Fatty acids, C8-10, C8-10-alkyl esters

Endpoint summary

Description of key information

Skin, rabbit (read-across): not irritating
Eye, rabbit (read-across): not irritating

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:

other: Basic data given. The test substance was applied under occlusive conditions for 24 hours, no experimental 48 h reading was performed, few data were reported.

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:

other: shaved and abraded

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, #3, #4, #5 and #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:

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:

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:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

CLP: not classified

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:

comparable to guideline study with acceptable restrictions

Remarks:

test substance purity not specified; no reading at 48 hours; observation time only 72 hours

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

test substance purity not specified; no reading at 48 hours; observation time only 72 hours

GLP compliance:

not specified

Species:

rabbit

Strain:

other: New Zealand males

Type of coverage:

occlusive

Preparation of test site:

other: intact and incised

Vehicle:

unchanged (no vehicle)

Controls:

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

Amount / concentration applied:

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

Duration of treatment / exposure:

24 hours

Observation period:

72 hours
- Reading time points: 24 and 72 hours

Number of animals:

6 males

Details on study design:

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

1.34

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: Since no reading was performed at 48 h, the score for this time point was assumed to be the same as the one observed at 24 h

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

0.17

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: Since no reading was performed at 48 h, the score for this time point was assumed to be the same as the one observed at 24 h

Table 1: Results of skin irritation study - intact skin

Observation time	Rabbit no.
	1		2		3		4		5		6
	E	O	E	O	E	O	E	O	E	O	E	O
24 h	1	0	2	1	2	0	1	0	1	0	2	0
48 h^1	1	0	2	1	2	0	1	0	1	0	2	0
72 h	1	0	1	0	1	0	0	0	1	0	2	1
Mean value 24 +48 + 72 h	1.00	0.00	1.67	0.67	1.67	0.00	0.67	0.00	1.00	0.00	2.00	0.33

Table 2: Results of skin irritation study - incised skin

Observation time	Rabbit no.
	1		2		3		4		5		6
	E	O	E	O	E	O	E	O	E	O	E	O
24 h	2	0	2	1	2	0	1	0	1	0	2	0
48 h^1	2	0	2	1	2	0	1	0	1	0	2	0
72 h	1	0	1	0	0	0	0	0	1	0	2	1
Mean value 24 +48 + 72 h	1.67	0.00	1.67	0.67	1.33	0.00	0.67	0.00	1.00	0.00	2.00	0.33

E: erythema, O: oedema (according to Draize Score)

¹ Since no reading was performed at 48 h, the score for this time point was assumed to be the same as the one observed at 24 h

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

CLP: not classified

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

11 - 18 Mar 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The exposure was performed under occlusive conditions, the analytical purity of the test substance was not specified.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

occlusive exposure

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated skin site of the same animal served as the control

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

72 h
Reading time points: 1, 24, 48 and 72 h

Number of animals:

3 males

Details on study design:

TEST SITE
- Type of wrap if used: occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated site was not washed after patch removal

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

1 hour after exposure, all the animals had slight to well-defined erythema, while 2/3 had very slight to slight edema. These effects gradually reduced in severity. 24 hours after exposure ended, 1/3 animals had very slight erythema and slight edema. the edema persisted until the 48-hour reading time point.All skin irritation effects had cleared completely within 72 hours after the exposure ended.

Table 1: Erythema and edema scores for skin irritation of the individual animals at different reading time points:

Observation time	Rabbit no.
	1		2		3
	Erythema	Edema	Erythema	Edema	Erythema	Edema
1 h	2	2	1	0	1	1
24 h	1	2	0	0	0	0
48 h	0	1	0	0	0	0
72 h	0	0	0	0	0	0
Mean value 24 + 48 + 72 h	0.33	1.00	0	0	0	0
Mean value 24 + 48 + 72 h all animals	0.11	0.33

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

CLP: not classified

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:

key study

Study period:

