Registration Dossier

Administrative data

Description of key information

Skin, rabbit (OECD 404): not irritating

Read-across from structural analogue source substances Decanoic acid, mixed esters with octanoic acid and pentaerythritol (CAS No. 68441-68-9), Fatty acids, C5-9 tetraesters with pentaerythritol (CAS No. 67762-53-2), Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS No. 68424-31-7), Fatty acids, C16-18 (even numbered), esters with pentaerythritol (CAS No. 85116-93-4), Fatty acids, C8-10 mixed esters with dipenaterythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS No. 189200-42-8), and 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS No. 62125-22-8)

Eye, rabbit (OECD 405): not irritating

Read-across from structural analogue source substances Fatty acids, C16-18 (even numbered), esters with pentaerythritol (CAS No. 85116-93-4), Fatty acids, C5-9 tetraesters with pentaerythritol (CAS No. 67762-53-2), Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS No. 68424-31-7), Fatty acids, C8-10 mixed esters with dipenaterythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS No. 189200-42-8), and 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS No. 62125-22-8)

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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (lack of data on test substance)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
lack of data on test substance
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HRP Inc., Denver, PA, USA
- Age at study initiation: 15 weeks
- Weight at study initiation: 2.2 - 2.6 kg
- Housing: animals were housed separately in suspended stainless steel and wire mesh cages with absorbent paper below the cages.
- Diet: certified Rabbit Diet 5322 (PMI Feeds Inc., Richmond, IN, USA), the amount of feed was limited on a not further specified daily basis
- Water: tap water, ad libitum
- Acclimation period: 8 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 21
- Humidity (%): 40 - 60
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 22 Aug 1995
To: 25 Aug 1995
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
- Concentration (if solution): undiluted
Duration of treatment / exposure:
4 h
Observation period:
72 h
Reading time points: 1, 24, 48 and 72 h
Number of animals:
6 males
Details on study design:
TEST SITE
- Area of exposure: ca. 6.5 cm² on the dorsal area from the shoulder to the lumbar region
- Type of wrap if used: the treated skin was covered with a non-irritating tape, held in place with a semi-occlusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the test site was wiped with paper towels and water.
- Time after start of exposure: 4h

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
out of all 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
out of all 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: not applicable
Irritant / corrosive response data:
The dermal application of the test substance did not result in erythema or edema in any of the animals tested at any observation time point.
Other effects:
Clinical signs were not observed in any animal during the study period. At the 72 h reading, two animals were observed with desquamation.
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:
weight of evidence
Study period:
18 Sep - 21 Sep 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (no data on test substance purity).
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
Adopted 12 May 1981
Deviations:
yes
Remarks:
(no data on test substance purity)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Van Zutphen Breeding Centre, Keldonk, The Netherlands
- Weight at study initiation: 2.6 - 3.4 kg
- Housing: individually in metal cages with perforated floors
- Diet: 120 g / day, LK-01, Hope Farms, Woerden, The Netherlands
- Water: tap-water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.5 - 21.5
- Humidity (%): 55 - 75
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Preparation of test site:
other: clipping
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
- Concentration: 100 %
Duration of treatment / exposure:
4 h
Observation period:
72 h
Reading time points: 1, 24, 48, 72 h
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: 6 cm²
- Type of wrap: surgical gauze attached with a drop of petrolatum to aluminium foil and mounted on tape, held in place with flexible bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: remaining test substance was removed, using a dry tissue
- 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:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility not applicable
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:
Very slight erythema (animal #3) and very slight edema (animal #2) was observed 1 h after treatment. Both effects were not obvious 24 h after treatment.
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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given (comparable to standards) (no data on test substance purity given).
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
(limited documentation, no data on test substance purity)
GLP compliance:
not specified
Species:
rabbit
Strain:
other: New Zealand (not further specified)
Observation period:
7 days
Reading time points: 1, 24, 48, 72 h, 7 d
Number of animals:
3 males
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 72 h
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:
0.3
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
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:
weight of evidence
Study period:
02 Feb - 05 Feb 1999
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (no analytical purity reported)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted in 1992
Deviations:
yes
Remarks:
no analytical purity reported
GLP compliance:
no
Species:
rabbit
Strain:
other: Albino Rabbits; New Zealand White, HM: (NZW)fBR
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hare-Marland, Inc., Hewitt, NJ, USA
- Age at study initiation: at least 8 weeks old
- Weight at study initiation: 2.5 – 2.8 kg
- Housing: individually housed in suspended, stainless steel cages with wire mesh bottoms
- Diet: certified Lab Rabbit Diet, HF, No. 5325; PMI Feeds, Inc. St. Louis, MO (approx 125 g/day while on test)
- Water: automatic watering system, municipal water supply, ad libitum
- Acclimation period: 60 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 22
- Humidity (%): 30 – 70
- Photoperiod (hrs dark / hrs light): 12/12


Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: 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: 24, 48, and 72 hours
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: intact skin of the dorsal trunk surface
- Type of wrap if used: 6 cm² gauze square placed directly on the intact test site per animal and directly held in place with tape. Gauze was then wrapped around the animal and secured with tape to keep the test material in contact with the skin.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The site was wiped free of test material with 0.9% saline and gauze
- Time after start of exposure: At the end of the exposure period

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: not applicable
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 hours
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:
All three animals showed a very slight or slight erythema 1 hour after the test item application. Within 48 hours after removal of the patches the dermal effect were completely reversible.
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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions. (Limited documentation but relevant data given)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
limited documentation but relevant data given
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 5.0 - 5.2 g

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
4 d
Reading time points: 30 - 60 min, 24, 48, 72 and 96 h
Number of animals:
3 (females)
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): cleansing with clean warm water
- Time after start of exposure: 4 h (upon removal of the dressing)

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h

Table 1: Erythema scores

Animal Number

24 hours

48 hours

72 hours

96 hours

Mean Score

26

2

1

1

0

1.3

35

2

2

1

0

1.7

36

2

1

1

0

1.3

 

Table 2: Edema Score

Animal Number

24 hours

48 hours

72 hours

96 hours

Mean Score

26

1

0

0

0

0.3

35

1

0

0

0

0.3

36

1

0

0

0

0.3

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:
weight of evidence
Study period:
12 - 15 Mar 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: Kleinrussen, Chbb:HM
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Thomae, Biberach, Germany
- Age at study initiation: 19 months
- Weight at study initiation: mean 2790 kg
- Housing: animals were housed individually (cages obtained from Heinkel, Kuchen, Germany)
- Diet: Altromin-Haltungsdiät 2023 (Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-70
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 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 males
Details on study design:
TEST SITE
- Area of exposure: 6 cm² on the back skin
- Type of wrap if used: the applied gauze patch was covered with an adhesive air- and vapour-permeable patch, which was fixed by using a hypoallergenic adhesive gauze-bandage.

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 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:
At the 24 h reading, very slight erythema formation (score 1) was observed in all 3 animals, which were fully reversible within 48 h after test substance application. No edema reaction was observed at any time in any animal over the complete duration of the test.
Other effects:
No further local or systemic effects were reported.

Erythema scores

 

Animal #1

Animal #2

Animal #3

1 h

0

0

0

24 h

1

1

1

48 h

0

0

0

72 h

0

0

0

 

Edema scores

 

Animal #1

Animal #2

Animal #3

1 h

0

0

0

24 h

0

0

0

48 h

0

0

0

72 h

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:
weight of evidence
Study period:
27 - 30 June 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
12 May 1981
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: ELEVAGE DES FEUILLETAS
- Weight at study initiation: 1.8 - 2.2 kg
- Housing: individually in stainless steel cages
- Diet: UAR 112, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 4 days under the same conditions with respect to housing and feeding as those used during the test

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 27
- Humidity (%): 30 - 80
- Air changes (per hr): 14
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 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: 14 cm x 14 cm on back and side of animals
- Type of wrap if used: the applied gauze patch was fixed with an hypoallergenic microporous adhesive strip, which was then covered with a stretchable band wrapped around the animal without any restraint for respiratory and abdominal movements.

