Fatty acids, C18 unsaturated, C12-14 (even numbered) alkyl esters

Endpoint summary

Description of key information

Tetradecyl myristate (CAS No 3234 -85 -3), a constituent of the registration substance, and Octyldodecyl isostearate (CAS No 93803 -87 -3), a structural analogue of the registration substance, were tested for their skin irritant properties in New Zealand White rabbits. The studies were performed according to OECD Guideline 404.With reference the reported scores and the full reversibility of effects it is concluded that the registration substance does not have to be classified as irritant to the skin according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

An in vivo eye irritation study in rabbits was perfromed with tetradecyl myristate (CAS No. 3234 -85 -3), a constituent of the registration substance, 2 -Ethylhexyl laurate and 2-octyldodecyl isooctadecanoate (CAS No 93803 -87 -3),

structural analogues of the registration substance. The studies were conducted according to OECD Guideline 405.

With reference the reported scores and the reversibility the registration substance does not have to be classified as irritant to the eyes according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

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

Study period:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

exposure period 24 h, occlusive conditions, no experimental 48 h reading performed, few details reported

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: not required, the untreated site of the same animal served as the control

Amount / concentration applied:

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

Duration of treatment / exposure:

24 h

Observation period:

72 h
Reading time points: 24 and 72 h

Number of animals:

6 males

Details on study design:

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other: no 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: no 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other: no 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other: no 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other: no 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other: no 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other: no 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)

Irritant / corrosive response data:

Intact skin:
1/6 animals had slight erythema (score 1 of 4) at the 24-hour reading time point, which had cleared completely by the 72-hour reading time point (see Table 1). No other skin irritation effects were observed in any animals.

Abraded skin:
1/6 animals had slight erythema (score 1 of 4) at the 24-hour reading time point. The skin irritation had cleared within 48 hours.

Table 1: individual erythema and edema scores for intact skin

Observation time	Rabbit No.
	1		2		3		4		5		6
	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema
24 h	0	0	1	0	0	0	0	0	0	0	0	0
48 h	No experimental data available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption)
72 h	0	0	0	0	0	0	0	0	0	0	0	0

 

Table 2: calculation of mean scores for intact skin

	Rabbit No.
	1		2		3		4		5		6
	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema
Mean value 24+48+72 h	0	0	0.67	0	0	0	0	0	0	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

With reference the reported scores and the full reversibility of effects within 72 h the test item does not have to be classified as irritant to the skin according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

Executive summary:

Tetradecyl myristate (CAS No 3234 -85 -3), a constituent of the registration substance, was tested for its skin irritant properties in 6 New Zealand White rabbits. The study was performed according to OECD Guideline 404.

With reference the reported scores and the full reversibility of effects within 72 h the test item does not have to be classified as irritant to the skin according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

17 - 20 Feb 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP - Guideline study. According to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
Please refer to cread across justification justification setcion 13.2

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Please refer to cread across justification justification setcion 13.2

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to cread across justification justification setcion 13.2

3. ANALOGUE APPROACH JUSTIFICATION
Please refer to cread across justification justification setcion 13.2

4. DATA MATRIX
Please refer to cread across justification justification setcion 13.2

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

3/3 animals had well-defined erythema at the 1-hr reading time point. The erythema had reduced in severity by 24 hours after exposure in 3/3 rabbits (score 1, 1, 1), and had cleared completely within 72 hours for 3/3 rabbits. No edema was observed in any animal at any time point (see Table 1).

Other effects:

There was no mortality, and no clinical signs were observed during the study period.

Table 1: Skin irritation scores

Observation time	Rabbit no.
	1		2		3
	Erythema	Edema	Erythema	Edema	Erythema	Edema
1 h*	2	0	2	0	2	0
24 h	1	0	1	0	1	0
48 h	1	0	0	0	0	0
72 h	0	0	0	0	0	0
Mean value 24 + 48 + 72 h	0.67	0	0.33	0	0.33	0

* Greasy remnants of the test substance was present on the test site in 3/3 rabbits

Interpretation of results:

GHS criteria not met

Conclusions:

With reference the reported scores and the full reversibility of effects within 72 h the test item does not have to be classified as irritant to the skin according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

Executive summary:

Octyldodecyl isostearate (CAS No 93803 -87 -3), a structural analogue of the registration substance, was tested for its skin irritant properties in 3 New Zealand White rabbits. The study was performed according to OECD Guideline 404. With reference the reported scores and the full reversibility of effects within 72 h the test item does not have to be classified as irritant to the skin according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1976

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 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

; purity not reported, 50% dilution of test substance

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 1.8-2.4 kg

Vehicle:

other: corn oil

Controls:

other: the left eye served as the control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 50% (w/w)

VEHICLE
- Concentration (if solution): 50% (w/w)

Duration of treatment / exposure:

Single application without washing

Observation period (in vivo):

7 days
Reading time points: 24, 48 and 72 h, and 7 days

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated eye was not washed after instillation.

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: hand-held lens

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of all 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

of all 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

Slight redness was observed in 4/6 animals at the 24-hour reading time point, which had cleared completely within 72 hours (see Table 1). No other eye irritation effects were observed in any of the animals.

