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Diss Factsheets

Administrative data

Description of key information

The substance is not irritating to the rabbit skin or eyes.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (non-GLP, 24-hour occlusive exposure, TS conc. 50% in vehicle)
Qualifier:
according to guideline
Guideline:
other: EPA guideline (§ 163.81-5 "Primary dermal irritation study". Federal Register, Vol. 43, No. 163, August 22, 1978)
GLP compliance:
no
Remarks:
pre-GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Exp. Toxicology Sisseln, CIBA-Geigy Ltd.
- Age at study initiation: adult animals
- Weight at study initiation: 2 - 3 kg
- Housing: single housing in metal cages
- Diet: standard rabbit food ad libitum (NAFAG, No. 814, Gossau SG)
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 14 / 10
Type of coverage:
occlusive
Preparation of test site:
other: shaved intact and scarified skin
Vehicle:
other: polyethylene glycol (PEG 400) + saline 0.9 % (70 : 30 parts)
Controls:
other: untreated skin of same animal
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g
- Concentration: 50%
Duration of treatment / exposure:
24 hours
Observation period:
7 days
Number of animals:
6 (3 males + 3 females)
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm on back and flank
- Type of wrap if used: impermeable

SCORING SYSTEM: according to Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
No irritant response data after a 24-hours occlusive exposure to intact skin. Grade 1 edema was noted after 24 and 48 h for some animals with abraded skin.

Individual cutaneous examinations and mean values (24-hour exposure, occlusive, intact skin):

Readings

Animal

Exposure period: 24 h, occlusive

Erythema

Edema

24 h

01

0

0

02

0

0

03

0

0

04

0

0

05

0

0

06

0

0

48 h

01

0

0

02

0

0

03

0

0

04

0

0

05

0

0

06

0

0

72 h

01

0

0

02

0

0

03

0

0

04

0

0

05

0

0

06

0

0

Mean

(24, 48, 72 h)

01

0

0

02

0

0

03

0

0

04

0

0

05

0

0

06

0

0

Mean

(24, 48, 72 h)

 

0.0

0.0

 

Interpretation of results:
not irritating
Remarks:
Migrated information
Conclusions:
The test material is not irritating to the rabbit skin.
Executive summary:

The test item contained 89% active ingredient and 10% urea and was applied at a concentration of 50% in vehicle (propylene glycol and saline, 70:30 parts). Three male and female New Zealand rabbits were shaved on the back. The left side was abraded. Gauze patches of 6.25 cm² were loaded with 0.5 g of the test item. Both the abraded and non abraded sites were treated and covered with an impermeable material for 24h. The skin irritation was assessed after 1, 2, 3, 4 and 7 days. Grade 1 edema was noted after 24 and 48 h for some animals with abraded skin only. Erythema could not be assessed due to the coloration by the dye.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment
Principles of method if other than guideline:
According to J. H. Draize: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. In Dermal Toxicity pp. 46 - 59, 1959. Austin, Tex.: Association of Food and Drug Officials of the United States, Texas, State Department of Health
GLP compliance:
no
Remarks:
pre-GLP
Species:
rabbit
Strain:
Vienna White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenbach/Main, FRG
- Weight at study initiation: 3-minutes exposure: male 2.95 kg, female: 3.57 kg; 4-hours exposure: male 2.95 kg, female: 3.57 kg
- Housing: single housing in stainless steel cages with wire mesh walk flaar, floor area: 40 cm x 51 cm
- Diet: about 130 g per animal per day (Ovator Solikanin 4 mm; Muskator-Werke Düsseldorf, FRG)
- Water: about 250 ml per animal per day: fully demineralized water (Monday - Friday), tap water (Saturday/Sunday)
- Acclimation period: about 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 -26
- Humidity (%): about 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
occlusive
Preparation of test site:
other: clipping of fur at least 15 hours before beginning of study
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of same animal
Amount / concentration applied:
TEST MATERIAL
- Amount applied: Dipping of the test patch (2.5 cm x 2.5 cm) in the undiluted substance, and thus about 0.5 ml of the test liquid is absorbed.
- Concentration: undiluted
Duration of treatment / exposure:
3 minutes and 4 hours
Observation period:
8 days
Number of animals:
2 (1 male + 1 female)
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm on upper third of the back or flank
- Type of wrap if used: occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing: with Lutrol and Lutrol/water (1 :1)
- Time after start of exposure: 3 minutes or 4 hours

SCORING SYSTEM: Draize scores
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: Erythema scores could not be read because of staining due to the test substance.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
3-minutes exposure: No erythema or edema.
4-hour exposure: Erythema scores could not be read because of staining due to the test substance. No edema occured.

