Registration Dossier

Administrative data

Description of key information

In the absence of data on irritation/corrosion on target substance Fatty acids, C14-22, C16-24-alkyl esters an analogue read-across approach was conducted on suitable source substances:

Skin, rabbit (OECD 404): not irritating

Eye, rabbit (OECD 405): not irritating

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:
experimental study
Adequacy of study:
key study
Study period:
17 - 20 Feb 1998
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:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
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
- Age at study initiation: 7 weeks
- Weight at study initiation: 1.34-1.48 kg
- Housing: the animals were housed individually in labelled cages with perforated floors (Scanbur, Denmark)
- Diet: standard laboratory rabbit diet, approximately 100 g/day (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands). Hay (BMI, Helmond, the Netherlands) was provided once a week.
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 17 Feb 1998 To: 20 Feb 1998
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: not required, untreated sites of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
72 h
Reading time points: 1, 24, 48 and 72 h
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: the test substance was applied to the skin using a surgical gauze patch measuring 2 x 3 cm
- Type of wrap if used: the gauze patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): remaining test substance was removed using a tissue moistened with tap water and then the test area was wiped with a dry tissue
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
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:
3/3 animals had well-defined erythema at the 1-hr reading time point. The erythema had reduced in severity by 24 hours after exposure in 3/3 rabbits (score 1, 1, 1), and had cleared completely within 72 hours for 3/3 rabbits. No edema was observed in any animal at any time point (see Table 1).
Other effects:
There was no mortality, and no clinical signs were observed during the study period.

Table 1: Skin irritation scores

Observation time

Rabbit no.

 

1

2

3

 

Erythema

Edema

Erythema

Edema

Erythema

Edema

 

1 h*

2

0

2

0

2

0

 

24 h

1

0

1

0

1

0

 

48 h

1

0

0

0

0

0

 

72 h

0

0

0

0

0

0

 

Mean value 24 + 48 + 72 h

0.67

0

0.33

0

0.33

0

 

 

* Greasy remnants of the test substance was present on the test site in 3/3 rabbits

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
15 - 18 Jan 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: 6 New Zealand albino rabbits were exposed dermally under occlusive conditions to the undiluted test substance for 24 h. The test substance was applied to abraded and non-abraded skin sites. The skin was observed for erythema and edema (Draize scoring system) 1 and 48 h after removal of the test substance.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Nottingham, UK
- Weight at study initiation: 2.59 - 3.35 kg (range: males and females)
- Housing: individually in suspended metal cages
- Diet: rabbit diet (John Waring (Feeds) Limited, Shardlow, Derbyshire, UK), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Air changes (per hr): at least 20
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
occlusive
Preparation of test site:
other: clipped and abraded
Remarks:
test site on right flank of the animals
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:
24 h
Observation period:
48 h
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: The test substance was introduced under a composite patch which consisted of a 2.5 cm square of absorbent lint B.P.C. backed by a 2.5 cm square of polythene with a final backing of a 4 cm square of lint. The patch was held in position by two lengths of sleek adhesive strapping in the form of a cross.

REMOVAL OF TEST SUBSTANCE
- Washing: Any residual test material was removed by gentle swabbing the test site with cotton wool soaked in lukewarm water.
- Time after start of exposure: 24 h

OBSERVATION TIME POINTS
1 and 48 h after removal of the patches


SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
animal: #3
Time point:
other: 1 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
erythema score
Basis:
animal: #1, #2, #4, #5 and #6
Time point:
other: 1 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 6 animals
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
other: not apllicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 1 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
Intact skin:
At the 1-h reading time point, very slight erythema (score 1) was observed in 1/6 animals. The erythema had cleared completely within 48 hours after patch removal. No oedema was observed in any animal at any time reading time point.

Abraded skin:
Very slight erythema (score 1) was observed in 2/6 animals 1 h after patch removal. All evidence of irritation had disappeared 48 h after patch removal.



Table 1. Results of irritation test on intact and abraded skin sites 1h and 48 h after patch removal

Observation time

Rabbit no.

