Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin

Skin irritation (OECD 404, occlusive): corrosive (Skin Corr. 1C); CAS# 142-62-1, C6; CAS#124-07-2, C8

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

Skin irritation (OECD 404, occlusive): not irritating; CAS# 57-10-3, C16

Skin irritation (Patch test acc. to national Guideline, 24 h, occlusive, readings: 24 and 72 h): not irritating; CAS# 544-63-8, C14, CAS# 57-11-4, C18

Skin irritation (4 h, occlusive, rabbit, reading: 20 h and 44h): not irritating; CAS# 112-80-1, C18:1

Skin irritation (24 h, occlusive, rabbit, reading: 48 h): not irritating; CAS# 112-80-1, C18:1

 

Based on read-across data, fatty acids, C8-24 (CAS# 71076-48-7) is considered to be corrosive (Skin Corr. 1C).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

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: Basic data given
Principles of method if other than guideline:
0.5 mL of the test substance was applied for 4 hours to the abraded and intact skin of 6 rabbits. Reading was performed upon removal of test substance and 24 and 48 h after initial application.
GLP compliance:
not specified
Species:
rabbit
Strain:
other: albino rabbit, not further specified
Type of coverage:
occlusive
Preparation of test site:
other: clipped as well as clipped and abraded test sites
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated sites of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
44 hours
Reading time points: upon removal of patches, 20 and 44 hours after patch removal (correspondingly to 24 and 48 h after initial application)
Number of animals:
6 animals, each with 4 test sites (1. control, intact, 2. control, abraded, 3. test material, intact, 4. test material, abraded)
Details on study design:
TEST SITE
- Type of wrap if used: The gauze patches (1.5 inch x 1.5 inch) were secured to the area by thin bands of adhesive tape. The entire trunks of the animals were then wrapped in clear plastic trunk bands.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): following the initial reading, all test sites were washed with appropriate solvent
- Time after start of exposure: ca. 4 hours

SCORING SYSTEM:
A: Erythema and eschar formation
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth):4

B: Edema Formation
Very slight edema (barely perceptible): 1
Slight edema (edges of area well defined by definite raising): 2
Moderate edema (area raised approx. 1 mm): 3
Severe edema (raised more than 1 mm, and extending beyond area of exposure): 4




Irritation parameter:
edema score
Basis:
mean
Remarks:
out of all 6 animals (intact sites)
Time point:
other: mean over 20 h and 44 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Remarks on result:
other: intact site
Irritation parameter:
erythema score
Basis:
mean
Remarks:
out of all 6 animals (intact sites)
Time point:
other: mean over 20 h and 44 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Remarks on result:
other: intact site
Irritant / corrosive response data:
After 4 hour exposure to the test substance all rabbits showed slight erythema-eschar (score 1) without a difference between intact and abraded skin. Following this initial reading, the test substance was washed up.
24 hours after initial application no erythema-eschar (score 1) were observed except at one abraded area of one of the six rabbits. The mean score after 48 hours after initial application was 0 for intact and abraded skin, respectively.
No edema were observed up to 48 hours after initial application.

Abraded skin sites were not taken into account for assessment.

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:
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:
comparable to guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
other: Hazardous Substances Act F.R. Sept. 17, 1964.
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
other: albino
Type of coverage:
occlusive
Preparation of test site:
other: clipped and one testing site of each animal was additionally abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): undiluted
Duration of treatment / exposure:
24 h
Observation period:
48 h
Reading time points: directly after removal of patches and again after 48 h
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: Fur was removed from the back of each of six rabbits by clipping the saddle area of the trunk. One area of skin was abraded by making minor incisions with a hypodermic needle.
- Type of wrap if used: 0.5 mL of test material was applied to 1 inch square 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.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The patches were removed and the skin cleaned by gently sponging with a moistened towel.
- Time after start of exposure: 24 h

SCORING SYSTEM: § 191.11 of the Regulations under the Federal Hazardous Substances Labeling Act
Irritation parameter:
erythema score
Basis:
mean
Remarks:
over all 6 animals
Time point:
other: 48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: intact sites
Irritation parameter:
edema score
Basis:
mean
Remarks:
over all 6 animals
Time point:
other: 48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: intact sites
Irritant / corrosive response data:
Slight erythema of both intact and abraded skin (score of 1) in all six animals was observed directly after patch removal. By the 48 hour reading, erythema was no longer present. No edema was observed in any animal at any reading during the study.

