2-hydroxyethyl acrylate

Endpoint summary

Description of key information

2-Hydroxyethyl acrylate is corrosive to skin and eyes. 2-Hydroxyethyl acrylate may be irritating to the respiratory tract.

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

Before OECD Guideline 404 was established in 1982, skin irritation was tested using an internal method (BASF test). White Vienna rabbits were used. 2 animals were treated for 1, 5, 15 minutes, and 20 hours using occlusive conditions. An application site of 2.5 x 2.5 cm was covered with the liquid test substance on a patch. After the application time of 1, 5, and 15 minutes, respectively, the skin was first washed with undiluted Lutrol 9, then with an aqueous Lutrol solution (50 %). After the application time of 20 hrs, the test site was not washed after exposure.
The animals were observed for 8 days and skin reactions were recorded on working days. The report describes findings after 24 hours and at the end of the observation period. Thus, for final evaluation, the findings after 48 and 72 hours from the raw data were taken into account.

GLP compliance:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2-Hydroxyethyl acrylate
- Physical state: liquid
- Analytical purity: no data
- Impurities (identity and concentrations): approx. 10 % free acrylic acid

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.65 and 2.5 kg


ENVIRONMENTAL CONDITIONS
no data

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: undiluted, no amount specified

Duration of treatment / exposure:

1 min, 5 min, 15 min, 20 hrs

Observation period:

8 days

Number of animals:

2 animals

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: patch, no further data

REMOVAL OF TEST SUBSTANCE
- Washing: yes (exposure 1, 5, 15 min) first with undiluted Lutrol 9, then with an aqueous Lutrol solution (50 %); no (exposure 20 hrs)
- Time after start of exposure: 1, 5, and 15 min, respectively

SCORING SYSTEM:
The original BASF grading was converted into the numerical grading according to the OECD Draize system.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: 15 min exposure

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: 15 min exposure

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: 15 min exposure

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 48 hrs

Remarks on result:

other: 15 min exposure

Mean erythema score after 24, 48 and 72 h:

 

Exposure time	Concentration [%]	24 h		48 h		72 h		mean
		Animal 1	Animal 2	Animal 1	Animal 2	Animal 1	Animal 2	Animal 1	Animal 2
1 min	100	1	1	0	0	0	0	0.3	0.3
5 min	100	1	2	1	2	1	2	1	2
15 min	100	2+	2+	2+	2+	2+	2+	2	2
20 h	100	*	*	*	**	*	***	n.a.	n.a.

+ necrotic, anemic

*blue-red soft necrosis, extending beyond the area of application

** soft grey necrosis, anemic, extending beyond the area of application

*** centre: soft anemic necrosis, surrounding area: parchment-like to leathery necrosis

n.a.: not assessable

 

 

Mean edema score after 24, 48 and 72 h:

Exposure time	Concentration [%]	24 h		48 h		72 h		mean
		Animal 1	Animal 2	Animal 1	Animal 2	Animal 1	Animal 2	Animal 1	Animal 2
1 min	100	0	0	0	0	0	0	0	0
5 min	100	2	2	0	0	0	0	0.7	0.7
15 min	100	0	2	0	0	0	0	0	0.7
20 h	100	*	*	*	**	*	***	n.a.	n.a.

*blue-red soft necrosis, extending beyond the area of application

** soft grey necrosis, anemic, extending beyond the area of application

*** centre: soft anemic necrosis, surrounding area: parchment-like to leathery necrosis

n.a.: not assessable

 

Findings at test termination:

 

Exposure time	Concentration [%]	Skin findings
		Animal 1	Animal 2
1 min	100	no findings	no findings
5 min	100	desquamation, necrosis	desquamation
15 min	100	desquamation	desquamation, necrosis
20 h	100	hard relocatable necrosis (full-thickness necrosis)	leathery red-brown necrosis, extending beyond area of application   (full-thickness necrosis)

 

 

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Six rabbits were treated with 0.5 mL of the undiluted material or a 10 % aqueous solution on cotton pads on skin areas of the back. The test substance was removed 24 h after the initiation of the exposure and washed with water. Skin reactions were observed 1 h (24 h reading) and 48 h (72 h reading) post-exposure. The scoring was according Draize scoring system.

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Type of coverage:

occlusive

Preparation of test site:

other: shaved, abraded and intact

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.25 mL

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: back, to areas of abraded an non-abraded shaved skin
- Type of wrap if used: occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with water
- Time after start of exposure: 24 hr

Readings were performed 1 h (24 h reading) and 48 h (72 h reading) later.