1

2

3

4

5

6

Erythema

Edema

Erythema

Edema

Erythema

Edema

Erythema

Edema

Erythema

Edema

Erythema

Edema

Intact skin

1 h

0

0

0

0

1

0

0

0

0

0

0

0

48 h

0

0

0

0

0

0

0

0

0

0

0

0

Abraded skin

1 h

0

0

1

0

1

0

0

0

0

0

0

0

48 h

0

0

0

0

0

0

0

0

0

0

0

0

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
26 -29 May 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The analytical purity of the test substance was not specified.
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: ESD (Chatillon sur Chalaronne, France)
- Weight at study initiation: 2-2.5 kg
- Housing: animals were housed individually in stainless steel cages with a wiremesh floor
- Diet: Food ref. 110-10 (U.A.R., Epinay sur Orge, France), ad libitum
- Water: filtered tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 30-80
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 26 May 1999 To: 29 May 1999
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: not required, untreated sites of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
3 days
Reading time points: 1, 24, 48 and 72 h
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: a gauze patch covering the test site was held in place by micropore tape; the trunk of the animals was wrapped in an elastic gauze band and semiocclusive, adhesive tape. Access to the test site was restricted with a plastified aerated wrapping fixed to the trunk of the animals with velcro tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the remnants of the test substance were removed with distilled water or, if necessary, a suitable solvent
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
No skin irritation effects were observed at any time point in any animal.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 - 31 Jan 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
limited documentation; no analytical purity of test substance given
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted Oct 2012
Deviations:
yes
Remarks:
limited documentation; no analytical purity of test substance given
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Nottingham, UK
- Weight at study initiation: 2.00 - 2.42 kg (range: males and females)
- Housing: individually in suspended metal cages
- Diet: rabbit diet (J. Waring (Feeds) Limited, Shardlow, Derbyshire, UK), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Air changes (per hr): at least 20
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
unchanged (no vehicle)
Controls:
other: left eye remained untreated and served as control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
72 h
Reading time points: 24, 48 and 72 h
Number of animals or in vitro replicates:
6
Details on study design:
SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: ophthalmoscope; Observation of corneal opacity was carried out under ultra-violet illumination preceded by the instillation of fluorescein into the eye.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #4 and #5
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal: #2, #3 and #6
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal: #2, #3, #4 and #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
3/6 animals showed conjunctival redness (score 1) 24 and 48 h after instillation, reversible within 72 h. 2/6 animals showed conjunctivae chemosis (score 1) 24 h after instillation of test substance, in one animal reversible within 48 h, in the second animal reversible within 72 h.

Table 1. Results of eye irritation study.

Alteration

Animal No.

Time (h)

 

24

 

48

 

72

mean 24/48/72 h

reversible within

Cornea

1

0

0

0

0

-

2

0

0

0

0

-

3

0

0

0

0

-

4

0

0

0

0

-

5

0

0

0

0

-

6

0

0

0

0

-

Iris

1

0

0

0

0

-

2

0

0

0

0

-

3

0

0

0

0

-

4

0

0

0

0

-

5

0

0

0

0

-

6

0

0

0

0

-

Conjunctivae Redness

1

0

0

0

0

-

2

1

1

0

0.67

72 h

3

1

1

0

0.67

72 h

4

0

0

0

0

-

5

0

0

0

0

-

6

1

1

0

0.67

72 h

Conjunctivae Chemosis

1

1

1

0

0.67

72 h

2

0

0

0

0

-

3

0

0

0

0

-

4

0

0

0

0

-

5

0

0

0

0

-

6

1

0

0

0.33

48 h

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
23 - 26 Feb 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, the Netherlands
- Age at study initiation: 8 weeks
- Weight at study initiation: 1.49-1.58 kg
- Housing: individually housed in labelled cages with perforated floors (Scanbur, Denmark)
- Diet: standard laboratory rabbit diet (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, the Netherlands), approximately 100 g/day. Hay (BMI, Helmond, the Netherlands) was provided once a week.
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23 Feb 1998 To: 26 Feb 1998
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
Single application without washing
Observation period (in vivo):
72 h
Reading time points: 1, 24, 48 and 72 h
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the eye was not washed after application

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: during the 24-hour reading time point, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal and the extent of corneal epithelial damage was assessed using a UV-light.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility not applicable
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritant / corrosive response data:
At the 1-hour reading time point 3/3 rabbits had slight conjunctivae (score 1, 1, 1), which was still present in 1/3 rabbits at the 24-hour reading time point. The effect had cleared completely within 48 hours. No other eye irritation effects were observed in any rabbit at any time point (see Table 1).
Other effects:
There was no mortality, and no clinical signs were observed during the study period.