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 24 h
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:
0.66
Max. score:
4
Reversibility:
fully reversible within: 72 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:
fully reversible within: 24 h
Irritant / corrosive response data:
At the 1h reading a slight erythema formation was observed in all 3 animals (score 2 in 1 animal and score 1 in the other two animals), which were fully reversible within 48 h after test substance application in 2/3 animals. The third animal showed no signs of erythema at the 72 h reading. No edema reaction was observed at any time in any animal over the complete duration of the test.
Other effects:
No further local or systemic effects were reported.

Erythema scores

 

Animal #1

Animal #2

Animal #3

1 h

2

1

1

24 h

1

0

1

48 h

0

0

1

72 h

0

0

0

 

 

Edema scores

 

Animal #1

Animal #2

Animal #3

1 h

0

0

0

24 h

0

0

0

48 h

0

0

0

72 h

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:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: Kleinrussen, Chbb:HM
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Thomae, Germany
- Age at study initiation: 19-20 months
- Weight at study initiation: approx. 2.7 kg
- Housing: single holding in cage
- Diet: ad libitum (Altromin Haltungsdiät 2023)
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-70
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g
Duration of treatment / exposure:
4 h
Observation period:
72 h
Reading time points: 1, 24, 48 and 72 h
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: 6 cm²

REMOVAL OF TEST SUBSTANCE
- Washing (if done): cleansing with clean warm water
- Time after start of exposure: 4 h (upon removal of the dressing)

SCORING SYSTEM: The application sites were assessed for signs of erythema and oedema and scored according to the Draize scoring system
Irritation parameter:
erythema 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:
edema score
Basis:
mean
Remarks:
mean out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility not applicable

Erythema score

Animal Number

1 day

2 days

3 days

Mean Score

1226

0

0

0

0

1230

0

0

0

0

1231

0

0

0

0

 

Edema Score

Animal Number

1 day

2 days

3 days

Mean Score

1226

0

0

0

0

1230

0

0

0

0

1231

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 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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (lack of data on test substance)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
lack of data on test substance
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: HRP Inc., Denver, PA, USA
- Age at study initiation: 12 - 13 weeks (female), 16 - 17 weeks (males)
- Weight at study initiation: 2.1 - 2.7 kg
- Housing: animals were housed separately in suspended stainless steel and wire mesh cages with absorbent paper below the cages.
- Diet: Purina Certified Diet 5322 (PMI Feeds Inc., Richmond, IN, USA), the amount of feed was limited on a not further specified daily basis
- Water: tap water, ad libitum
- Acclimation period: 15 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 21
- Humidity (%): 40 - 60
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 29 Aug 1995
To: 05 Sep 1995
Vehicle:
unchanged (no vehicle)
Controls:
other: not required, the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): undiluted
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
7 d
reading timepoints: 1, 24, 48 and 72 h and 7 d
Number of animals or in vitro replicates:
5 males and 1 female
Details on study design:
SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: 2% sodium fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
out of all 6 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 6 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 6 animals
Time point:
24/48/72 h
Score:
0.44
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
out of all 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: not applicable
Irritant / corrosive response data:
One hour after instillation of the test substance, slight conjunctivae redness and chemosis were observed in all animals. After 24 h and 48 h, slight conjunctivae redness was observed in 3 animals. At the 72 h reading timepoint, slight conjunctivae redness was observed in 2 animals. The effect was reversible in all animals within 7 days. The test substance did not affect the other irritation parameters in any animal at any timepoint.
Flurescein staining of the cornea was observed in three animals at the 48 h reading timepoint. At the 72 h reading, no staining of the cornea was observed indicating that the corneal response was superficial and transient.
Other effects:
There were no clinical signs observed in any animal during the study period.
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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study similar to guideline, but with restrictions (limited information on test substance, observation period only 72 hours).
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
Adopted 24 April 2002
Deviations:
yes
Remarks:
limited information on test substance, observation period only 72 h
Qualifier:
according to
Guideline:
other: U.S. Federal Register, 1973, Vol. 38, No. 187, Section 1500:42
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Housing: in grid bottomed galvanised metal cages
- Diet: 90 - 95 g / day, Product Ref. 16934, Spillers Agriculture Limited
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Air changes: air conditioned room
- Photoperiod (hrs dark / hrs light): 14 / 10
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL
- Concentration: 100 %
Duration of treatment / exposure:
72 h
Observation period (in vivo):
72 h
Reading time points: 24, 48 and 72 h
Number of animals or in vitro replicates:
6 females
Details on study design:
REMOVAL OF TEST SUBSTANCE: no