SCORING SYSTEM: Draize scoring system

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

8

Max. score:

8

Reversibility:

not fully reversible within: 72 hrs

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

2-Hydroxyethyl acrylate produced necrosis, subcutaneous hemorrhage and pitting edema over a wide area of skin. Total scores for erythema were 96 and for edema 96. Mean irritation index (erythema and edema) was 8.0.

The authors assessed the test material as being severly irritating.

Interpretation of results:

other: highly irritating based on primary dermal irritation index (PDII)

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

The study was conducted prior to the advent of GLP regulations (1982).

Guideline:

other: Patch test

Principles of method if other than guideline:

Patch test

GLP compliance:

no

Remarks:

(Study was conducted prior to the advent of GLP regulations)

Species:

rabbit

Strain:

not specified

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

water

Controls:

no

Amount / concentration applied:

Concentration : Undiluted or 10%

Duration of treatment / exposure:

15 minutes, 1 hour or 4 hours for undiluted test material and 15 minutes, 1 hour, 3 hours 15 min or 6 hours 15 min for 10% solution in water.

Observation period:

No data

Number of animals:

No data

Irritation parameter:

edema score

Time point:

24/48/72 h

Remarks on result:

positive indication of irritation

Remarks:

undiluted

Irritation parameter:

erythema score

Time point:

24/48/72 h

Remarks on result:

positive indication of irritation

Remarks:

undiluted

Irritant / corrosive response data:

The undiluted liquid caused slight hyperemia and moderate edema when in contact with the skin of rabbit for 15- 60 minutes, moderate hyperemia extensive swelling (edema) and slight burn upon contact for 4 hours.
10% aqueous solution caused no irritation when in contact with the skin of rabbit for 15 minutes, slight hyperemia was observed in 1 hour contact. 3 hours 15 minutes contact results in slight to moderate hyperemia and slight swelling. 6 hours 15 minutes contact of a 10% aqueous solution with a skin of a rabbit produced moderate hyperemia, edema and slight burn. Skin healed with slight scab and exfoliation.

The undiluted material is moderately to severely irritating to the skin. Short contacts of a few minutes would likely result in no injury but prolonged contacts for an hour or more would be expected to produce skin redness, considerable swelling and probably a burn. The material is rapidly absorbed through intact skin. Short contact with relatively small amounts of material might be absorbed and produce systemic injury or even death.

Interpretation of results:

other: considered highly irritating under the test conditions

Reference 4

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

Skin Irritation - Patch Test:
Two New Zealand albino rabbits were treated with 0.5 mL of the undiluted material or a 10 % aqueous solution on cotton pads on four skin areas of the back. Skin reactions were observed for various exposure periods up till 6 hours as well as 24 hrs and 9 days post-exposure.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

other: undiluted or 10 % aqueous solution

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentration: 10 % aqueous solution or undiluted

Duration of treatment / exposure:

15 min, 1 hr, 4 hrs, 6 hrs (undiluted);
15 min, 1 hr, 3 hrs, 6 hrs (10 % aqueous solution)

Observation period:

9 days

Number of animals:

2

Remarks on result:

probability of severe irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Conc.	Exposure duration	Response
		Immediately			24 hrs			9 days
		erythema	edema	additional	erythema	edema	additional	erythema	edema	additional
100 %	15 min	slight	none	none	slight	moderate	none	none	none	none
100 %	1 hr	slight	none	none	slight	moderate	none	none	none	none
100 %	4 hrs	slight	slight	eschar	moderate	severe	slight necrosis	slight	none	none
100 %	6 hrs	moderate	severe	eschar	moderate	severe	moderate necrosis	none	none	scab
10 %	15 min	none	none	none	none	none	none	none	none	none
10 %	1 hr	slight	none	none	slight	none	none	none	none	none
10 %	3 hrs	slight	slight	eschar	slight	slight	none	slight	none	none
10 %	6 hrs	slight	moderate	slight necrosis	slight	slight	slight necrosis	slight	slight	slight scab

Interpretation of results:

other: considered highly irritating under the tested conditions

Reference 5

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

In the study report, test parameters didn’t totally comply with the specific testing guideline, but were sufficient to accept data and study was conducted prior to the advent of GLP regulations (1982).

Principles of method if other than guideline:

The test substance was applied in 0.01 mL amounts to the clipped intact skin of 5 rabbit bellies either undiluted or in progressive dilutions of 10, 1, 0.1, and 0.01 % in solvent. Ten grades were recognised based on the appearance of moderate or marked capillary injection, erythema, edema, necrosis within 24 hr. No injury from undiluted = grade 1.

