Registration Dossier

Administrative data

Description of key information

Skin, rabbit: not irritating
Eye, rabbit: not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
9 Apr -17 Apr 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study. Lack of test material details.
Justification for type of information:
refer to category justification report provided in IUCLID section 13
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
lack of test material details
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: 19-20 months
- Weight at study initiation: 2770 g
- Housing: animals were housed individually in cages (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:
other: not required, untreated sites of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
7 days
Reading time points: 1, 24, 48 and 72 h and 7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm² on the dorsal area of the trunk
- Type of wrap if used: The treated skin was covered with gauze, held in place with an adhesive hypoallergenic tape.

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean over 24, 48 an 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
After 1h 2/3 animals showed slight erythema being reversible within 24h and 7 days, respectively. After 48 h 1/3 animals showed slight erythema being reversible after 72 h. Edema formation was apparent in 1/3 animals at the 48 and 72 h reading time point and was reversible within 7 days.

Table 1.Results of skin irritation study

observation time

Rabbit no.

 

1

2

3

 

Erythema

Edema

Erythema

Edema

Erythema

Edema

1 h

0

0

1

0

1

0

24 h

0

0

0

0

1

0

48 h

1

0

0

0

2

1

72 h

0

0

0

0

1

1

7 days

0

0

0

0

0

0

Mean value 24 + 48 + 72 h

0.3

0.0

0.0

0.0

1.3

0.7

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996-03-11 to 1996-03-26
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP guideline study, tested with the source substance glyceryl citrate/lactate/linoleate/oleate (CAS 91744-23-9). According to the ECHA guidance document ‘Practical guide 6: How to report read-across and categories' (ECHA, 2012), the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance
Justification for type of information:
refer to category justification report provided in IUCLID section 13
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Age at study initiation: adult, no further details mentioned
- Weight at study initiation: 3 - 4.4 kg
- Housing: conventionally, singly in stainless steel cages
- Diet (e.g. ad libitum): Ssniff K 4- Complete feed for rabbits, supplied by Ssniff, Soest, Germany, ad libitum
- Water (e.g. ad libitum): Drinking water ad libitum, supplied by Gelsenwasser, Wasserwerk, Haltern, Germany
- Acclimation period: at least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: an adjacent area of untreated skin
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): undiluted
Duration of treatment / exposure:
4 hours
Observation period:
30-60 minutes, 24, 48 and 72 hours, 6, 8, and 14 days after patch removal
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: approx. 6 cm²
- % coverage: not mentioned
- Type of wrap if used: gauze patch covered with a non-irritant plaster and a semiocclusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to OECD Guideline 404
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.11
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
AVERAGE SCORE
- Erythema: 1.67
- Edema: 1.11
Other effects:
The following effects were noted:
2-3 days: slightly oedema
day 8:light brown discoloration and dryness of skin.
day 10: subsided irritations

Table: Irritant/corrosive response data for each animal at each observation time of each animal from the test

Score at time point / Reversibility

Erythema

Edema

Max. score: 4

Max. score: 4

30 - 60 min

2/2/2

 2/1/1

24 h

 2/2/2

 1/1/2

48 h

1/2/1

 1/1/1

72 h

 1/2/2

 1/1/1

Average 24h, 48h, 72h

 1.67

 1.11

Reversibility*)

c. 

 c.

Average time (unit) for reversion

 14 days

14 days 

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is slightly irritating but does not warrant classification according to CLP.
Executive summary:

Dermal irritation of the test substance (CAS 91744-23-9, Glyceryl Citrate/Lactate/Linoleate/Oleate) was investigated in a study according to OECD 404 and GLP. 0.5 g of the test substance were applied to the shaved skin of three New Zealand White rabbits (semi-occlusive coverage). Total exposure was 4 h. Thereafter, the test substance was removed using warm water.

Observations were made after 30-60 minutes, 24, 48, and 72 h, as well as 6, 8, and 14 days after patch removal. An adjacent area of untreated skin served as control.

Mean erythema and edema scores after 24, 48, and 72 h were 1.67 and 1.11, respectively. Both were fully reversible within 14 days.

Based on the results of this test the substance is slightly irritating but does not warrant classification according to CLP.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
refer to category justification report provided in IUCLID section 13
Reason / purpose:
read-across source
Species:
rabbit
Strain:
other: Kleinrussen, Chbb:HM
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Thomae, Biberach, Germany
- Age at study initiation: 19-20 months
- Weight at study initiation: 2770 g
- Housing: animals were housed individually in cages (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:
other: not required, untreated sites of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
7 days
Reading time points: 1, 24, 48 and 72 h and 7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm² on the dorsal area of the trunk
- Type of wrap if used: The treated skin was covered with gauze, held in place with an adhesive hypoallergenic tape.

