2-Propenoic acid, 2-propylheptyl ester

Endpoint summary

Description of key information

2-propylheptyl acrylate was irritant to the skin but not to the eye. 2-propylheptyl acrylate may be irritating to the respiratory system.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-01-11 to 2008-02-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study according to OECD TG No. 404 and in compliance with GLP regulations.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

April 24, 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Rabbits / New Zealand white A 1077 INRA (SPF) from Centre Lago S. A., 01540 Vonnas, France
- Age at study initiation: 7 – 8 months
- Weight at study initiation: 3.78 kg – 4.36 kg
- Housing: Single housing in stainless steel wire mesh cages with grating, floor area: 3000 cm2. The animals were housed in fully air-conditioned rooms.
- Diet: Kliba-Labordiaet (Kaninchen & Meerschweinchenhaltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g/animal per day)
- Water: tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 20 – 24°C
- Humidity: 30 – 70%
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin of animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): undiluted test substance

Duration of treatment / exposure:

Exposure for 4 h.

Observation period:

Immediately after removal of the patch, approx. 1, 24, 48 and 72 h after removal of the patch and then in weekly intervals maximally up to day 14.

Number of animals:

3 animals (2 male/1 female)

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: The test substance was covered with a test patch (Idealbinde, Pfaelzische Verbandstoff-Fabrik, Kaiserslautern) and Fixomull® stretch (adhesive fleece), Beiersdorf AG

REMOVAL OF TEST SUBSTANCE
- Washing: The test substance was removed at the end of the exposure period with Lutrol® and Lutrol®/water (1 : 1).
- Time after start of exposure: 4h

SCORING SYSTEM:
According to OECD guideline 404

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

2.9

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24-72 h

Score:

2.3

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24-72 h

Score:

3.3

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24-72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24-72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24-72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24-72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritant / corrosive response data:

Mean scores over 24, 48 and 72 hours for each animal were 2.3, 3.3 and 3.0 for erythema and 0.3, 1.3 and 1.3 for edema (see table 1).

Table 1: Individual cutaneous examinations and mean values.

		Exposure period 4 h
	Animal	Erythema	Edema	Additional findings
0 h	1	2	0
	2	2	0
	3	2	0
1h	1	2	0	15
	2	2	1	15,16
	3	2	1	15,16
24 h	1	3	1	15,16
	2	4	2	15,16
	3	4	2	15,16
48 h	1	2	0	15
	2	3	1	15,16
	3	3	1	15,16
72 h	1	2	0	15
	2	3	1	15,16
	3	2	1	15,16
7 d	1	2	0	S, 15, 17
	2	2	0	S, 15, 17
	3	2	0	S, 15, 17
14 d	1	2	0	S, 15, 17
	2	2	0	S, 15, 17
	3	2	0	S, 15, 17
Mean 24 – 72 h	1	2.3	0.3
	2	3.3	1.3
	3	3.0	1.3
Mean		2.9	1.0
		15: erythema extending beyond the area of exposure
		16: edema extending beyond the area of exposure
		S: scaling 17: scaling extending beyond the area of exposure

Interpretation of results:

Category 2 (irritant)

Remarks:

Migrated information Criteria used for interpretation of results: EU

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

Study period:

2008-01-11 to 2008-02-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study according to OECD TG No. 405 and in compliance with GLP regulations.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Rabbits / New Zealand white A 1077 INRA (SPF) from Centre Lago S. A., 01540 Vonnas, France
- Age at study initiation: 5 – 6 months
- Weight at study initiation: 3.52 kg – 4.03 kg
- Housing: Stainless steel wire mesh cages with grating, floor area: 3000 cm². Single housing.
- Diet: Kliba-Labordiaet (Kaninchen & Meerschweinchenhaltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g/animal per day)
- Water: Tap water ad libitum
- Acclimation period: at least 5 days before application

ENVIRONMENTAL CONDITIONS
- Temperature: 20-24°C
- Humidity: 30-70%
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated left eye of the animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL
- Concentration: undiluted

Duration of treatment / exposure:

Exposure for 24 h.

Observation period (in vivo):

72 h (the study was discontinued since all animals were without findings 48 h after test start)

Number of animals or in vitro replicates:

3 animals (2 female, 1 male)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: rinsed with 3 to 6 mL of hand warm tap water for 1 to 2 minutes using a syringe with a blunt probe.
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scoring system according to OECD Tg 405

TOOL USED TO ASSESS SCORE:
-Daylight tubes "Lumilux" (L 58W/860 PLUS ECO 25X1, Osram, Germany)

Readings:
Approx. 1, 24, 48 and 72 h after application.
Mortality check:
A check for any dead or moribund animal was made twice each workday (at the beginning and end of work) and once daily at weekends and on public holidays.
Evaluation/Scoring:
The evaluation is based on the criteria of the Commission Directive 67/548/EEC and the OECD Harmonized Integrated Classification System that were in place on the date of report signature.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24-72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24-72 h