GLP compliance:

no

Remarks:

(Study was conducted prior to the advent of GLP regulations)

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2-Hydroxyethyl acrylate
- Analytical purity: no data
- Additional: liquid and inhibited with 50 ppm hydroquinone

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Fasting period before study: non-fasted
- Diet (ad libitum): Rockland diet
- Water: ad libitum

Type of coverage:

open

Preparation of test site:

clipped

Vehicle:

other: undiluted or acetone

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.01 mL
- Concentration: 10 % in acetone

Duration of treatment / exposure:

24 hr

Observation period:

14 days

Number of animals:

5 animals/dose

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

6

Max. score:

10

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

The undiluted material caused marked necrosis in one animal, moderate edema in 3 others and moderate erythema in a fifth. A 10 % solution in acetone produced moderate to marked capillary injection in 5 other animals. Grade 6/10.

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

BASF test: Before OECD Guideline 405 was established, eye irritation was tested using an internal method (BASF test). White Vienna rabbits were used. Usually, 50 uL of the test substance was applied to the conjunctival sac of one eye of 2 animals. The saline-treated adjacent eye served as control. The animals were observed several times on the day of treatment and up to 4 days afterwards. Findings were recorded on working days. The eyes were not washed out after 24 hours as specified in OECD Guideline 405. The report usually describes findings after 1 and 24 hours and at the end of the observation period. Thus, for final evaluation, the findings after 48 and 72 hours from the raw data were taken into account (if available).

GLP compliance:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2-Hydroxyethyl acrylate
- Physical state: liquid
- Analytical purity: no data
- Impurities: approx. 10 % free acrylic acid

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMAL
- Body weight at study initiation: 3.11 kg (mean of 2 rabbits)


ENVIRONMENTAL CONDITIONS
no details given

Vehicle:

unchanged (no vehicle)

Controls:

other: The adjacent, saline treated eye of same animals served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 50 µL

Duration of treatment / exposure:

once

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

2 animals

Details on study design:

Eye irritation was tested using an internal method (BASF test). White Vienna rabbits were used. The saline-treated adjacent eye served as control. The animals were observed several times on the day of treatment and up to 4 days afterwards. Findings were recorded on working days. The eyes were not washed out after 24 hours. The report usually describes findings after 1 and 24 hours and at the end of the observation period. Thus, for final evaluation, the findings after 48 and 72 hours from the raw data were taken into account.

SCORING SYSTEM: The original BASF grading was converted into the numerical grading according to the OECD Draize system.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48 h

Score:

2.5

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48 h

Score:

0

Max. score:

2

Reversibility:

other: no findings during the first 48 hrs

Remarks on result:

other: iritis on day 5 until study termination (score 1)

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48 h

Score:

0

Max. score:

2

Reversibility:

not specified

Remarks:

no findings during the first 48 hrs

Remarks on result:

other: iritis (score 1) on day 5

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48 h

Score:

1.5

Max. score:

3

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48 h

Score:

1.5

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48 h

Score:

1.5

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Mean scores after 24, and 48 h*:

 

Scores	24 h		48 h		mean
	Animal 1	Animal 2	Animal 1	Animal 2	Animal 1	Animal 2
Conjunctivae	1	1**	2	3**	1.5	2
Cornea	2	2	3	2	2.5	2
Chemosis	2	2	1	1	1.5	1.5
Iritis	0	0	0	0	0	0
Discharge	smeary overlay	0	smeary overlay	smeary overlay	-	-

*72 hrs-scores were missing in the raw data.

** Nictitating membrane white

 

 

Findings at test termination:

 

Scores	8 d		Additional Findings
	Animal 1	Animal 2	Animal 1	Animal 2
Conjunctivae	1	2	-	Nictitating membrane white
Cornea	2	3	-	staphyloma
Chemosis	0	0	-	-
Iritis	1	0	-	-
Discharge	0	smeary overlay	-	-

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

The study was conducted prior to the advent of GLP regulations (1982).

Principles of method if other than guideline:

Method: other

GLP compliance:

no

Remarks:

(Study was conducted prior to the advent of GLP regulations)

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2-hydroxyethyl acrylate
- Analytical purity: no data

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

Age and body weight : No data

Vehicle:

water

Controls:

no

Details on study design:

Additional information about test conditions : Washed and unwashed treatments of, undiluted test substance or its 10 % aqueous solution given to the rabbits

Post dose observation period : No data

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

7 d

Score:

3

Max. score:

3

Remarks on result:

other:

Remarks:

undiluted

Irritation parameter:

iris score

Basis:

mean

Time point:

7 d

Score:

2

Max. score:

2

Remarks on result:

other:

Remarks:

undiluted

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

The undiluted test substance caused extensive injury to the eye and its 10 % aqueous solution was slightly irritating to the eye.

