Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From February 16,1988 to March 02, 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Not GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
other: Small White Russian
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach, Germany
- Weight at study initiation: 2.2 - 2.7 kg
- Housing: steel cages
- Diet (e.g. ad libitum): K4 diet for rabbit, Ssniff Special Diets, Soet, Germany
- Water (e.g. ad libitum): tap water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/-1°C
- Humidity (%): 60 +/- 5%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light):12/12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of product with 0.5 cm3 water
Duration of treatment / exposure:
4 h
Observation period:
14 d
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- Type of wrap if used: exposure site covered with 2.5 x 2.5 cm patch. 6 x 6 cm Polyethylene wrapping placed on top and fixed with an elastic band.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing with warm water directly after patch removal.
- Time after start of exposure: 4 h


SCORING SYSTEM: OECD 404 method
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 2.44
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 1.11
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
14 d
Score:
ca. 3.67
Max. score:
8
Reversibility:
fully reversible within: 14 days

Table 1: Skin irritation responses in rabbit exposed to test substance

 Animal N°  1 h        24 h    48 h    72 h      6 d 8 d     10 d    

   14 d

 S  R
 2  1  2  1  2  1  x2  1  Sc SciA 0 0 0  0
2  2  2  3  1  2  1  x2  1  Sc  SciA  SciA 0  0
3  2  3  3  2  3  1  x3  1 Sc SciA  SciA 0  0

R: redness (erythema); S: swelling (oedema); x: spotty skin reaction; Sc: eschar; iA: detaching

Absolute average

4,00 4,00 3,33 3,33 => 14.66/4 = 3.67

Assessment according to Appendix VI of Directive 79/831/EC:

Redness (erythema): average = 2.44

Swelling (oedema): average = 1.11

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Under the study conditions, the test substance was considered to be moderately irritating to rabbit skin.
Executive summary:

A study was conducted to assess the skin irritation potential of the test substance, C8-18 and C18-unsatd. MEA (100% active), in rabbits according to OECD Guideline 404. The substance was applied in water to the shaved skin of three Small White Russian rabbits using an occlusive bandage. After 4 h, the exposed skin was rinsed, then observed for 14 d. Redness (erythema), swelling (oedema) and eschar formation was apparent in all animals. The effects were reversible within 14 d. The overall irritation index was 3.67 (on a total possible of 8). Under the study conditions, the test substance was considered to be moderately irritating to rabbit skin (Mürmann, 1988).

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Batch no.: DM5/282
Appearance: amber cloudy liquid
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Source: "l'elevage Cunicole de Val de Seile, 80160 Prouzel, France"
Acclimation: at least 5 days
Weight: 2.4 +/- 0.2 kg
Temperature: 20 +/- 3°C
Relative humidity: 50 +/- 20%
Light period: 12h light / 12h dark
Feed: "Lapins entretien reference 112 C" (U.A.R., 91360 Villemoisson-Sur-Orge, France), ad libitum
Water: filtered tap water, ad libitum
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Remarks:
6 cm2
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
At 1, 24, 48 and 72 h and daily thereafter (for 9 d)
Number of animals:
3 (males)
Details on study design:
Skin reactions (erythema and oedema) were evaluated using the Draize scoring (and every other symptoms was recorded as well).
They were measured after 24, 48 and 72 hours.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal:
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: No edema observed
Irritant / corrosive response data:
Important skin reactions were observed during at least 48 hours in the 3 rabbits. They worsened for 3 days thereafter (until Day 5) with the development of an erythema. No oedema was observed. From Day 5, the erythema decreased and disappeared on Day 8. The skin remained dry until Day 8. As 2 animals out of 3 presented an erythema of 2.0 and the reactions were reversible within 8 days, the test substance was not considered irritant to rabbit skin.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the test substance was not considered to be irritating to rabbit skin.
Executive summary:

