Fatty acids, C8-16

Endpoint summary

Description of key information

Skin

Skin irritation (OECD 404, occlusive): corrosive (Cat. 1C); CAS# 124-07-2, C8

Skin irritation (OECD 404): not irritating; CAS# 143-07-7, C12

Skin irritation (Patch test acc. to national Guideline, 24 h, occlusive, readings: 24 and 72 h): not irritating; CAS# 544-63-8, C14

Based on read-across data, fatty acids, C8-16 is considered to be corrosive (Skin Corr. 1C).

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:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP - Guideline study, tested with the source substance CAS 124-07-2. In accordance to the ECHA guidance document "Practical guide: How to use alternatives to animal testing" (July 2016), the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Van Zutphen Breeding Centre, Keldonk, The Netherlands
- Weight at study initiation: 2779 g, 2886 g and 2949 g (measured 5 days before dose administration)
- Housing: individually in metal cages with perforated floors
- Diet: standard laboratory animal diet (LK-01, pellet diameter 4 mm)
- Water: tap water, ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-22
- Humidity (%): 50-75
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin sites of same animals

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration: 100%

Duration of treatment / exposure:

4 hours

Observation period:

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

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: right flank
- Type of wrap if used: 6 cm patch of surgical gauze, which was attached with a bit of petrolatum to aluminium foil and mounted on tape (Micropore@, 3M, St. Paul, USA). Finally, the animals were wrapped in flexible bandage (Coban@, 3M, St. Paul, USA).


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no, removal of substance by tissue
- Time after start of exposure: 4 h


SCORING SYSTEM:
Erythema:
0 - no erythema
1 - very slight erythema (barely pereptible)
2 - well-defined erythema
3 - moderate to severe erythema
4 - severe erythema (beet redness) to slight eschar formation (injuries in deep)

edema:
0 - no edema
1- very slight edema (barely perceptible)
2 - slight edema (edges of area well defined by definite raising)
3 - moderate edema (raised appr. 1 mm)
4 - severe edema (raised >1 mm and extending beyond area of exposure)

Irritation parameter:

erythema score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: full thickness necrosis was observed at reading time point 48 h in all animals

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

1.8

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritant / corrosive response data:

Only slight edema and moderate erythema were observed 1, 24, 48, and 72 h after removal of the test material. However, the also observed light-brown staining of the skin proved to indicate skin necrosis, since a crust had formed 48 h after exposure.
In one animal the hairs in the exposed area continued to grow, indicating that the hair roots, lying in the deeper layers of the dermis, had not been affected in this animal. The other two animals revealed no hair growth in the treated area. On day 7, in each of the animals the hairs failed to grow. After the formation and loosening of the crust, the skin had almost returned to normal 14 days after exposure in the two animals, while the one animal showed a rather scurfy skin and only partial restoration of hair growth.
In conclusion, since the test material produced full thickness destruction of the skin tissue in the treated animals, the test material is considered to be corrosive.

Results:

Time	Animal	Erythema	Edema	Other findings
1 h	1	1	2
	2	1	1	b
	3	1	1	b
24 h	1	1	3	b
	2	1	2	b
	3	1	2	b
48 h	1	4	2	n
	2	4	2	n
	3	4	2	n
72 h	1	4	0	e
	2	4	0	e
	3	4	0	e
mean 24 - 48 - 72 h	1	3.0	2.7
	2	3.0	1.3
	3	3.0	1.3
mean		3.0	1.8

b: exposed skin brownish

n: skin necrotic

e: eschar formation

Interpretation of results:

other: classification as Skin Corr. 1C, H314 required according to Regulation (EC) No 1272/2008

Conclusions:

CLP: Skin Corr. 1C, H314

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

01 - 08 Feb 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other:

Remarks:

GLP - Guideline study, tested with the source substance CAS 143-07-7. In accordance to the ECHA guidance document "Practical guide: How to use alternatives to animal testing" (July 2016), the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

