		Edema formation	0	0
	shaved/scarified	Erythema and scras formation	0	0
		Edema formation	0	0
2	shaved	Erythema and scras formation	0	0
		Edema formation	0	0
	shaved/scarified	Erythema and scras formation	1	1
		Edema formation	1	1
3	shaved	Erythema and scras formation	0	0
		Edema formation	0	0
	shaved/scarified	Erythema and scras formation	1	0
		Edema formation	1	0
4	shaved	Erythema and scras formation	0	0
		Edema formation	0	0
	shaved/scarified	Erythema and scras formation	0	0
		Edema formation	0	0
5	shaved	Erythema and scras formation	0	0
		Edema formation	0	0
	shaved/scarified	Erythema and scras formation	0	0
		Edema formation	0	0
6	shaved	Erythema and scras formation	0	0
		Edema formation	0	0
	shaved/scarified	Erythema and scras formation	1	1
		Edema formation	0	0

 

1. Primary irritation index of the shaved skin

 

Animal No.	Primary irritation index
1	0.00
2	0.00
3	0.00
4	0.00
5	0.00
6	0.00
X1	0.00

 

 

2. Primary irritation index of the shaved/scarifized skin

 

Animal No.	Primary irritation index
1	0.00
2	1.00
3	0.50
4	0.00
5	0.00
6	0.50
X2	0.33

 

Total index: X₁ +   X₂= 0.33

 

 

• = fragmentary value

 

 

Reevaluation according to OECD 404

 

	Erythema		Edema
	24h	72h	24h	72h
Tier 1	0	0	0	0
Tier 2	0	0	0	0
Tier 3	0	0	0	0
Tier 4	0	0	0	0
Tier 5	0	0	0	0
Tier 6	0	0	0	0
Mean	0	0	0	0
Total mean	0		0
	Erythema		Edema

 

 

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: EU-GHS

Conclusions:

In a read across approach with Hydroxypropyl methacrylate (HPMA, CAS 27813-02-1), Tetrahydrofurfuryl methacrylate (THFMA) and Hydroxyethyl methacrylate (HEMA, CAS 868-77-9), Glycerolformal methacrylte is not irritating to skin.

Executive summary:

Hydroxypropyl methacrylate (HPMA, CAS 27813-02-1) was used additionally to Tetrahydrofurfuryl methacrylate (THFMA, CAS 2455-24-5) and Hydroxyethyl methacrylate  (HEMA, CAS 868-77-9) in a read across approach to assess the skin irritation of Glycerolformal methacrylate.

2 -Hydroxypropyl methacrylate was tested in a primary skin irritation test to rabbits according to "Appraisal of the safety of chemicals in food, drugs and cosmetics by the Staff of the Division of Parmacology, FDA, 1959 in food, drugs and cosmetics". .Therefore Hydroxypropyl methacrylate is not irritating according to EU-CLP requirements.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.

Justification for type of information:

se attached justification

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: Appraisal of the safety of chemicals in foods, drugs and cosmetics (1959)

Principles of method if other than guideline:

Method: Appraisal of the safety of chemicals in foods, drugs and cosmetics by the Staff of the Division of Pharmacology, FDA, Hautgiftigkeit nach Draize (1959)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 2.5 kg (average)
- Housing: individual cages
- Diet: rabbit standard diet (Höing 222)
- Water ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 -1 (max. limitation)
- Humidity (%): 50-60
- Photoperiod ( hrs light): 12

Type of coverage:

occlusive

Preparation of test site:

other: shaved, shaved and scarified

Vehicle:

unchanged (no vehicle)

Controls:

other: as a contol 2 areas of the treated animals were also shaved ans scrarified but remained untreated

Amount / concentration applied:

TEST MATERIAL
- Amount applied (volume): 0.5 ml

Duration of treatment / exposure:

24 hour(s)

Observation period:

72 h

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: rubberized cloth

CONTROL.
- as a contol 2 areas of the treated animals were also shaved and scrarified but remained untreated

REMOVAL OF TEST SUBSTANCE
- Washing : no wahing was done


SCORING SYSTEM:
1. Erythema and scars formation
no erythema 0
very slight erythema 1
clear erythema 2
moderate to severe erythema 3
severe erythema (scarlet red) 4
and slightly scars formation

2. Edema formation
no edema 1
very slight edema 2
moderate edema (thickness ca. 1mm) 3
severe edema (thickness more than 4
1mm, large than the edge of the
contact)

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).