The animals were immobilized during exposure for 24 hours in wooden stocks.The skin was examined immediately after removal of the patches (24 h reading) and again at 72 h. At each examination the skin was scored for presence and severity of erythema/eschar formation and edema formation.

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:
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
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
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:
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:
29 Jan - 04 Feb 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981
Deviations:
yes
Remarks:
occlusive dressing; no details on reading time points
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
Commission Directive 84/449/EEC
Deviations:
yes
Remarks:
occlusive dressing; no details on reading time points
GLP compliance:
yes
Species:
rabbit
Strain:
other: Kleinrusse, Chbb: HM
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Fa. Thomae, Biberach, Germany
- Weight at study initiation: mean: 2452.5 g
- Housing: individually housed in rabbit batteries, Fa. Heinkel, Kuchen, Germany
- Diet: Zucht- /Haltungsdiät 20 ZH 5, Fa. Nohrlin GmbH, Bad Salzuflen, Germany, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): approx. 20 - 21
- Humidity (%): approx. 45 - 50
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
3 days
Number of animals:
4 males
Details on study design:
TEST SITE
- Area of exposure: dorsal area
- Type of wrap if used: The substance was applied to the intact skin using a patch (2.5x2.5 cm), which was covered by a plastic foil using adhesive plasters and an acrylastic band aid.

SCORING SYSTEM: Draize Scoring System
Irritation parameter:
erythema score
Basis:
animal: #1, #2, #3 and #4
Time point:
other: mean over all reading time points
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal: #1, #2, #3 and #4
Time point:
other: mean over all reading time points
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No skin reactions were observed.
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:
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 according to national standard standard methods performed with the source substance CAS 57-11-4. 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:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
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 hours 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 all 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 sites
Irritation parameter:
edema score
Basis:
mean
Remarks:
out of all 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 sites
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

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:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation of fatty acids, C8-24 (CAS# 71076-48-7) was evaluated in a study performed according to GLP and OECD Guideline 404 (1988). Four Himalayan Chbb:HM rabbits received a dermal application of 0.5 g fatty acids, C8-24 to the shaved skin of the back under occlusion for 4 hours. The resulting individual mean scores after 24/48/72 hours for erythema were 1, 1, 1 and 1.67, respectively. The erythema reactions were reversible within 8 days. No edema reactions were observed. Based on this finding, fatty acids, C8-24 is considered to be not irritant to skin.

Since the batch tested in this skin irritation study contained much less of the corrosive constituents C6 fatty acid (hexanoic acid) and C8 fatty acid (octanoic acid) than the maximum upper concentration limit defined in IUCLID Section 1.2 Composition, skin irritation effects are predicted from adequate and reliable data of the constituents of fatty acids, C8-24.

Reliable studies with C6 fatty acid (hexanoic acid), C8 fatty acid (octanoic acid), C12 fatty acid (lauric acid), C14 fatty acid (myristic acid), C16 fatty acid (palmitic acid), C18 fatty acid (stearic acid) and C18:1 fatty acid (oleic acid) are used for hazard assessment. These substances were constituents contributing to the hazard or main constituents (>10%) of fatty acids, C8-24. Since fatty acids, C8-24 hexanoic acid, octanoic acid, lauric acid, myristic acid, palmitic acid, stearic acid and oleic acid belong to the same category based on similar 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).

 

Skin irritation by hexanoic acid (CAS# 142-62-1) was evaluated in a study performed according to OECD Guideline 404 (1984).0.5 mL of hexanoic acid was applied to the shaved skin of five New Zealand White rabbits under occlusion for 4 hours. Immediately after removal of the plaster, intensive erythema and edema was observed. The edema had disappeared after seven days; the erythema, however, persisted and passed into a full thickness necrosis. 10 days after initiation of the study eschar started to separate from treated skin. Another 7 days later eschar was completely separated from skin. 21 days after treatment a red scar tissue with single eschar rest had developed. Around the scar tissue, an intensified growth of hair appeared and on the treated skin area, there were just single flocci indicating the full thickness destruction of all epidermal layers. Based on the findings the test material is considered corrosive under the experimental conditions chosen. Corrosive effects are expected even if the study would had been conducted under semiocclusive conditions as the test material has a very low vapour pressure so that evaporating of the test material from the skin through the semiocclusive dressing is rather unlikely.