Response data, exposure period 4 hours, occlusive:

Reading

Animal

Intact Skin

Erythema

Edema

24 h

1

*

0

2

*

0

48 h

1

*

0

2

*

0

8 d

1

*

0

2

0

0

* assessment could not be made because of staining due to the test substance

Interpretation of results:
not irritating
Remarks:
Migrated information
Conclusions:
The TS is considered to be not irritating to the skin.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (non-GLP, 24-hour occlusive exposure, TS conc. 50% in vehicle)
Principles of method if other than guideline:
Patch test technique described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO).
GLP compliance:
no
Remarks:
pre-GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: IVANOVAS, 7964 Kisslegg/Allgäu, Germany and MADOERIN AG, 4414 Fullinsdorf, Switzerland
- Age at study initiation: adult animals
- Weight at study initiation: 2 - 3 kg
- Housing: individually in metal cages
- Diet: standard rabbit food ad libitum (NAFAG, No. 814, Gossau SG)
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 14 / 10
Type of coverage:
occlusive
Preparation of test site:
other: shaved intact and scarified skin
Vehicle:
other: propylene glycol + saline (70 : 30 parts)
Controls:
other: untreated skin of same animal
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g
- Concentration: 50%
Duration of treatment / exposure:
24 hours
Observation period:
7 days
Number of animals:
6 (3 males + 3 females)
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm on back and flank
- Type of wrap if used: impermeable

SCORING SYSTEM: according to Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
No irritant response data after a 24-hours occlusive exposure to intact and scarified skin.
Interpretation of results:
not irritating
Remarks:
Migrated information
Conclusions:
The TS was found to cause no irritation when applied to intact and abraded rabbit skin.
Executive summary:

The test item contained 67% active ingredient and was applied at a concentration of 50% in vehicle (propylene glycol and saline, 70:30 parts). Three male and female New Zealand rabbits were shaved on the back. The left side was abraded. Gauze patches of 6.25 cm² were loaded with 0.5 g of the test item. Both the abraded and non abraded sites were treated and covered with an impermeable material for 24 h. The skin irritation was assessed after 1, 2, 3, 4 and 7 days. No erythema and no edema were noted at any observation time.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with detailed documentation (non-GLP)
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: approx. 12-14 weeks old
- Weight at study initiation: 2300 - 2420 g
- Housing: individually in metal cages
- Diet: standard rabbit pellet ad libitum (Nafag No. 814, Gossau, Switzerland)
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of same animal
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 ml
- Concentration: undiluted
Duration of treatment / exposure:
4 hours
Observation period:
72 hours (because no reactions were observed at 24 hours to 72 hours after removing the bandages)
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: 20 cm² on flank
- Type of wrap if used: The patches were loosely covered with an aluminium foil (36 cm²) and held in place for 4 hours by an adhesive tape (Isoplast, Isoplast AG, CH-5200 Brugg).

SCORING SYSTEM: OECD scoring system
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
No reactions were observed at 24 hours to 72 hours after removing the bandages.
Interpretation of results:
not irritating
Remarks:
Migrated information
Conclusions:
It can be concluded thatthe TS has no primary skin irritant potency in albino rabbits.
Executive summary:

The test item contained 20% active ingredient, 79% water and 1% TEA-HCl buffer. Three male albino rabbits were treated with 0.5 ml in a gauze patch of 20 cm². The patches were covered with aluminium foil and held in place for four hours with adhesive tape. Skin reactions were observed 1, 24, 48 and 72 hours after patch removal. No erythema or edema were noted at any observation time point.

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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (non-GLP)
Qualifier:
according to guideline
Guideline:
other: EPA guideline (§ 163.81-4 "Primary eye irritation study". Federal Register, Vol. 43, No. 163, August 22, 1978)
GLP compliance:
no
Remarks:
pre-GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Exp. Toxicology Sisseln, CIBA-Geigy Ltd.
- Weight at study initiation: 2 - 3 kg
- Housing: single housing in metal cages
- Diet: standard rabbit food ad libitum (NAFAG, No. 814, Gossau SG)
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 14 / 10
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of same animal
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 g
Duration of treatment / exposure:
30 seconds (rinsed) or unspecified (unrinsed)
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
6 (3 males + 3 females)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: In 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 ml of physiological saline.