SCORING SYSTEM: Draize scoring system
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
out of all 6 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 6 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 6 animals
Time point:
24/48/72 h
Score:
0.78
Max. score:
3
Reversibility:
not specified
Remarks:
observation only for 72 h, reversibility was not studied
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
out of all 6 animals
Time point:
24/48/72 h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
24 h after exposure, chemosis was observed in 4 of 6 animals, which disappeared the next day. All 6 animals showed redness of the conjunctivae, which dissapeared in 3 animals the next day. At 72 h observation, redness was still observed in 2 animals. Since the observation was stopped after 72 h, there is no information on the reversibility of these effects in the remaining 2 animals.
Adverse effects on the cornea and the iris were not observed in any of the animals.

Table 1: Evaluation of the eye reaction

Rabbit No. / sex

Scoring [h]

Cornea

Iris

Conjunctiva

Redness

Chemosis

1 / f

24

0

0

2

0

48

0

0

0

0

72

0

0

0

0

Mean (24, 48, 72 h)

0

0

0.67

0

2 / f

24

0

0

2

1

48

0

0

0

0

72

0

0

0

0

Mean (24, 48, 72 h)

0

0

0.33

0.33

3 / f

24

0

0

2

0

48

0

0

1

0

72

0

0

1

0

Mean (24, 48, 72 h)

0

0

1.33

0

4 / f

24

0

0

1

1

48

0

0

1

0

72

0

0

0

0

Mean (24, 48, 72 h)

0

0

0.67

0.33

5 / f

24

0

0

1

1

48

0

0

1

0

72

0

0

1

0

Mean (24, 48, 72 h)

0

0

1.0

0.33

6 / f

24

0

0

1

1

48

0

0

0

0

72

0

0

0

0

Mean (24, 48, 72 h)

0

0

0.33

0.33

Group mean (24, 48, 72h)

0

0

0.78

0.22

 

 

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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given (comparable to standards) (no data on test substance purity).
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
(no data on test substance purity given)
GLP compliance:
not specified
Species:
rabbit
Strain:
other: New Zealand (not further specified)
Observation period (in vivo):
7 days
Reading time points: 1, 24, 48, 72 h, 7 d
Number of animals or in vitro replicates:
3 males
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1 - #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1 - #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: Reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1 + #2
Time point:
24/48/72 h
Score:
0.11
Max. score:
3
Reversibility:
fully reversible within: 48 h
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:
of all animals
Time point:
24/48/72 h
Remarks on result:
other: No information on chemosis in study report
Irritant / corrosive response data:
All animals showed slight effects on the conjunctiva 1 hour after removal of the test substance. This effect lessened but was still visible for 2 animals 24 hours later and fully reversible thereafter.