 

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.

 

Skin irritation by palmitic acid (CAS# 57-10-3) was evaluated in a study performed under GLP according to OECD Guideline 404 with the exception, that the test was performed under occlusive conditions (1988). Four male rabbits received an application of 0.5 g palmitic acid to the shaved skin under occlusion for 4 hours. Skin reactions were evaluated according to Draize for 3 days after application. The readings did not reveal any signs of irritation, thus resulting in mean scores of 0 for erythema and edema, respectively. Based on the results, palmitic acid can be regarded as not irritating to skin.

 

Skin irritation by stearic acid (CAS# 57-11-4) was evaluated in a study performed in accordance with Federal Guidelines (1974). 0.5 mL of stearic acid was applied to the abraded skin of 6 New Zealand White rabbits under occlusion for 24 h. Readings at 24 and 72 h after application revealed no signs of irritation. The resulting scores were 0 for erythema and edema, respectively, although the exposure duration was under occlusive conditions and longer than suggested according to current OECD Guideline. Based on this, stearic acid can be regarded as not irritating to skin.

 

In a skin irritation study 0.5 mL of oleic acid (CAS# 112-80-1) was applied under occlusive conditions for 4 h to the abraded and intact skin of 6 rabbits (1973). Reading was performed upon removal of test substance and 20 and 44 h after patch removal. All animals showed very slight erythema (barely perceptible; score 1) on the intact and abraded skin sites upon removal of the occlusive patch. Within 20 h this reaction was reversible on all intact sites and on 5 abraded sites. At the 44 h reading time point no more erythema skin reactions or eschar formation were observed in any of the animals. No edema formation was noted on the three reading time points. The mean score for erythema and edema on the basis of only the 20 and 44 h time points and restricted to the results obtained from intact skin, is 0.

In a single insult occlusive patch test, 6 albino rabbits were administered a 0.5 mL dose of oleic acid for 24 hours to abraded and intact skin sites (1973). Slight erythema of both intact and abraded skin (score of 1) in all six animals was observed directly after patch removal. By the 48 hour reading, erythema was no longer present. No edema was observed in any animal at any reading during the study. Thus, based on this available data, oleic acid is considered to have no skin irritation potential.

In conclusion, fatty acids, C8-24 has to be classified as corrosive to skin taking into account its content on classified constituents including hexanoic acid and octanoic acid (additivity approach).

 

Eye

Irritation to eyes of fatty acids, C8-24 (CAS# 71076-48-7) was analyzed in a study performed according to OECD Guideline 405 and in compliance with GLP (1988). 0.1 g of fatty acids C8-24 was instilled into the right eyes of three Kleinrussen rabbits, while the left eyes served as controls. No reactions on iris or cornea were observed which was confirmed after fluorescein treatments. Slight effects (grade 1) on the conjunctiva (redness) were observed in 3 animals which were fully reversible within 24 to 48 h in all animals.

The resulting mean scores after 24/48/72 h for corneal opacity, iris, conjunctival erythema and chemosis were found to be 0, 0, 0.17 and 0, respectively. Thus, fatty acids, C8-24 was not irritating to eyes.

In this eye irritation study also a batch was tested, that contained much less of the corrosive constituents C6 fatty acid (hexanoic acid) and C8 fatty acid (octanoic acid) than the maximum upper concentration limit defined in Section 1.2 Composition for these two constituents. However, no read-across to the constituents is performed. The Guidance to the CLP Criteria clearly states that when a substance is classified as Skin Corrosive Category 1 then serious damage to the eyes is implicit. Since fatty acids, C8-24 is classified as skin corrosive based on its constituents hexanoic acid and octanoic acid, there is no need to proceed with a separate classification for eye effects.

Justification for classification or non-classification

Skin

The substance contains hexanoic acid (C6) and octanoic acid (C8), which are classified as Skin Corr. 1C, H314 according to Regulation (EC) 1272/2008.

SCL is assigned as 60% for Skin Corr. 1C to hexanoic acid (C6).

Fatty acids, C8-24 has to be classified as Skin Corr. 1C, H314 based on the content of its classified constituents including hexanoic acid and octanoic acid (additivity approach).

Eye

Since corrosion of the skin is considered, fatty acids, C8-24 has to be regarded as serious eye damaging according to the Guidance on CLP criteria.