Table 1: Eye irritation scores

Rabbit #

 

Time [h]

 

conjunctivae

 

iris

 

cornea

 

redness

swelling

1

 

 

 

 

1

1 (AB)

0

0

0

24

1 (A)

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0.33

0.0

0.0

0.0

2

 

 

 

 

1

1 (ABC)

0

0

0

24

0

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0.00

0.0

0.0

0.0

3

 

 

 

 

1

1 (AB)

0

0

0

24

0

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0.00

0.0

0.0

0.0

 

 

Time [h]

conjunctivae

 

iris

cornea

 

redness

swelling

 

 

average

score

1

1.00

0.00

0.00

0.00

24

0.33

0.00

0.00

0.00

48

0.00

0.00

0.00

0.00

72

0.00

0.00

0.00

0.00

24+48+72

0.11

0.00

0.00

0.00

A = eyelids

B = nictating membrane

C = sclera

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
26 - 31 May 1999
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The analytical purity of the test substance was not specified.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: ESD (Chatillon sur Chalaronne, France)
- Weight at study initiation: 2-2.5 kg
- Housing: animals were housed individually in high impact polystyrene cages with a mesh floor
- Diet: Food ref. 112 (U.A.R., Epinay sur Orge, France)
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 30-80
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 26 May 1999 To: 31 May 1999
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
Single application without washing
Observation period (in vivo):
7 days
Reading time points: 1, 24, 48 and 72 h, and 7 days
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated eye was not washed

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: After instilling 2% fluorescein into the eyes, any damage was assessed with a UV-lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritant / corrosive response data:
At the 1-hour reading time point, 3/3 rabbits had slight-moderate conjunctivae (scores 1, 1, 2) and 2/3 slight chemosis (scores 0, 1, 1). The chemosis had cleared by the 24-hour reading time point, while 3/3 animals still had slight conjunctivae (scores 1, 1, 1). All eye irritation effects were fully reversible within 48 hours.

Table 1: Eye irritation score

Rabbit #

 

Time [h]

 

conjunctivae

 

iris

 

cornea

 

redness

swelling

1

 

 

 

 

1

1

0

0

0

24

1

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0.33

0.0

0.0

0.0

2

 

 

 

 

1

2

1

0

0

24

1

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0.33

0.0

0.0

0.0

3

 

 

 

 

1

1

1

0

0

24

1

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0.33

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.
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
3 Jan 2005
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
The analytical purity of the test substance was not specified; a 15% test substance solution was used without justification.
Principles of method if other than guideline:
Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) assay, recommended by ICCVAM; applied to 4 eggs. The potential of the test substance to cause (severe) ocular irritancy was measured by its ability to induce toxicity in the chorioallantoic membrane of a chicken egg. Effects were measured by the onset of: (1) hemorrhage; (2) coagulation; and (3) vessel lysis. These assessments were considered individually and then combined to derive a score, which was used to classify the irritancy level of the test substance.
GLP compliance:
no
Species:
other: eggs from chicken
Strain:
other: White Leghorn
Details on test animals or tissues and environmental conditions:
TEST EGGS
- Source: INRA-PAP, 37380 Nouzilly, France
- Age at study initiation: 10 d
- Weight at study initiation: 50-60 g


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 37-38 (dry temperature)
Vehicle:
other: paraffin oil
Controls:
other: yes, negative control eggs treated with paraffin oil, positive control eggs treated with 3% sodium lauryl sulfate
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.3 mL
- Concentration (if solution): 15%. The test substance was dissolved in paraffin oil at 60°C.

VEHICLE
- Concentration (if solution): 85% paraffin oil
Duration of treatment / exposure:
20 sec
Observation period (in vivo):
5 min
Reading time points: 30 sec, 2 min and 5 min.
Number of animals or in vitro replicates:
4 eggs (test substance)
3 eggs (paraffin; negative control)
4 eggs (3 % sodium lauryl sulphate; positive control)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): 5 mL saline (37 °C)
- Time after start of exposure: 20 sec.