A study was conducted to determine the skin irritation / corrosion potential of the test substance according to EU Method B.4, in compliance with GLP. Three male rabbits (New-Zealand White) were exposed for 4 h to 0.5 mL undiluted test substance, under a semiocclusive bandage. The left flank remained untreated and served as control. Observations were made at 1, 24, 48 and 72 h and daily thereafter (for 9 d). Skin reactions (erythema and oedema) were evaluated using the Draize scoring and measured after 24, 48 and 72 h. The skin reactions were present until Day 5 with the development of erythema. No oedema was observed. From Day 5, the erythema decreased and disappeared on Day 8. The skin remained dry until Day 8. Under the study conditions, the test substance was not considered to be irritating to rabbit skin (Clouzeau, 1992).

Endpoint:
skin irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
From February 16,1988 to March 02, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
KL2 due to RA
Justification for type of information:
Refer to the section 13 for details on the category justification.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
other: Small White Russian
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach, Germany
- Weight at study initiation: 2.2 - 2.7 kg
- Housing: steel cages
- Diet (e.g. ad libitum): K4 diet for rabbit, Ssniff Special Diets, Soet, Germany
- Water (e.g. ad libitum): tap water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/-1°C
- Humidity (%): 60 +/- 5%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light):12/12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of product with 0.5 cm3 water
Duration of treatment / exposure:
4 h
Observation period:
14 d
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- Type of wrap if used: exposure site covered with 2.5 x 2.5 cm patch. 6 x 6 cm Polyethylene wrapping placed on top and fixed with an elastic band.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing with warm water directly after patch removal.
- Time after start of exposure: 4 h


SCORING SYSTEM: OECD 404 method
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 2.44
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 1.11
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
14 d
Score:
ca. 3.67
Max. score:
8
Reversibility:
fully reversible within: 14 days

Table 1: Skin irritation responses in rabbit exposed to test substance

 Animal N°  1 h        24 h    48 h    72 h      6 d 8 d     10 d    

   14 d

 S  R
 2  1  2  1  2  1  x2  1  Sc SciA 0 0 0  0
2  2  2  3  1  2  1  x2  1  Sc  SciA  SciA 0  0
3  2  3  3  2  3  1  x3  1 Sc SciA  SciA 0  0

R: redness (erythema); S: swelling (oedema); x: spotty skin reaction; Sc: eschar; iA: detaching

Absolute average

4,00 4,00 3,33 3,33 => 14.66/4 = 3.67

Assessment according to Appendix VI of Directive 79/831/EC:

Redness (erythema): average = 2.44

Swelling (oedema): average = 1.11

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Under the study conditions, the test substance was considered to be moderately irritating to rabbit skin.
Executive summary:

A study was conducted to assess the skin irritation potential of the read across substance, C8-18 and C18-unsatd. MEA (100% active), in rabbits according to OECD Guideline 404. The substance was applied in water to the shaved skin of three Small White Russian rabbits using an occlusive bandage. After 4 h, the exposed skin was rinsed, then observed for 14 d. Redness (erythema), swelling (oedema) and eschar formation was apparent in all animals. The effects were reversible within 14 d. The overall irritation index was 3.67 (on a total possible of 8). Under the study conditions, the read across substance was considered to be moderately irritating to rabbit skin (Mürmann, 1988). Based on the result of the read across study, the test substance is also expected to have similar skin irritation potential.

