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Diss Factsheets

Administrative data

Description of key information

Skin, rabbit (OECD 404, OPP 81-5): not irritating

Eye, rabbit (OECD 405, OPP 81-4): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
01 Dec -05 Dec 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted in 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
adopted in 1992
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Ministerium für Umwelt, Raumordnung und Landwirtschaft des Landes Nordrhein-Westfalen, Düsseldorf, Germany
Species:
rabbit
Strain:
other: White New Zealand albino, HsdPoc:NZW
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Age at study initiation: adult animals
- Weight at study initiation: 2.3, 2.7 and 2.6 kg (animals #1, 2 and 3, respectively)
- Housing: conventional, single housing in stainless steel cages
- Diet: Ssniff K 4 complete feed for rabbits (Ssniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- 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)
Remarks:
moistened with demineralised water
Controls:
other: not required, untreated sites of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g

VEHICLE
- Amount applied: The grinded powdery test substance was moistened with 0.5 mL demineralised water.
Duration of treatment / exposure:
4 h
Observation period:
72 h
Reading time points: 30-60 min, 24, 48 and 72 h
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: approx. 6 cm² on the dorsal area of the trunk
- Type of wrap if used: the treated skin was covered with a gauze patch which was secured in place with a non-irritant plaster. The patch was held in contact with the skin using a suitable semi-occlusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated skin area was washed with warm water to remove residual test substance.
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritant / corrosive response data:
No skin reactions were observed in any animal at any reading time point.
Other effects:
No further local or systemic effects were reported.
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:
25 - 28 May 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
No details on analytical purity of the substance.
Qualifier:
according to guideline
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Deviations:
yes
Remarks:
no details on analytical purity of the substance
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Cheshire, UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.24-2.64 kg
- Housing: individually in suspended metal cages
- Diet: Rabbit Diet (Preston Farmers Ltd., Lincolnshire, UK), ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-20
- Humidity (%): 68-75
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
other: 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
The test material was warmed to approx. 40 ºC and applied as a liquid to the skin.
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: dorsal flank area
- % coverage: 2.5 cm x 2.5 cm
- Type of wrap if used: gauze patch, surgical adhesive tap, elasticated corset (TUBIGRIP)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): any residual test material was removed by gentle swabbing with cotton wool soaked in diethyl ether.
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: mean after 24/48/72 h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: mean after 24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritant / corrosive response data:
1 h post-application: slight erythema was observed in 1/6 animals.
24 h post-application: slight erythema was observed in 1/6 animals.
48 h post-application: slight erythema was observed in 3/6 animals. In one of these animals, the reaction extended up to 4 cm beyond the treatment site.
72 h post-application: no skin reactions were noted.
No edema was observed in any animal at any reading time point.
Other effects:
No further local or systemic effects were reported.

Table1 . Results of skin irritation study.

