Fatty acids, C8-10

Endpoint summary

Description of key information

Skin irritation/corrosion (weight of evidence of available OECD 404 studies and in vitro TER tests): corrosive

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:

key study

Study period:

13 Nov - 13 Dec 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted May 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: Charles River Wiga, Sulzfeld, Germany
- Age at study initiation: approx. 14 weeks
- Weight at study initiation: 2884 - 3069 g
- Housing: individually in cages with perforated floors equipped with an automatic drinking system (ITL, Bergen, The Netherlands)
- Diet: standard laboratory diet (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, The Netherlands) approx. 100 g per day
- Water: free access to tap water diluted with decalcified water
- Acclimation period: at least five days under test conditions


ENVIRONMENTAL CONDITIONS
Standard Laboratory Conditions
- Temperature (°C): 21 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin sites of same animals

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

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

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: dorsal skin
- Site preparation: approximately 24 hours before treatment, the dorsal fur was shaved with an electric clipper, exposing an area of approximately 100 square centimetres (10 cm x 10 cm). Prior to test substance administration, the animals were physically examined and the skin. found to be intact and normal.
- Type of wrap if used: surgical gauze patch 2x3 cm mounted on Micropore tape (3M, U.S.A.). The dressing was wrapped around the abdomen and secured with an elastic bandage (Coban, 3M, U.S.A.)


REMOVAL OF TEST SUBSTANCE
- Washing: tissue moistened with tap-water and subsequently a dry tissue
- Time after start of exposure: 4 h


SCORING SYSTEM:
In order to facilitate the scoring, the skin area concerned of all animals was shaved again before the observation on days 2, 3, 4, 8, 15 and 22.
Scoring acc. to Draize (1994):

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:

4

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3.7

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 21 days

Remarks on result:

other: edema could not be scored after 48 and 72 h due to eschar formation; 48 and 72 h scores were assumed to be the same as at 24 h

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Max. score:

2

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: mean value could not be calculated for animal #2 due to the omission of edema scores due to eschar formation at 24, 48 and 72 h

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

The observed skin irritation consisted of eschar formation and slight to moderate edema.
The irritation was reversible within 14 days after exposure in animal #3, within 21 days after exposure in animal #1, but had not resolved by day 22 in animal #2. Animal #2 showed new skin formation with very slight erythema and slight edema on day 22. No corrosive effect was evident on the skin.

Other effects:

In the area of application brown staining of the treated skin by the test substance and adherence of the test article was observed. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Readings:

Time	Animal	Erythema	Edema	Additional findings
1 h	1	2	2	b
	2	2	2	b
	3	2	2	b
24 h	1	4	3	eschar formation
	2	4	-	n
	3	3	3	-
48 h	1	4	-	n
	2	4	-	n
	3	4	3	± 5% eschar formtation
72 h	1	4	-	n
	2	4	-	n
	3	4	3	± 50% eschar formation
7 d	1	4	-	n
	2	4	-	n
	3	1	1	± 50% new skin formation
14 d	1	1	1	± 50% new skin formation
	2	1	1	new skin formation
	3	0	0	scaliness
21 d	1	0	0	± 25% new skin formation
	2	1	2	± 50% new skin formation
	3	0	0	-
mean 24 - 48 - 72 h	1	4	3
	2	4	-
	3	3.7	3
mean		3.9	3

b: brown test substance adhered to skin

n: edema could not be scored due to eschar formation

Interpretation of results:

other: Skin Irrit. 2, H315 according to Regulation (EC) No 1272/2008

Conclusions:

CLP: Skin Irrit. 2, H315

Reference 2

Endpoint:

skin 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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

observation time was only 72 hours

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
- Age at study initiation: young adults
- Weight at study initiation: 3204 - 3385 g
- Housing: individually in metal cages with perforated floors (Ruco, Valkenswaard)
- Diet: standard laboratory diet LK-01, pelleted diameter 4 mm (Hope Farms, Woerden)
- Water: tap water; ad libitum


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

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin of same animal

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

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

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: central back
- Site preparation: one day before dose application the fur was removed by clipping exposing an area of about 15x15 cm
- Type of wrap if used: 6 cm² patch of surgical gauze , which was attached by a bit of petrolatum to aluminium foil and mounted on tape (Micropore, 3M), fixed by a flexible bandage (Coban, 3M) wrapped around the animal.