Table 1: Eye irritation scores (no information on the calculation of the scores available in the report. No individual scores are available)

Animal#

1 h

24 h

48 h

72 h

7 d

 

Co

Cor

Ir

Co

Cor

Ir

Co

Cor

Ir

Co

Cor

Ir

Co

Cor

Ir

1

1

0

0

0.33

0

0

0

0

0

0

0

0

0

0

0

2

1

0

0

0.33

0

0

0

0

0

0

0

0

0

0

0

3

0.67

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Co = conjunctiva

Cor = cornea

Ir = iris

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:
weight of evidence
Study period:
5 Feb 1999 - 12 Feb 1999
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (no details on analytical purity given)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
no data on test substance purity given
GLP compliance:
no
Species:
rabbit
Strain:
other: albino rabbits; New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hare-Marland, Inc., Hewitt, NJ, USA
- Age at study initiation: at least 8 weeks
- Weight at study initiation: 2.8 – 2.9 kg
- Housing: individually housed in suspended, stainless steel cages with wire mesh bottoms
- Diet: certified Lab Rabbit Diet HF, No. 5325; PMI Feeds, Inc. St. Louis, MO (approximately 125 g/day while on test)
- Water: automatic watering system (municipal water supply), ad libitum
- Acclimation period: 53 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 34-54
- Photoperiod (hrs dark / hrs light): 12/12
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:
24 h, single application without washing
Observation period (in vivo):
3 days
reading time points: 24, 48, and 72 h
Number of animals or in vitro replicates:
3 (1 male and 2 females)
Details on study design:
SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein
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:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 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:
One animal exhibited moderate conjunctival redness whereas the other 2 animals showed mild conjuctival redness; all three animals exhibited severe discharge. No iridial or corneal changes were evident throughout the study. At 24 h post-treatment, one animal was free of conjuctival redness. All 3 animals were free of ocular irritation within 72 h after treatment.
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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (lack of data on test substance and animal husbandry).
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
(lack of details on test substance and animal husbandry)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 3.6 - 4.6 kg

Vehicle:
unchanged (no vehicle)
Controls:
not required
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):
3 d
Number of animals or in vitro replicates:
3 females
Details on study design:
SCORING SYSTEM: Draize scoring system
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
out of all three 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 three 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 three animals
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 three animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility not applicable
Irritant / corrosive response data:
No corneal or iridial effects were observed. Conjunctival effects included slight redness (1 animal) and slight discharge (1 animal) and were transiently seen approx. 1 h after dosing.
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:
weight of evidence
Study period:
21 May - 24 May 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: Kleinrussen, Chbb:HM
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Thomae, Germany
- Age at study initiation: 4 months
- Weight at study initiation: approx.2.1 kg
- Housing: single holding in cage
- Diet: ad libitum (Ssniff rabbit diet K4)
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-70
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
unchanged (no vehicle)
Controls:
other: left, untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL (bump-volume)


Duration of treatment / exposure:
single application, 24 h
Observation period (in vivo):
72 h
Reading time points: 1, 24, 48 and 72 h
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eye was thoroughly rinsed with warm water.
- Time after start of exposure: 24 h

SCORING SYSTEM: According to Council Directive 84/449/EEC

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
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:
No effects were observed except a very mild and reversible exsudation reaction in one out of three animals 24 h after application.
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)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for grouping of substances and read-across

The analogue approach comprises aliphatic esters of poly-functional alcohols containing four to six reactive hydroxyl groups and one to six fatty acid chains. The read-across analogue approach contains mono constituent, multi-constituent and UVCB substances with fatty acid carbon chain lengths ranging from C5 - C20, which are mainly saturated but also mono unsaturated C16 and C18, polyunsaturated C18 and branched C5, C7 and C9, building mono-, di-, tri-, and tetra esters with the polyol. The available data allow for an accurate hazard and risk assessment of the target substance and the source substances and the read-across concept is applied for the assessment of environmental fate and environmental and human health hazards. Thus, where applicable, environmental and human health effects are predicted from adequate and reliable data for source substances within the read-across analogue approach by interpolation to the target substances in accordance with Annex XI, Item 1.5, of Regulation (EC) No. 1907/2006 (REACH). In particular, for each specific endpoint the source substance or substances 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 substance and target substances are the basis of read-across.

A detailed justification for the read-across applied is provided in the technical dossier (see IUCLID Section 7.1 and 13) and within Chapter 5.1 of the CSR.

Skin irritation / corrosion

Several studies assessing the skin irritation potential of structural analogue source substances are available.