SCORING SYSTEM:
Observations were scored according to Table 1 and classification was done according to Table 2.
Irritation parameter:
other: Primary irritancy index
Run / experiment:
30 sec, 2 min or 5 min
Value:
1
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: mean score out of 4 eggs; scores depending on the time point of the first reaction; max. score 21.0
Other effects / acceptance of results:
Hyperemia with a score of 1 was observed in all eggs (see Table 3). No other effects were noted. The irritation index (IP-CAM) was 1.0.

Table 3: Irritation scores

 

Hyperaemia

Haemorrhage

Coagulation

Summed scores

Egg No. 1

1

0

0

1

Egg No. 2

1

0

0

1

Egg No. 3

1

0

0

1

Egg No. 4

1

0

0

1

The primary irritation index was 1.0.

The positive control, 3% SDS, induced clear irritating effects on every membrane (hyperaemia and haemorrhage observed after 30 s in all 4 eggs). The primary irritation index, IP-CAM, for the positive control was 10.0.

Interpretation of results:
other: non-corrosive according to Regulation (EC) No 1272/2008
Conclusions:
There is regulatory acceptance in the EU that a substance can be considered a severe eye irritant (Serious eye damage Category 1) based on a positive result in one of the available in vitro test methods, e.g. the Hen's Egg Test on Chorioallantoic Membrane (HET-CAM) test. Negative in vitro corrosivity responses are not conclusive with respect to non-classification or classification as irritant (Category 2) and shall therefore be subject to further evaluation.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Analogue justification

No data on the skin and eye irritation of Fatty acids, C14-22, C16-24-alkyl esters (CAS 92797-30-3) are available. The assessment of skin and eye irritation was therefore based on studies conducted with source substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

 

Skin irritation

In vivo

CAS 93803-87-3

A study was performed according to OECD guideline 404 to assess the skin irritation potential of 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) (Key, 1998). 0.5 g test substance was applied to the shaved skin of rabbits under semi-occlusive conditions for 4 hours. 3/3 animals had well-defined erythema (score 2) at the 1-hr reading time point. The erythema had reduced in severity by 24 hours after exposure in 3/3 rabbits (score 1, 1, 1), and had cleared completely within 72 hours for 3/3 rabbits. The mean score for the 24, 48 and 72 evaluation times was 0.67, 0.33 and 0.33, respectively. No edema was observed in any animal at any time point.

 

CAS 90990-29-7

A skin irritation study was performed with Fatty acids, C16 and C18-22 - unsatd., C16-18 and C18 unsatd. alkyl ester (CAS 90990-29-7) (Supp., 1982). No current guideline was followed. 0.5 mL of the undiluted test substance was applied to the clipped or clipped and abraded skin of 6 New Zealand White rabbits and held in place by an occlusive dressing for 24 h. The severity of erythema and edema was scored 1 and 48 h after patch removal. The test material produced minimal erythema (score 1) in 1/6 rabbits at the intact test site and in 2/6 rabbits at the abraded test site, respectively, 1 h after patch removal. All skin irritation effects were reversible within 48 h after patch removal. No other skin irritation effects were observed in any animal (6/6) at any reading time point. The test substance is not considered to be irritating to the skin.

CAS 72576-80-8

A skin irritation study was performed with hexadecanoic acid isooctadecyl ester (CAS 72576-80-8), according to OECD guideline 404 and under GLP conditions (Supp., 1999). 0.5 mL of the test substance was applied to the shaved skin of 3 New Zealand White rabbits and held in place by a semi-occlusive dressing for 4 hours. The severity of erythema and edema was scored 1, 24, 48 and 72 hours after patch removal. No skin irritation was observed at any time point in any animal; all erythema and edema scores were 0. The test substance is not considered to be irritating to the skin.

Human data

CAS 17671-27-1

In a single exposure patch test (Supp., 2005) the undiluted Docosyl docosanoatewas applied to the back skin of 11 volunteers for 24 h under occlusive conditions. The skin irritation effects (erythema and edema) were assessed 30 minutes and 24 h after patch removal. Slight to moderate erythema (score 1-1.5) was observed at the test site in 3/10 subjects at the 30-minute reading time point and in 1/10 subjects 24 h after patch removal. The positive control (1% sodium sulphate) was shown to be valid. 1/11 subjects were excluded as moderate erythema was noted at the negative control site (water).