Remarks:

mean 24+72 h

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: before end of test, animal died, not treatment related

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).

Remarks:

24+72 h

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).

Remarks:

24+72 h

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).

Remarks:

24+72 h

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).

Remarks:

24+72 h

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).

Remarks:

24+72 h

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).

Remarks:

24+72 h

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).

Remarks:

24+72 h

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).

Remarks:

24+72 h

Irritation parameter:

edema score

Basis:

animal #6

Time point:

other:

Score:

0

Max. score:

4

Remarks on result:

other: occlusive, exposure time 24 h, observation time 72 h, intact skin, reevaluated acc. DSD (overall mean).

Animal Nr.			Scores (24 h)	Scores (72 h)
1	shaved	Erythema and scras formation	1	0
		Edema formation	0	0
	shaved/scarified	Erythema and scras formation	2	1
		Edema formation	1	0
2	shaved	Erythema and scras formation	1	*
		Edema formation	0	*
	shaved/scarified	Erythema and scras formation	0	*
		Edema formation	0	*
3	shaved	Erythema and scras formation	0	0
		Edema formation	0	0
	shaved/scarified	Erythema and scras formation	1	0
		Edema formation	1	0
4	shaved	Erythema and scras formation	0	0
		Edema formation	0	0
	shaved/scarified	Erythema and scras formation	0	1
		Edema formation	0	0
5	shaved	Erythema and scras formation	0	0
		Edema formation	0	0
	shaved/scarified	Erythema and scras formation	0	0
		Edema formation	0	0
6	shaved	Erythema and scras formation	0	0
		Edema formation	0	0
	shaved/scarified	Erythema and scras formation	0	0
		Edema formation	0	0

*= animal died prio to the end of the test, death not attributed to the treatment with the substance

1. Primary irritation index of the shaved skin

 

Animal No.	Primary irritation index
1	0.25
2	0.25*
3	0.00
4	0.00
5	0.00
6	0.08
X1	0.08

 

 

2. Primary irritation index of the shaved/scarified skin

 

Animal No.	Primary irritation index
1	1.00
2	0.00*
3	0.50
4	0.25
5	0.00
6	0.00
X2	0.29

 

Total index: X₁ +   X₂= 0.37

 * = fragmentary value

Reevaluation according to OECD 404

 

	Erythema		Edema
	24h	72h	24h	72h
Tier 1	1	0	0	0
Tier 2	1	*	0	*
Tier 3	0	0	0	0
Tier 4	0	0	0	0
Tier 5	0	0	0	0
Tier 6	0	0	0	0
Mean	0,33333333	0	0	0
Total mean	0,16666667		0
	Erythema		Edema

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: other: EU-GHS

Conclusions:

In a read across approach with Hydroxyethyl methacrylate (HEMA, CAS 868-77-9), Tetrahydrofurfuryl methacrylate (THFMA) and Hydroxypropyl methacrylate (HPMA, CAS 27813-02-1), Glycerolformal methacrylte is not irritating to skin.

Executive summary:

Hydroxyethyl methacrylate  (HEMA, CAS 868-77-9) was used additionally to Tetrahydrofurfuryl methacrylate (THFMA, CAS 2455-24-5) and Hydroxypropyl methacrylate (HPMA, CAS 27813-02-1) in a read across approach to assess the skin irritation of Glycerolformal methacrylate.

2 -Hydroxyethyl methacrylate was tested in a primary skin irritation test to rabbits according to "Appraisal of the safety of chemicals in food, drugs and cosmetics by the Staff of the Division of Parmacology, FDA, 1959 in food, drugs and cosmetics". 6 animals were treated with the test substance for 24 h, occlusive. After 24 hours, 2 animals showed slight erythema (one of them died during the test not related to the test substance). Within 72 hours erythema were fully reversible. None of the 6 animals showed edema during the test.

According CLP criteria 2 -Hydroxyethyl methacrylate is not irritating to skin.

 

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:

21.05.2013 to 13.08.2013

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

Remarks:

New Zealand White Rabbits, Crl: KBL (NZW)

Details on test animals or tissues and environmental conditions:

Species/strain: healthy New Zealand White Rabbits, Cr!: KBL (NZW)
Source: Charles River Deutschland, 97633 Sulzfeld, Germany
Sex: female
Body weight at the beginning of the study: > 2 kg
Age at the beginning of the study: approximately 33-42 weeks old
Number of animals: 3
The animals were derived from a controlled full-barrier maintained breeding system (SPF). According to Art. 9.2, No. 7 of the German Act on Animal Welfare the animals were bred for experimental purposes.