Decanoic acid, mixed esters with octanoic acid and pentaerythritol (CAS No. 68441-68-9) has been investigated for its skin irritation / corrosion potential in a study performed according to OECD Guideline 404 and under GLP conditions (WoE, RA-A, 68441-68-9, 1989). 0.5 mL of the neat test substance was applied to the clipped skin of 3 New Zealand White rabbits and kept under semiocclusive conditions for an exposure duration of 4 h. The overall observation period was 72 h with readings for skin reaction after 1, 24, 48 and 72 h. At the 1-h reading a slight erythema formation was observed in all 3 animals (score 2 in 1 animal and score 1 in the other two animals), which was fully reversible within 48 h after test substance application in 2/3 animals. The third animal showed no signs of erythema at the 72 h reading. The 24/48/72 h erythema mean score values determined have been 0.33 for animal #1, 0 for animal #2 and 0.66 for animal #3. No edema reaction was observed at any time in any animal over the complete duration of the test. Therefore, the test substance was not considered to be irritating to the skin in this study.

In a second study with Decanoic acid, mixed esters with octanoic acid and pentaerythritol (CAS No. 68441-68-9), the primary dermal irritation was investigated according to OECD Guideline 404 and GLP (BASF, 1991a). The shaved skin of three male Kleinrussen, Chbb:HM rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semiocclusive conditions. Skin reactions were assessed 1, 24, 48 and 72 h after removal of the test substance. At the 24 h reading, very slight erythema was observed in all 3 animals (score 1), which was fully reversed 48 h after test substance removal. All treated skin sites appeared normal at the 72 hour observation. The mean erythema score was 1 for all animals, while edema score was zero in all animals after 24, 48 and 72 h treatment. The test material is not considered irritating to the skin in this study.

A primary dermal irritation study was performed comparable to OECD Guideline 404 with Fatty acids, C5-9 tetraesters with pentaerythritol (CAS No. 67762-53-2) (Exxon, 1999b). The clipped skin of three female New Zealand White rabbits was exposed to 0.5 mL unchanged test material for 4 h under semiocclusive conditions. Skin reactions were assessed 1, 24, 48 and 72 h after removal of the test substance. All three animals showed a very slight or slight erythema 1 hour after the test item application. Within 48 h after removal of the patches the dermal effect was completely reversible. All treated skin sites appeared normal at the 72 h observation. The mean erythema scores over 24, 48 and 72 h were 0 for animal #1 and #2 and 0.33 for animal #3. No edema occurred in any of the tested animals at any reading time point. The test material is not considered irritating to the skin in this study.

In a primary skin irritation study with Fatty acids, C5-10, esters with pentaerythritol (CAS No. 68424-31-7), which was performed according to OECD Guideline 404 (WoE, RA-A, 68424-31-7, 1991b), the shaved skin of three female New Zealand White rabbits was exposed to 0.5 mL unchanged test substance for 4 hours under semiocclusive conditions. Skin reactions were assessed 1, 24, 48, 72 and 96 h after removal of the test substance. The exposure period of 4 h caused slight edema (grade 1) in all animals 24 h after removal of the test substance. The effect fully reversed within 48 h. Erythema was seen at the test site of one animal (grade 2) and slightly at the test site of the other two animals (grade 1). Erythema reactions were completely reversed within 96 h after removal of the test substance in all three animals. The mean erythema score over 24, 48 and 72 h was 1.3 for animal #1 and #3 and 1.7 for animal #2. The mean edema score over 24, 48 and 72 h was 0.3 for all three animals. All treated skin sites appeared normal at the 96 h observation.

A primary dermal irritation study was performed with Fatty acids, C16-18, esters with pentaerythritol (CAS No. 85116-93-4) according to OECD Guideline 404 and GLP (BASF, 1991b). The shaved backs of three male Kleinrussen Chbb:HM rabbits were exposed to 0.5 g unchanged test material for 4 h under semiocclusive conditions. The rabbits were observed for 3 days following exposure. Skin reactions were assessed 1, 24, 48 and 72 h after removal of the test substance. No erythema and no edema occurred in any of the tested animals at any reading time point. Thus, the test material is not considered irritating to the skin in this study.