REMOVAL OF TEST SUBSTANCE
- Washing: no washing, but removal by a tissue
- 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:

Remarks:

#1 and #2

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal:

Remarks:

'#1 and #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Irritant / corrosive response data:

Exposure of the clipped skin of all three animals to the test substance using a semi-occlusive dressing during 4 hours initially produced only slight erythema and slight to moderate edema. However, the also observed brown staining of the skin proved to indicate skin necrosis since a crust (eschar) had formed 48 hours after exposure.
After the formation and loosening of the crust, the skin of one animal had almost returned to normal 14 days after treatment, although hair growth was still incomplete. The skin of two animals showed a brownish-pink staining, a scurfy appearance and incomplete restoration of the hair growth.
Since the test substance produced full thickness destruction of skin tissue in the treated animals, the test substance is considered to be corrosive.

Readings:

Time	Animal	Erythema	Edema	Additional findings
1 h	1	1	1	b
	2	1	1	b
	3	1	1	b
24 h	1	2	2	b
	2	2	2
	3	1	3
48 h	1	4	2	n
	2	4	2	n
	3	4	3	n
72 h	1	4	0	e
	2	4	0	e
	3	4	3	e
mean 24 - 48 - 72 h	1	3.3	1.3
	2	3.3	1.3
	3	3.0	3.0
mean		3.2	1.9

b: exposed skin brown

n: skin necrotic

e: eschar formation

Interpretation of results:

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

Conclusions:

CLP: Skin Corr. 1C, H314

Reference 3

Endpoint:

skin 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 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

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: Charles River Wiga, Sulzfeld, Germany
- Age at study initiation: ca. 14 weeks
- Selection of animals: Animals for testing were selected from stock on the basis of background history. Each animal was used on a maximum of 3 previous occasions (in up to 2 eye irritation studies - one test each eye, and for possibly 1 skin irritation study). No significant response was noted on any previous occasion. An area of flank skin not previously treated was used for the test.
- Weight at study initiation: 2876 - 3083 g
- Housing: individually in cages with perforated floors equipped with an automatic drinking system (ITL, Bergen, The Netherlands)
- Diet: Standard laboratory rabbit diet (LKK-PO, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands) approx. 100 gram per day
- Water: tap-water diluted with decalcified water, ad libitum
- Acclimation period: at least five days under test conditions


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin of same animal

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL
- Concentration: 100%

Duration of treatment / exposure:

4 h

Observation period:

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

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: dorsal skin
- Site preparation: approximately 24 hours before treatment, the dorsal fur was shaved with an electric clipper, exposing an area of approximately 100 square centimetres (10 cm x 10 cm). Prior to test substance administration, the animals were physically examined and the skin found to be intact and normal.
- Type of wrap if used: surgical gauze patch 2x3 cm mounted on Micropore tape (3M, U.S.A.). The dressing was wrapped around the abdomen and secured with an elastic bandage (Coban, 3M, U.S.A.)


REMOVAL OF TEST SUBSTANCE
- Washing (if done): tissue moistened with tap-water and subsequently a dry tissue
- Time after start of exposure: 4 h


SCORING SYSTEM:
In order to facilitate the scoring, the skin area concerned of all animals was shaved again before the observation on days 2, 3, 4, 8, 15 and 22.
Scoring acc. to Draize (1994):

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:

4

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 21 days

Remarks on result:

other: edema could not be scored after 48 and 72 h due to eschar formation; 48 and 72 h scores were assumed to be the same as at 24 h

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: edema could not be scored after 48 and 72 h due to eschar formation; 48 and 72 h scores were assumed to be the same as at 24 h

Irritant / corrosive response data:

The observed skin irritation consisted of eschar formation and moderate to severe edema. The irritation was not reversible at termination of the study. All three animals showed very slight erythema and one animal slight edema on day 22. No corrosive effect was evident on the skin.

Other effects:

In the area of application no staining of the treated skin by the test substance was observed. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Readings:

Time	Animal	Erythema	Edema	Additional findings
1 h	1	2	1
	2	1	2
	3	1	2
24 h	1	4	3	e
	2	2	4
	3	4	4	e
48 h	1	4	-	n
	2	2	4
	3	4	-	n
72 h	1	4	-	n
	2	2	4
	3	4	-	n
7 d	1	4	-	n
	2	4	-	n
	3	4	-	n
14 d	1	1	1	s
	2	1	1	ss
	3	0	1	s
21 d	1	1	0	± 50% s
	2	1	0	± 50% s
	3	1	2
mean 24 - 48 - 72 h	1	4	3
	2	2	4
	3	4	4
mean		3.3	3.7

e: eschar formation

n: edema could not be scored due to eschar formation

s: new skin formation on the treated skin

ss: new skin formation with scaling

Interpretation of results:

other: Skin Irrit. 2, H315 according to Regulation (EC) No 1272/2008

Conclusions:

CLP: Skin Irrit. 2, H315

Reference 4

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

10 Nov - 11- Nov 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication/study report which meets basic scientific principles

Principles of method if other than guideline:

In vitro skin corrosion test as described by Oliver, Pemberton & Rhodes (1986 & 1988). Skin discs were prepared from the shaved pelt of male Wistar rats. The skin discs were sealed onto tubes and suspended in physiological magnesium sulphate solution. The test substance was applied to the epidermal surface of the skin disc for 24 hours. After the exposure the test substance was removed and any deterioration in the skin was assessed by measuring the transcutaneous electrical resistance (TER).

