Acrylic acid, monoester with propane-1,2-diol

Endpoint summary

Description of key information

Hydroxypropyl acrylate is corrosive to skin and eyes. Hydroxypropyl 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:

other: Well documented study report, acceptable for assessment, with restrictions (occlusive exposure conditions)

Principles of method if other than guideline:

The undiluted chemical was applied to the clipped dorsal skin of two White Vienna rabbits for 1 hr under occlusive conditions. Skin reactions were scored repeatedly during the 8-day post-exposure period.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: M.GAUKLER, 6050 Offenbach
- Weight at study initiation: approx. 3.3 kg (mean)
- Diet (ad libitum): Ssniff K, standard diet for rabbits, INTERMAST GMBH, Soest
- Water: ad libitum

Type of coverage:

occlusive

Preparation of test site:

other: 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:

1 hour

Observation period:

8 days

Number of animals:

2

Details on study design:

TEST SITE
- Area of exposure: 2 x 2 cm, dorsal skin area
- Type of wrap if used: test patch with the test substance covered with a linen patch


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


SCORING SYSTEM: Draize scoring system
Skin readings were performed after removal of the test patch and then daily on workdays until the end of the observation period (8 days).

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24-48 h

Score:

1.5

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: desquamation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24-48 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: desquamation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24-48 h

Score:

1.5

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24-48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Exposure: 1 hour

 

Mean erythema and edema score:

 

Score	Concentration	24 h		48 h		5 d		8 d		mean 24 – 48 h
	[%]	Animal 1	Animal 2	Animal 1	Animal 2	Animal 1	Animal 2	Animal 1	Animal 2	Animal 1	Animal 2
erythema	100	1*	2*	2*	2*	1s	2ss	0s	1s	1.5	2
edema	100	1*	2*	2*	2*	0	1	0	0	1.5	2

 

*: extending beyond the area of application

s: desquamation

ss: severe desquamation

Interpretation of results:

Category 2 (irritant) 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:

other: Well documented study report, acceptable for assessment, with restrictions (occlusive exposure conditions)

Principles of method if other than guideline:

The undiluted chemical was applied to the clipped dorsal skin of two White Vienna rabbits for 4 hrs under occlusive conditions. Skin reactions were scored repeatedly during the 8-day post-exposure period.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: M.GAUKLER, 6050 Offenbach
- Weight at study initiation: approx. 3 kg (mean)
- Diet (ad libitum): Ssniff K, standard diet for rabbits, INTERMAST GMBH, Soest
- Water: ad libitum

Type of coverage:

occlusive

Preparation of test site:

other: 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:

4 hours

Observation period:

8 days

Number of animals:

2

Details on study design:

TEST SITE
- Area of exposure: 2 x 2 cm, dorsal skin area
- Type of wrap if used: test patch with the test substance covered with a linen patch


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


SCORING SYSTEM: Draize scoring system
Skin readings were performed after removal of the test patch and then daily on workdays until the end of the observation period (8 days).

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24-48 h

Score:

3.5

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: full-thickness necrosis

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24-48 h

Score:

2.5

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: full-thickness necrosis

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24-48 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24-48 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Irritant / corrosive response data:

Histopathological examination of the treated skin areas confirmed the clinical findings as full thickness necrosis in both rabbits.

Exposure: 4 hours

 

Mean erythema and edema score:

 

Score	Concentration	24 h		48 h		5 d		8 d		mean 24 – 48 h
	[%]	Animal 1	Animal 2	Animal 1	Animal 2	Animal 1	Animal 2	Animal 1	Animal 2	Animal 1	Animal 2
erythema	100	3*	2	4ns*	3*	4np*	3ss	4n,ss	4np,ss	3.5	2.5
edema	100	3	3	3	3	2	2	2	2	3	3

*: extending beyond the area of application

ns: soft necrosis

np: parchment-like necrosis, anemic

n: necrosis, anemic

ss: severe desquamation

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:

other: Well documented, acceptable study report which meets generally accepted scientific standards

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.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

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

Amount / concentration applied:

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

Duration of treatment / exposure:

once

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

2 animals

Details on study design:

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


SCORING SYSTEM: Ocular reactions were judged using the scoring scale as published by Draize and Kelley (Drug. Cosmet. Industr. 71: 36, 1952)
The eyes were examined at one hour, 24, 48, 72 hours and 7 days after instillation of the test material.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24-48-72 hr

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24-48-72 hr

Score:

1.7

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24-48-72 hr

Score:

1

Max. score:

2

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24-48-72 hr

Score:

1

Max. score:

2

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24-48-72 hr

Score:

2

Max. score:

3

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24-48-72 hr

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24-48-72 hr

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24-48-72 hr

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24-48-72 hr

Score:

57

Max. score:

110

Reversibility:

not reversible

Irritant / corrosive response data:

During the first day after instillation the eyes showed slight or moderate corneal damage, slight iritis and severe lesions of the conjunctivae.
In the course of the seven-day observation period the degree of the ocular lesions remained unchanged or decreased very slightly. After seven days the following ocular lesions were observed: moderate opacity of the cornea, slight iritis and moderate to severe conjunctivitis.
Because of these findings it was decided to use only two rabbits instead of six.