Observation time Rabbit no.
1 2 3 4 5 6
Erythema Edema Erythema Edema Erythema Edema Erythema Edema Erythema Edema Erythema Edema
1 h 0 0 0 0 0 0 1 0 0 0 0 0
24 h 0 0 0 0 0 0 1 0 0 0 0 0
48 h 1 0 0 0 0 0 1 0 0 0 1 0
72 h 0 0 0 0 0 0 0 0 0 0 0 0
Mean value 24 + 48 + 72 h 0.33 0.00 0.00 0.00 0.00 0.00 0.67 0.00 0.00 0.00 0.33 0.00
Mean value 24 + 48 + 72 h all animals 0.22 0.00                    
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:
20 Nov - 23 Nov 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Ministerium für Umwelt und Naturschutz, Landwirtschaft und Verbraucherschutz des Landes Nordrhein-Westfalen, Düsseldorf, Germany
Species:
rabbit
Strain:
other: Crl:KBL(NZW)BR
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Kißlegg, Germany
- Age at study initiation: young adults
- Weight at study initiation: 3.1-3.5 kg
- Housing: individually in cage units Metall/Noryl. Excrement trays below the cages contained low dust wood granulate bedding. The wood granulate was changed at least twice weekly. The animals were regularly transferred to clean cages. The animal room was provided with sound from a radio program.
- Diet: standard diet "Ssniff K-Z" 4mm (Ssniff Spezialdiäten GmbH, Soest, Germany), approx. 100 g per animal per day. To satisfy the needs of roughage, hay was offered additionally (hay, irradiated, delivered by Harlan Winkelmann, Borchen, Germany; respectively hay pellets delivered by Ssniff Spezialdiäten GmbH, Soest, Germany).
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 50 ± 25
- 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 applied: 0.5 mL
Duration of treatment / exposure:
Initial test: 3 min, 1 and 4 h
Confirmatory test: 4 h
Observation period:
72 h
Reading time points: 1, 24, 48 and 72 h
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: approx. 2.5 cm by 2.5 cm on the dorso-lateral areas of the trunk
- Type of wrap if used: the treated skin was covered with a gauze patch, held in place with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the exposed skin area was carefully washed with water without altering the existing response or the integrity of the epidermis.
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system

TESTING PROCEDURE
- Initial test: due to a possible irritant potential of the test substance, in the first step only one animal was used and three patches were applied successively to this animal. The first patch was removed after 3 min. As no serious skin reactions were observed, the second patch was applied and removed after 1 h. At this stage, the observations indicated that with respect to animal welfare the exposure can be allowed to extend to 4 h. Therefore, the third patch was applied and removed after 4 h and the responses were graded 1 h later.
- Confirmatory test: the test was completed using two additional animals exposed for 4 h.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0.7
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 and 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:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritant / corrosive response data:
Initial test
In the first animal, no skin reactions were observed immediately after patch removal following 3 min and 1 h of exposure, respectively.

Confirmatory test
1 h post-application: very slight erythema was observed in 2/3 animals, being fully reversible in one animal at the 24 h reading. No edema was noted in any animal.
24-48 h post-application: very slight erythema was observed in 1/3 animals at both reading time points, being fully reversible at the 72 h reading. No edema was noted in any animal.
72 h post-application: No skin reactions were observed in any animal.
Other effects:
No further local effects were reported. There were no systemic intolerance reactions.

Table 1. Results of skin irritation study.

Observation time Rabbit no.
1 2 3
Erythema Edema Erythema Edema Erythema Edema
1 h 1 0 0 0 1 0
24 h 1 0 0 0 0 0
48 h 1 0 0 0 0 0
72 h 0 0 0 0 0 0
Mean value 24 + 48 + 72 h 0.67 0.00 0.00 0.00 0.00 0.00
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
Study period:
27 Nov - 30 Nov 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Ministerium für Umwelt und Naturschutz, Landwirtschaft und Verbraucherschutz des Landes Nordrhein-Westfalen, Düsseldorf, Germany
Species:
rabbit
Strain:
other: Crl:KBL(NZW)BR
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River, Kißlegg, Germany
- Age at study initiation: young adults
- Weight at study initiation: 3.1-3.5 kg
- Housing: individually in cage units Metall/Noryl. Excrement trays below the cages contained low dust wood granulate bedding. The wood granulate was changed at least twice weekly. The animals were regularly transferred to clean cages. The animal room was provided with sound from a radio program.
- Diet: standard diet "Ssniff K-Z" 4mm (Ssniff Spezialdiäten GmbH, Soest, Germany), approx. 100 g per animal per day. To satisfy the needs of roughage, hay was offered additionally (hay, irradiated, delivered by Harlan Winkelmann, Borchen, Germany; respectively hay pellets delivered by Ssniff Spezialdiäten GmbH, Soest, Germany).
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 50 ± 25
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: not required, the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount 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 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h

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:
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:
conjunctivae score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis 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:
chemosis score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
1 h post-instillation: moderate conjunctival redness and very slight chemosis were observed in all 3 animals. No corneal opacity or iritis was noted in any animal.
24 h post-instillation: slight conjunctival redness and very slight chemosis were observed in 3/3 and 2/3 animals, respectively. Both effects were fully reversible after further 24 h (48 h reading). No corneal opacity or iritis was noted in any animal.
48-72 h post-instillation: no eye effects were observed in any animal.
Other effects:
No further local effects were reported. There were no systemic intolerance reactions.