A primary dermal irritation study was performed with Fatty acids C8-10, mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tridipentaerythritol (CAS No. 189200-42-8) comparable to OECD Guideline 404 and GLP (Exxon, 1995a). The shaved skin of six male New Zealand White rabbits was exposed to 0.5 mL unchanged test material for 4 h under semiocclusive conditions. Skin reactions were assessed 1, 24, 48 and 72 h after removal of the test substance. No erythema and no edema occurred in any of the tested animals at any reading time point. At the 72 h time point two animals showed desquamation. The test material is not considered irritating to the skin in this study.

Two studies were conducted to assess the skin irritation potential of 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS No. 62125-22-8). The test material is not considered irritating to the skin in these studies. The first dermal irritation study was performed according to OECD Guideline 404 and GLP (WoE, RA-A, 62125-22-8, 1984c). The clipped skin of three female New Zealand White rabbits was exposed to 0.5 mL unchanged test material for 4 h under semiocclusive conditions. The rabbits were observed for three days following exposure. Skin reactions were assessed 1, 24, 48 and 72 h after removal of the test substance. Very slight erythema and very slight edema was observed 1 h after treatment, each in one animal. Effects were fully reversed within 24 h after treatment. The third animal was free of any skin irritation effect.

In a second primary dermal irritation study performed according to OECD Guideline 404 (Stearinerie, 1997b) the skin of three male New Zealand rabbits was exposed to the test material for 4 h. Skin reactions were assessed 1, 24, 48 and 72 h as well as 7 days after removal of the test substance. The exposure period of 4 h caused only slight erythema (score 1) in two animals which was completely reversed within 48 and 72 h, respectively. The mean score erythema score over 24, 48 and 72 h were 1.3, 0, and 0.3 for animal #1, #2, and #3 respectively. The third animal was free of any skin irritation. All treated skin sites appeared normal at the 72 h observation.

Eye irritation

Again, several adequate and reliable studies investigating the eye irritation potential using structural analogue source substances are available.

Fatty acids, C16-18 (even numbered), esters with pentaerythritol (CAS No. 85116-93-4) was tested for its acute eye irritation potential in a study performed according to OECD Guideline 405 under GLP conditions (BASF, 1991c). The undiluted test material (0.1 mL) was applied into the conjunctival sac of three male Kleinrussen, Chbb:HM rabbits each. The animals were observed for 72 h and reactions were assessed 1, 24, 48, and 72 h after instillation according to the Draize scoring system. No effects were observed except a very mild and reversible exsudation reaction in one of three animals 24 h after application. Thus, the test material is not considered irritating to the eyes.

Fatty acids, C5-9, tetraesters with pentaerythritol (CAS No. 67762-53-2) was tested for its acute eye irritation potential in a study performed comparable to OECD Guideline 405 (Exxon, 1999c). The undiluted test material (0.1 mL) was applied into the conjunctival sac of 3 (1 male, 2 female) New Zealand White rabbits each. The animals were observed for 3 days and reactions were assessed 1, 24, 48 and 72 h after instillation according to the Draize scoring system. One animal exhibited moderate conjunctival redness and two animals showed mild conjuctival redness. All three animals exhibited severe discharge. No iridial or corneal changes were evident throughout the study. At 24 h post treatment, one animal was free of conjuctival redness. All three animals were free of ocular irritation within 72 h of treatment. The mean conjunctivae score out of all three animals over 24, 48 and 72 h was 0.67. Thus, the test material is not considered irritating to the eyes in this study.

Fatty acids, C5-10, esters with pentaerythritol (CAS No. 68424-31-7) was tested for its acute eye irritation potential in a study performed comparable to OECD Guideline 405 (WoE, RA-A, 68424-31-7, 1991c). The undiluted test material (0.1 mL) was applied into the conjunctival sac of three female New Zealand White rabbits each. The animals were observed for three days and reactions were assessed 1, 24, 48 and 72 h after instillation according to the Draize scoring system. No corneal or iridial effects were observed. Conjunctival effects included slight redness (1 animal) and slight discharge (1 animal) and were transiently seen approximately 1 h after dosing. Thus, the test material is not considered irritating to the eyes in this study.