SCORING SYSTEM: according to Draize

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: unrinsed
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: rinsed
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: unrinsed
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: rinsed
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.4
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: unrinsed
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
other: rinsed
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.2
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: unrinsed
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: rinsed
Irritant / corrosive response data:
The TS was found to cause a minimal irritation when applied to the rabbit eye mucosa. Irritation was fully reversible within 72 hours. When the application site was rinsed, no irritation was found.
Other effects:
During the whole observation period parts of the cornea and sclera were reddish stained.

Individual ocular examinations and mean values, unrinsed eyes (24, 48, 72 hours):

Readings

Animal

Cornea

Iris

Conjunctiva

Opacity

Area of cornea involved

Redness

Chemosis

Discharge

24 h

01

0

0

0

2

1

0

02

0

0

0

0

0

0

03

0

0

0

1

1

1

48 h

01

0

0

0

0

0

0

02

0

0

0

1

0

0

03

0

0

0

0

0

0

72 h

01

0

0

0

0

0

0

02

0

0

0

0

0

0

03

0

0

0

0

0

0

Mean

01

0.0

 

0.0

0.7

0.3

 

02

0.0

 

0.0

0.3

0.0

 

03

0.0

 

0.0

0.3

0.3

 

Mean

 

0.0

 

0.0

0.4

0.2

 

 

Individual ocular examinations and mean values, rinsed eyes (24, 48, 72 hours):

Readings

Animal

Cornea

Iris

Conjunctiva

Opacity

Area of cornea involved

Redness

Chemosis

Discharge

24 h

01

0

0

0

0

0

0

02

0

0

0

0

0

0

03

0

0

0

0

0

0

48 h

01

0

0

0

0

0

0

02

0

0

0

0

0

0

03

0

0

0

0

0

0

72 h

01

0

0

0

0

0

0

02

0

0

0

0

0

0

03

0

0

0

0

0

0

Mean

01

0.0

 

0.0

0.0

0.0

 

02

0.0

 

0.0

0.0

0.0

 

03

0.0

 

0.0

0.0

0.0

 

Mean

 

0.0

 

0.0

0.0

0.0

 

 

Interpretation of results:
not irritating
Remarks:
Migrated information
Conclusions:
Under the conditions of this experiment the test material was found to cause a minimal irritation when applied to the rabbit eye mucosa and no irritation when the application site was rinsed. Taken together, the test material is considered to be not irritating to the eye.
Executive summary:

The test item contained 89% active ingredient and 10% urea. Three male and female New Zealand rabbits were treated with 0.1 g by insertion into the conjunctival sac of the left eye. The lids were gently closed for a few seconds. In three of the rabbits, the treated eye was flushed with 10 ml of physiological saline after ca. 30 seconds. The eye irritation was assessed after 1, 2, 3, 4 and 7 days. Only in non-rinsed eyes, redness, chemosis and discharge were observed on the first and second day. These findings were no longer noted on the third day. During the whole observation period, parts of the cornea and sclera were reddish stained.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (non-GLP)
Qualifier:
according to guideline
Guideline:
other: Fed. Reg. 38, No. 187, § 1500.42, p. 27019 of Sept. 27, 1973
GLP compliance:
no
Remarks:
pre-GLP
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenbach/Main, FRG
- Weight at study initiation: mean males 3.32 kg, mean females: 2.69 kg
- Housing: single housing in stainless steel cages with wire mesh walk flaar, floor area: 40 cm x 51 cm
- Diet: about 130 g per animal per day (Ovator Solikanin 4 mm; Muskator-Werke Düsseldorf, FRG)
- Water: about 250 ml per animal per day: fully demineralized water (Monday - Friday), tap water (Saturday/Sunday)
- Acclimation period: about 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 -26
- Humidity (%): about 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of same animal
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 ml
- Concentration: undiluted
Duration of treatment / exposure:
unspecified (no removal of TS by washing)
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
6 (3 males + 3 females)
Details on study design:
REMOVAL OF TEST SUBSTANCE: No

SCORING SYSTEM: according to Draize
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.05
Max. score:
4
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.15
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
See table below.