Endpoint:
skin irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Read across study
Justification for type of information:
Refer to the section 13 for details on the read across justification. The skin irritation study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Source: "l'elevage Cunicole de Val de Seile, 80160 Prouzel, France"
Acclimation: at least 5 days
Weight: 2.4 +/- 0.2 kg
Temperature: 20 +/- 3°C
Relative humidity: 50 +/- 20%
Light period: 12h light / 12h dark
Feed: "Lapins entretien reference 112 C" (U.A.R., 91360 Villemoisson-Sur-Orge, France), ad libitum
Water: filtered tap water, ad libitum
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Remarks:
6 cm2
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
At 1, 24, 48 and 72 h and daily thereafter (for 9 d)
Number of animals:
3 (males)
Details on study design:
Skin reactions (erythema and oedema) were evaluated using the Draize scoring (and every other symptoms was recorded as well).
They were measured after 24, 48 and 72 hours.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal: All
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: No edema observed
Irritant / corrosive response data:
Important skin reactions were observed during at least 48 hours in the 3 rabbits. They worsened for 3 days thereafter (until Day 5) with the development of an erythema. No oedema was observed. From Day 5, the erythema decreased and disappeared on Day 8. The skin remained dry until Day 8. As 2 animals out of 3 presented an erythema of 2.0 and the reactions were reversible within 8 days, the test substance was not considered irritant to rabbit skin.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the test substance was not considered to be irritating to rabbit skin.
Executive summary:

A study was conducted to determine the skin irritation / corrosion potential of the read across substance, isostearic acid monoisopropanolamide, according to EU Method B.4, in compliance with GLP. Three male rabbits (New-Zealand White) were exposed for 4 h to 0.5 mL undiluted test substance, under a semiocclusive bandage. The left flank remained untreated and served as control. Observations were made at 1, 24, 48 and 72 h and daily thereafter (for 9 d). Skin reactions (erythema and oedema) were evaluated using the Draize scoring and measured after 24, 48 and 72 h. The skin reactions were present until Day 5 with the development of erythema. No oedema was observed. From Day 5, the erythema decreased and disappeared on Day 8. The skin remained dry until Day 8. Under the study conditions, the test substance was not considered to be irritating to rabbit skin (Clouzeau, 1992).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
From February 16, 1988 to March 09, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
KL2 due to RA
Justification for type of information:
Refer to the section 13 for details on the category justification.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
other: Small White Russian
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach, Germany
- Weight at study initiation: 2.4 - 32.5 kg
- Housing: wire mesh cages, one animal/cage
- Diet (e.g. ad libitum): K4 diet for rabbits, Ssniff Special diet GmbH, Soest, Germany
- Water (e.g. ad libitum): tap water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1°C
- Humidity (%): 60 +/- 5%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: Right eye treated, left eye served as a control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g of ground material
Duration of treatment / exposure:
72 h after application, the treated eyes were analysed for cornea damage using a Na-fluorescein solution, then rinsed with warm physiological solution.
Observation period (in vivo):
21 d
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): after 72 h


SCORING SYSTEM: Draize (Appraisal of the safety of chemicals in foods, drugs and cosmetics, FDA, Austin 1, Texas 1959)


TOOL USED TO ASSESS SCORE: fluorescein and a slit lamp
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: up to 21 d
Score:
26.8
Max. score:
110
Reversibility:
other: Irreversible effects (cornea, iris) in 1/3 animals
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
4
Reversibility:
fully reversible
Remarks:
in 2/3 animals
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0.55
Max. score:
2
Reversibility:
fully reversible
Remarks:
in 2/3 animals
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 2.67
Max. score:
3
Reversibility:
fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0.89
Max. score:
4
Reversibility:
fully reversible within: 21 days
Remarks on result:
positive indication of irritation

Table 1: Scores for corneal effects (opacity) according to Draize, 1959

 Animal N° 1 h  24 h  48 h  72 h  6, 8, 10, 13, 17 and 21 d 
 39653 0 20  20  10 
 39657  0 30 20  10  0
 39689  0  30  30  20  10
 Absolute average  26.67  23.33  13.33  3.33

Table 2: Scores for iris effects according to Draize, 1959

 Animal N° 1 h  24 h  48 h  72 h  8, 10, 13, 17 and 21 d 
 39653 0 5x 5* 0 0
 39657 5x 0  0 0
 39689  5x  5*  0 5c
 Absolute average 0  5.00 3.33   1.67

x: clear redness of the iris; * partial redness of the iris; c: circumcorneal injection

Table 3a: Scores for conjunctival effects (redness, swelling exsudation) according to Draize, 1959

