4-hydroxybutyl acrylate

Endpoint summary

Description of key information

Test substance is irritating to skin and corrosive to eyes.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

occlusive conditions; readings after 72 hrs missing, only two animals tested

Principles of method if other than guideline:

Occlusive conditions were used during exposure. Reading after 72 h is missing and only two animals were tested.

GLP compliance:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): Butanediolmonoacrylate
- Chemical name: 2-Propenoic acid, 4-hydroxy ester
- Analytical purity: >= 94 %
- Substance No.: 77/759

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gaukler, 6050 Offenbach / Main, Germany
- Sex: male
- Age at study initiation: no data
- Mean body weight at study initiation: males 3.0 kg
- Diet (ad libitum): Ssniff K, standard diet for rabbits, INTERMAST GmbH, Soest, Germany
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
no details given

Type of coverage:

occlusive

Preparation of test site:

clipped

Remarks:

15 - 24 hrs before test start

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin areas of the same animals

Amount / concentration applied:

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

Duration of treatment / exposure:

4 hours or 5 min

Observation period:

8 days

Number of animals:

2 per timepoint

Details on study design:

4 h exposure:
TEST SITE
- Area of exposure: flank and back, 2 x 2 cm
- Type of wrap if used: the test patch which was wetted with the test substance was applied to the dorsal skin of the rabbits by means of a gummed linen patch that was fastened by an adhesive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with lutrol or lutrol:water (1:1)
- Time after start of exposure: 4 hrs

SCORING SYSTEM: Draize Scoring System (1959)


5 min exposure:
TEST SITE
- Area of exposure: flank and back, 2.5 x 2.5 cm
- Type of wrap if used: the test patch which was wetted with the test substance was applied to the dorsal skin of the rabbits by means of a gummed linen patch that was fastened by an adhesive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing: yes, with lutrol or lutrol:water (1:1)
- Time after start of exposure: 5 min

SCORING SYSTEM: Draize Scoring System (1959)

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(4h exposure)

Time point:

24/48 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: findings extending far beyond the area of application

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(4h exposure)

Time point:

24/48 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: findings (ery., ed.) extending beyond the area of application

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(4h exposure)

Time point:

24/48 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: findings (ery., ed.) extending beyond the area of application

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(4h exposure)

Time point:

24/48 h

Score:

2.5

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: findings (ery., ed.) extending beyond the area of application

Irritation parameter:

erythema score

Basis:

animal: #1, #2

Remarks:

(5 min exposure)

Time point:

24/48 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal: #1, #2

Remarks:

(5 min exposure)

Time point:

24/48 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Application for 4 hours produced marked erythema (grade 3) and slight to very strong edema (grades 2-4) in 2/2 rabbits (observed at 4, 24 and 48 hours). After 8 days, slight erythema (grade 2) and slight edema (grade 2) still persisted in 2/2 and 1/2 rabbits, respectively. Scaling respectively severe scaling was observed in both animals. Corrosive effects in form of necrosis were not observed in any animal.
Both animals did not show a local irritation reaction upon 5 min exposure to the test substance.

Raw data for 4 h exposure:

Readings	Animal No.	Erythema	Edema	Additional findings
4 h	1	3	4	findings (ery., ed.) extending far beyond the area of application
	2	3	3	findings (ery., ed.) extending beyond the area of application
24 h	1	3	4	findings (ery., ed.) extending far beyond the area of application
	2	3	3	findings (ery., ed.) extending beyond the area of application
48 h	1	3	2	findings (ery., ed.) extending far beyond the area of application, severe desquamation
	2	3	2	findings (ery., ed.) extending beyond the area of application
8 d	1	2	0	scaling
	2	2	2	findings (ery., ed.) extending beyond the area of application, severe scaling

 

No effects were visible following a 5 min application.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

other: Fed. Reg. 28 (119): 5582, 1963

Deviations:

not specified

Principles of method if other than guideline:

Draize Test: In general, the techniques of tests as published by the FDA of the United States (Fed. Reg. 28 (119): 5582, 1963) and Draize and Kelley (Drug Cosmet. Industr. 71: 36, 1952) were followed. Only an observation period of up to 7 days was examined.