Individual ocular examinations and mean values (24, 48, 72 hours):

Readings

Animal

Cornea

Iris

Conjunctivae

Opacity

Area of cornea involved

Redness

Chemosis

Discharge

24 h

01

0

0

0

0

0

0

02

0

0

0

0

0

0

03

0

0

0

0

0

0

04

0

0

0

0*

0

0

05

0

0

0

0*

0

0

06

0

0

0

0*

0

0

48 h

01

0

0

0

0

0

0

02

0

0

0

1

0

0

03

0

0

0

0

0

0

04

0

0

0

1

0

0

05

0

0

0

1

0

0

06

0

0

0

0

0

0

72 h

01

0

0

0

0

0

0

02

0

0

0

0

0

0

03

0

0

0

0

0

0

04

1

1

0

0

0

0

05

0

0

0

0

0

0

06

0

0

0

0

0

0

Mean

01

0.0

 

0.0

0.0

0.0

 

02

0.0

 

0.0

0.3

0.0

 

03

0.0

 

0.0

0.0

0.0

 

04

0.3

 

0.0

0.3

0.0

 

05

0.0

 

0.0

0.3

0.0

 

06

0.0

 

0.0

0.0

0.0

 

Mean

 

0.05

 

0.0

0.15

0.0

 

* If at one reading assessments referring to the same characteristic cannot be made in 1 – 5 animals, the mean of the specific values rounded to the nearest whole number that could be read was inserted instead.

Interpretation of results:
not irritating
Remarks:
Migrated information
Conclusions:
The TS is considered to be not irritating to the eye.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (non-GLP)
Principles of method if other than guideline:
Test for eye irritants described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO).
GLP compliance:
no
Remarks:
pre-GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: IVANOVAS, 7964 Kisslegg/Allgäu, Germany and MADOERIN AG, 4414 Fullinsdorf, Switzerland
- Age at study initiation: adult animals
- Weight at study initiation: 2 - 3 kg
- Housing: individually in metal cages
- Diet: standard rabbit food ad libitum (NAFAG, No. 814, Gossau SG)
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 14 / 10
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of same animal
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 g
Duration of treatment / exposure:
30 seconds (rinsed) or unspecified (unrinsed)
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
6 (3 males + 3 females)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: In 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 ml of physiological saline.

SCORING SYSTEM: according to Draize

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: unrinsed
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: rinsed
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: unrinsed
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: rinsed
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: unrinsed
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: rinsed
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.4
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: unrinsed
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: rinsed
Irritant / corrosive response data:
The TS was found to cause a minimal irritation when applied to the rabbit eye mucosa. Irritation was fully reversible within 48 hours. Rinsing the eyes following instillation was of no effect.

Individual ocular examinations and mean values, unrinsed eyes (24, 48, 72 hours):

Readings

Animal

Cornea

Iris

Conjunctiva

Opacity

Area of cornea involved

Redness

Chemosis

Discharge

24 h

01

0

0

0

1

1

1

02

0

0

0

1

2

1

03

0

0

0

1

1

1

48 h

01

0

0

0

0

0

0

02

0

0

0

0

0

0

03

0

0

0

0

0

0

72 h

01

0

0

0

0

0

0

02

0

0

0

0

0

0

03

0

0

0

0

0

0

Mean

01

0.0

 

0.0

0.3

0.3

 

02

0.0

 

0.0

0.3

0.7

 

03

0.0

 

0.0

0.3

0.3

 

Mean

 

0.0

 

0.0

0.3

0.4

 

 

Individual ocular examinations and mean values, rinsed eyes (24, 48, 72 hours):

Readings

Animal

Cornea

Iris

Conjunctiva

Opacity

Area of cornea involved

Redness

Chemosis

Discharge

24 h

01

0

0

0

1

1

2

02

0

0

0

1

1

1

03

0

0

0

1

1

1

48 h

01

0

0

0

0

0

0

02

0

0

0

0

0

0

03

0

0

0

0

0

0

72 h

01

0

0

0

0

0

0

02

0

0

0

0

0

0

03

0

0

0

0

0

0

Mean

01

0.0

 

0.0

0.3

0.3

 

02

0.0

 

0.0

0.3

0.3

 

03

0.0

 

0.0

0.3

0.3

 

Mean

 

0.0

 

0.0

0.3

0.3

 

 