Table 1. Results of eye irritation study.

Rabbit # Time [h] conjunctivae    iris cornea
redness swelling
1 1 2 1 0 0
24 1 0 0 0
48 0 0 0 0
72 0 0 0 0
average 0.3 0.0 0.0 0.0
2 1 2 1 0 0
24 1 1 0 0
48 0 0 0 0
72 0 0 0 0
average 0.3 0.3 0.0 0.0
3 1 2 1 0 0
24 1 1 0 0
48 0 0 0 0
72 0 0 0 0
average 0.3 0.3 0.0 0.0
   
Time [h] conjunctivae    iris cornea
  redness swelling    
average
score		 1 2.00 1.00 0.00 0.00
24 1.00 0.67 0.00 0.00
48 0.00 0.00 0.00 0.00
72 0.00 0.00 0.00 0.00
24+48+72 0.33 0.22 0.00 0.00
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:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to guideline
Guideline:
other: "Appraisal of the safety of chemicals in foods, drugs and cosmetics" by the Staff of the Division of Pharmacology", FDA, according to Draize (1959)
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.4-2.6 kg
- Housing: individually caged
- Diet: standard diet (Höing 222), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18
- Humidity (%): 50-60
- 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 applied: 0.1 g
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
7 days
Reading time points: 1, 2, 8, 24, 48 and 72 h and 4, 5, 6 and 7 days
Number of animals or in vitro replicates:
6
Details on study design:
SCORING SYSTEM: Draize scoring system
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
out of all 6 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 72-96 h
Remarks on result:
other: individual mean scores ranged between 0.0 and 1.0
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of all 6 animals
Time point:
other: mean over 24, 48 and 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:
other: mean over 24, 48 and 72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 48 h - 6 days
Remarks on result:
other: individual mean scores ranged between 0.3 and 2.0
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
out of all 6 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 h - 6 days
Remarks on result:
other: individual mean scores ranged between 0.3 and 1.7
Irritant / corrosive response data:
Within the first 1, 2 and 8 h post-instillation, no corneal opacity and no iritis were observed. At this time points, slight to moderate conjunctival redness and moderate to strong chemosis and discharge were seen in all animals.
Corneal opacity was observed in 2/6 animals and was fully reversible within 48 h and 72 h, respectively.
No effects on the iris were observed in any animal at any time point.
Slight to moderate conjunctival redness was observed in all animals 24 h post-instillation. Effects were fully reversible within 48 h (2 animals), 72 h (1 animal) or 5 days (3 animals).
Slight to strong discharge was observed in all animals 24 h post-instillation. Effects were fully reversible within 72 h (5 animals) or 4 days (1 animal).
Other effects:
No further local or systemic effects were reported.

Table 1. Results of eye irritation study.

 

Rabbit #

Time [h]

conjunctivae

iris

cornea

redness

swelling

1

1

1

2

0

0

24

2

1

0

0

48

2

1

0

0

72

1

1

0

0

average

1.7

1.0

0.0

0.0

2

1

1

2

0

0

24

2

1

0

0

48

1

1

0

0

72

1

1

0

0

average

1.3

1.0

0.0

0.0

3

1

1

2

0

0

24

2

2

0

0

48

1

1

0

0

72

0

0

0

0

average

1.0

1.0

0.0

0.0

4

1

1

3

0

0

24

1

1

0

0

48

0

0

0

0

72

0

0

0

0

average

0.3

0.3

0.0

0.0

5

1

1

2

0

0

24

2

1

0

1

48

2

1

0

1

72

2

1

0

1

average

2.0

1.0

0.0

1.0

6

1

2

2

0

0

24

2

2

0

1

48

2

2

0

1

72

1

1

0

0

average

1.7

1.7

0.0

0.7

 