15 May - 16 Jul 1987

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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: The Broekman Institute, Someren, The Netherlands
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 2693 - 2894 g
- Housing: individually in plastic cages with perforated floors
- Diet: standard animal diet (100 g per day), obtained from Hope Farms, Woerden (LK-01, pellet diameter 4 mm)
- Water: tap-water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21
- Humidity (%): 60 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

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

Duration of treatment / exposure:

Single eye instillation

Observation period (in vivo):

72 hours (in the absence of any persistent sign of irritation)

Reading time points: 1, 24, 48 and 72 hours after instillation

Number of animals or in vitro replicates:

3 females

Details on study design:

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein

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: 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: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: 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: not applicable

Irritant / corrosive response data:

2 out of 3 animals showed only slight swelling of the blood-vessels in the conjunctivae 1 hour after instillation. The effects were fully reversible 24 hours after instillation. The fluorescein analysis 24 hours after instillation did not reveal any epithelial damage.

Other effects:

Signs of systemic intoxication were not observed.

Table 1: Results of eye irritation test

Rabbit No. / sex	Scoring [h]	Cornea	Iris	Conjunctiva
				Redness	Chemosis
1 / f	1	0	0	1	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
Mean (24, 48, 72 h)		0	0	0	0
2 / f	1	0	0	0	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
Mean (24, 48, 72 h)		0	0	0	0
3 / f	1	0	0	1	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
Mean (24, 48, 72 h)		0	0	0	0
Group mean		0	0	0	0

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

CLP: not classified

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

test substance purity not specified, methodological differences, only 0.05 mL test substance evaluated, only 24-h reading, only 24-h observation period

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

test substance purity not specified, methodological differences, only 0.05 mL test substance evaluated, only 24-h reading, only 24-h observation period

GLP compliance:

no

Species:

rabbit

Strain:

other: New Zealand

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated left eye served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.05 mL undiluted test substance

Duration of treatment / exposure:

single eye instillation

Observation period (in vivo):

24 hours

Reading time points: 2, 6 and 24 h after instillation

Number of animals or in vitro replicates:

2 (male)

Details on study design:

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

SCORING SYSTEM: Draize scoring system

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all 2 animals

Time point:

other: 24 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of all 2 animals

Time point:

other: 24 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

out of all 2 animals

Time point:

other: 24 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of all 2 animals

Time point:

other: 24 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

One animal showed mild conjunctival erythema 2 hours after instillation, which disappeared completely within 6 hours.

Interpretation of results:

study cannot be used for classification

Conclusions:

The test substance was not irritating in this test, however, observation period was only 24 hours long.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for read-across

There are no available data on the skin and eye irritation effects of Fatty acids C8-10, C8-10 alkyl esters (CAS 129677-93-6). The assessment was therefore based on studies conducted with analogue substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13) and within Chapter 5.1 of the CSR.

 

Skin irritation

 

CAS 95912-86-0

A skin irritation study was performed with Fatty acids, C8-10, C12-18 alkyl esters (CAS 95912-86-0), according to a protocol similar to OECD guideline 404 (WoE, 1991). 0.5 mL of the test substance was applied to the shaved skin of 3 male rabbits and held in place by an occlusive dressing for 4 hours. 1 hour after exposure, all the animals had slight to well-defined erythema (score 1 – 2), while 2/3 had very slight to slight edema (score 1 – 2). These effects gradually reduced in severity. 24 hours after exposure ended, 1/3 animals had very slight erythema and slight edema. The edema persisted until the 48-hour reading time point. All skin irritation effects had cleared completely within 72 hours after the exposure ended. The mean erythema scores (over 24, 48 and 72 hours) were 0.33, 0 and 0 while the mean edema scores (over 24, 48 and 72 hours) were 1, 0 and 0. The test substance is not considered to be irritating to the skin.