Interpretation of results:
not irritating
Remarks:
Migrated information
Conclusions:
Under the conditions of this experiment the test material was found to cause a minimal irritation when applied to the rabbit eye mucosa. Irritation was fully reversible within 48 hours. Rinsing the eyes following instillation was of no effect. Taken together, the test material is considered to be not irritating to the eye.
Executive summary:

The test item contained 67% active ingredient. Three male and female New Zealand rabbits were treated with 0.1 g by insertion into the conjunctival sac of the left eye. The lids were gently closed for a few seconds. In three of the rabbits, the treated eye was flushed with 10 ml of physiological saline after ca. 30 seconds. The eye irritation was assessed after 1, 2, 3, 4 and 7 days. In both rinsed and non-rinsed eyes, redness, chemosis and discharge were observed on the first day. These findings were no longer noted on the second day. No other findings were noted at any observation time.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with detailed documentation (non-GLP)
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: approx. 12-14 weeks old
- Weight at study initiation: 2450 - 2480 g
- Housing: individually in metal cages
- Diet: standard rabbit pellet ad libitum (Nafag No. 814, Gossau, Switzerland)
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of same animal
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 ml
- Concentration: undiluted
Duration of treatment / exposure:
unspecified
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 males
Details on study design:
SCORING SYSTEM: according to OECD guideline

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 ,48, 72 hours
Score:
0.1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Slight redness of the conjunctiva was noted after 1h and 24h. The mean score was 0.0, 0.0, 0.33 and 0.0 for cornea, iris, conjunctivae and chemosis, respectively. The eye reactions observed were fully reversible until the end of the observation period on day 3.

Individual ocular examinations and mean values (24, 48, 72 hours):

Readings

Animal

Cornea

opacity

Iris

Conjunctiva

Redness

Chemosis

1 h

01

0

0

1

1

02

0

0

1

1

03

0

0

1

1

24 h

01

0

0

1

0

02

0

0

1

0

03

0

0

1

1

48 h

01

0

0

0

0

02

0

0

0

0

03

0

0

0

0

72 h

01

0

0

0

0

02

0

0

0

0

03

0

0

0

0

Mean

01

0.0

0.0

0.3

0.0

02

0.0

0.0

0.3

0.0

03

0.0

0.0

0.3

0.3

Mean

 

0.0

0.0

0.3

0.1

 

Interpretation of results:
not irritating
Remarks:
Migrated information
Conclusions:
Under the experimental conditions employed the TS induced very slight irritation of the conjunctiva when applied into the conjunctival sac of albin rabbits. The eye reactions observed were fully reversible until the end of the observation period on day 3. Taken together, the TS is considered to be not irritating to the eye.
Executive summary:

The test item contained 20% active ingredient, 79% water and 1% TEA-HCl buffer. One eye of each three male rabbits was treated with 0.1 ml. Slight redness of the conjunctiva was noted after 1h and 24h. The mean score was 0.0, 0.0 and 0.33 for cornea, iris and conjunctiva, respectively. The eye reactions observed were fully reversible until the end of the observation period on day 3.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

A pre-GLP study according to EPA guideline (§ 163.81-5 "Primary dermal irritation study". Federal Register, Vol. 43, No. 163, August 22, 1978) was performed (Ciba 801995 (1980)). The test item contained 89% active ingredient and 10% urea and was applied at a concentration of 50% in vehicle (propylene glycol and saline, 70:30 parts). Three male and female New Zealand rabbits were shaved on the back. The left side was abraded. Gauze patches of 6.25 cm² were loaded with 0.5 g of the test item. Both the abraded and non abraded sites were treated and covered with an impermeable material for 24h. The skin irritation was assessed after 1, 2, 3, 4 and 7 days. Grade 1 edema was noted after 24 and 48 h for some animals with abraded skin only. Erythema could not be assessed due to the coloration by the dye. The test material is not irritating to the rabbit skin.

In support of this study several other studies are available. Firstly, in a study by CIBA-Geigy Ltd.(Ciba 785731 (1979)), according to "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics; US Association of Food and Drug Officials), the test item (which contained 67% active ingredient) was applied at a concentration of 50% in vehicle (propylene glycol and saline, 70:30 parts). Three male and female New Zealand rabbits were shaved on the back. The left side was abraded. Gauze patches of 6.25 cm² were loaded with 0.5 g of the test item. Both the abraded and non abraded sites were treated and covered with an impermeable material for 24 h. The skin irritation was assessed after 1, 2, 3, 4 and 7 days. No erythema and no edema were noted at any observation time.