Eye irritation

CAS 93803-87-3

The eye irritation potential of 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) was evaluated in a study performed according to OECD guideline 405 (Key, 1998). 0.1 mL was instilled into one eye of 3 rabbits and left without washing. Remains of the test substance were noted in the treated eye of 3/3 animals on Day 1, while remains were present on the outside of the eyelids on Day 2 in 1/3 animals. At the 1-hour reading time point 3/3 rabbits had slight conjunctivae (score 1, 1, 1), which was still present in 1/3 rabbits at the 24-hour reading time point. The effect had cleared completely within 48 hours. No other eye irritation effects were observed in any rabbit at any time point.

 

CAS 90990-29-7

The eye irritation potential of Fatty acids, C16 and C18-22 - unsatd., C16-18 and C18 unsatd. alkyl ester was investigated in six albino rabbits, following a protocol similar to OECD guideline 405 (Supp., 1982) and in compliance with GLP. 0.1 g of the test substance was instilled into one eye of each animal. The other eye remained untreated and served as control. The eyes were examined and scored according to the Draize scoring system 24, 48 and 72 h after application. 3/6 animals showed conjunctival redness (score 1) 24 and 48 h after instillation, reversible within 72 h. 2/6 animals showed conjunctivae chemosis (score 1) 24 h after instillation of test substance, in one animal reversible within 48 h, in the second animal reversible within 72 h. The cornea and iris were not affected. The mean 24/48/72 h scores of all 6 animals for redness were 0.0, 0.67, 0.67, 0.0, 0.0 and 0.67, respectively , while mean 24/48/72 h scores for chemosis were 0.67, 0.0, 0.0, 0.0, 0.0 and 0.33, respectivley.Based on the results of this study, the test substance is not considered to be irritating to the eyes.

CAS 72576-80-8

The eye irritation potential of hexadecanoic acid, isooctadecyl ester (CAS 72576-80-8) was evaluated in a study performed according to OECD guideline 405 and in compliance with GLP (Supp., 1999). 0.1 mL test substance was instilled into one eye of 3 male rabbits, and the eyes remained unwashed. The eye irritation effects were scored according to the Draize scoring system 1, 24, 48, and 72 hours, and 7 days after application.At the 1-hour reading time point, 3/3 rabbits had slight to moderate conjunctivae (scores 1, 1, 2), and 2/3 had slight chemosis (score 1).The chemosis had cleared by the 24-hour reading time point; while 3/3 animals still had slight conjunctivae (score 1). All eye irritation effects were fully reversible within 48 hours. No cornea opacity or iris changes were observed in any rabbit at any time point. The mean conjunctivae score (over 24, 48 and 72 hours) was 0.33, 0.33 and 0.33, while the mean chemosis score (over 24, 48 and 72 hours) was 0, 0 and 0, respectively. The mean cornea score and iris score (over 24, 48 and 72 hours) was 0 for all animals. Based on the results of the study, the test substance is not considered to be irritating to the eyes.

CAS 17671-27-1

A non-guideline in vitro study was performed to assess the eye corrosion effects of docosyl docosanoate (CAS 17671-27-1). The Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) assay was applied according to a protocol endorsed by ICCVAM (Supp., 2005). The potential of the test substance to cause (severe) ocular irritancy was measured by its ability to induce toxicity in the chorioallantoic membrane of a chicken egg. A 15% dilution of docosyl docosanoate in paraffin oil was applied to the chorioallantoic membrane of 4 eggs for 20 seconds before rinsing the membrane with 5 mL saline (at 37 °C). The effects were measured by scoring the occurrence and intensity of haemorrhage, coagulation and vessel lysis (hyperaemia). The score is used to classify the irritancy level of the test substance, with a maximum score of 21 indicating a corrosive effect. Hyperaemia score 1 (of 5) was noted in 4/4 eggs, adding up to a combined score of 1.0. This indicates slight irritation according to the scoring system, but no corrosive effects.

 

Overall conclusion for skin and eye irritation

The available data on suitable source substances did not show any skin or eye irritation effects. Therefore, the target substance Fatty acids, C14-22, C16-24-alkyl esters (CAS 92797-30-3) is not expected to be a skin irritant or an eye irritant.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met.Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Fatty acids, C14-22, C16-24-alkyl esters (CAS 92797-30-3), data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the read-across approach, the available data on skin and eye irritation do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.