Tetradecyl acrylate

Endpoint summary

Description of key information

Several read across substances were tested in three skin irritating studies and in three eye irritating studies. The read across substances were not found to be skin or eye irritating.

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:

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

Method: Draize Test

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

abraded

Remarks:

and intact skin

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 mL of the undiluted test substance

Duration of treatment / exposure:

24 hour(s)

Observation period:

7 days

Number of animals:

12 (6 animals were treated on intact skin)

Details on study design:

TEST PROCEDURE
- Primary irritation to the skin was measured by a patch-test technique on the abraded and intact skin of albino rabbits. Twelve healthy adult New Zealand White albino rabbits were used for the test substance.
- Pretreatment: 24 hours prior to applying the material, the hair was removed from the backs of the animals with an electric clipper in such a way as to avoid abrasions
- Application procedure: The test substance was brought on the intact or abraded skin under a surgical patch measuring 1 inch x 1 inch. The patches were fixed to the application site by means of adhesive tape and the entire trunk of the rabbits was wrapped with an impervious material to maintain the test patches in position and to retard evaporation of volatile substances.
- Abrasions: The abrasions are minor incisions through the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding.
- Exposure: After an exposure period of 24 hours the patches and the material applied were removed.
- Readings of skin reactions: Readings were performed after 24 and 72 hours. If, at the second reading, distinct irritation was observed a third reading was performed after seven days. After the final reading all rabbits were killed and, in the case of eschar formation, the scab was removed to examine the nature of the underlying tissue damage.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24, 72 h

Score:

2.4

Max. score:

8

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 72 h

Score:

1.42

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 72 h

Score:

0.6

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: intact skin

Irritant / corrosive response data:

After 24 hours, intact skin : very slight or well-defined erythema and very slight edema .
After 24 hours, abraded skin: very slight or well-defined erythema, slight ischemia and slight edema.
After 72 hours, intact skin: very slight or well-defined erythema, slight scaliness and very slight edema.
After 72 hours, abraded skin: very slight erythema, slight scaliness and very slight edema.
On the abraded skin the test compound caused edema to a slightly higher degree than on the intact skin .
As to the other dermal effects observed there were no differences between reactions of the intact skin and those of the abraded skin .

Generally, the following dermal effects were observed:
After 24 hours, intact skin: very slight or well-defined erythema and  very slight edema.
After 72 hours, intact skin: very slight or well-defined erythema, slight  scaliness and very slight edema.
On the abraded skin the test compound caused edema to a slightly higher  degree than on the intact skin.
As to the other dermal effects observed, there were no differences  between reactions of the intact skin and those of the  abraded skin.

Individual and average skin irritation scores:

	Intact skin					Abraded skin
No. Animal	24 h		72 h		No. animal	24 h		72 h
	A	B	A	B		A	B	A	B
1	2	1	1	0		2	2	1	1
2	2	1	1	0		4	2	1	0
3	1	0	1	0		2	2	1	0
4	1	1	1	0		2	2	1	1
5	2	1	2	1		2	2	1	0
6	2	1	1	1		1	1	1	0
average	1.7	0.8	1.2	0.3		2.1	1.8	1.0	0.3
Sum	2.5		1.5			4.0		1.3

A: erythema
B: edema


Mean values over 24 and 72 hours (intact skin):

No. Rabbit	Erythema	Edema
1	1.5	0.5
2	1.5	0.5
3	1.0	0.0
4	1.0	0.5
5	2.0	1.0
6	1.5	1.0
average	1.42	0.6

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not 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:

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

Remarks:

Acceptable, well documented study report which meets basic scientific principles Read across was performed with Laurylacrylate 1214 (mixture of laurylacrylate (CAS No.: 2156-97-0) and tetradecylacrylate (CAS No.: 21643-42-5) . Please refer to IUCLID section 13 for read across justification.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

Method: Draize Test

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

undiluted
Amount applied: 0.1 mL

Duration of treatment / exposure:

168 hour(s)

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6

Details on study design:

- Comment: not rinsed
- 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.
- Pretest: The eyes of the animals were examined before testing and only those animals without observable eye defects are used.
- Total dose: 0.1 mL of the undiluted test material
- Instillation procedure: 0.1 mL of the undiluted test substance was allowed to fall on the everted lower lid of one eye of each rabbit; the upper and lower eye lid were then carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material. The other eye remaining untreated, served as a control. The eyes were not washed following instillation.
- Readings of eye reactions: The eyes were examined at one hour, 24, 48, 72 hours and 7 days after instillation of the test material.
- Evaluation of eye reactions: Eye reactions were evaluated by the method published by Draize and Kelley (1952). Drug. Cosmet. Industr. 71: 36

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

The test compound caused slight lesions of the conjunctivae in all  rabbits. After 24 hours these lesions had subsided completely.