Secondly, CIBA-Geigy Ltd.(Ciba 875185 (1987)) conducted a study according to OECD Guideline 404 (Acute Dermal Irritation / Corrosion) but not in compliance with GLP. The test item contained 20% active ingredient, 79% water and 1% TEA-HCl buffer. Three male albino rabbits were treated with 0.5 ml in a gauze patch of 20 cm². The patches were covered with aluminium foil and held in place for four hours with adhesive tape. Skin reactions were observed 1, 24, 48 and 72 hours after patch removal. No erythema or edema were noted at any observation time point.

Thirdly, BASF AG 81/115 (1981) performed a study according to J. H. Draize: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. In Dermal Toxicity pp. 46 - 59, 1959. Austin, Tex.: Association of Food and Drug Officials of the United States, Texas, State Department of Health. The study was not performed in compliance with GLP. Three rabbits (1 male and 2 females) were used in this study. The backs of the rabbits were shaved (2.5 x 2.5 cm). Test patches (2.5 x 2.5 cm) were loaded with undiluted test material (containing 14.5% active ingredient, 83% water, 1.5% NPG and 1% salts) and covered with an occlusive dressing. The material was removed by washing 3 minutes and 4 hours after application. No effect was found on edema but unfortunately erythema could not be scored due to red staining by the test substance.

Eye irritation:

A pre-GLP study according to EPA guideline (§ 163.81-4 "Primary eye irritation study". Federal Register, Vol. 43, No. 163, August 22, 1978) was conducted (Ciba 801994 (1981)). The test item contained 89% active ingredient and 10% urea. Three male and female New Zealand rabbits were treated with 0.1 g by insertion into the conjunctival sac of the left eye. The lids were gently closed for a few seconds. In three of the rabbits, the treated eye was flushed with 10 ml of physiological saline after ca. 30 seconds. The eye irritation was assessed after 1, 2, 3, 4 and 7 days. Only in non-rinsed eyes, redness, chemosis and discharge were observed on the first and second day. These findings were no longer noted on the third day. During the whole observation period, parts of the cornea and sclera were reddish stained. Under the conditions of this experiment the test material was found to cause a minimal irritation when applied to the rabbit eye mucosa and no irritation when the application site was rinsed. Taken together, the test material is considered to be not irritating to the eye.

In support of this conclusion several studies are available. A pre-GLP study (Ciba 785730 (1979)) was performed according to Test for eye irritants described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO). The test item contained 67% active ingredient. Three male and female New Zealand rabbits were treated with 0.1 g by insertion into the conjunctival sac of the left eye. The lids were gently closed for a few seconds. In three of the rabbits, the treated eye was flushed with 10 ml of physiological saline after ca. 30 seconds. The eye irritation was assessed after 1, 2, 3, 4 and 7 days. In both rinsed and non-rinsed eyes, redness, chemosis and discharge were observed on the first day. These findings were no longer noted on the second day. No other findings were noted at any observation time. Under the conditions of this study, the substance was not irritating to the eye.

The second supporting study, non-GLP, (Ciba 875184 (1987)) was performed according to OECD TG 405. Three male albino rats were treated with 0.1 mL undiluted test substance (which contained 20% active ingredient). The untreated eye of the same animal served as control. Eye irritation was assessed at 1, 24, 48 and 72 hours after application. The substance induced very slight irritation of the conjunctiva (slight redness at 1 hr and 24 hr, mean score 0.33). The eye reactions observed were fully reversible until the end of the observation period on day 3. Under the conditions of this study, the substance was not irritating to the eye.

The third non-GLP supporting study (Ciba 81/115 (1981)) was performed according to Fed. Reg. 38, No. 187, § 1500.42, p. 27019 of Sept. 27, 1973. Three male and three female Vienna white rabbits were treated with 0.1 mL undiluted test substance (which contained 14.5% active ingredient, 83% water, 1.5% NPG and 1% salts); the untreated eye of the same animal served as control. Eye irritation was assessed at 24, 48 and 72 hours after application. The substance induced slight redness of the conjunctivae at 48 hours in three rabbits and slight corneal opacity in one rabbit at 72 hours (last observation time point). Under the conditions of this study, the substance was not irritating to the eye.

Justification for classification or non-classification

The test substance does not have to be classified for skin and eye irritation to according to Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.