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Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
February 16,1988 to March 02, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across
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:
read-across source
Qualifier:
according to
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 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 days
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:
overall irritation score
Basis:
mean
Time point:
24/48/72 h
Score:
3.67
Max. score:
8
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal: All
Time point:
24 h
Score:
>= 2 - <= 3
Max. score:
3
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal: All
Time point:
48 h
Score:
>= 2 - <= 3
Max. score:
3
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal: All
Time point:
72 h
Remarks on result:
other: Spotty skin reaction
Irritation parameter:
edema score
Basis:
animal: All
Time point:
24/48/72 h
Score:
>= 1 - <= 3
Max. score:
3
Reversibility:
not fully reversible within: 14 d

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 therefore 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, amides, C8-18 and C18-unsatd., N-(hydroxyethyl), to rabbits according to OECD Guideline 404. The substance was applied in water to the shaved skin of three rabbits under an occlusive bandage. After 4 h, the exposed skin was rinsed then observed for 14 days. 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 therefore considered to be moderately irritating to rabbit skin (Mürmann, 1988). 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
February 16, 1988 to March 09, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across
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:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
other:
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GnbH, 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 hours


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:
animal: All
Time point:
24/48/72 h
Score:
>= 10 - <= 30
Max. score:
30
Reversibility:
not fully reversible within: 21 d
Remarks:
Not reversible in 1/3 animals
Irritation parameter:
iris score
Basis:
animal: All
Time point:
24/48/72 h
Score:
>= 0 - <= 5
Max. score:
5
Reversibility:
not fully reversible within: 21 d
Remarks:
Not reversible in 1/3 animals
Irritation parameter:
conjunctivae score
Basis:
animal: All
Time point:
24/48/72 h
Score:
>= 2 - <= 12
Max. score:
12
Reversibility:
fully reversible within: 21 d
Irritation parameter:
chemosis score
Basis:
animal: All
Time point:
24/48/72 h
Remarks on result:
other: Not specified

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 conditions of the study, the test substance was considered to be moderately irritating to rabbit eye. In one animal, irreversible effects (cornea, iris) occurred.
Executive summary:

A study was conducted to assess the eye irritation potential of the read across substance, amides, C8-18 and C18-unsatd., N-(hydroxyethyl), to rabbit eyes according to OECD Guideline 405. An amount equivalent to 0.1 g of ground substance was placed in the lid of the right eye of each rabbit. The treated eyes were analysed 72 h after application for cornea 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 still present after 21 d was considered irreversible. The mean overall score was 26.8 (maximum possible: 110). Under the conditions of the study, the test substance was considered to be moderately irritating to rabbit eye. In one animal, irreversible effects (cornea, iris) occurred (Mürmann, 1988).

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, amides, C8-18 and C18-unsatd., N-(hydroxyethyl), to rabbits according to OECD Guideline 404. The substance was applied in water to the shaved skin of three rabbits under an occlusive bandage. After 4 h, the exposed skin was rinsed then observed for 14 days. 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 therefore considered to be moderately irritating to rabbit skin (Mürmann, 1988). 

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).

Eye

A study was conducted to assess the eye irritation potential of the read across substance, amides, C8-18 and C18-unsatd., N-(hydroxyethyl), to rabbit eyes according to OECD Guideline 405. An amount equivalent to 0.1 g of ground substance was placed in the lid of the right eye of each rabbit. The treated eyes were analysed 72 h after application for cornea 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 still present after 21 d was considered irreversible. The mean overall score was 26.8 (maximum possible: 110). Under the conditions of the study, the test substance was considered to be moderately irritating to rabbit eye. In one animal, irreversible effects (cornea, iris) occurred (Mürmann, 1988).

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).

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.