Fatty acids C8-10, mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tridipentaerythritol (CAS No. 189200-42-8) was tested for its acute eye irritation potential in a study performed comparable to OECD Guideline 405 under GLP conditions (Exxon, 1995b). The undiluted test material (0.1 mL) was applied into the conjunctival sac of 6 (5 male and 1 female) New Zealand White rabbits each. The animals were observed for 7 days and reactions were assessed 1, 24, 48, 72 h and 7 days after instillation according to the Draize scoring system. 1 h after instillation of the test substance, slight conjunctival redness and chemosis were observed in all animals. Chemosis was reversible within 24 h whereas conjunctival redness was reversible in all animals within 7 days. The mean conjuctivae score out all six animals over 24, 48 and 72 h was 0.44. Fluorescein staining of the cornea was observed in three animals at the 48 h reading time point. At the 72 h reading, no staining of the cornea was observed indicating that the corneal response was superficial and transient. Thus, the test material is not considered irritating to the eyes under the conditions of this study.

Two eye irritation studies were conducted to assess the eye irritation potential of 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS No. 62125-22-8). In the first in vivo study performed comparable to OECD Guideline 405 (WoE, RA-A, 62125-22-8, 1982) the undiluted test material (0.1 mL) was applied into the conjunctival sac of six female New Zealand White rabbits. The animals were observed for 72 h and reactions were assessed 1, 24, 48, and 72 h after instillation according to the Draize scoring system. 24 h after exposure, chemosis was observed in 4 of 6 animals, which disappeared the next day. All 6 animals showed redness of the conjunctivae, which disappeared in three animals the next day. At 72 h observation, redness was still observed in two animals. Since the observation was stopped after 72 h, there is no information on the reversibility of these effects in the remaining two animals. The mean conjuctivae and chemosis score out of all six animals over 24, 48 and 72 h were 0.78 and 0.22 respectively. Adverse effects on the cornea and the iris were not observed in any of the animals. Thus, the test material is not considered irritating to the eyes in this study.

In a second in vivo study performed comparable to OECD Guideline 405 (Stearinerie, 1997c) the test material was applied into the conjunctival sac of three male New Zealand rabbits each. The animals were observed for 72 hours and reactions were assessed 1, 24, 48, 72 h and 7 days after instillation according to the Draize scoring system. All animals showed slight effects on the conjunctiva 1 h after removal of the test substance. This effect lessened but was still visible for 2 animals 24 h later but fully reversible thereafter. The mean conjuctivae score over 2 animals was 0.11, and 0 for the remaining animal. Thus, the test material is not considered irritating to the eyes in this study.

Conclusion for skin and eye irritation

Based on the results of the available studies, none of structural analogue source substances is considered skin irritating. Therefore, on the basis of these findings, also no skin irritation potential for the target substance Fatty acids lanolin, di-, tri- and tetraesters with pentaerythritol and rape fatty acid is identified. Several acute eye irritation studies have been performed in rabbits in vivo. None of the structural analogue source substances showed an eye irritation potential. Therefore, no eye irritation potential is also identified for the target substance.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 (REACH) information on intrinsic properties of substances may be generated by means other than tests, e.g. using information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI states that “substances whose physico-chemical, 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 read-across concept is applied to the target substance Fatty acids lanolin, di-, tri- and tetraesters with pentaerythritol and rape fatty acid, data gaps can be filled by interpolation from representative structural analogue source substances to avoid unnecessary animal testing.

The read-across concept is also used to derive the classification of the target substance taking the properties of the source substances into account. Based on the read-across concept, all available data on skin and eye irritation / corrosion do not meet the classification criteria according to Regulation (EC) No. 1272/2008 (CLP) and are therefore conclusive but not sufficient for classification.