May 1981

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

Directive 84/449/EEC, Sep 1984

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands (SPF-Quality)
- Age at study initiation: 13 weeks
- Weight at study initiation: 2427 - 2547 g
- Housing: individually in cages with perforated floors equipped with an automatic drinking system (ITL, Bergen, The Netherlands).
- Diet: standard laboratory rabbit diet (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, The Netherlands); approx. 100 g / day.
- Water: tap-water diluted with decalcified water, ad libitum
- Acclimation period: at least five days under test conditions


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): air-conditioned with 7.5 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: substance was moistened with water

Controls:

other: untreated skin sites of same animals

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 h

Observation period:

8 days
Reading time points: 1, 24, 48 and 72 h and 7 d

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 10 cm x 10 cm
- Type of wrap if used: The test substance was applied to the intact skin using a Metalline patch (2x3 cm, Lohman, Neuwied, Germany) mounted on Micropore tape (3M, St. Paul, USA). The dressing was wrapped around the abdomen and secured with an elastic bandage (Coban, 3M, St. Paul, USA).


REMOVAL OF TEST SUBSTANCE
- Washing: The remaining test substance was removed using a dry tissue and subsequently a tissue moistened with tap water.
- Time after start of exposure: 4 h


SCORING SYSTEM:
Erythema:
0 - no erythema
1 - very slight erythema (barely perceptible)
2 - well-defined erythema
3 - moderate to severe erythema
4 - severe erythema (beet redness) to slight eschar formation (injuries in deep)

Edema:
0 - no edema
1 - very slight edema (barely perceptible)
2 - slight edema (edges of area well defined by definite raising)
3 - moderate edema (raised appr. 1 mm)
4 - severe edema (raised >1 mm and extending beyond area of exposure)

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

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:

0.33

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:

The observed skin irritation consisted of very slight erythema. The irritation was reversible in one animal within 24 hours, in the second animal within 48 hours and in the third animal within 7 days after exposure.
No corrosive effect was evident on the skin.

Other effects:

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Readings:

Time	Animal	Erythema	Edema	Other findings
1 h	1	1	0
	2	1	0
	3	1	0
24 h	1	1	0	+/- 50% of exposed area
	2	0	0
	3	1	0	+/- 50% of exposed area
48 h	1	1	0	+/- 50% of exposed area
	2	0	0
	3	0	0
72 h	1	1	0	+/- 5% of exposed area
	2	0	0
	3	0	0
7 d	1	0	0
	2	0	0
	3	0	0
mean 24 - 48 - 72 h	1	1.0	0.0
	2	0.0	0.0
	3	0.3	0.0
mean		0.4	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 3

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

test procedure in accordance with national standard methods, performed with the source substance CAS 544-63-8. In accordance to the ECHA guidance document "Practical guide: How to use alternatives to animal testing" (July 2016), the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Qualifier:

according to guideline

Guideline:

other: Patch test / Revised (1964) Federal Hazardous Substance Act

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

other: shaved & abraded

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

24 hours

Observation period:

72 hours
Reading time points: 24 and 72 hours

Number of animals:

6

Details on study design:

Fur was removed from the back of each of six rabbits by clipping the saddle of the trunk area. One area of skin was abraded by making minor incisions with a hypodermic needle. 0.5 mL of test material was applied to 1 in2 gauze patches. The patches were placed on both intact skin and abraded skin of each rabbit and secured with adhesive tape, rubber dental damming secured with staples, and gauze wound loosely around the trunk. The animals were then immobilized for 24 hours in wooden stocks. After 24 hours, the patches were removed and the skin cleaned by gently sponging with a moistened towel. The skin was examined immediately after removal of the patches (24 hour reading) and again at 72 hours. At each examination the skin was scored for presence and severity of erythema/eschar formation and edema formation.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

out of 6 animals

Time point:

other: mean over 24 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of 6 animals

Time point:

other: 24 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other: intact skin

Irritant / corrosive response data:

No signs of skin irritation were observed on intact or abraded sites at either scoring time point.

Material (0.5 ml) was applied via a one-inch-square surgical gauze patch to intact and abraded-skin sites. Patches were held in place for 24 hours. Reactions were scored immediately after patch removal and two days later (72 hours).