GLP compliance:

no

Specific details on test material used for the study:

- Name of test material: Butanediolmonoacrylate
- Chemical name: 2-Propenoic acid, 4-hydroxy ester
- Analytical purity: >= 94 %
- Substance No.: 77/759

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Sex: no data
- Weight at study initiation: no data
- Housing: one animal/cage
- Diet (ad libitum): They received no hay or other extraneous material that might have entered the eyes.
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
no details given

Vehicle:

unchanged (no vehicle)

Controls:

other: The other eye remaining untreated, served as a control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL

Duration of treatment / exposure:

once

Observation period (in vivo):

1, 24, 48, 72 hours and 7 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM:
- According to Draize and Kelly (Drug . Cosmet . Industr . 71 (1952) 36)

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

other: animal died after 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Ulcus corneae was found after 7 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

other: animal died after 7 days

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Ulcus corneae was found after 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

other: animal died after 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3.33

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Ulcus corneae was found after 7 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

other: animal died after 7 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Ulcus corneae was found after 7 days

Irritant / corrosive response data:

The test substance caused moderate to severe corneal damage, slight iritis and severe lesions of the conjunctivae. One rabbit died in the course of the observation period; the death occurred between the 72-hour reading and the 7-day reading; however, the cause of death was not considered to be substance-related. Another rabbit showed an ulcer of the cornea at the 7th day; according to the authors, this may be treatment-related.
 
According to the authors, the test substance was severely irritating to the eyes. Eye irritation score was 69 (maximum eye irritation index = 110).

Other effects:

One rabbit died in the course of the observation period; the death occurred between the 72-hour reading and the 7-day reading; however, the cause of death was not considered to be substance-related.

Individual eye irritation scores:

Time	Rabbit no.	Cornea		Iris	Conjunctivae			Total score
		Opacity	Area		Redness	Chemosis	Discharge
1 hr	1	0	0	0	2	4	2	16
	2	1	4	1	2	4	2	41
	3	1	4	1	2	3	2	39
24 hr	1	2	4	1	2	3	3	61
	2	2	4	1	2	4	3	63
	3	3	4	1	2	4	3	83
48 hr	1	2	4	1	2	3	2	59
	2	2	4	1	2	3	3	61
	3	3	4	1	2	3	3	81
72 hr	1	3	4	1	2	3	2	79
	2	2	4	1	2	2	2	57
	3	3	4	1	2	3	2	79
7 d	1*	-	-	-	-	-	-	-
	2	3	4	1	2	2	0	71
	3**	4	3	1	2	2	3	79

* dead

** Rabbit no. 3 showed an ulcus corneae

Interpretation of results:

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

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin irritation

Several studies demonstrated that undiluted 4-hydroxybutyl acrylate is severely irritating to skin.

Key study

In a study comparable to OECD TG 404, 0.5 mL of the undiluted test substance was applied to the intact dorsal skin (2.0 cm x 2.0 cm) of 2 White Vienna rabbits under occlusive conditions (BASF, 1979). The test material was applied to 2 rabbits for 4 hours and to two rabbits for 5 min. At the end of the exposure period, the application sites were washed with Lutrol or Lutrol:water 1:1. The application sites were scored according to the Draize scale (maximum grade = 4) immediately after removal of the test patch, and at 24 hours, 48 hours and 8 days after beginning of the application. Untreated skin areas of the same animals served as negative controls. The application for 5 min produced no local irritation reaction. Application for 4 hours produced marked erythema (grade 3) and slight to very strong edema (grades 2-4) in both rabbits (observed at 4, 24 and 48 hours). After 8 days, slight erythema (grade 2) and slight edema (grade 2) still persisted in 2/2 and 1/2 rabbits, respectively. Scaling respectively severe scaling was observed in both animals. However, necrosis was not observed in both rabbits, indicating that the test substance is irritating rather than corrosive.