 Animal N° 1 h  24 h  48 h  72 h  6 d 
 39653 10 12 
 39657 10 12 8 2 0
 39689 10 12 10 8 8
 Absolute average 10.00  12.00  8.67  4.67  3.33

Table 3b: Scores for conjunctival effects (redness, swelling, exsudation) according to Draize, 1959 (cont'd)

 Animal N° 8 d  10 + 13 d 17 d 21 d 
 39653 0
 39657 0 0 0 0
 39689 6 2 2 0
 Absolute average 2.00  0.67  0.67  0
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Under the study conditions, the test substance was considered to be highly irritating to rabbit eyes.
Executive summary:

A study was conducted to assess the eye irritation potential of the read across substance, C8-18 and C18-unsatd. MEA, in rabbits according to OECD Guideline 405. Ground neat read across substance (0.1 g) was placed in the lid of the right eye of each Small White Russian rabbit. Seventy-two h after application, the treated eyes were analysed for corneal damage using a Na-fluorescein solution, then rinsed with warm physiological solution. Effects were evaluated at 1, 24, 48 and 72 h, as well as at 6, 8, 10, 13, 17 and 21 d after application, according to Draize (1959). Damage to the cornea and iris of one animal was still present after 21 d. This was considered irreversible. The mean overall score was 26.8 (maximum possible: 110). Under the study conditions, the read across substance was considered to be highly irritating to rabbit eyes (Mürmann, 1988). Based on the result of the read across study, the test substance is also expected to have similar eye irritation potential.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From February 16, 1988 to March 09, 1988
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
GLP compliance:
no
Species:
rabbit
Strain:
other: Small White Russian
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach, Germany
- Weight at study initiation: 2.4 - 32.5 kg
- Housing: wire mesh cages, one animal/cage
- Diet (e.g. ad libitum): K4 diet for rabbits, Ssniff Special diet GmbH, Soest, Germany
- Water (e.g. ad libitum): tap water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1°C
- Humidity (%): 60 +/- 5%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: Right eye treated, left eye served as a control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g of ground material
Duration of treatment / exposure:
72 h after application, the treated eyes were analysed for cornea damage using a Na-fluorescein solution, then rinsed with warm physiological solution.
Observation period (in vivo):
21 d
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): after 72 h


SCORING SYSTEM: Draize (Appraisal of the safety of chemicals in foods, drugs and cosmetics, FDA, Austin 1, Texas 1959)


TOOL USED TO ASSESS SCORE: fluorescein and a slit lamp
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: up to 21 d
Score:
26.8
Max. score:
110
Reversibility:
other: Irreversible effects (cornea, iris) in 1/3 animals
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
4
Reversibility:
fully reversible
Remarks:
in 2/3 animals
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0.55
Max. score:
2
Reversibility:
fully reversible
Remarks:
in 2/3 animals
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 2.67
Max. score:
3
Reversibility:
fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0.89
Max. score:
4
Reversibility:
fully reversible within: 21 days
Remarks on result:
positive indication of irritation

Table 1: Scores for corneal effects (opacity) according to Draize, 1959

 Animal N° 1 h  24 h  48 h  72 h  6, 8, 10, 13, 17 and 21 d 
 39653 0 20  20  10 
 39657  0 30 20  10  0
 39689  0  30  30  20  10
 Absolute average  26.67  23.33  13.33  3.33

Table 2: Scores for iris effects according to Draize, 1959

 Animal N° 1 h  24 h  48 h  72 h  8, 10, 13, 17 and 21 d 
 39653 0 5x 5* 0 0
 39657 5x 0  0 0
 39689  5x  5*  0 5c
 Absolute average 0  5.00 3.33   1.67

x: clear redness of the iris; * partial redness of the iris; c: circumcorneal injection

Table 3a: Scores for conjunctival effects (redness, swelling exsudation) according to Draize, 1959

 Animal N° 1 h  24 h  48 h  72 h  6 d 
 39653 10 12 
 39657 10 12 8 2 0
 39689 10 12 10 8 8
 Absolute average 10.00  12.00  8.67  4.67  3.33