 

CAS 34316 -64 -8

An acute skin irritation study was performed with hexyl laurate (CAS 34316-64-8) according to a protocol similar to OECD guideline 404 (WoE, 1987). The intact and abraded skin of 6 male New Zealand rabbits was treated with 0.5 mL of the test material (no data on purity) for 24 hours under occlusive conditions. The animals were observed for 72 hours and scoring according to the Draize scoring system was performed 24 and 72 hours after patch removal. Slight to moderate erythema (score 1 - 2) was observed in all animals at both reading time points, with the severity remaining the same at the 72-hour reading time point for 3/6 animals. Slight oedema was noted in 1/6 animals at the 24-hour reading time point, and in 1/6 (a different animal) at the 72-hour reading time point. The skin irritation had cleared within 72 hours for 1/6 animals. The results of the abraded skin sites were comparable, but not taken into account for hazard assessment. To be able to calculate the mean scores, the 48-hour scores were assumed to be the same as those determined 24 h after patch removal (worst case assumption). The mean erythema scores (over 24, 48 and 72 hours) were 1.0, 1.67, 1.67, 0.67, 1.0, and 2.0 while the mean edema scores (over 24, 48 and 72 hours) were 0, 0.67, 0, 0, 0, and 0.33. The test substance is not considered to be irritating to the skin.

CAS 3234-85-3

A skin irritation study was performed according to a protocol similar to OECD guideline 404 with tetradecanoic acid, tetradecyl ester (CAS 3234-85-3) (WoE, 1985). The test substance was applied to the shaved or abraded skin of 6 male rabbits and held under occlusive conditions for 24 hours. The reading time points were 24- and 72 hours after patch removal. 1/6 animals had slight erythema (score 1 of 4) on the intact skin at the 24-hour reading time point, which had cleared completely by the 72-hour reading time point. No other skin irritation effects were observed in any animals (6/6). The results of the abraded skin sites were comparable, but not taken into account for hazard assessment. To be able to calculate the mean scores, the 48-hour scores were assumed to be the same as those determined 24 h after patch removal (worst case assumption). The mean erythema scores (over 24, 48 and 72 hours) were 0, 0.67, 0, 0, 0, and 0 while the mean edema scores (over 24, 48 and 72 hours) were all 0. The test substance is not considered to be irritating to the skin.

 

 

Eye irritation

 

CAS 92044-87-6

An eye irritation study was performed with Fatty acids, coco, 2-ethylhexyl ester (CAS 92044-87-6) according to OECD guideline 405 (Key, 1987). 0.1 mL of the test substance was instilled into the eyes of 3 female New Zealand White rabbits. The animals were observed for 72 hours and scoring according to Draize was performed 1, 24, 48, and 72 hours after application. The eyes were not rinsed. At the 1-hour reading time point 2/3 rabbits had slight conjunctivae (score 1). The effects had cleared completely by the 24-hour reading time point. No effects on the cornea and iris were noted, and no chemosis was reported at any time point in any animal. The mean cornea score and iris score (over 24, 48 and 72 hours) was 0 for all animals, respectively. The mean conjunctivae score and chemosis score (over 24, 48 and 72 hours) was 0 for all animals, respectively. Based on the results of the study, the test substance is not considered irritating to the eyes.

 

CAS 91031 -48 -0

Fatty acids, C16-18, 2-ethylhexyl esters (CAS 91031-48-0) was examined for its eye irritation potential in a study performed similar to OECD Guideline 405 (Supporting, 1978). 0.05 mL undiluted test substance (no data on purity) was instilled into the right eye of 2 rabbits. One animal showed mild conjunctival erythema 2 hours after instillation, which disappeared completely within 6 hours. 24 hours after instillation, no ocular lesions were observed. All the scores for both rabbits were 0 for cornea, iris, conjunctivae and chemosis effects. Based on the study results, the test substance showed no eye irritating potential.

 

Overall conclusion for skin and eye irritation

The available data on suitable source substances did not show any skin or eye irritation effects. Therefore, the target substance Fatty acids C8-10, C8-10 alkyl esters is not considered to be a skin irritant or an eye irritant.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Fatty acids C8-10, C8-10 alkyl esters (CAS 129677-93-6), data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

 

The available data on skin and eye irritation do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.