 

Time [h]

conjunctivae

iris 

cornea

redness

swelling

average
score

1

1.17

2.17

0.00

0.00

24

1.83

1.33

0.00

0.33

48

1.33

1.00

0.00

0.33

72

0.83

0.67

0.00

0.17

24+48+72

1.33

1.00

0.00

0.28
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:
20 Apr - 27 Apr 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted in 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
adopted in 1992
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Ministerium für Umwelt, Raumordnung und Landwirtschaft des Landes Nordrhein-Westfalen, Düsseldorf, Germany
Species:
rabbit
Strain:
other: Small White Russian, Mol. Russian, Chbb:MH
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Møllegaard Breeding & Research Center Ltd., Lille Skensved, Denmark
- Age at study initiation: adult animals
- Weight at study initiation: 2.2, 2.4 and 2.4 kg (animals #1, 2 and 3, respectively)
- Housing: conventional, single housing in stainless steel cages
- Diet: Ssniff K 4 complete feed for rabbits (Ssniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- 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 served as control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 g
Duration of treatment / exposure:
24 h
Observation period (in vivo):
6 days
Reading time points: 1, 24, 48 and 72 h and 6 days
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated eyes were were rinsed with warm physiological saline
- Time after start of exposure: 24 h

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:
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:
conjunctivae score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 6 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 6 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 6 days
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:
1 h post-instillation: some definitely hyperaemic (injected) blood vessels in 1 animal, diffuse, crimson red coloured mucous membranes (individual vessels were not easily discernible) in 2 animals. Swelling above normal of lids (and nictating membranes) and discharge in form of white mucous were observed in all 3 animals.
24-72 h post-instillation: the conjunctivae of all 3 animals still showed some definitely hyperaemic blood vessels.
6 days post-instillation: no more irritations on eye and mucous membrane were observed in any animal.
During the whole observation period, cornea and iris of all animals were free of any irritations.
Other effects:
No further local or systemic effects were reported.

Table 1. Summary of results.

 

Rabbit #

Time [h]

conjunctivae

iris

cornea

redness

swelling

1

1

2

1

0

0

24

1

0

0

0

48

1

0

0

0

72

1

0

0

0

average

1.0

0.0

0.0

0.0

2

1

1

1

0

0

24

1

0

0

0

48

1

0

0

0

72

1

0

0

0

average

1.0

0.0

0.0

0.0

3

1

2

1

0

0

24

1

0

0

0

48

1

0

0

0

72

1

0

0

0

average

1.0

0.0

0.0

0.0

 

 

 

 

 

 

 

Time [h]

conjunctivae

iris

cornea

 

redness

swelling

average score

1

1.66

1.00

0.00

0.00

24

1.00

0.00

0.00

0.00

48

1.00

0.00

0.00

0.00

72

1.00

0.00

0.00

0.00

24+48+72

1.00*

0.00

0.00

0.00

 

* On Day 6 post-instillation, the conjuctival redness score was 0 in all animals.

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:
30 Jun - 04 Jul 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Purity of test substance not given.
Qualifier:
according to guideline
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
yes
Remarks:
purity of test substance not given
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
purity of test substance not given
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Cheshire, UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.52-2.99 kg
- Housing: individually in suspended metal cages
- Diet: Rabbit Diet (Preston Farmers Ltd., Lincolnshire, UK), ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-19
- Humidity (%): 60-75
- Air changes (per hr): 15
- 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 (= 97 mg)
The material was warmed until molten and instilled in the eye in the form of a paste.
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
72 h
Reading time points: 1, 24, 48 and 72 h
Number of animals or in vitro replicates:
5 males, 1 female
Details on study design:
SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: mean after 24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: mean after 24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: mean after 24/48/72 h
Score:
0.1
Max. score:
3
Reversibility:
fully reversible within: 24 h in 4/6 animals and 48 h in 2/6 animals
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: mean after 24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritant / corrosive response data:
No corneal opacity, iritis or chemosis were observed in any animal at any reading time point.
1 h post-instillation: slight or moderate conjunctval redness was observed in 2/6 and 4/6 animals respectively. Slight or moderate chemosis was observed in 4/6 and 1/6 animals, respectively. Slight discharge was observed in 4/6 animals.
24 h post-instillation: slight conjunctival redness was observed in 2/6 animals, the effect being fully reversible within the following 24 h.
48-72 h post-instillation: no conjunctival redness was observed in any animal.
Other effects:
No further local or systemic effects were reported.