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean over 24, 48 an 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
After 1h 2/3 animals showed slight erythema being reversible within 24h and 7 days, respectively. After 48 h 1/3 animals showed slight erythema being reversible after 72 h. Edema formation was apparent in 1/3 animals at the 48 and 72 h reading time point and was reversible within 7 days.

Table 1. Results of skin irritation study

observation time

Rabbit no.

 

1

2

3

 

Erythema

Edema

Erythema

Edema

Erythema

Edema

1 h

0

0

1

0

1

0

24 h

0

0

0

0

1

0

48 h

1

0

0

0

2

1

72 h

0

0

0

0

1

1

7 days

0

0

0

0

0

0

Mean value 24 + 48 + 72 h

0.3

0.0

0.0

0.0

1.3

0.7

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
refer to category justification report provided in IUCLID section 13
Reason / purpose:
read-across source
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Age at study initiation: adult, no further details mentioned
- Weight at study initiation: 3 - 4.4 kg
- Housing: conventionally, singly in stainless steel cages
- Diet (e.g. ad libitum): Ssniff K 4- Complete feed for rabbits, supplied by Ssniff, Soest, Germany, ad libitum
- Water (e.g. ad libitum): Drinking water ad libitum, supplied by Gelsenwasser, Wasserwerk, Haltern, Germany
- Acclimation period: at least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: an adjacent area of untreated skin
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): undiluted
Duration of treatment / exposure:
4 hours
Observation period:
30-60 minutes, 24, 48 and 72 hours, 6, 8, and 14 days after patch removal
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: approx. 6 cm²
- % coverage: not mentioned
- Type of wrap if used: gauze patch covered with a non-irritant plaster and a semiocclusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to OECD Guideline 404
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.11
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
AVERAGE SCORE
- Erythema: 1.67
- Edema: 1.11
Other effects:
The following effects were noted:
2-3 days: slightly oedema
day 8:light brown discoloration and dryness of skin.
day 10: subsided irritations

Table: Irritant/corrosive response data for each animal at each observation time of each animal from the test

Score at time point / Reversibility

Erythema

Edema

Max. score: 4

Max. score: 4

30 - 60 min

2/2/2

 2/1/1

24 h

 2/2/2

 1/1/2

48 h

1/2/1

 1/1/1

72 h

 1/2/2

 1/1/1

Average 24h, 48h, 72h

 1.67

 1.11

Reversibility*)

c. 

 c.

Average time (unit) for reversion

 14 days

14 days 

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is slightly irritating but does not warrant classification according to CLP.
Executive summary:

Dermal irritation of the test substance (CAS 91744-23-9, Glyceryl Citrate/Lactate/Linoleate/Oleate) was investigated in a study according to OECD 404 and GLP. 0.5 g of the test substance were applied to the shaved skin of three New Zealand White rabbits (semi-occlusive coverage). Total exposure was 4 h. Thereafter, the test substance was removed using warm water.

Observations were made after 30-60 minutes, 24, 48, and 72 h, as well as 6, 8, and 14 days after patch removal. An adjacent area of untreated skin served as control.

Mean erythema and edema scores after 24, 48, and 72 h were 1.67 and 1.11, respectively. Both were fully reversible within 14 days.

Based on the results of this test the substance is slightly irritating but does not warrant classification according to CLP.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
7 May - 10 May 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-Guideline study. Lack of test material details.
Justification for type of information:
refer to category justification report provided in IUCLID section 13
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
lack of test material details
GLP compliance:
yes
Species:
rabbit
Strain:
other: Kleinrussen, Chbb:HM
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Thomae, Biberach, Germany
- Age at study initiation: 21-24 months
- Weight at study initiation: 2560 g
- Housing: animals were housed individually in cages (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
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL
Duration of treatment / exposure:
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
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: the treated eye was rinsed with lukewarm water
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: hand-slit lamp and fluorescein
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility: not applicable
Irritation parameter:
cornea opacity 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: reversibility: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
chemosis 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: reversibility: not applicable
Irritant / corrosive response data:
No corneal opacity, iritis, conjunctivae or chemosis were observed in any animal at any reading time point. All animals showed slight to moderate exudation exclusively at the 1 h reading time point.
Other effects:
No further local or system effects were reported.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not irritating
DSD: not irritating
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996-03-18 to 1996-03-22
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study. Read-across from analogue substance. For justification of read-across and for further details please refer to the read-across report.
Justification for type of information:
refer to category justification report provided in IUCLID section 13
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Age at study initiation: young adult, no further details mentioned
- Weight at study initiation: 2.8 - 3.8 kg
- Housing: conventional, singly in stainless steel cages
- Diet (e.g. ad libitum): Ssniff K4 - Complete feed for rabbits, supplied by Ssniff, Spezialfutter GmbH, Soest, Germany, ad libitum
- Water (e.g. ad libitum): Drinking water ad libitum, supplied by Gelsenwasser, Wasserwerk, Haltern, Germany
- Acclimation period: at least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 cm³
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
1, 24, 48 and 72 hours after administration
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm physiological saline
- Time after start of exposure: 24 hours