Scores for Skin Irritation

Rabbit No.		24 hrs	72 hrs
43	Intact      Erythema-Eschar      Edema Abraded      Erythema-Eschar      Edema	0     0 0 0	0 0 0 0
44	Intact      Erythema-Eschar      Edema Abraded      Erythema-Eschar      Edema	0     0 0 0	0 0 0 0
45	Intact      Erythema-Eschar      Edema Abraded      Erythema-Eschar      Edema	0     0 0 0	0 0 0 0
46	Intact      Erythema-Eschar      Edema Abraded      Erythema-Eschar      Edema	0     0 0 0	0 0 0 0
47	Intact      Erythema-Eschar      Edema Abraded      Erythema-Eschar      Edema	0     0 0 0	0 0 0 0
48	Intact      Erythema-Eschar      Edema Abraded      Erythema-Eschar      Edema	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

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin

No data on skin irritation are available for fatty acids, C8-16. Therefore, skin irritation effects are predicted from adequate and reliable data for source substances by read-across to the target substance within the group applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. Reliable studies with C8 fatty acid (octanoic acid), C12 fatty acid (lauric acid) and C14 fatty acid (myristic acid) are used for hazard assessment. These substances were constituents contributing to the hazard (additivity approach) or main constituents (>10%) of fatty acids, C8-16.

Since fatty acids, C8-16, octanoic acid, lauric acid and myristic acid belong to the same category based on similar structural and toxicological properties this approach can be regarded as scientifically justified (for details refer to category justification in IUCLID chapter 13).

 

Skin irritation after application of octanoic acid (CAS# 124-07-2) was investigated in a GLP-study performed according to OECD Guideline 404 (1984). 0.5 mL of octanoic acid was applied to the clipped skin of three New Zealand White rabbits under semi-occlusive conditions for 4 hours. The resulting mean scores over 24, 48 and 72 hours after application were 3.0 and 1.8 for erythema and edema, respectively. The also observed light-brown staining of the skin proved to indicate skin necrosis, since a crust had formed 48 h after exposure. In each of the animals the hairs failed to grow on day 7 after treatment, showing that the dermis was affected in the deep. After the formation and loosening of the crust, the skin had almost returned to normal 14 days after exposure in the two animals, while the third animal showed a rather scurfy skin and only partial restoration of hair growth. Based on the findings, octanoic acid has to be considered as corrosive.

According to the harmonised classification and labelling (ATP07) approved by the European Union, this substance causes severe skin burns and eye damage.

 

Skin irritation of lauric acid (CAS# 143-07-7) was analyzed in a study performed according to OECD Guideline 404 and in compliance with GLP (1989). 3 New Zealand White rabbits received an application of 0.5 g lauric acid to the shaved skin for 4 hours under semi-occlusive conditions. The resulting mean scores for erythema and edema after 24, 48 and 72 hours were 0.4 and 0, respectively. Thus, lauric acid was found to be not irritating to the skin.

 

Irritation to skin of myristic acid (CAS# 544-63-8) was evaluated in a Patch test performed in accordance with Federal Guidelines (1974). 0.5 mL of the substance was applied to the intact and abraded skin of 6 New Zealand White rabbits under occlusion for 24 hours. Readings at 24 and 72 hours after application revealed no signs of irritation. Although a longer application under occlusion than in accordance with the recent OECD 404 Guideline, the resulting scores are 0, both for erythema and edema, respectively. Based on this result, myristic acid can be regarded as not irritating to skin.

 

In conclusion, fatty acids, C8-16 has to be classified as corrosive to skin taking into account its content on octanoic acid (additivity approach).

Eye

Based on the fact, that corrosion of the skin was found, fatty acids, C8-16 has to be regarded as serious eye damaging according to the Guidance on CLP criteria. A study on eye irritation does not need to be conducted.

Justification for classification or non-classification

Skin

The substance contains octanoic acid (C8), which is classified as Skin Corr. 1C, H314 according to Regulation (EC) 1272/2008.

Fatty acids, C8-16 has to be classified as Skin Corr. 1C, H314 based on the content of its classified constituent octanoic acid (additivity approach).

Eye

Since corrosion of the skin is considered, fatty acids, C8-16 has to be regarded as serious eye damaging according to the Guidance on CLP criteria.