Time	Rabbit no.	Cornea		Iris	Conjunctivae			Total score
		Opacity	Area		Redness	Chemosis	Discharge
1 hr	1	1	4	1	2	3	2	39
	2	1	4	1	2	4	2	41
24 hr	1	2	4	1	2	4	2	61
	2	1	4	1	2	4	2	41
48 hr	1	2	4	1	2	4	2	61
	2	2	4	1	2	3	3	61
72 hr	1	2	3	1	2	4	2	51
	2	2	4	1	2	2	3	59
7 d	1	2	3	1	2	4	2	51
	2	2	4	1	1	2	2	55

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:

other: Meets generally accepted scientific standards, well documented and acceptable for assessment

Principles of method if other than guideline:

BASF-Test

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMAL
- Body weight at study initiation: 2.98 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(s) applied (volume or weight with unit): 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:

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

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:

other: 24-48 hr

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24-48 hr

Score:

2.5

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24-48 hr

Score:

0

Max. score:

2

Reversibility:

other: iritis observed on day 5 after application, not reversible

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24-48 hr

Score:

0.5

Max. score:

2

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24-48 hr

Score:

1.5

Max. score:

3

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24-48 hr

Score:

2

Max. score:

3

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24-48 hr

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24-48 hr

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

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**	2	2**	2	1.5	2
Cornea	2	2	2	3	2	2.5
Chemosis	2	2	2	2	2	2
Iritis	0	0	0	1	0	0.5
Discharge	greasy overlay	greasy overlay	suppuration	greasy 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	2	2	-	-
Cornea	3	3	loss of corneal tissue	-
Chemosis	0	0	-	-
Iritis	1	1	ciliary injection	-
Discharge	greasy overlay	greasy overlay	-	-

 

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 hydroxypropyl acrylate is severely irritating or corrosive to skin. The key study is summarized below.

Undiluted hydroxypropyl acrylate was applied to the skin of New Zealand White rabbits with an occlusive covering for one and four hours, respectively (BASF AG 1980). Skin readings were performed after removal of the test patch and then daily on workdays until the end of the observation period (8 days) and skin reactions were scored according to the Draize scoring system. After the 4-hour application full-thickness necrosis was observed in both treated animals at test termination. Erythema scores for the time period 24-48 hrs in the two animals were 2.5 and 3.5, respectively, and edema scores for the same skin readings were 3.0 and 3.0, respectively. After the 1-hour application erythema scores (24-48 hrs ) were 1.5 and 2, respectively, and edema scores were also 1.5 and 2, respectively. Erythema was not completely reversible until test termination, and at the end of the observation period desquamation was observed on both animals.

Taking together the results of both studies, it is concluded, that the test substance is corrosive (cat. 1C).

Eye irritation:

Several studies have shown that undiluted hydroxypropyl acrylate is severely irritating and can cause serious damage to the eye. The two most reliable studies are summarized below.

Undiluted hydroxypropyl 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 1.75, 0.25, 2.25, and 2.0, respectively. After 8 days the cornea showed severe opacity (mean score 3.0), and in one animal loss of corneal tissue was diagnosed. In addition, slight iritis (mean score 1) and moderate lesions of the conjunctivae were noticeable (mean score 2) (BASF AG, 1974).

In another study HPA was investigated in a Draize test in New Zealand Albino rabbits. In general the techniques of tests as published by the FDA of the United States (1963) and Draize and Kelley (1952) were followed. The undiluted substance (0.1 mL) was instilled into the conjunctival sac of one eye in two rabbits (BASF AG 1978). The eyes were not washed out and examined at one hour, 24, 48, 72 hours and 7 days after instillation of the test material. During the first day after instillation the eyes showed slight or moderate corneal damage, slight iritis and severe lesions of the conjunctivae. In the course of the seven-day observation period the degree of the ocular lesions remained unchanged or decreased very slightly. Mean scores (24-48-72 hrs) for cornea, iris, conjunctivae and chemosis were 1.85, 1.0, 2.0, and 3.5. After seven days the following ocular lesions were observed: moderate opacity of the cornea, slight iritis and moderate to severe conjunctivitis. Undiluted hydroxypropyl acrylate caused severe irritation with corneal injury when instilled directly into the eyes of laboratory rabbits. Thus, based on the presented experimental evidence, HPA was assessed to have the potential to cause serious eye damage.

- FDA of the United States, Fed. Reg. 28 (119), 5582, 1963

- Draize and Kelley, Drug Cosmet. Industr. 71: 36, 1952

Respiratory irritation:

There exists no standard test method for the assessment of respiratory irritation. There is some evidence from several inhalation hazard tests that hydroxypropyl acrylate vapours may be irritating to the nose and respiratory tract of rats (BASF AG 1974, Union Carbide Corporation 1971). This assessment is confirmed by data on the structural analogue 2-hydroxyethyl acrylate. Since the substance is classified as corrosive, the potential to cause respiratory tract irritation is implicitly covered.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

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