Housing and Feeding Conditions:
Semi barrier in an air-conditioned room
Temperature: 18 ± 3 °C (recommendations ofTVT [11], GV-SOLAS 0)
Relative humidity: 55 ± 10%
Artificial light, sequence being 12 hours light, 12 hours dark
Air change: at least 10 x I hour
Free access to autoclaved hay and to Altromin 2123 maintenance diet for rabbits (lot no. 105 6), rich in crude fibre
Free access to tap water ( drinking water, municipal residue control, microbiological controls at regular intervals)
Housed in ABS - plastic rabbit cages, floor 4200 cm2
Adequate acclimatisation period (at least 5 days) under laboratory conditions

Preparation of the Animals
Approximately 24 hours before the test and immediately prior to the application both eyes of each animal were examined. A health inspection was performed to ensure the good state of health of the animals.
Approximately 20 hours before the application the eyes were also examined with the aid of a fluorescein solution. The eyes were rinsed with physiological saline 0.9% NaCl after the examination.
None of the animals showed eye irritation, ocular defects, or pre-existing corneal injury.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

24 h

Observation period (in vivo):

Animal no. 1 was observed for 72 hours after dosing. To determine the reversibility of the observed effects, the observation period was extended up to 15 days after dosing.
Animals no. 2 and 3 were observed for 72 hours after dosing.

Details on study design:

REMOVAL OF TEST SUBSTANCE
animal No. 1 was rinsed with physiological saline 0.9% NaCl 24 hours after the application
animal No. 2 and 3 was not rinsed 24 hours after the application

SCORING SYSTEM:
GRADING OF OCULAR LESIONS
Cornea Grade
Opacity: degree of density (readings should be taken from most dense area)*
No ulceration or opacity .............................................................................................................. 0
Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details
of iris clearly visible ................................................................................................................... 1
Easily discernible translucent area; details of iris slightly obscured ........................................... 2
Nacrous area; no details of iris visible; size of pupil barely discernible ..................................... 3
Opaque cornea; iris not discernible through the opacity ............................................................. 4
Maximum possible: 4
* The area of corneal opacity should be noted
Iris
Normal ......................................................................................................................................... 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia;
or injection; iris reactive to light (a sluggish reaction is considered to be an effect .................... 1
Hemorrhage, gross destruction, or no reaction to light ............................................................... 2
Maximum possible: 2
Conjunctivae
Redness (refers to palpebral and bulbar conjunctivae; excluding cornea and iris)
Normal ......................................................................................................................................... 0
Some blood vessels hyperaemic (injected) ................................................................................. 1
Diffuse,crimson colour; individual vessels not easily discernible ............................................... 2
Diffuse beefy red ......................................................................................................................... 3
Maximum possible: 3
Chemosis
Swelling (refers to lids and/or nictating membranes)
Normal ......................................................................................................................................... 0
Some swelling above normal ....................................................................................................... 1
Obvious swelling, with partial eversion of lids ........................................................................... 2
Swelling, with lids about half closed ........................................................................................... 3
Swelling, with lids more than half closed.................................................................................... 4
Maximum possible:



TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 15 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.34

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.67

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal: #2, #3

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:

1

Max. score:

2

Reversibility:

fully reversible within: 5 days

Irritation parameter:

iris score

Basis:

animal: #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.34

Max. score:

4

Reversibility:

fully reversible within: 11 days

Irritation parameter:

cornea opacity score

Basis:

animal: #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Eye irritation scores

 

Animal No. 1	Single data
		Time post application				Average score (24, 48 and 72 hours)
		1 hour	24 hours	48 hours	72 hours
		T/C	T/C	T/C	T/C
	Conjunctival Redness	2/0	3/0	3/0	3/0	3.00
	Conjunctival Chemosis	3/0	3/0	4/0	4/0	3.67
	Iris	0/0	1/0	1/0	1*/0	1.00
	Cornea	2/0	2/0	2/0	3/0	2.34

 

Animal No. 1	Single data- Prologed Observation period
		Time post application
		4 days	5 days	6 days	7 days	8 days
		T/C	T/C	T/C	T/C	T/C
	Conjunctival Redness	3/0	2/0	2/0	2/0	2/0
	Conjunctival Chemosis	3/0	1/0	1/0	1/0	0/0
	Iris	1*/0	0/0	0/0	0/0	0/0
	Cornea	3/0	1/0	1/0	1/0	1/0