SCORING SYSTEM: according to OECD Guideline 405

TOOL USED TO ASSESS SCORE: ophthalmic lamp, fluorescein 24 hours after administration
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
1
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritant / corrosive response data:
AVERAGE SCORE
- Cornea: 0.0
- Iris: 0.0
- Conjuntivae (Redness): 0.0
- Conjuntivae (Chemosis): 0.0
Other effects:
marked hyperaemias of some blood vessels in all animals one hour after application, after 24 hours no effects was noticed.

Table #: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

0/0/0

0/0/0

1/1/1

0/0/0 

24 h

0/0/0 

0/0/0

0/0/0

0/0/0

48 h

0/0/0

0/0/0

0/0/0

0/0/0

72 h

0/0/0

0/0/0

0/0/0

0/0/0

Average 24h, 48h, 72h

0

0

0

0

Area effected

 -

-

-

-

Maximum average score (including area affected, max 110)

 0

0

 0

0

Reversibility*)

 -

-

-

-

Average time (unit) for reversion

 -

 -

 -

 -

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of this test the test item is not irritating to the eye.
Executive summary:

Eye irritation of the test substance (CAS 91744-23-9, Glyceryl Citrate/Lactate/Linoleate/Oleate) was investigated in a study according to OECD 405 and GLP. 0.1 cm³ of the test substance were instilled in one eye each of the three New Zealand White rabbits. Total exposure was 24 h. Thereafter, the test substance was removed using warm physiological saline.

Observations were made after 1, 24, 48, and 72 h after administration. The untreated eye of each animal served as control.

Marked hyperaemias of some blood vessels could be observed in all animals 1 h after application, after 24 hours no effects was noticed. Mean scores for cornea, iris, conjunctivae redness and conjunctivae chemosis after 24, 48, and 72 h were 0 for each endpoint.

Based on the results of this test the substance is classified as not irritating.

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
refer to category justification report provided in IUCLID section 13
Reason / purpose:
read-across source
Species:
rabbit
Strain:
other: Kleinrussen, Chbb:HM
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Thomae, Biberach, Germany
- Age at study initiation: 21-24 months
- Weight at study initiation: 2560 g
- Housing: animals were housed individually in cages (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
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL
Duration of treatment / exposure:
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
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: the treated eye was rinsed with lukewarm water
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: hand-slit lamp and fluorescein
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility: not applicable
Irritation parameter:
cornea opacity 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: reversibility: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
chemosis 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: reversibility: not applicable
Irritant / corrosive response data:
No corneal opacity, iritis, conjunctivae or chemosis were observed in any animal at any reading time point. All animals showed slight to moderate exudation exclusively at the 1 h reading time point.
Other effects:
No further local or system effects were reported.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not irritating
DSD: not irritating
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
refer to category justification report provided in IUCLID section 13
Reason / purpose:
read-across source
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Age at study initiation: young adult, no further details mentioned
- Weight at study initiation: 2.8 - 3.8 kg
- Housing: conventional, singly in stainless steel cages
- Diet (e.g. ad libitum): Ssniff K4 - Complete feed for rabbits, supplied by Ssniff, Spezialfutter GmbH, Soest, Germany, ad libitum
- Water (e.g. ad libitum): Drinking water ad libitum, supplied by Gelsenwasser, Wasserwerk, Haltern, Germany
- Acclimation period: at least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 cm³
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
1, 24, 48 and 72 hours after administration
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm physiological saline
- Time after start of exposure: 24 hours

SCORING SYSTEM: according to OECD Guideline 405

TOOL USED TO ASSESS SCORE: ophthalmic lamp, fluorescein 24 hours after administration
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
1
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritant / corrosive response data:
AVERAGE SCORE
- Cornea: 0.0
- Iris: 0.0
- Conjuntivae (Redness): 0.0
- Conjuntivae (Chemosis): 0.0
Other effects:
marked hyperaemias of some blood vessels in all animals one hour after application, after 24 hours no effects was noticed.

Table #: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

0/0/0

0/0/0

1/1/1

0/0/0 

24 h

0/0/0 

0/0/0

0/0/0

0/0/0

48 h

0/0/0

0/0/0

0/0/0

0/0/0

72 h

0/0/0

0/0/0

0/0/0

0/0/0

Average 24h, 48h, 72h

0

0

0

0

Area effected

 -

-

-

-

Maximum average score (including area affected, max 110)

 0

0

 0

0

Reversibility*)

 -

-

-

-

Average time (unit) for reversion

 -

 -

 -

 -

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of this test the test item is not irritating to the eye.
Executive summary:

Eye irritation of the test substance (CAS 91744-23-9, Glyceryl Citrate/Lactate/Linoleate/Oleate) was investigated in a study according to OECD 405 and GLP. 0.1 cm³ of the test substance were instilled in one eye each of the three New Zealand White rabbits. Total exposure was 24 h. Thereafter, the test substance was removed using warm physiological saline.