Table 3b: Scores for conjunctival effects (redness, swelling, exsudation) according to Draize, 1959 (cont'd)

 Animal N° 8 d  10 + 13 d 17 d 21 d 
 39653 0
 39657 0 0 0 0
 39689 6 2 2 0
 Absolute average 2.00  0.67  0.67  0
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Under the study conditions, the test substance was considered to be highly irritating to rabbit eyes.
Executive summary:

A study was conducted to assess the eye irritation potential of the test substance, C8-18 and C18-unsatd. MEA, in rabbits according to OECD Guideline 405. Ground neat test substance (0.1 g) was placed in the lid of the right eye of each Small White Russian rabbit. Seventy-two h after application, the treated eyes were analysed for corneal damage using a Na-fluorescein solution, then rinsed with warm physiological solution. Effects were evaluated at 1, 24, 48 and 72 h, as well as at 6, 8, 10, 13, 17 and 21 d after application, according to Draize (1959). Damage to the cornea and iris of one animal was still present after 21 d. This was considered irreversible. The mean overall score was 26.8 (maximum possible: 110). Under the study conditions, the test substance was considered to be highly irritating to rabbit eyes (Mürmann, 1988).

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Batch no.: DM5/282
Appearance: amber cloudy liquid
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Source: "l'elevage Cunicole de Val de Seile, 80160 Prouzel, France"
Acclimation: at least 5 days
Weight: 2.6 +/- 0.2 kg
Temperature: 20 +/- 3°C
Relative humidity: 50 +/- 20%
Light period: 12h light / 12h dark
Feed: "Lapins entretien reference 112 C" (U.A.R., 91360 Villemoisson-Sur-Orge, France), ad libitum
Water: filtered tap water, ad libitum
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 mL in the conjunctival sac of the left eye
Duration of treatment / exposure:
One application
Observation period (in vivo):
1, 24, 48 and 72 h
Number of animals or in vitro replicates:
3
Details on study design:
Eye reactions were evaluated and scored (0 - 4) for chemosis (lids), eye watering and redness (conjunctive tissues, cornea and iris).
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: after 1 h
Score:
>= 0 - <= 2
Max. score:
3
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: chemosis, enanthema and redness
Irritation parameter:
other: eye watering
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 24 h
Remarks on result:
not determinable
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritant / corrosive response data:
Some slight conjunctival reactions (chemosis with a score < or = to 1, enanthema with a score of 1 to 2, and redness with a score of < or = to 1.3) were observed in the 3 rabbits after 1h. Neither iris irritation nor corneal opacity were recorded. Reactions were fully reversible; no effects were seen at 24, 48 and 72h.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the test substance was not considered to be irritating to rabbit eye.
Executive summary:

A study was conducted to determine the eye irritation potential of the test substance according to EU Method B.5, in compliance with GLP. Three male rabbits (New-Zealand White) received 0.1 mL of the undiluted test substance in the conjunctival sac of the left eye. The right eye remained untreated and served as control. Observations were made at 1, 24, 48 and 72 h. Eye reactions were evaluated and scored (0 - 4) for chemosis (lids), eye watering and redness (conjunctive tissues, cornea and iris). Some slight conjunctival reactions (chemosis with a score of 1 and enanthema with a score of 1 to 2) were observed in the 3 rabbits after 1 h. Neither iris irritation nor corneal opacity were recorded. Reactions were fully reversible; no effects were seen at 24, 48 and 72 h. Under the study conditions, the test substance was not considered to be irritating to rabbit eye (Clouzeau, 1992).

