2-Propenoic acid, heptadecyl ester, branched

Endpoint summary

Description of key information

Skin irritation:

shows a skin irritating potential (OECD 404) (BASF,2018)

does not show a skin irritation potential (EpiDerm™ skin corrosion/irritation test) (BASF,2014)

Eye irritation:

does not show an eye irritation potential (OECD 405) (BASF,2018)

does not show an eye irritation potential (EpiOcular) (BASF, 2014)

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

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: Envigo RMS GmbH, Germany
- Age at study initiation: Approx. 6 - 8 months
- Weight at study initiation: 3.40 - 4.01 kg
- Housing: single housing
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum): tap water (ad libitum)
- Acclimation period: al least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3°C
- Humidity (%): 30 - 70%
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: negative control: untreated skin sites same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml (2.5 cm x 2.5 cm)

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

2

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): removed at the end of the exposure period with Lutrol®** and Lutrol® / water (1 : 1)
- Time after start of exposure: 4 h

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Readings	Animal No.	Erythema	Edema	Additional Findings
0h	1	2	0	Erythema beyond the application area
	2	2	0	-
1h	1	2	1	Erythema and edema beyond the application area
	2	2	0	-
24h	1	3	3	Erythema and edema beyond the application area
	2	2	1	Erythema beyond the application area
48h	1	4	3	Erythema and edema beyond the application area
	2	3	1	Erythema beyond the application area
72h	1	3	2	Erythema and edema beyond the application area
	2	3	2	Erythema and edema beyond the application area
7d	1	3	2	Erythema and edema beyond the application area, severe scaling
	2	2	1	Severe scaling, Scaling,erythema and edema beyond the application are
14d	1	3	1	Erythema and edema beyond the application area, severe sacaling
	2	1	0	Scaling
Mean   24h – 72h	1	3.3	2.7
	2	2.7	1.3
Mean	-

The cutaneous reactions were not reversible in both animals within 14 days after removal of the patch. On study day 14, moderate erythema (grade 3) and very slight edema (grade 1) beyond the application site and scaling was noted while the other animal showed very slight erythema (grade1) and scaling at study termination.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Considering the not fully reversible cutaneous reactions within the observation period as well as the average score for irritation, Heptadecyl Acrylate (C17A) shows a skin irritating potential under the test conditions chosen.

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:

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

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS GmbH, Germany
- Age at study initiation: approx. 3 months
- Weight at study initiation: 2.46 kg - 2.53 kg
- Housing:single housing
- Diet (e.g. ad libitum): STANRAB (P) SQC; SDS Special Diets Services, 67122 Altrip, Germany (ad libitum)
- Water (e.g. ad libitum): tap water (ad libitum)
- Acclimation period: alt least 5 days before application

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3°C
- Humidity (%): 30 - 70%
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: neagtive control: untreated left eye

Amount / concentration applied:

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

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eye of the animal(s) was rinsed with 3 to 6 mL of lukewarm tap water for 1 to 2 minutes using a syringe with a blunt probe.
- Time after start of exposure: 24 hours

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.2

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.1

Max. score:

4

Reversibility:

fully reversible

		Cornea		Iris	Conjunctiva
Readings	Animal No.	Opacity	Area of cornea involved		Redness	Chemosis	Discharge	Additional Findings
1 h	1	0	0	0	1	1	0	48
	2	0	0	0	1	1	0	48
	3	0	0	0	1	1	0	48
24 h	1	0	0	0	1	1	0	48, FL.neg.
	2	0	0	0	0	0	0	FL.neg.
	3	0	0	0	0	0	0	FL.neg.
48 h	1	0	0	0	1	0	0	FL.neg.
	2	0	0	0	0	0	0	FL.neg.
	3	0	0	0	0	0	0	FL.neg.
72 h	1	0	0	0	0	0	0	SD
	2	0	0	0	0	0	0	SD
	3	0	0	0	0	0	0	SD
Mean                 24h - 72 h	1	0.0	-	0.0	0.7	0.3	-
	2	0.0	-	0.0	0.0	0.0	-
	3	0.0	-	0.0	0.0	0.0	-
Mean	-	0.0	-	0.0	0.2	0.1	-

48: scleral vessels injected, circumscribed area, central ingrown

FL.: fluorescein

neg.: negative

SD: study discontinued because the animal was free of findings

Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.0 for corneal opacity and for iris lesions, 0.7, 0.0 and 0.0 for redness of the conjunctiva and 0.3, 0.0 and 0.0 for chemosis.