Table 1. Results of eye irritation study

Rabbit #

Time [h]

conjunctivae

 

iris

cornea

redness

chemosis

1

1

2

2

0

0

24

1

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0

0

0

0

2

1

2

1

0

0

24

0

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0

0

0

0

3

1

2

1

0

0

24

1

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0

0

0

0

4

1

1

1

0

0

24

0

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0

0

0

0

5

1

2

1

0

0

24

0

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0

0

0

0

6

1

1

0

0

0

24

0

0

0

0

48

0

0

0

0

72

0

0

0

0

average

0

0

0

0

 

 

Time [h]

conjunctivae

 

iris

cornea

 

redness

swelling

 

 

average
score

1

1.67

1

0

0

24

0.33

0

0

0

48

0

0

0

0

72

0

0

0

0

24+48+72

0.11

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)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Analogue justification

No data on the skin and eye irritation / corrosion potential of target substance Glycerol trimyristate (CAS 555-45-3) are available. The assessment was therefore based on studies conducted with analogue (source) substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with 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 read across approach is provided in the technical dossier (see IUCLID Section 13).

 

Skin irritation

CAS 97593-30-1

The skin irritation potential of Glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates was investigated in a study performed according to OECD guideline 404 and under GLP conditions (WoE, 2008). 0.5 mL of the undiluted test substance was applied to the dorsal skin of 3 female Crl:KBL(NZW)BR rabbits under semiocclusive conditions. In the initial test, one female was exposed to the test substance for 3 min, 1 h and 4 h. As no corrosive effect was observed in the initial test, a confirmatory test was performed using two additional animals treated with the test substance for a period of 4 h. Skin reactions were assessed 1, 24, 48 and 72 h after removal of the test substance. In 2/3 animals, slight erythema (score 1) was observed 1 h after exposure ended. In 1/3 animals the slight erythema persisted until the 48-h reading time point and was fully reversible within 72 h. In the other 2 animals, no erythema was seen 24, 48 and 72 h after patch removal. No edema was noted in any of the tested animals at any reading time point. No signs of systemic toxicity were observed. The mean erythema scores over the 24, 48 and 72 h reading time points were 0.67, 0 and 0, respectively. The test substance is considered to not be irritating to the skin.

CAS 555-43-1

The skin irritation potential of Glycerol tristearate was investigated in a GLP-conform study according to OECD guideline 404 and under GLP conditions(WoE, 1998). The undiluted test substance (0.5 g) was moistened with demineralised water and applied for 4 h to the shaved skin of 3 male White New Zealand albino rabbits, under semiocclusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 30-60 min, 24, 48 and 72 h after removal of the dressing. No skin reactions were observed in the animals at any reading time point. During the study period, no signs of systemic toxicity were observed in the animals. The mean erythema and edema scores over 24, 48 and 72 h were 0 for all 3 animals. The test substance is considered to be non-irritating to the skin.