Table 1: Individual eye irritation scores

 

Rabbit #	Time [h]	conjunctivae		iris	cornea		conjunctivae		iris	cornea
		redness	swelling				redness	swelling
1
	24	1	0	0	0
	48	1	0	0	0
	72	0	0	0	0
	average	0.67	0.0	0.0	0.0	Time to reversion	72.0	0.0	0.0	0.0
2
	24	1	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.33	0.0	0.0	0.0	Time to reversion	48.0	0.0	0.0	0.0
3
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.0	0.0	0.0	0.0	Time to reversion	0.0	0.0	0.0	0.0
4
	24	1	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.33	0.0	0.0	0.0	Time to reversion	48.0	0.0	0.0	0.0
5
	24	1	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.33	0.0	0.0	0.0	Time to reversion	48.0	0.0	0.0	0.0
6
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.0	0.0	0.0	0.0	Time to reversion	0.0	0.0	0.0	0.0
	Time [h]	conjunctivae		iris	cornea
		redness	swelling			avg. time to reversion	36.0	0.0	0.0	0.0
average score
	24	0.67	0.00	0.00	0.00
	48	0.17	0.00	0.00	0.00
	72	0.00	0.00	0.00	0.00
	24+48+72	0.28	0.00	0.00	0.00

 

Interpretation of results:

GHS criteria not met

Conclusions:

not irritating to the eyes

Executive summary:

An in vivo eye irritation study in rabbits was perfromed with tetradecyl myristate (CAS No. 3234 -85 -3), a constituent of the registration substance. Mean scores for cornea, iris, conjunctiva redness and chemosis for all 6 animals after 24, 48, and 72 hours were 0, 0 and in the range of 0.33 to 0.66. All effects were fully reversible within 72 h. Thus, the substance does not have to be classified according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

23 - 26 Feb 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
Please refer to cread across justification justification setcion 13.2

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Please refer to cread across justification justification setcion 13.2

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to cread across justification justification setcion 13.2

3. ANALOGUE APPROACH JUSTIFICATION
Please refer to cread across justification justification setcion 13.2

4. DATA MATRIX
Please refer to cread across justification justification setcion 13.2

Reason / purpose for cross-reference:

read-across source

Number of animals or in vitro replicates:

3

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

At the 1-hour reading time point 3/3 rabbits had slight conjunctivae (score 1, 1, 1), which was still present in 1/3 rabbits at the 24-hour reading time point. The effect had cleared completely within 48 hours. No other eye irritation effects were observed in any rabbit at any time point (see Table 1).

Other effects:

There was no mortality, and no clinical signs were observed during the study period.

Table 1: Eye irritation scores

Rabbit #	Time [h]	conjunctivae		iris	cornea
		redness	swelling
1	1	1 (AB)	0	0	0
	24	1 (A)	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.33	0.0	0.0	0.0
2	1	1 (ABC)	0	0	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.00	0.0	0.0	0.0
3	1	1 (AB)	0	0	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.00	0.0	0.0	0.0

 

	Time [h]	conjunctivae		iris	cornea
		redness	swelling
average score	1	1.00	0.00	0.00	0.00
	24	0.33	0.00	0.00	0.00
	48	0.00	0.00	0.00	0.00
	72	0.00	0.00	0.00	0.00
	24+48+72	0.11	0.00	0.00	0.00

A = eyelids

B = nictating membrane

C = sclera

Interpretation of results:

GHS criteria not met

Conclusions:

With reference the reported scores and the reversibility the test item does not have to be classified as irritant to the eyes according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

Executive summary:

2-octyldodecyl isooctadecanoate (CAS No 93803 -87 -3), a strucutral analogue of the registration substance, was tested for its eye irritant properties in 3 Albino-Himalayan rabbits. The study was performed according to OECD Guideline 405.

Effects on conjunctivae were observed in only one animal after application. These signs were fully reversible within 48 hours..

With reference the reported scores and the reversibility the test item does not have to be classified as irritant to the eyes according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

19 Dec - 21 Dec 1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
Please refer to cread across justification justification setcion 13.2

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Please refer to cread across justification justification setcion 13.2

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to cread across justification justification setcion 13.2

3. ANALOGUE APPROACH JUSTIFICATION
Please refer to cread across justification justification setcion 13.2

4. DATA MATRIX
Please refer to cread across justification justification setcion 13.2

Reason / purpose for cross-reference:

read-across source

GLP compliance:

not specified

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: no details reported

Table 1: Results of eye irritation test

Rabbit No. / sex	Scoring [h]	Cornea	Iris	Conjunctiva
1 / m	1	0	0	1
	24	0	0	1
	48	0	0	0
	72	0	0	0
	7 days	0	0	0
Mean (24, 48, 72 h)		0	0	0.33
2 / m	1	0	0	2
	24	0	0	1
	48	0	0	0
	72	0	0	0
	7 days	0	0	0
Mean (24, 48, 72 h)		0	0	0.33
3 / m	1	0	0	2
	24	0	0	1
	48	0	0	0
	72	0	0	0
	7 days	0	0	0
Mean (24, 48, 72 h)		0	0	0.33

Interpretation of results:

GHS criteria not met

Conclusions:

With reference the reported scores and reversibility of effects within 48 hours the test itemdoes not have to be classified as irritant to the eyes according to the criteria laid down in the EU Classification & Labelling and Packaging Regulation (1272/2008/EC).

Executive summary:

2 -Ethylhexyl laurate, a structural analogue of the registration substance, was tested for its eye irritant properties in 3 New Zealand White rabbits. The study was performed according to OECD Guideline 405.

Effects on conjunctivae were observed in one animal after application. These signs were fully reversible within 48 hours.

With reference the reported scores and reversibility of effects within 48 hours the test itemdoes not have to be classified as irritant to the eyes according to the criteria laid down in the EU Classification & Labelling and Packaging Regulation (1272/2008/EC).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

With reference the reported scores and the full reversibility of effects it is concluded that the registration substance does not have to be classified neither as irritant to the skin nor as eye irritating according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).