GLP compliance:

yes

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan - Olac
- Age at study initiation: 21 - 23 days

Type of coverage:

open

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: other substances were also tested during the study

Duration of treatment / exposure:

24 h

Observation period:

not applicable

Number of animals:

not applicable
The test was performed in triplicate (three skin discs).

Details on study design:

SKIN PREPARATION
When aged 22 - 24 days the animals were clipped of their dorsal and flank hair and washed in antibiotic solution. The antibiotic washing was repeated 72 hours later. When aged 27 - 29 days the animals were killed and their pelts removed.

SUBSTANCE APPLICATION
The skin discs were sealed to polytetrafluoroethylene (PTFE) tubes and suspended in physiological magnesium sulphate solution. 150 µl of the test substance was applied to the epidermal surface of the skin disc for 24 hours. After each exposure time the test substance was removed using a jet of water.

ASSESSMENT
Any deterioration in the skin was assessed by the measurement of the transcutaneous electrical resistance (TER). All TER values were assessed using an AIM 6401 LCR databridge. A mean TER reading value of < 5.0 kOhm/disc, after a 24 hour exposure, indicates that the test substance under the conditions of this assay, displayed properties characteristic of those substances which may be corrosive in vivo. A mean TER reading value of > 5.0 kOhm/disc, after a 24 hour exposure, indicates that the test substance under the conditions of this assay, did not display properties characteristic of those substances which may be corrosive in vivo.

Irritation / corrosion parameter:

transcutaneous electrical resistance (in kΩ)

Value:

4.7

Remarks on result:

other:

Remarks:

Basis: mean. Time point: 24 h incubation. Reversibility: other: not applicable. Remarks: standard deviation: ± 0.6 kΩ/disc. (migrated information)

Other effects / acceptance of results:

Under the conditions of this in vitro test, the test substance produced a significant reduction in the transcutaneous electrical resistance following a 24 hour contact period, thus it did display properties characteristic of those substances which may be corrosive to animal skin in vivo.

Interpretation of results:

other: corrosive

Conclusions:

The test substance revealed a corrosive potential when applied on rat skin discs according to the mentioned protocol.
The TER test does not allow sub-categorisation of corrosive substances as permitted in the Globally Harmonised System for Hazard Classification and Labelling (GHS).

Reference 5

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

10 Nov - 11 Nov 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication/study report which meets basic scientific principles

Principles of method if other than guideline:

In vitro skin corrosion test as described by Oliver, Pemberton & Rhodes (1986 & 1988). Skin discs were prepared from the shaved pelt of male Wistar rats. The skin discs were sealed onto tubes and suspended in physiological magnesium sulphate solution. The test substance was applied to the epidermal surface of the skin disc for 24 hours. After the exposure the test substance was removed and any deterioration in the skin was assessed by measuring the transcutaneous electrical resistance (TER).

GLP compliance:

yes

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan - Olac
- Age at study initiation: 21 - 23 days

Type of coverage:

open

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: other substances were also tested during the study

Duration of treatment / exposure:

24 h

Observation period:

not applicable

Number of animals:

not applicable
The test was performed in triplicate (three skin discs).

Details on study design:

SKIN PREPARATION
When aged 22 - 24 days the animals were clipped of their dorsal and flank hair and washed in antibiotic solution. The antibiotic washing was repeated 72 hours later. When aged 27 - 29 days the animals were killed and their pelts removed.

SUBSTANCE APPLICATION
The skin discs were sealed to polytetrafluoroethylene (PTFE) tubes and suspended in physiological magnesium sulphate solution. 150 µl of the test substance was applied to the epidermal surface of the skin disc for 24 hours. After each exposure time the test substance was removed using a jet of water.

ASSESSMENT
Any deterioration in the skin was assessed by the measurement of the transcutaneous electrical resistance (TER). All TER values were assessed using an AIM 6401 LCR databridge. A mean TER reading value of < 5.0 kOhm/disc, after a 24 hour exposure, indicates that the test substance under the conditions of this assay, displayed properties characteristic of those substances which may be corrosive in vivo. A mean TER reading value of > 5.0 kOhm/disc, after a 24 hour exposure, indicates that the test substance under the conditions of this assay, did not display properties characteristic of those substances which may be corrosive in vivo.