Observations were made after 1, 24, 48, and 72 h after administration. The untreated eye of each animal served as control.

Marked hyperaemias of some blood vessels could be observed in all animals 1 h after application, after 24 hours no effects was noticed. Mean scores for cornea, iris, conjunctivae redness and conjunctivae chemosis after 24, 48, and 72 h were 0 for each endpoint.

Based on the results of this test the substance is classified as not irritating.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for read-across

Reliable data on the skin and eye irritation potential of glycerides, C16-18 and C18-unsaturated, mono-and di-citrates (CAS 91052-16-3) are not available. The assessment was therefore based on studies conducted with analogue 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

CAS 91744-13-7

The skin irritation potential of glycerides, C14-18 and C16-22-unsatd, mono- and di- was investigated in a GLP-conform study performed according to OECD guideline 404 (Steiling, 1990). 0.5 mL of the test substance was applied for 4 h to the shaved skin of 3 Kleinrussen, Chbb:HM rabbits under semi-occlusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 1, 24, 48, 72 h as well as 7 days after removal of the dressing. In one animal, slight erythema persisted up to the 72 h, but was fully reversible within the 7-day observation period. In the two other animals, slight erythema was either seen at the 1 or 48 h reading, but was fully reversible 24 h or 72 h after patch removal. Slight edema was only noted in one animal at both the 48 and 72 h reading time points, but fully reversed during the 7-day observation period. No signs of systemic toxicity were seen during the study. The mean erythema and edema scores over the 24, 48 and 72 h reading time points were 0.3/0/1.3 and 0/0/7 for the 3 animals. Thus, the test substance is considered to be non-irritating to the skin.

CAS 91744-23-9

The dermal irritation potential of glyceryl citrate/lactate/linoleate/oleate was investigated in a study according to OECD 404 and GLP (Kruegar, 1996c). 0.5 g of the test substance was applied to the shaved skin of three New Zealand White rabbits (semi-occlusive coverage). Total exposure was 4 h. Thereafter, the test substance was removed using warm water. Observations were made after 30-60 minutes, 24, 48, and 72 h, as well as 6, 8, and 14 days after patch removal. An adjacent area of untreated skin served as control. Mean erythema and edema scores after 24, 48, and 72 h were 1.67 and 1.11, respectively. Both were fully reversible within 14 days. Based on the results of this test the substance is slightly irritating but does not warrant classification according to CLP.

Eye irritation

CAS 91744-13-7

The eye irritation potential of glycerides, C14-18 and C16-22-unsatd, mono- and di- was investigated according to OECD guideline 405 and in compliance with GLP (Steiling, 1990). The undiluted test material (0.1 mL) was placed into the conjunctival sac of one eye of 3 male Kleinrussen (Chbb:HM) rabbits each. The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h after application. No corneal opacity, iritis, conjunctivae or chemosis were observed in any animal at any reading time point. All animals showed slight to moderate exudation exclusively at the 1 h reading time point. No further local or systemic toxic effects were reported. The mean cornea, iris, conjunctivae and chemosis scores after 24, 48, and 72 h were 0 for all 3 animals, respectively. Thus, the test substance was not considered as eye irritant.

 

CAS 91744-23-9

The eye irritation potential of glyceryl citrate/lactate/linoleate/oleate was investigated in a study according to OECD 405 and GLP (Kruegar, 1996d). 0.1 cm³ of the test substance were instilled in one eye each of the three New Zealand White rabbits. Total exposure was 24 h. Thereafter, the test substance was removed using warm physiological saline. Observations were made after 1, 24, 48, and 72 h after administration. The untreated eye of each animal served as control. Marked hyperaemias of some blood vessels could be observed in all animals 1 h after application, after 24 hours no effects was noticed. Mean scores for cornea, iris, conjunctivae redness and conjunctivae chemosis after 24, 48, and 72 h were 0 for each endpoint. Based on the results of this test the substance is classified as not irritating.

Overall conclusion for skin and eye irritation

The reliable data available for the read-across analogue substances did not show any skin or eye irritation effects. Therefore, glycerides, C16-18 and C18-unsaturated, mono-and di-citrates (CAS 91052-16-3) is not considered to be a skin irritant or an eye irritant.


Justification for selection of skin irritation / corrosion endpoint:
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between the source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of eye irritation endpoint:
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between the source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

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 glycerides, C16-18 and C18-unsaturated, mono-and di-citrates (CAS 91052-16-3) 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 analogue 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.