Other effects:

Extensive conjunctivitis with moderate corneal injury and severe iritis observed in undiluted HEA dose group; not subsided in 1 week.
Moderate pain and slight conjunctivitis observed in 10 % animal dose group; subsided in 1 week.

HEA reacts very rapidly with eye tissue. The undiluted material caused extensive injury to the eye. 10 % aqueous solution is only slightly irritating to the eye.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

Approx. 0.1 mL of the test substance, undiluted or as a 10 % aqueous solution, were instilled into the conjunctival sac of both eyes of two rabbits. Within 30 sec following instillation, one eye of each rabbit was washed for 2 min with rapid flowing tap water. The other eye was left unwashed. The eyes were immediately examined for signs of conjunctival irritation, corneal injury or internal effects. All eyes were again examined at 1 hr, 24 hrs, and one week after instillation.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Vehicle:

other: undiluted or water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL
- Concentration: undiluted or 10 % aqueous solution

Duration of treatment / exposure:

once

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

2

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: one eye of each animal was washed within 30 sec after instillation for 2 min
- Time after start of exposure: 30 sec

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 7days

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

One hour after instillation of the undiluted material, the unwashed and the washed eye displayed inflammed conjunctival membranes, corneal opacityover 50 % of the eye, and on staining with fluorescein dye shallow lesions over 50 % of the eye. At the 24 hr reading the conjunctival membranes of both eyes appeared more inflammed, the cornea unchanged, and the iris was inflammed. These responses were essentially unchanged at the 48-hr and 7-day readings.
Instillation of the 10 % aqueous solution of HEA caused slight conjunctival membrane irritation which persisted in the unwashed eye through the 48 hr reading. The washed eye was without signs of irritation one hour post-instillation.

Other effects:

Instillation of 2-Hydroxyethyl acrylate, undiluted and as a 10 % aqueous solution, caused slight and moderate degree of pain, respectively.

Under the conditions of the study, 2 -hydroxyethyl acyrlate was a severe eye irritant causing serious eye damage.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Reference 4

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Study was conducted prior to the advent of GLP regulations (1982).

Principles of method if other than guideline:

Single instillations of 0.005, 0.02, 0.10 or 0.5 mL undiluted or of 0.5 mL of 5, and 1 % dilutions were made into the conjunctival sac of 5 rabbits. Reactions were read within one hour unstained and after fluorescein at 24 hr, with ten grades recognised.

GLP compliance:

no

Remarks:

(Study was conducted prior to the advent of GLP regulations)

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2-Hydroxyethyl acrylate
- Analytical purity: no data
- Additional: liquid and inhibited with 50 ppm hydroquinone

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Fasting period before study: non-fasted
- Diet (ad libitum): Rockland diet
- Water: ad libitum

Vehicle:

other: undiluted or propylene glycol

Controls:

yes, concurrent no treatment

Amount / concentration applied:

Undiluted, 5 % or 1 % dilutions

Duration of treatment / exposure:

24 hr

Observation period (in vivo):

24 hr

Number of animals or in vitro replicates:

5

Details on study design:

Eyes not staining with 5% fluoroscein in 20 seconds contact are accepted. Single instillations of 0.005 mL undiluted or of 0.5 mL of 5%or 1% dilutions are made into conjuntival sacs of 5 rabbits. Read with in 1 hour unstained and after fluorescein, at 24 hours with 10 grades recognized. Trace or no injury from 0.5 mL undiluted, Grade 1.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Score:

9

Max. score:

10

Remarks on result:

other: Internal grading system by Union Carbide Corp.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

Severe corneal necrosis and eyelid irritation resulted from instillation of 0.005 mL amounts of undiluted test substance, and from an excess (0.5 mL) of a 5 % solution in propylene glycol. An excess of a 1 % solution caused minor corneal injury. Grade 9/10.

Under the conditions of the study, the test compound caused severe eye irritation, Grade 9.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Several studies demonstrated that undiluted 2-hydroxyethyl acrylate is severely irritating and potentially corrosive to skin. The two most reliable studies are summarized below.

2-hydroxyethyl acrylate was applied to the skin of rabbits with an occlusive covering for one minute, 5 minutes, 15 minutes and 20 hours. After 24 hours, slight to moderate erythema and edema were observed in nearly all exposure groups except the one-minute exposure group. Mean erythema scores (24-48-72 hours) for the 15-min exposure were 2.0 and 2.0, respectively. Mean edema scores (24-48-72 hours) for the 15-min exposure were 0 and 0.7, respectively. Edema was not fully reversible within 8 day. At test termination eight days after the applications, desquamation and necrosis were observed for the 5- and 15 -minute applications. The 20-hour application caused full-thickness necrosis in both rabbits, in one animal extending beyond the area of application (BASF, 1974).

