Fatty acids, C12-14

Endpoint summary

Description of key information

Skin

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

Skin irritation (TER test): non-corrosive; CAS# 334-48-5, C10

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, C12-14 is considered to be skin irritating (Skin Irrit. 2).

Eye

Eye irritation (OECD 405): not irritating (73.6% CAS# 143-07-7, C12)

Eye irritation (OECD 405): serious eye damage; CAS# 143-07-7, C12

Based on read-across data, fatty acids, C12-14 is considered to be serious eye damaging (Eye Damage 1).

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 vitro / ex 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:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 430 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test Method (TER))

Version / remarks:

adopted April 2004

Deviations:

yes

Remarks:

A positive control is missing. The O-ring was sealed with soft paraffin instead of petroleum jelly.

GLP compliance:

not specified

Species:

rat

Strain:

Wistar

Type of coverage:

open

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: concurrent control tissues treated with distilled water (negative control)

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 150 µL
- Concentration: 100%

Duration of treatment / exposure:

24 h

Observation period:

Not applicable.

Number of animals:

Not applicable.
The test was performed at least in triplicates.

Details on study design:

SKIN PREPARATION
Full-thickness dorsal and flank tissue was obtained from humanelykilled Wistar rats. The rats were aged 27 - 29 days and had been shaved of dorsal and flank hair when ages 22 - 24 days.

SUBSTANCE APPLICATION
Tissue with epidermis uppermost was attached to polytetrafluorethylene tubes using a rubber "O" ring and sealed with soft paraffin wax. As supporting electrolyte, physiological magnesium sulfate solution (154 mM MgSO4 in distilled water) was used. 150 µL of the test substance was added to the epidermis of each skin disc for 24 h.

REMOVAL OF TEST SUBSTANCE
- Washing: The test substance was thoroughly washed away with a controlled jet of water.

TRANSCUTANEOUS ELECTRICAL RESISTANCE MEASUREMENTS/ASSESSMENT
After washing, tissues were treated briefly with 20 µL 70% ethanol. Subsequently, 3 mL electrolyte solution was added to the tissue surface before resistance measurements occured using an AIM 6401 Databridge (H. Tinsley, Croydon, England). Corrosivity to rat skin was considered when the TER is reduced to below 5.0 kΩ.

Irritation / corrosion parameter:

transcutaneous electrical resistance (in kΩ)

Remarks:

mean of three tissue samples

Run / experiment:

24 h

Value:

14.2

Remarks on result:

other: Standard deviation: ± 5.6 (kΩ/disc

Other effects / acceptance of results:

The transcutaneous electrical resistance was not decreased below 5 kΩ after 24 h exposure to decanoic acid. Thus decanoic aicd is considered to be non-corrosive.

Interpretation of results:

other: non-corrosive

Conclusions:

Decanoic acid showed no corrosive potential in the in vitro transcutaneous electrical resistance test in rat tissue samples.

Reference 4

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 (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

28 Jan - 01 Mar 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP-Guideline study, tested with the source substance lauric acid (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.e fact that the study was conducted with a read-across substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 24 Feb 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye 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 tissues and environmental conditions:

TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: ca. 14 weeks
- Weight at study initiation: 2670 - 2834 g
- Housing: individually in cages with perforated floors
- Diet: pelleted standard LKK-20 rabbit maintenance diet (Hope Farms, Woerden, The Netherlands), ca. 100 g/day
- Water: tap water diluted with decalcified water; ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Air changes (per hr): 7.5 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of same animal

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 52.45 +/- 0.45 mg (equivalent to 0.1 mL)

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

21 days
Reading time points: 1, 24, 48 and 72 h and 7, 14 and 21 days

Number of animals or in vitro replicates:

3 females

Details on study design:

SCORING SYSTEM: Draize Scoring System

TOOL USED TO ASSESS SCORE: fluorescein (2% in water adjusted to pH 7.0; 24 and 72 hours after application and on days 7, 14 and 21 in all animals)

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0.9

Max. score:

4

Reversibility:

not reversible

Remarks:

within 21 days

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0.8

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

2.9

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

1.6

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritant / corrosive response data:

Instillation of the test substance affected the cornea, the iris and the conjunctivae. The irritation was still present at termination of the study, but decreased in course of time after installation the test substance.
Lacrimation was observed in all animals.
Fluorescein treatment revealed corneal epithelial damage in all animals 24 and 72 hours and 7, 14 and 21 days after test substance instillation.

Other effects:

No toxic symptoms were observed in the animals during the test period and no mortality occurred.