 

 

Animal No. 1	Single data- Prologed Observation period
		Time post application
		9 days	10 days	11 days	12 days	13 days
		T/C	T/C	T/C	T/C	T/C
	Conjunctival Redness	2/0	1/0	1/0	1/0	1/0
	Conjunctival Chemosis	0/0	0/0	0/0	0/0	0/0
	Iris	0/0	0/0	0/0	0/0	0/0
	Cornea	1/0	1/0	0/0	0/0	0/0

 

 

Animal No. 1	Single data- Prologed Observation period
		Time post application
		14 days	15 days
		T/C	T/C
	Conjunctival Redness	1/0	0/0
	Conjunctival Chemosis	0/0	0/0
	Iris	0/0	0/0
	Cornea	0/0	0/0

 

Animal No. 2	Single data
		Time post application				Average score (24, 48 and 72 hours)
		1 hour	24 hours	48 hours	72 hours
		T/C	T/C	T/C	T/C
	Conjunctival Redness	1/0	1/0	1/0	0/0	0.67
	Conjunctival Chemosis	1/0	0/0	0/0	0/0	0.00
	Iris	0/0	0/0	0/0	0/0	0.00
	Cornea	0/0	0/0	0/0	0/0	0.00

 

Animal No. 3	Single data
		Time post application				Average score (24, 48 and 72 hours)
		1 hour	24 hours	48 hours	72 hours
		T/C	T/C	T/C	T/C
	Conjunctival Redness	1/0	1/0	0/0	0/0	0.34
	Conjunctival Chemosis	1/0	0/0	0/0	0/0	0.00
	Iris	0/0	0/0	0/0	0/0	0.00
	Cornea	0/0	0/0	0/0	0/0	0.00

 

T-test item, C=control; *=detailed observation of iris was not possible due to sanois discharge

 

 

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present study, a single ocular application of the test item Glycerinformal methacrylate to rabbits at a dose of 0.1 mL produced irritant effects, which were fully reversible within 48 hours (animal no.3), 72 hours (animal no. 2) or 15
days (animal no. !). Neither mortalities nor significant clinical signs of toxicity were observed.
In conformity with the EC criteria for classification and labelling requirements for dangerous substances and preparations according to Annex VI of Commission Directive 2001/59/EC [7], the test item Glycerinformal methacrylate has no obligatory labelling
requirement for eye irritation.
According to Annex I of Regulation (EC) 1272/2008 , the test item Glycerinformal methacrylate has no obligatory labelling requirement for eye irritation.
According to GHS (Globally Harmonized Classification System)] the test item Glycerinformal methacrylate has no obligatory labelling requirement for eye irritation.

Executive summary:

In an acute in vivo eye irritation/corrosion test according OECD 405 with Glycerolformal methacrylate, a single ocular application of the test item to rabbits at a dose of 0.1 mL produced irritant effects,

which were fully reversible within 48 hours (animal no.3), 72 hours (animal no. 2) or 15 days (animal no.!).Neither mortalities nor significant clinical signs of toxicity were observed.

Inconformity with the EC criteria for classification and labelling requirements for dangerous substances and preparations according to Annex VI of Commission Directive

2001/59/EC [7], the test item Glycerinformal methacrylate has no obligatory labelling requirement for eye irritation.

According to Annex I of Regulation (EC) 1272/2008 the test item Glycerinformal methacrylate has no obligatory labelling requirement for eye irritation.

According to GHS (Globally Harmonized Classification System) the test item Glycerinformal methacrylate has no obligatory labelling requirement for eye irritation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

One in vitro skin irritation study (Human EpiSkin) is available with Glycerolformal methacrylate. The result of three experiments in this study were inconclusive so that the assessement of skin irritation of Glycerolformal methacrylate was performend by a read across approach with three analoge methacrylates which are Tetrahydrofurfuryl methacrylate, Hydroxyethyl methacrylate and Hydroxypropyl methacrylate. Log Kow of these read across substances is in the range of the registrered substance Glycerol methacrylate. Based on read across with in vivo skin irritation studies of Tetrahydrofurfuryl methacrylate, Hydroxyethyl methacrylate and Hydroxypropyl methacrylate, Glycerolformal methacrylate is not irritating to skin.

One in vivo eye irritaion study is available with Glycerolformal methacrylate. Based on this study Glycerolformal methacrylate is not irritating to eyes.

Justification for classification or non-classification

Glycerolformal methacrylate is not irritating to skin and eyes and no classification is reqiured.