Irritation / corrosion parameter:

transcutaneous electrical resistance (in kΩ)

Value:

2.7

Remarks on result:

other:

Remarks:

Basis: mean. Time point: 24 h incubation. Reversibility: other: not applicable. Remarks: standard deviation: ± 1.4 kΩ/disc. (migrated information)

Other effects / acceptance of results:

Under the conditions of this in vitro test, the test substance produced a significant reduction in the transcutaneous electrical resistance following a 24 hour contact period, thus it did display properties characteristic of those substances which may be corrosive to animal skin in vivo.

Interpretation of results:

other: corrosive

Conclusions:

The test substance revealed a corrosive potential when applied on rat skin discs according to the mentioned protocol.
The TER test does not allow sub-categorisation of corrosive substances as permitted in the Globally Harmonised System for Hazard Classification and Labelling (GHS).

Reference 6

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

10 Nov - 11 Nov 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented study report which meets basic scientific principles

Principles of method if other than guideline:

In vitro skin corrosion test as described by Oliver, Pemberton & Rhodes (1986 & 1988). Skin discs were prepared from the shaved pelt of male Wistar rats. The skin discs were sealed onto tubes and suspended in physiological magnesium sulphate solution. The test substance was applied to the epidermal surface of the skin disc for 24 hours. After the exposure the test substance was removed and any deterioration in the skin was assessed by measuring the transcutaneous electrical resistance (TER).

GLP compliance:

yes

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan - Olac
- Age at study initiation: 21 - 23 days

Type of coverage:

open

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: other substances were also tested during the study

Duration of treatment / exposure:

24 h

Observation period:

not applicable

Number of animals:

not applicable
The test was performed in triplicate (three skin discs).

Details on study design:

SKIN PREPARATION
When aged 22 - 24 days the animals were clipped of their dorsal and flank hair and washed in antibiotic solution. The antibiotic washing was repeated 72 hours later. When aged 27 - 29 days the animals were killed and their pelts removed.

SUBSTANCE APPLICATION
The skin discs were sealed to polytetrafluoroethylene (PTFE) tubes and suspended in physiological magnesium sulphate solution. 150 µl of the test substance was applied to the epidermal surface of the skin disc for 24 hours. After each exposure time the test substance was removed using a jet of water.

ASSESSMENT
Any deterioration in the skin was assessed by the measurement of the transcutaneous electrical resistance (TER). All TER values were assessed using an AIM 6401 LCR databridge. A mean TER reading value of < 5.0 kOhm/disc, after a 24 hour exposure, indicates that the test substance under the conditions of this assay, displayed properties characteristic of those substances which may be corrosive in vivo. A mean TER reading value of > 5.0 kOhm/disc, after a 24 hour exposure, indicates that the test substance under the conditions of this assay, did not display properties characteristic of those substances which may be corrosive in vivo.

Irritation / corrosion parameter:

transcutaneous electrical resistance (in kΩ)

Value:

2.8

Remarks on result:

other:

Remarks:

Basis: mean. Time point: 24 h incubation. Reversibility: other: not applicable. Remarks: Standard deviation: ± 0.5 kΩ/disc. (migrated information)

Other effects / acceptance of results:

Under the conditions of this in vitro test, the test substance produced a significant reduction in the transcutaneous electrical resistance following a 24 hour contact period, thus it did display properties characteristic of those substances which may be corrosive to animal skin in vivo.

Interpretation of results:

other: corrosive

Conclusions:

The test substance revealed a corrosive potential when applied on rat skin discs according to the mentioned protocol.
The TER test does not allow sub-categorisation of corrosive substances as permitted in the Globally Harmonised System for Hazard Classification and Labelling (GHS).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study need not be conducted because the available information indicates that the criteria are met for classification as corrosive to the skin or irritating to eyes

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There are several in vivo and in vitro studies on the assessment of skin irritation/corrosion of fatty acids, C8-10 available.