Readings:

Time point	Animal	Corneal Opacity		Iris	Conjunctival		Discharge	Additional findings
		Opacity	Area		Erythema	Edema
1 h	1	1	4	1	0	3	0	L
	2	2	4	1	0	3	0	L
	3	1	4	1	0	3	0	L
24 h	1	1	1	1	3	2	1	L
	2	1	4	1	3	2	1	L
	3	1	1	1	3	1	1	L
48 h	1	1	3	0	3	1	2	L
	2	1	2	1	3	1	2	L
	3	0	2	0	3	1	2	L
72 h	1	1	4	1	3	2	3	L
	2	1	4	1	2	2	3	L
	3	1	2	1	3	2	3	L
7 days	1	2	4	0	3	1	1	v
	2	2	4	0	2	1	0	v
	3	2	1	0	3	1	0	v
14 days	1	2	3	0	1	0	1	v
	2	2	3	0	1	0	0	v
	3	2	1	0	2	1	0	v
21 days	1	1	4	0	1	0	0	v
	2	2	1	0	1	0	0	v
	3	2	1	0	1	0	0	v
mean 24/48/72 hours	1	1.0	2.7	0.7	3.0	1.7	2.0
	2	1.0	3.3	1.0	2.7	1.7	2.0
	3	0.7	1.7	0.7	3.0	1.3	2.0
Mean		0.9		0.8	2.9	1.6

L: lacrimation

v: neovascularisation on the cornea

Interpretation of results:

other: classification as Eye Damage 1, H318 required according to Regulation (EC) No 1272/2008

Conclusions:

CLP: Eye Dam. 1, H318

Reference 2

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)

Version / remarks:

adopted 24 Apr 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

Commission Regulation (EC) No 440/2008, 30 May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

Aug 1998

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: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: ca. 12 weeks
- Weight at study initiation: >2 kg
- Housing: Housed in ABS - plastic rabbit cages, floor 4200 cm2
- Diet: autoclaved hay and Altromin 2123 maintenance diet for rabbits, rhich in crude fibers, ad libitum
- Water: drinking water, municipal residue control, ad libtum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/- 3
- Humidity (%): 55 +/- 10
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated yes of same animals

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 g

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

21 days
Reading time points: 1, 24, 48 and 72 h and once daily up to Day 21

Number of animals or in vitro replicates:

3 females

Details on study design:

SCORING SYSTEM:
Draize Scoring System:
Cornea:
0 – No ulceration or opacity
1 – Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details of iris clearly visible
2 - Easily discernible translucent area; details of iris slightly obscured
3 - Nacrous area; no details of iris visible; size of pupil barely discernible
4 - Opaque cornea; iris not discernible through the opacity

Iris:
0 – Normal
1 - Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia;
or injection; iris reactive to light (a sluggish reaction is considered to be an effect
2 - Hemorrhage, gross destruction, or no reaction to light

Conjunctivae
Erythema
0 – Normal
1 - Some blood vessels hyperaemic (injected)
2 - Diffuse, crimson colour; individual vessels not easily discernible
3 - Diffuse beefy red

Chemosis
0 – Normal
1 - Some swelling above normal
2 - Obvious swelling, with partial eversion of lids
3 - Swelling, with lids about half closed
4 - Swelling, with lids more than half closed


TOOL USED TO ASSESS SCORE: fluorescein (readings: 72 h and 21 days)

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects noted

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects noted

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0.78

Max. score:

3

Reversibility:

fully reversible within: 4 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

Upon fluorescein examinations 72 hours post-application as well as at the end of the observation period, o corneal lesions were found in any animal.

Other effects:

Neither mortalities nor significant clinical signs of toxicity were observed until 21 days after the test item application. There were no significant body weight changes during the observation period.

Readings:

Time	Animal	Cornea	Iris	Conjunctiva		Additional findings
				Erythema	Chemosis
1 h	1	0	1	2	3	d
	2	0	1	2	3	d
	3	0	1	2	3	d
24 h	1	0	0	1	2
	2	0	0	1	1	d
	3	0	0	1	1	d
48 h	1	0	0	1	0
	2	0	0	1	1
	3	0	0	1	1
72 h	1	0	0	1	0
	2	0	0	0	0
	3	0	0	0	0
4 days	1	0	0	0	0
	2	0	0	0	0
	3	0	0	0	0
5 days	1	0	0	0	0
	2	0	0	0	0
	3	0	0	0	0
6 days	1	0	0	0	0
	2	0	0	0	0
	3	0	0	0	0
7 days	1	0	0	0	0
	2	0	0	0	0
	3	0	0	0	0
8 days	1	0	0	0	0
	2	0	0	0	0
	3	0	0	0	0
9 days	1	0	0	0	0
	2	0	0	0	0
	3	0	0	0	0
10 days	1	0	0	0	0
	2	0	0	0	0
	3	0	0	0	0
11 days	1	0	0	0	0
	2	0	0	0	0
	3	0	0	0	0
12 days	1	0	0	0	0
	2	0	0	0	0
	3	0	0	0	0
13 days	1	0	0	0	0
	2	0	0	0	0
	3	0	0	0	0
14 days	1	0	0	0	0
	2	0	0	0	0
	3	0	0	0	0
21 days	1	0	0	0	0
	2	0	0	0	0
	3	0	0	0	0
mean 24 - 48 - 72 h	1	0	0	1.00	0.67
	2	0	0	0.67	0.67
	3	0	0	0.67	0.67
mean		0.00	0.00	0.78	0.67

d: discharge

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 (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin

No data on skin irritation are available for fatty acids, C12-14. 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), C10 fatty acid (decanoic 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, C12-14.

Since fatty acids, C12-14, octanoic acid, decanoic 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.

 

Whittle et al. published results of an in vitro test with decanoic acid (CAS# 334-48-5) on rat skin using the transcutaneous electrical resistance test (1996). The experiment was performed similar to OECD Guideline 430 released in April 2004. 150 µL of decanoic acid was added to the epidermis of each freshly prepared rat skin disc for 24 hours. After washing, the resistance measurements were conducted and resulted in a TER of 14.2 kΩ. Since the TER did not decrease below 5 kΩ (threshold value for corrosion), decanoic acid is considered to be non-corrosive to rat skin.

The available data indicate, that decanoic acid is non-corrosive to skin, but should be considered as skin irritant. According to the harmonised classification and labelling (ATP07) approved by the European Union, this substance causes skin irritation.

 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, C12-14 has to be classified as skin irritant based on the content of its classified constituents including octanoic acid and decanoic acid (additivity approach).

Eye

Fatty acids, C12-14 was found to be not irritating to eyes, when it was tested in a study performed according to GLP and OECD Guideline 405 (2010). 0.1 g of the test substance was instilled into the eyes of three New Zealand White rabbits. While neither mortality nor significant clinical signs of toxicity were observed until 21 days after the test item application, the resulting mean scores after 24/48/72 h for corneal opacity, iris, conjunctival erythema and chemosis were 0, 0, 0.78, and 0.67, respectively.

Since the batch tested only contained 73.6% C12 fatty acid (lauric acid), a study with lauric acid is also used for hazard assessment. Since fatty acids, C12-14 and lauric acid belong to the same category based on structural and toxicological properties, this approach can be regarded as scientifically justified. Thus, read-across is performed based on a category approach (for details refer to IUCLID chapter 13).

Eye irritation was evaluated in a study performed under GLP according to OECD Guideline 405, where 52.45 +/- 0.45 mg of lauric acid (equivalent to 0.1 mL) was instilled into the eyes of 3 New Zealand White rabbits (1989). The mean scores for corneal opacity, iris, and conjunctival erythema and chemosis after 24/48/72 h were 0.9, 0.8, 2.9 and 1.6, respectively. While the effect on the iris and the edema disappeared within 7 and 21 days, respectively, corneal opacity and erythema were still present at the end of the 21 day observation period. In addition, neovacularisation starting from day 7 until day 21 was found. Thus, lauric acid was found to cause serious damage to eyes.

Based on the available data and due to the similar structural and toxicological properties of the members within the category including fatty acids, C12-14 and its constituent lauric acid, fatty acids, C12-14 are serious damaging to eyes based on the content of lauric acid and its eye damaging properties.

 

 

Justification for classification or non-classification

The substance contains octanoic acid (C8, Skin Corr. 1C), decanoic acid (C10, Skin Irrit. 2 and Eye Irrit. 2) and lauric acid (C12, Eye Dam. 1). SCL is assigned as 73.6% for Eye Damage 1 to lauric acid (C12).

Skin

Fatty acids, C12-14 has to be classified as Skin Irrit. 2, H315 based on the content of its classified constituents including octanoic acid and decanoic acid (additivity approach).

Eye
Fatty acids, C12-14 has to be classified as Eye Damage 1, H318 based on the content of the classified constituent lauric acid (>73.6%).