CAS 67701-26-2

The skin irritation potential of Glycerides, C12-18 was investigated study performed according to EPA OPP 81-5 and under GLP conditions (WoE, 1988). The test substance (0.5 mL) was applied for 4 h onto the shaved skin of 6 New Zealand White rabbits under semiocclusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h after removal of the dressing. At the 1-h reading time point, slight erythema (score 1) was observed in 1/6 animals, persisting in the same animal until the 48-h reading time point. In addition, slight erythema (score 1) was observed in 2/6 rabbits at the 48-h reading time point only. No edema was observed in the animals at any reading time point. No signs of systemic toxicity were seen during the study. The mean erythema scores over the 24, 48 and 72 h reading time points were 0.33, 0, 0, 0.67, 0 and 0.33, respectively. The test substance is considered to be non-irritating to the skin.

Eye irritation

CAS 97593-30-1

An eye irritation study was performed with Glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates according to OECD guideline 405 and under GLP conditions (WoE, 2008). 0.1 mL of the undiluted test substance was installed into one eye of 3 female Crl:KBL(NZW)BR rabbits each. The eye was not rinsed after instillation. Scoring of irritation effects on the eyes was performed 1, 24, 48 and 72 h after test substance application. 1 h after instillation, moderate conjunctival redness (score 2) and very slight chemosis (score 1) were observed in all 3 animals. At the 24-h reading time point slight conjunctival redness (score 1) was observed in 3/3 animals, while very slight chemosis was noted in 2/3 animals. Both conjunctivae and chemosis were fully reversible within the 48-h reading time point. No corneal opacity or iritis was noted in any animal at any reading time point. No systemic toxic effects were observed. The mean scores for conjunctivae over 24, 48, and 72 h were 0.33, 0.33 and 0.33, while the mean scores for chemosis over 24, 48, and 72 h were 0, 0.33 and 0.33. The test substance was not considered to be an eye irritant.

CAS 555-43-1

An eye irritation study was performed with Glycerol tristearate according to OECD guideline 405 and under GLP conditions (WoE, 1998). The solid test substance (0.1 g) was instilled into one eye of 3 male Small White Russian (Mol. Russian, Chbb:MH) rabbits each. The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h, and 6 days after instillation. At the 1-h reading time point, slight to moderate conjunctivae (score 1-2) was observed in 3/3 rabbits and slight conjunctivae (score 1) persisted in 3/3 animals until the 72-h reading time point. The conjunctival effects were fully reversible within the 6-day observation period. Very slight chemosis (score 1) was reported in 3/3 animals 1 h after installation, however, the chemosis was fully reversible within 24 h. No systemic toxicity was observed. The mean score for conjunctivae over 24, 48, and 72 h was 1.0, 1.0 and 1.0, respectively. The mean score for chemosis over 24, 48, and 72 h was 0 for all 3 animals. The test substance was not considered to be an eye irritant.

CAS 67701-26-2

The eye irritation potential of Glycerides, C12-18 was investigated according to EPA OPP guideline 81-4 and in compliance with GLP (WoE, 1988). The undiluted test material (0.1 mL) was applied into the conjunctival sac of one eye of 6 New Zealand White rabbits each (5 males and 1 female). The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h after application. At the 1-h reading time point, slight to moderate conjunctival redness (score 1-2) was observed in 6/6 animals. At the 24-h reading time point 2/6 rabbits showed slight conjunctival redness (score 1), which had cleared completely within 48 h. One hour after installation 5/6 animals showed very slight-slight chemosis (score 1-2); this irritating effect had cleared completely within 24 h. No corneal opacity or iritis was observed in any animal at any reading time point. No systemic toxicity was observed. The mean score for conjunctival redness over 24, 48 and 72 h was 0.33, 0, 0.33, 0, 0 and 0, while the mean score for chemosis was 0 in 6/6 animals. The test substance was not considered to be an eye irritant.

 

Overall conclusion for skin and eye irritation

The available data on suitable source substances did not show any skin or eye irritation effects. Therefore, the target substance Glycerol trimyristate is not expected to be a skin irritant or an eye irritant.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Glycerol trimyristate (CAS 555-45-3), data will be generated from data available 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 data on the target substance and the analogue read across approach, the available data on skin and eye irritation / corrosion do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.