Score:

0

Max. score:

2

Reversibility:

other: no effect

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24-72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24-72 h

Score:

0.1

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24-72 h

Score:

0

Max. score:

3

Reversibility:

other: no effect

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24-72 h

Score:

0

Max. score:

3

Reversibility:

other: no effect

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24-72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

Moderate conjunctival redness (grade 2) was noted in all animals 1 hour after application and decreased to slight (grade 1) in one animal until the 24-hour reading. Moderate or severe discharge (grade 2 or 3) was noted in all animals 1 hour after application, only. In addition injected scleral vessels ina circumscribed area or circular were noted during the observation period.
The ocular reactions were reversible in two animals within 24 hours and in one animal within 48 hours after application.
Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0 for corneal opacity and for iris lesions, 0.0, 0.0 and 0.3 for redness of the conjunctiva and 0.0 for chemosis. (see details in table 1)

Table 1: Individual ocular examinations and mean values.

Readings	Animals	Cornea		Iris	Conjunctiva			Additional findings
		Opacity	Area of cornea involved		Redness	Chemosis	Discharge
1 h	1	0	0	0	2	0	0	scleral vessels injected, circumscribed area
	2	0	0	0	2	0	0
	3	0	0	0	2	0	0	scleral vessels injected, circular
24 h	1	0	0	0	0	0	0
	2	0	0	0	0	0	0
	3	0	0	0	1	0	0	scleral vessels injected, circumscribed area
48 h	1	0	0	0	0	0	0
	2	0	0	0	0	0	0
	3	0	0	0	0	0	0
72 h	1	0	0	0	0	0	0
	2	0	0	0	0	0	0
	3	0	0	0	0	0	0
Mean 24-72 h	1	0.0		0.0	0.0	0.0	0.0
	2	0.0		0.0	0.0	0.0	0.0
	3	0.0		0.0	0.3	0.0	0.0
Mean		0.0		0.0	0.1	0.0	0.0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

In a test conducted in accordance to OECD TG No. 404, undiluted 2-propylheptyl acrylate was irritating to the skin of rabbits, when applied to 3 animals (two males, one female) for 4 hours under semiocclusive conditions. At the end of the observation period erythema (grades 2-3 of the Draize scoring system) were still present, while no edema was observed. All animals showed scaling at the end of the observation period. Mean erythema and edema scores (24-72 h) were 2.9 and 1.0, respectively. Erythema and edema were most severe at 24 h after the end of exposure (grades 4 and 2) and slowly decreased in intensity during the following days. Between 7 and 14 days after end of exposure no further decrease of erythema intensity was observed. Based on this study the test substance is irritating to the intact skin of New Zealand white rabbits (BASF SE, 2008).

Eye irritation:

In a test conducted in accordance to OECD TG No. 405, undiluted 2-propylheptyl acrylate (0.1 mL) was instilled into the eye of 2 female and 1 male rabbit for 24 h that followed rinsing for 1-2 minutes with 3-6 mL water. Moderate conjunctival redness (grade 2) was noted in all animals 1 hour after application and decreased to slight (grade 1) in one animal until the 24-hour reading. Moderate or severe discharge (grade 2 or 3) was noted in all animals 1 hour after application, only. In addition injected scleral vessels were observed in one animal at the readings after 1 h and 24 h, and in a second animal at the reading after 1h after beginning of exposure.

The ocular reactions were reversible in two animals within 24 hours and in one animal within 48 hours after application. Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0 for corneal opacity and for iris lesions, 0.0, 0.0 and 0.3 for redness of the conjunctiva and 0.0 for chemosis. Based on this study 2-propylheptyl acrylate is not irritant to the eye. (BASF SE, 2008).

Respiratory irritation:

There exists no standard test method for the assessment of respiratory irritation. 2-propylheptyl acrylate has shown a skin irritating potential, whereas no irritation to the eye was observed. The structural analogue 2-ethylhexyl acrylate is classified as irritating to skin and respiratory tract. These data indicate a potential for respiratory irritation of 2-propylheptyl acrylate.

Justification for selection of skin irritation / corrosion endpoint:
GLP and guideline compliant study.

Justification for selection of eye irritation endpoint:
GLP and guideline compliant study.

Effects on skin irritation/corrosion: irritating

Effects on respiratory irritation: irritating

Justification for classification or non-classification

Based on the results the test substance has to be classified and labelled as Xi, R37/R38 (Irritating to respiratory system and skin) according to Directive 67/548/EEC (DSD)and as skin irrit. cat. 2, H315 (Causes skin irritation), STOT SE cat. 3, H335 ( May cause respiratory irritation) according to Regulation (EC) No 1272/2008 (CLP).