Endpoint:
eye irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Read across study
Justification for type of information:
Refer to the section 13 for details on the read across justification. The eye irritation study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Source: "l'elevage Cunicole de Val de Seile, 80160 Prouzel, France"
Acclimation: at least 5 days
Weight: 2.6 +/- 0.2 kg
Temperature: 20 +/- 3°C
Relative humidity: 50 +/- 20%
Light period: 12h light / 12h dark
Feed: "Lapins entretien reference 112 C" (U.A.R., 91360 Villemoisson-Sur-Orge, France), ad libitum
Water: filtered tap water, ad libitum
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 mL in the conjunctival sac of the left eye
Duration of treatment / exposure:
One application
Observation period (in vivo):
1, 24, 48 and 72 h
Number of animals or in vitro replicates:
3
Details on study design:
Eye reactions were evaluated and scored (0 - 4) for chemosis (lids), eye watering and redness (conjunctive tissues, cornea and iris).
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: after 1 h
Score:
>= 0 - <= 2
Max. score:
3
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: chemosis, enanthema and redness
Irritation parameter:
other: eye watering
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 24 h
Remarks on result:
not determinable
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritant / corrosive response data:
Some slight conjunctival reactions (chemosis with a score < or = to 1, enanthema with a score of 1 to 2, and redness with a score of < or = to 1.3) were observed in the 3 rabbits after 1h. Neither iris irritation nor corneal opacity were recorded. Reactions were fully reversible; no effects were seen at 24, 48 and 72h.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the test substance was not considered to be irritating to rabbit eye.
Executive summary:

A study was conducted to determine the eye irritation potential of the read across substance, isostearic acid monoisopropanolamide, according to EU Method B.5, in compliance with GLP. Three male rabbits (New-Zealand White) received 0.1 mL of the undiluted test substance in the conjunctival sac of the left eye. The right eye remained untreated and served as control. Observations were made at 1, 24, 48 and 72 h. Eye reactions were evaluated and scored (0 - 4) for chemosis (lids), eye watering and redness (conjunctive tissues, cornea and iris). Some slight conjunctival reactions (chemosis with a score of1 and enanthema with a score of 1 to 2) were observed in the 3 rabbits after 1 h. Neither iris irritation nor corneal opacity were recorded. Reactions were fully reversible; no effects were seen at 24, 48 and 72 h. Under the study conditions, the test substance was not considered to be irritating to rabbit eye (Clouzeau, 1992).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

A study was conducted to assess the skin irritation potential of the read across substance, C8-18 and C18-unsatd. MEA, in rabbits according to OECD Guideline 404. The substance was applied in water to the shaved skin of three Small White Russian rabbits using an occlusive bandage. After 4 h, the exposed skin was rinsed, then observed for 14 d. Redness (erythema), swelling (oedema) and eschar formation was apparent in all animals. The effects were reversible within 14 d. The overall irritation index was 3.67 (on a total possible of 8). Under the study conditions, the read across substance was considered to be moderately irritating to rabbit skin (Mürmann, 1988).

Eye

A study was conducted to assess the eye irritation potential of the read across substance, C8-18 and C18-unsatd. MEA, in rabbits according to OECD Guideline 405. Ground neat read across substance (0.1 g) was placed in the lid of the right eye of each Small White Russian rabbit. Seventy-two h after application, the treated eyes were analysed for corneal damage using a Na-fluorescein solution, then rinsed with warm physiological solution. Effects were evaluated at 1, 24, 48 and 72 h, as well as at 6, 8, 10, 13, 17 and 21 d after application, according to Draize (1959). Damage to the cornea and iris of one animal was still present after 21 d. This was considered irreversible. The mean overall score was 26.8 (maximum possible: 110). Under the study conditions, the read across substance was considered to be highly irritating to rabbit eyes (Mürmann, 1988).

Justification for classification or non-classification

Skin

Based on the available in vivo skin irritation data, the substance is considered to be a skin irritant, warranting classification as Skin Irrit. 2 - H315 (causes skin irritation) according to CLP (EC 1272/2008) criteria.

Eye

The available in vivo eye irritation studies suggest that the substance has the potential to be highly irritating to eyes. Therefore, classification as Eye Damage 1 - H318 (causes serious eye damage) is warranted according to CLP (EC 1272/2008) criteria.