Registration Dossier

Administrative data

Description of key information

Skin irritation:

In the key study (1976), performed according to the procedure employed by the Consumer Product Safety Commission of the U.S.A., US Code of Federal Regulations, Title 16, Section 1500.41, the primary irritation to the skin was measured by a patch test technique in six albino rabbits.

 

WS-23 (0.1% solution in 1% ethanol) was applied to one intact and one abraded skin site on the clipped dorsum of rabbits.

After 24 hours of exposure, the patches were removed and the skin reactions, i.e. erythema and eschar formation as well as edema formation,

were evaluated

 

None of the treated animals showed any observable response throughout the 72 hours observation period.

 

It was concluded based on the results, that WS-23 as a 0.1% solution in 1% ethyl alcohol was not an irritant to rabbit skin.

Eye irritation:

In key study (1976), 0.1  mL of the  test item, WS-23 (0. 1%  solution  in 1 % of ethyl  alcohol), was applied  into one eye of each animal. In total 6 rabbits were used in this testing. The lids of animals were  then  gently held together  for approximately one second.  The other eye,  remaining untreated,  serves as a control. WS-23 was not washed from the eye during the observation period of 7 days.

One animal gave a positive reaction. A diffuse crimson red colouration of  the  conjunctivae  was observed  in this animal  two days after instillation. Temporary  mild  conjunctival  inflammation  was  observed  in  four other  animals.  One  animal  did not show any  observable  response  to the treatment  throughout  the 7 days observation  period.

 

Based on these results, it was concluded that WS 23 (0.1% solution  in 1%  ethyl  alcohol) gave  a negative response for eye  irritation, according to the definition given  in  the Code of Federal  Regulations as well as according to OECD TG 405.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
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:
other: U.S.A. Code of Federal Regulations, Title 16, Section 1500.41
Version / remarks:
the procedure employed was that prescribed by the Consumer Product Safety Commission of the U.S.A. Code of Federal Regulations, Title 16, Section 1500.41
Principles of method if other than guideline:
- Principle of test: Primary irritation to the skin is measured by a patch-test technique on the abraded and intact skin of the albino rabbit, clipped free of hair.

- Short description of test conditions: Six rabbits are used in abraded and intact skin tests. Introduce under a square patch, such as surgical gauze measuring 1 inch by 1 inch and two single layers thick, 0.5 milliliter (in the case of liquids) or 0.5 gram (in the case of solids and semisolids) of the test substance. Dissolve solids in an appropriate solvent and apply the solution as for liquids. The animals are immobilized with patches secured in place by adhesive tape. The entire trunk of the animal is then wrapped with an impervious material, such as rubberized cloth, for the 24-hour period of exposure. This material aids in maintaining the test patches in position and retards the evaporation of volatile substances. After 24 hours of exposure, the patches are removed and the resulting reactions are evaluated on the basis of the designated values.

- Parameters analysed / observed: erythema and eschar formation, oedema formation
GLP compliance:
not specified
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- test material: WS 23, 0.1 % solution in 1% ethyl alcohol.

Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- albino rabbits
Type of coverage:
other: patch-test technique
Preparation of test site:
other: the abraded and intact skin of the albino rabbit, clipped free of hair
Vehicle:
other: ethyl alcohol
Remarks:
1%
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- WS23, 0.1% solution in 1% ethyl alcohol.

VEHICLE
-no information available

NEGATIVE CONTROL
-no information available

POSITIVE CONTROL
- no information available
Duration of treatment / exposure:
24 hours
Observation period:
24 and 72 hours
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: a square patch, such as surgical gauze measuring 1 inch by 1 inch and two single layers thick, 0.5 milliliter of the test substance.
- % coverage: 100% (the entire trunk of the animal is wrapped)
- Type of wrap if used: an impervious material, such as rubberized cloth, for the 24-hour period of exposure.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not specified

OBSERVATION TIME POINTS
- 24 and 72 hours

SCORING SYSTEM:
- Method of calculation: GRADING OF SKIN REACTIONS (according to Code of Federal Regulations, Title 16, Section 1500.41. and OECD TG 404).
The "value" recorded for each reading (24 and 72 hours) is the average value of the six animals subject to this test.
Irritation parameter:
overall irritation score
Basis:
other: mean of animals
Time point:
24 h
Score:
ca. 0
Max. score:
0
Reversibility:
other: no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
overall irritation score
Basis:
other: mean of animals
Time point:
72 h
Score:
ca. 0
Max. score:
0
Reversibility:
other: no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
other: mean of animals
Time point:
24/48/72 h
Score:
ca. 0
Remarks on result:
other: no edema observed
Remarks:
only 24 and 72 hours reading
Irritation parameter:
erythema score
Basis:
other: mean of animals
Time point:
24/48/72 h
Score:
ca. 0
Remarks on result:
other: no erythema observed
Remarks:
only 24 and 72 hours reading

GRADING OF SKIN REACTIONS (according to Code of Federal Regulations, Title 16, Section 1500.41. and OECD TG 404):

Evaluation of skin reactions

Erythema and eschar formation

value

No erythema

0

Very slight erythema (barely perceptible)

1

Well defined erythema

2

Moderate to severe erythema

3

Severe erythema (beef redness) to slight eschar information (injures in depth)

4

Evaluation of skin reactions

Oedema formation

value

No oedema

0

Very slight oedema (barely perceptible)

1

Slight oedema (edges of area well defined by definite raising)

2

Moderate oedema (raised approximately 1 mm)

3

Severe oedema (raised more than 1 mm and extending beyond area of exposure)

4

Interpretation of results:
other: Not classified according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008
Remarks:
EU criteria used for interpretation of results
Conclusions:
WS-23 as a 0.1% solution in 1% ethyl alcohol is not considered to be an irritant to rabbit skin.
Executive summary:

In this key study, performed according to the procedure employed by the Consumer Product Safety Commission of the U.S.A., US Code of Federal Regulations, Title 16, Section 1500.41, the primary irritation to the skin was measured by a patch test technique in six albino rabbits.