Interpretation of results:

GHS criteria not met

Conclusions:

Considering the described ocular reactions as well as the average score for irritation, Heptadecyl Acrylate (C17A) does not show an eye irritating potential under the test conditions chosen.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

skin irritation:

in vivo:

The potential of C17 Acrylate (Heptadecyl Acrylate) to cause acute dermal irritation or corrosivity was assessed by a single topical application of an amount of 0.5 mL of the test item for 4 hours to the intact skin of two New Zealand White rabbits (stepwise procedure starting with one animal and supplementing one additional animal), using a patch of 2.5 cm x 2.5 cm, covered with semi-occlusive dressing. After removal of the patch the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch and at weekly intervals until day 14. Clinical observation are very slight to severe erythema (grade 1 to 4), very slight to moderate edema (grade 1 to 3), scaling to severe scaling and severe scaling, erythema and edema beyond the application area. The cutaneous reactions were not reversible in both animals within 14 days after removal of the patch (study termination). On study day 14, moderate erythema (grade 3) and very slight edema (grade 1) beyond the application site and scaling was noted in one animal while the other animal showed very slight erythema (grade1) and scaling. Mean scores over 24, 48 and 72 hours for each animal were 3.3 and 2.7 for erythema and 2.7 and 1.3 for edema. Considering the not fully reversible cutaneous reactions within the observation period as well as the average score for irritation, C 17 Acrylate (Heptadecyl Acrylate) shows a skin irritating potential under the test conditions chosen [BASF, 2018].

in vitro:

The potential of C17 Acrylate to cause dermal irritation was assessed by a single topical application of 30μL of the undiluted test substance to a reconstructed three dimensional human epidermis model (EpiDerm™). Three EpiDerm™ tissue samples were incubated with the test substance for 1 hour followed by a 42-hours post-incubation period. Tissue destruction was determined by measuring the metabolic activity of the tissue after exposure/ post-incubation using a colorimetric test. The reduction of mitochondrial dehydrogenase activity, measured by reduced formazan production after incubation with a tetrazolium salt (MTT) was chosen as endpoint. The formazan production of the test substance treated epidermal tissues is compared to that of negative control tissues. The quotient of both values indicates the relative tissue viability. The EpiDerm skin irritation test showed the following results, the test substance is not able to reduce MTT directly. The mean viability of the test-substance treated tissues determined after an exposure period of 1 hour with about 42 hours post-incubation was 103%. Based on the observed results and applying the evaluation criteria it was concluded, that C17 Acrylate does not show a skin irritation potential in the EpiDerm™ skin irritation test under the test conditions chosen. [BASF, 2014]

eye irritation:

in vivo:

The potential of C17 Acrylate (Heptadecyl Acrylate) to cause damage to the conjunctiva, iris or cornea was assessed by a single ocular application of 0.1 mL volume of the undiluted test item to one eye of three New Zealand White rabbits (stepwise procedure starting with one animal and supplementing two additional animals). About, and not less than 24 hours after application the eye was rinsed with tap water. The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application. Additional eye examinations were performed 24 and 48 h after application with the instillation of a fluorescein solution. Due to absence of detectable lesions following fluorescein instillation, all subsequent readings were performed without the aid of fluorescein. clinical observations were slight conjunctival redness, slight conjunctival chemosis and injected scleral vessels in a circumscribed area were noted in the animals at hour 1 and persisted in obe of these animals until hour 24. The ocular reactions were reversible in two animals within 24 hours and in one animal within 72 hours after application. Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.0 for corneal opacity and for iris lesions, 0.7, 0.0 and 0.0 for redness of the conjunctiva and 0.3, 0.0 and 0.0 for chemosis. Considering the described ocular reactions as well as the average score for irritation, C17 Acrylate (Heptadecyl Acrylate) does not show an eye irritating potential under the test conditions chosen [BASF, 2018].

in vitro:

The potential of C17 Acrylate to cause ocular irritation was assessed by a single topical application of 50μL of the test substance to a reconstructed three dimensional human cornea model (EpiOcular™). Two EpiOcular™ tissue samples were incubated with the test substance for 30 minutes followed by a 2-hours post-incubation period. Tissue destruction was determined by measuring the metabolic activity of the tissue after exposure/post-incubation using a colorimetric test. The reduction of mitochondrial dehydrogenase activity, measured by reduced formazan production after incubation with a tetrazolium salt (MTT) was chosen as endpoint. The formazan production of the test substance treated epidermal tissues is compared to that of negative control tissues. The quotient of the values indicates the relative tissue viability. The EpiOcular™ eye irritation test showed the following results: The test substance is not able to reduce MTT directly. The mean viability of the test-substance treated tissues was 102%. Based on the observed results and applying the evaluation criteria it was concluded, that C17 Acrylate does not show an eye irritation potential in the EpiOcular™eye irritation test under the test conditions chosen. [BASF, 2014].

Justification for classification or non-classification

Based on the available studies data on skin and eye irritating properties the test item would have to be classified and labelled as skin irrit. cat.2 (H315) according to according to Regulation (EC) No 1272/2008 (CLP).

Nevertheless, for the group of substances (monoalkyl or monoaryl or monoalkyaryl esters of acrylic acid) an entry in Table 3.1 of Annex VI of Regulation (EC) No 1272/2008 exists which has to be adopted for heptadecyl acrylate although obtainded data show the opposite. Thus, the substance is classified as skin irrit. cat. 2 (H315, causes skin irritation), eye irrit. cat. 2 (H319, causes serious eye irritation) and as STOT SE cat. 3 (May cause respiratory irritation) according to Regulation (EC) No 1272/2008 (CLP).