 

In vivo

Skin irritation was evaluated in a study performed according to OECD guideline 404 and in compliance with GLP (1990a). Three female New Zealand White rabbits received a dermal application of 0.5 mL fatty acids, C8-10 (CAS# 68937-75-7) to the shaved dorsal skin under semiocclusive conditions for 4 hours. No symptoms of systemic toxicity were observed in the animals during the 21 day observation period and no mortality occurred. In the area of application brown staining of the treated skin by the test substance and adherence of the test article was observed. The observed skin irritation consisted of eschar formation and slight to moderate edema. The mean scores for erythema over 24/48/72 h for each animal were found to be 4.0, 4.0 and 3.7, respectively. Edema could not be scored for animal #1 and #2 at the reading time points 24 (only animal #2), 48, 72 h and 7 days due to eschar formation. The mean score for edema for animal #3 over 24/48/72 h was 3.0. The irritation was reversible within 14 days after exposure in animal #3, within 21 days after exposure in animal #1, but had not resolved by day 22 in animal #2. Animal #2 showed new skin formation with very slight erythema and slight edema on day 22. No corrosive effect was evident on the skin.

One further study by the same author (1990b) and similar to the method described above resulted in skin irritation consisting of eschar formation and moderate to severe edema. The irritation was not reversible at termination of the study. All three animals showed very slight erythema and one animal slight edema on day 22. No corrosive effect was evident on the skin. The mean scores for erythema over 24/48/72 h for each animal were found to be 4.0, 2.0 and 4.0, respectively. Edema could not be scored for animal #1 and #3 at the reading time points 48 and 72 h and at 7 days due to eschar formation. The mean score for edema for animal #2 over 24/48/72 h was 4.0. In the area of application no staining of the treated skin by the test substance was observed. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

A further study for assessment the skin irritation/corrosion of fatty acids, C8-10 was conducted according to GLP and OECD guideline 404 (1984). Three New Zealand White rabbits received a dermal application of 0.5 mL fatty acid C8-10 to the shaved dorsal skin under semiocclusive conditions for 4 hours. The means scores for erythema over 24/48/72 h for each animal were found to be 3.3, 3.3 and 3.0, respectively. The mean scores for edema over 24/48/72 h for each animal were 1.3, 1.3 and 3.0, respectively.

The observed brown staining of the skin was considered as an indication of skin necrosis since a crust (eschar) had formed 48 hours after exposure. After the formation and loosening of the crust, the skin of one animal had almost returned to normal 14 days after treatment, although hair growth was still incomplete. In contrast to that, the skin of two animals showed a brownish-pink staining, a scurfy appearance and incomplete restoration of the hair growth at the end of the 14-day observation period. Thus, fatty acids C8-10 have to be regarded as corrosive based on the findings of the study.

In a publication by Nixon et al. (1975) fatty acids, C8-10 produced very slight reactions in guinea pigs and moderate to severe erythema in rabbits after application of the test substance for 4 hours on intact and abraded skin. Skin responses were graded at 4, 24 and 48 hours after application of the test substance. The given data are not sufficient for risk assessment since only summed up mean values of erythema and edema scores over all animals are shown. Therefore, these studies are not taken into account for assessment.

 

In vitro

In addition to the in vivo studies, three in vitro studies by the same author were available for assessment (1994). In these studies using the method described by Oliver, Pemberton & Rhodes (1986 & 1988), 150 µL of three different fatty acids, C8-10 were applied onto discs of freshly prepared rat skin for 24 hours. After the incubation period, the deterioration in the skin was assessed by measuring the transcutaneous electrical resistance. In all three cases, a significant reduction in the transcutaneous electrical resistance following a 24 hour contact period was found. In detail, mean values of 4.7, 2.7 and 2.8 kΩ were measured, respectively. Since the measured values were below 5 kΩ, fatty acids, C8-10 displayed properties characteristic of those substances which may be corrosive to animal skin in vivo.

 

Human

Human volunteers were exposed to fatty acids, C8-10 for 4 hours on intact skin and skin responses were graded at 4, 24 and 48 h after application of the test item (Nixon et al., 1975). Moderate skin reactions with a sum of mean scores for erythema/edema formation of 2.3 (max. value 8) were reported. Weeping of serum with resultant eschar formation was observed in 2 out of 7 volunteers. No tissue destruction was observed in any of the volunteers.

 

In conclusion, in GLP compliant guideline studies according to OECD 404 fatty acids, C8-10 revealed either irritating or corrosive properties to the skin. In in vitro studies measuring the transcutaneous electrical resistance, fatty acids, C8-10 of different composition displayed a corrosive potential. Thus, in a weight of evidence approach fatty acids, C8-10 have to be considered as corrosive to skin.

 

Eye

Based on the fact, that corrosion of the skin was found, fatty acids, C8-10 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

The available data on skin irritation/corrosion of fatty acids, C8-10 meet the criteria for classfication as Skin Corr. 1C, H314 according to Regulation (EC) No 1272/2008.

Based on the fact, that corrosion of the skin was found, fatty acids, C8-10 have to be regarded as serious eye damaging according to the Guidance on CLP criteria.