Individual eye irritation scores:
---------------------------------
 
rabbit         cornea          iris             conjunctivae                     Total score
          opacity   area                 redness  chemosis  discharge     
-------------------------------------------------------------------------- -----------------
                                       after 1 hour
  1          0       0           0          1         0         0                    2
  2          0       0           0          1         1         0                    4
  3          0       0           0          1         0         0                    2
  4          0       0           0          1         0         0                    2
  5          0       0           0          1         0         0                    2
  6          0       0           0          1         0         0                    2

                                        after 24 hours
  1          0       0           0          0         0         0                    0
  2          0       0           0          0         0         0                    0
  3          0       0           0          0         0         0                    0
  4          0       0           0          0         0         0                    0
  5          0       0           0          0         0         0                    0
  6          0       0           0          0         0         0                    0

After 48, 72 hours and 7 days all scores were recorded as 0.
-------------------------------------------------------------------------- ------------------

Mean values over 24, 48, and 72 hours for the single animals for cornea,  iris and conjunctivae were without exception zero.  
Thus, the eye irritation score was calculated to be zero.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

In the key study, a read across substance (mixture of laurylacrylate (CAS No.: 2156-97-0) and tetradecylacrylate (CAS No.: 21643-42-5)) was examined for primary skin irritating properties with 6 albino rabbits. Primary irritation to the skin was measured by a patch-test technique on the abraded and intact skin of albino rabbits. Healthy adult New Zealand White albino rabbits were used for the test substance. The total dose is 0.5 mL of the undiluted test material. The test substance was brought on the intact or abraded skin under a surgical patch measuring 1 inch x 1 inch. The patches were fixed to the application site by means of adhesive tape and the entire trunk of the rabbits was wrapped with an impervious material to maintain the test patches in position and to retard evaporation of volatile substances. Readings were performed after 24 and 72 hours. After the final reading all rabbits were killed and, in the case of eschar formation, the scab was removed to examine the nature of the underlying tissue damage. After 24 hours, intact skin: very slight or well-defined erythema and very slight edema. After 72 hours, intact skin: very slight or well- defined erythema, slight scaliness and very slight edema. On the abraded skin the test compound caused edema to a slightly higher degree than on the intact skin. As to other dermal effects observed, there were no differences between reactions of the intact skin and those of the abraded skin. Based on the results of this study, the scores were smaller than the threshold value (the erythema score (mean, intact skin, 24, 72 h) was 1.42 and the edema score (mean, intact skin, 24, 72 h) was 0.6). There were no data for the recovery. Therefore, the read across substance is not considered to be skin irritating in this study.

 

In supporting studies, several other read-across substances were tested .

The mono-constituent source substance Octadecyl acrylate (CAS 4813 -57 -4) was tested in a skin irritation test (OECD 404) with three White Vienna rabbits. The rabbits were dermally exposed to Octadecyl acrylate to the clipped skin as 50 % suspension in water and covered by semi-occlusive dressing for 30 – 60 min. The animals were observed for 72 hours. The mean erythema and edema scores were 0. Therefore, the test item is considered to be not irritating to skin.

The potential of the mixture 2-Propenoic acid, C16-18-alkyl esters (CAS90530 -21 -5) to cause dermal corrosion / irritation was assessed by a single topical application of 50 µL (corrosion test) or 30 µL (irritation test) of the test substance to a reconstructed three dimensional human epidermis model (EpiDerm^TM). For the corrosion test two EpiDerm tissue samples were incubated with the test substance for 3 minutes and 1 hour, respectively. The irritation test was performed with three EpiDerm tissue samples, which 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 the values indicates the relative tissue viability.

The EpiDerm skin corrosion / irritation test showed the following results:

The test substance is able to reduce MTT directly. However, this ability of direct MTT reduction did not impair the study result as demonstrated by the concurrently performed exposure of control tissues inactivated by freeing (performed with corrosion test, only).

In the corrosion test, the mean viability of the test substance treated tissues determined after an exposure period of 3 minutes was 99 %, and it was 98 % after an exposure period of 1 hour.

In the irritation test, the mean viability of the test substance treated tissues determined after an exposure period of 1 hour with about 42 hours post-incubation was 117 %.

Based on the observed results and applying the evaluation criteria it was concluded, that 2-Propenoic acid, C16-18-alkyl esters does not show a skin irritation potential in the EpiDerm skin corrosion / irritation test under the test conditions chosen.