In another study (Dow Chem. Co., 1980), the abdominal skin of two New Zealand White rabbits was shaved and 0.5 ml of the substance undiluted or as a 10% solution was placed under a cotton pad on four skin areas. The undiluted HEA produced slight erythema and moderate edema after 15 minutes and 1 hour exposure. After 4 and 6 hours of exposure moderate erythema, severe edema and slight (4 h) and moderate (6 h) necrosis were observed, respectively. Treatment with the 10 % solution for 15 minutes did not produce skin irritation. Treatment with the 10 % solution for 1 or 3 hours produced slight erythema, and /or edema. The 6-hour treatment with a 10% solution produced moderate redness, swelling and slight necrosis which healed with a scab after 9 days.

Conclusion:

Undiluted HEA was a severe irritant to rabbit skin and direct contact for 20 hours was corrosive to the skin. Dermal contact with undiluted HEA for times up to and including 4 hours produced severe, but reversible irritation with no corrosive effect in rabbits. Direct contact with undiluted HEA for 6 hours produced irritation and tissue damage with evidence for recovery. Thus, HEA was assessed to be severely irritating to the skin (OECD SIDS, 2006). However, according to current EU regulations 2-hydroxyethyl acrylate is labelled with R34, corrosive (Annex I of Directive 67/548/EEC) and classified in Skin Corrosion Category 1B (Table 3.1 of the REGULATION (EC) No 1272/2008), respectively.

Eye irritation:

Several studies have shown that undiluted 2-hydroxyethyl acrylate is severely irritating and can cause serious damage to the eye.

Undiluted 2-hydroxyethyl acrylate (0.05 mL) was instilled into one eye of two rabbits. The adjacent eyes were treated with saline and served as control. The eyes were not washed out after 24 hours as specified in OECD Guideline 405. Mean scores for cornea, iris, conjunctivae and chemosis (24-48 hours) were 2.25, 0, 1.75, and 1.5, respectively. After 8 days the cornea showed moderate to severe opacity (mean score 2.5). In addition, slight iritis (score 1 in one animal) and slight to moderate lesions of the conjunctivae were noticeable (mean score 1.5). At test termination, staphyloma and white discolouration of the nictitating membrane were present in one rabbit (BASF, 1974).

In another study HEA was instilled in undiluted form and as a 10 % aqueous solution directly into the conjunctival sacs of New Zealand Albino rabbits. Within about 30 seconds of treatment one eye of each animal was washed with flowing water, while the other treated eye was left unwashed (Dow Chem. Co., 1980). One hour after instillation of the undiluted material, the unwashed and the washed eye displayed inflammed conjunctival membranes, corneal opacity over 50 % of the eye, and on staining with fluorescein dye shallow lesions over 50 % of the eye. At the 24 hrs reading the conjunctivitis was more severe, the cornea unchanged, and iritis was observed. These responses were essentially unchanged at the 48-hrs and 7-day readings. Instillation of the 10 % aqueous solution of HEA caused slight conjunctival membrane irritation which persisted in the unwashed eye through the 48 hrs reading. The washed eye was without signs of irritation one hour post-instillation.

Union Carbide Corporation (1966) also reported that a single instillation of 0.005 mL of undiluted HEA into the conjunctival sac of rabbits produced corneal necrosis and eye irritation.

The Dow Chemical Company (1962) reported that HEA reacted very rapidly with eye tissue and the undiluted material caused extensive injury to the eye.

Conclusion:

Undiluted 2-hydroxyethyl acrylate caused severe irritation with corneal injury when instilled directly into the eyes of laboratory rabbits. Treatment with the 10 % aqueous solution of HEA without immediate washing caused slight eye irritation which persisted for 2 days. Thus, based on the presented experimental evidence, HEA was assessed to have the potential to cause serious eye damage.

Respiratory irritation:

There exists no standard test method for the assessment of respiratory irritation. There is some evidence from several inhalation hazard tests that 2-hydroxyethyl acrylate vapours may be irritating to the nose and respiratory tract of rats (Union Carbide Corporation 1966, BASF AG 1974). This assessment is confirmed by human data (Dow Chemical Co., 1967, 1980) and data on the structural analogue 2-hydroxypropyl acrylate. Since the substance is classified as corrosive, the potential to cause respiratory tract irritation is implicitly covered.

Justification for classification or non-classification

Based on the available data, the substance has to be classified as Skin Corr. 1B: H314: Causes severe skin burns and eye damage in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.