The obtained results of the reading were also evaluated in accordance to the OECD TG 404.

 

WS-23 (0.1% solution in 1% ethanol) was applied to one intact and one abraded skin site on the clipped dorsum of rabbits.

After 24 hours of exposure, the patches were removed and the skin reactions, i.e. erythema and eschar formation as well as edema formation,

were evaluated.

 

None of the treated animals showed any observable response throughout the 72 hours observation period.

 

It was concluded based on the results, that WS-23 as a 0.1% solution in 1% ethyl alcohol was not an irritant to rabbit skin.

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to
Guideline:
other: U.S. Code of Federal Regulation, Title 16, Section 1500.42
Version / remarks:
The Consumer Product Safety Commission of the U.S.A.
Principles of method if other than guideline:
- Principle of test: test for eye irritants

- Short description of test conditions:
Animal facilities for such procedures shall be so designed and maintained as to exclude sawdust, wood chips, or other extraneous materials that might produce eye irritation. Both eyes of each animal in the test group shall be examined before testing, and only those animals without eye defects or irritation shall be used. The test material is placed in one eye of each animal by gently pulling the lower lid away from the eyeball to form a cup into which the test substance is dropped. The lids are then gently held together for one second and the animal is released. The other eye, remaining untreated, serves as a control.

- Parameters analysed / observed:
An animal shall be considered as exhibiting a positive reaction if the test substance produces at any of the readings ulceration of the cornea (other than a fine stippling), or opacity of the cornea (other than a slight dulling of the normal lustre), or inflammation of the iris (other than a slight deepening of the folds
(or rugae) or a slight circumcorneal injection of the blood vessels), or if such substance produces in the conjunctive (excluding the cornea and iris) an obvious swelling with partial eversion of the lids or a diffuse crimson-red with individual vessels not easily discemible.

The eyes are examined and the grade of ocular reaction is recorded at 24, 48 and 72 hours. Reading of reaction is facilitated by use of a binocular loupe, hand slit-lamp, or other expert means.

The test shall be considered positive, if four or more of the animals in the test group exhibit a positive reaction. If only one animal exhibits a positive reaction, the test shall be regarded as negative. If two or three animals exhibit a positive reaction, the test is repeated using a different group of six animals.
The second test shall be considered positive if three or more of the animals exhibit a positive reaction. If only one or two animals in the second test exhibit a positive reaction, the test shall be repeated with a different group of six animals. Should a third test be needed, the substance will be regarded as an irritant if any animal exhibits a positive response.
GLP compliance:
not specified
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- test material: WS-23
Species:
rabbit
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source:albino rabbits
Vehicle:
other: 1% ethyl alcohol
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 0.1%

VEHICLE
- Concentration (if solution): 1% ethanol
Duration of treatment / exposure:
7 days
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: not

SCORING SYSTEM: grades from ocular lesion From: "Illustrated Guide for Grading Eye Irritation by Hazardous Substances" U.S. Department of Health, Education and Welfare, Food and Drug Administration Washington, D. C. 20204

TOOL USED TO ASSESS SCORE: hand-slit lamp, binocular loupe
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
7 d
Score:
> 0 - <= 2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: not irritating
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
1
Reversibility:
fully reversible within:
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness and chemosis
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
2
Reversibility:
fully reversible within: 7
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0
Remarks on result:
no indication of irritation
Interpretation of results:
other: Not classified according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008
Remarks:
EU criteria used for interpretation of results
Conclusions:
WS-23 as a 0.1% solution in 1% ethyl alcohol gave a negative response for eye irritation.
Executive summary:

In this study, 0.1  mL of the  test item, WS-23 (0. 1%  solution  in 1 % of ethyl  alcohol), was applied  into one eye of each animal. In total 6 rabbits were used in this testing. The lids of animals were gently held together  for approximately one second.  The other eye,  remaining untreated,  serves as a control. WS-23 was not washed from the eye during the observation period of 7 days.

One animal gave a positive reaction. A diffuse crimson red colouration of  the  conjunctivae  was observed  in this animal  two days after instillation. Temporary  mild  conjunctival  inflammation  was  observed  in  four other  animals.  One  animal  did not show any  observable  response  to the treatment  throughout  the 7 days observation  period.

 

Based on these results, it was concluded that WS 23 (0.1% solution  in 1%  ethyl  alcohol) gave  a negative response for eye  irritation, according to the definition given  in  the Code of Federal  Regulations as well as according to OECD TG 405.

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

Additional information

Justification for classification or non-classification

Based on available in vivo data, WS-23 is not classified as skin irritant nor eye irritant according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008