In another in vitro skin irritation study, the potential of the mixture 2-Propenoic acid, C18-22-alkyl esters (CAS 85085 -17 -2) to cause dermal irritation was assessed by a single topical application of the substance to a reconstructed three dimensional human epidermis model (EpiDerm^TM). Because the waxy test substance could not be applied with a pipette, a metal pin was covered with about 50 mg of the undiluted test substance. 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 able to reduce MTT directly. Subsequent testing of MTT reduction control was not performed, because no visible residues of the test substance remained on the tissues after washing.

The mean viability of the test substance treated tissues determined after an exposure period of 1 hour with about 42 hours post-incubation was 96 %.

Based on the observed results and applying the evaluation criteria it was concluded, that 2-Propenoic acid, C18-22-alkyl esters does not show a skin irritation potential in the EpiDerm skin irritation test under the test conditions chosen.

Eye irritation: 

In the key study, a read across substance (mixture of laurylacrylate (CAS No.: 2156 -97 -0) and tetradecylacrylate (CAS No.: 21643 -42 -5)) was tested according to Draize test. Six healthy adult New Zealand White albino rabbits were used for the test substance. The total dose was 0.1 mL of the undiluted test material. 0.1 mL of the undiluted test substance was allowed to fall on the everted lower lid of one eye of each rabbit; the upper and lower eye lid were then carefully closed and subsequently held together for at least one second before releasing, to preventloss of material. 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 cornea, iris, conjunctivae and chemosis scores (mean, 24, 48, 72 h) were 0. The read across substance was not eye damaging.

 

In supporting studies, several other read-across substances were tested .

The mono-constituent source substance Octadecyl acrylate (CAS 4813 -57 -4) was tested in an eye irritation test (OECD 405) with three white Vienna rabbits. The rabbits were singly exposed to 0.1 mL bulk volume of undiluted Octaecyl acrylate in one eye. No washing was done and the animals were observed for 72 hours. The mean cornea, chemosis and iris scores were 0. The mean redness scores were 0.44. Therefore, the test item is considered to be not irritating to eye (BASF AG. 1985).

The potential of the mixture 2-Propenoic acid, C16-18-alkyl esters (CAS 90530 -21 -5) to cause serious damage to the eyes was assessed by a single topical application of 750 µL of the undiluted test substance to the epithelial surface of isolated bovine corneas. Three corneas were treated with the test substance for 10 minutes followed by a 2-hours post-incubation period. Corneal opacity was measured quantitatively as the amount of light transmission through the cornea. Permeability was measured quantitatively as the amount of sodium fluorescein dye that passes across the full thickness of the cornea. Both measurements were used to calculate an In Vitro Irritancy Score of the test substance relative to the control corneas. The mean opacity value was 1.1, the mean permeability value 0.002 and the In Vitro Irritancy Score was 1.2. Based on the observed results and applying the evaluation criteria it was concluded, that 2-Propenoic acid, C16-18-alkyl esters does not cause serious eye damage in the Bovine Corneal Opacity and Permeability Test (BCOP Test) under the test conditions chosen (BASF SE, 2012).

 

In another eye irritation study, the potential of the mixture 2-Propenoic acid, C18-22-alkyl esters (CAS 90530 -21 -5) to cause ocular irritation was assessed by a single topical application of the test substance to a reconstructed three dimensional human cornea model (EpiOcular). Because the waxy test substance could not be applied with a pipette, a metal pin was covered with about 50 mg of the undiluted test substance. Two EpiOcular tissue samples were incubated with the test substance for 90 minutes followed by a 18-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 able to reduce MTT directly. However, this ability of direct MTT reduction did not impair the study result as demonstrated by the concurrently performed exposure of control tissues inactivated by freezing.

The mean viability of the test substance treated tissues was 96 %.

Based on the observed results and applying the evaluation criteria it was concluded, that 2-Propenoic acid, C18-22-alkyl esters does not show an eye irritation potential in the EpiOcular eye irritation test under the test conditions chosen (BASF SE, 2012).

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

In conclusion, the long-chain acrylate esters (≥ C12) show neither skin irritating properties nor eye irritating properties. The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. One key and several supporting studies with adequate read-across substances are available for skin (similar to OECD 404) and eye irritation (similar to OECD 405), respectively. For both endpoints, the scores for the test item treated tissues were below the thresholds for classification as an irritant. As a result the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008, as amended for the tenth time in Regulation (EC) No. 2017/776.

Nevertheless, for the group of substances (monoalkyl or monoaryl or monoalkylaryl esters of acrylic acid) an entry in Table 3.1 and 3.2 of Annex VI of Regulation (EC) No. 1272/2008 exists which has to be adopted for tetradecyl acrylate although obtained data show the opposite. Thus, the substance is classified as Skin Irrit. 2 (H315), Eye Irrit. 2 (H319) and as STOT SE 3 (H335) according to Regulation (EC) No. 1272/2008 .