Supporting study

In a study comparable to OECD TG 404 , undiluted test substance was applied to the skin of White Vienna rabbits with an occlusive covering for three minutes (2 rabbits), one (4 rabbits) and four hours (2 rabbits), respectively (BASF, 1981). After the application time of 3 minutes, mean erythema scores (24 and 48 hours) were 0 and 2, and mean edema scores were 0 and 1, respectively. At test termination after 8 days, one animal showed desquamation, whereas the other rabbit was without findings. Application for 1 hour produced mean erythema scores (24 and 48 hours) of 1.5, 3, 1, and 2, and mean edema scores of 1, 3, 0, and 1.5, respectively. After 8 days, 2 of 4 rabbits showed superficial or patchy necrosis besides erythema and edema. The third animal showed erythema and scaling. No skin irritation was observed in the fourth animal after 8 days. The superficial respectively patchy necrosis observed in 2 of 4 rabbits was confirmed by gross-pathological examination. After the test substance application for 4 hours, mean erythema scores (24 and 48 hours) were 2 and 2, and mean edema scores were 2.5 and 2.5, respectively. Patchy necrosis of the skin was observed after 8 days in both animals; this finding was confirmed by gross-pathological examination. As the necrosis observed did not reach the dermis, the substance is classified as severely irritating (and not corrosive).

In an in vitro EpiDerm Skin Corrosion / Irritation Test (BASF, 2013) it was concluded, that that 4-hydroxybutyl acrylate shows a skin irritation potential.

Eye irritation

Key study

A Draize test was performed in three New Zealand White rabbits by TNO for BASF (1978). 100 microlitres of the undiluted test substance (4 -hydroxybutyl acrylate) were instilled in the conjunctival sac of one eye. The other eye remaining untreated, served as a control. The eyes were not washed following instillation. The eyes were examined at one hour, 24, 48, 72 hours and 7 days after instillation of the test material. The test substance caused moderate to severe corneal damage, slight iritis and severe lesions of the conjunctivae. One rabbit showed an ulcer of the cornea at the 7th day; according to the authors, this may be treatment-related. Mean scores from the readings at 24, 48, and 72 hours were: cornea 2.4, iris 1.0, conjunctivae 2.0, and chemosis 3.1. These effects were not reversible within the observation period of 7 days (BASF AG, 1978).

Supporting study

Before OECD Guideline 405 was established, eye irritation was tested using an internal method (BASF test). White Vienna rabbits (Gaukler) were used. Initial body weights were at test start 2.62 kg (male) and 2.37 kg (female). 50 µL of 4 -hydroxybutyl acrylate were applied to the conjunctival sac of one eye in 2 animals. The saline-treated adjacent eyes served as control. The animals were observed several times on the day of treatment and up to 8 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 describes findings after 1 and 24 hours and at the end of the observation period. Thus, for final evaluation, the findings after 48 and 120 hours from the raw data were also taken into account. The original BASF grading was converted into the numerical grading according to the OECD Draize system. At the 1-hour reading, slight redness, moderate edema and smeary overlays were observed. At the 24-hour reading, moderate redness, moderate edema, moderate corneal opacity, hemorrhages of the nictitating membrane and smeary overlays were noted. After 8 days, moderate redness, slight edema, moderate corneal opacity, vascularization, staphyloma, scars, smeary overlays and alopecia were present. The control eyes were without any sign of ocular irritation.  

Respiratory irritation

There exists no standard test method for the assessment of respiratory irritation. The inhalation hazard test available for 4-hydroxybutyl acrylate did not give any evidence that test substance vapours may be irritating to the nose and respiratory tract of rats (BASF, 1976). In comparison to its structural analogues 2-hydroxyethyl acrylate (CAS 818-61-1) and hydroxypropyl acrylate (CAS 25584-83-2) which were demonstrated to cause respiratory irritation in rats and humans, 4-hydroxybutyl acrylate shows a lower vapour pressure (0.005 hPa).

Justification for classification or non-classification

Based on the results the test substance has to be classified as Skin Irrit. 2, H315 (Causes skin irritation) and Eye Damage 1, H318 (Causes serious eye damage) in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.