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Description of key information

Skin Irritation
One key study is provided. No signs of dermal irritation were observed.
Eye Irritation
One key study is provided. No signs of ocular irritation were observed.

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:
5 November 1990 - 8 November 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.
Qualifier:
equivalent or similar to
Guideline:
other: FHSA 16 CFR 1500.41
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Acclimation period: 12 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23 °C

IN-LIFE DATES: From: 5 November 1990 To: 8 November 1990
Type of coverage:
occlusive
Preparation of test site:
other: abraded and shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 g of the test material was placed on each of the test sites (i.e. abraded and intact skin).
Duration of treatment / exposure:
24 hours
Observation period:
72 hours. Evaluation occurred 24 and 72 hours after exposure.
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm² (two per rabbit, one intact and one abraded).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the test sites were gently wiped clean of any residual test material.
- Time after start of exposure: after 24 hours of exposure.

SCORING SYSTEM:

Erythema and eschar formation:
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) or eschar formation (injuries in depth) preventing erythema reading 4

Oedema formation:
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (edges raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Remarks:
of 6 animals
Time point:
other: mean at 24 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: mean at 24 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: Intact skin
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: mean at 24 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: Abraded skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: mean at 24 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: Intact skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: mean of 24 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: Abraded skin
Irritant / corrosive response data:
All sites were clear of irritation during the test period.
Other effects:
All animals appeared active and healthy.

Table 1 Primary Dermal Irritation (PDI) Scores - Individual Results

Rabbit

24 hours

72 hours

Abraded

Intact

Abraded

Intact

7740

7741

7742

7743

7744

7745

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

Total

0/0

0/0

0/0

0/0

Mean

0/0

0/0

0/0

0/0

Key: erythema and eschar / oedema

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the test material is not irritating to skin and requires no classification in accordance with the EU criteria.
Executive summary:

The primary skin irritation potential of the test material was investigated in a study which was broadly conducted in accordance with the FHSA guideline 16 CFR 1500.41.

During the study 0.5 g of the test material was applied to both an intact and abraded site on each of six New Zealand White rabbits. The sites were occluded for 24 hours. The patches were then removed and the test sites wiped to prevent further exposure. Evaluation occurred 24 and 72 hours after exposure.

All sites were clear of irritation during the test period and the Primary Dermal Irritation Index was 0.0.

Under the conditions of this study, the test material is not irritating to skin and requires no classification in accordance with the EU criteria.

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
Study period:
13 November 1990 - 16 November 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.
Qualifier:
equivalent or similar to
Guideline:
other: FHSA 16 CFR 1500.42
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22 °C

IN-LIFE DATES: From: To: 25 October 1990 - 16 November 1990
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
undiluted
Amount applied: 0.1 g
Duration of treatment / exposure:
Three of the treated eyes were rinsed 30 seconds post-installation.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
6; 3 male, 3 female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): three of the treated eyes were rinsed with 30 cc of saline solution.
- Time after start of exposure: 30 seconds post-exposure.

- Scoring system: according to the method of Draize. Ocular lesions were evaluated at 24, 48 and 72 hours post installation. Fluorescein was used at the 24 hour evaluation.

Draize Scale for Scoring Ocular Irritation

1. CONJUNCTIVAE

(A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal............................................................................................................................................0
Vessels definitely injected above normal................................................................................................1
More diffuse, deeper crimson red, individual vessels not easily discernible....................................2
Diffuse beefy red.........................................................................................................................................3

(B) Chemosis
No swelling..................................................................................................................................................0
Any swelling above normal (includes nictitating membrane).............................................................1
Obvious swelling with partial eversion of lids.......................................................................................2
Swelling with lids about half closed.........................................................................................................3
Swelling with lids half closed to completely closed...............................................................................4

(C) Discharge
No discharge...............................................................................................................................................0
Any amount different from normal (does not include small amounts observed in inner
canthus of normal animals)......................................................................................................................1
Discharge with moistening of the lids and hairs just adjacent to lids...............................................2
Discharge with moistening of the lids and hairs a considerable area around the eye...................3

THE TOTAL SCORE = (A + B + C) x 2 MAXIMUM TOTAL = 20

2. IRIS

(D) Values
Normal.........................................................................................................................................................0
Folds above normal, congestion, swelling, circumcorneal injection (any or all
of these or combination of any thereof) iris still reacting to light
(sluggish reaction is positive).................................................................................................................1
No reaction to light, haemorrhage, gross destruction (any or all of these)....................................2

THE TOTAL SCORE = D x 5 MAXIMUM TOTAL = 10

3. CORNEA

(E) Degree of Opacity (most dense area used)
No opacity...................................................................................................................................................0
Scattered or diffuse areas, details of iris clearly visible......................................................................1
Easily discernible translucent areas, details of iris slightly obscured..............................................2
Opalescent areas, no details of iris visible, size of pupil barely discernible....................................3
Opaque, iris not discernible through the opacity................................................................................4

(F) Area of Cornea Involved
One quarter (or less) but not zero..........................................................................................................1
Greater than one quarter but less than half...........................................................................................2
Greater than half but less than three quarters......................................................................................3
Greater than three quarters, up to whole area.......................................................................................4

THE TOTAL SCORE = (E x F) x 5 MAXIMUM TOTAL = 80

MAXIMUM TOTAL SCORE POSSIBLE = 110
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: n/a
Remarks on result:
other: Unwashed
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Unwashed
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
1.22
Max. score:
2
Reversibility:
other: 1 animal still exhibited a hyperaemia score of 1 at 72 hours
Remarks on result:
other: Unwashed
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.78
Max. score:
2
Reversibility:
other: 1 animal still exhibited a chemosis score of 1 at 72 hours
Remarks on result:
other: Unwashed
Irritation parameter:
other: Discharge
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.89
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Unwashed
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: n/a
Remarks on result:
other: Washed
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: n/a
Remarks on result:
other: Washed
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
1
Max. score:
2
Reversibility:
other: 1 animal still exhibited a hyperaemia score of 1 at 72 hours
Remarks on result:
other: Washed
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.89
Max. score:
1
Reversibility:
other: 2 animals still exhibited a chemosis score of 1 at 72 hours
Remarks on result:
other: Washed
Irritation parameter:
other: Discharge
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.44
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Washed
Irritant / corrosive response data:
-No corneal opacity was noted in any of the treated eyes.
-Iritis was observed in two unwashed eyes 24 hours post installation and in one eye at 48 hours. By 72 hours all eyes were free of iritis. Iritis was not observed in any of the washed eyes.
-Conjunctival irritation was noted in all eyes 24 and 48 hours after administration. This remained in one unwashed and two washed eyes after 72 hours.
Other effects:
All animals appeared active and healthy. No signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour were observed.

Table 1 Individual Results

Time Point (hours)

Rabbit Number

Cornea

Iris

Conjunctivae

Chemosis

Discharge

 

 

24

7806

7807

7808

7809

7810

7811

0

0

0

0

0

0

1

0

1

0

0

0

2

2

2

2

1

1

2

1

1

1

1

1

3

2

2

1

2

1

 

 

48

7806

7807

7808

7809

7810

7811

0

0

0

0

0

0

0

0

1

0

0

0

1

2

1

1

1

2

1

1

0

1

1

1

1

0

0

0

0

0

 

 

72

7806

7807

7808

7809

7810

7811

0

0

0

0

0

0

0

0

0

0

0

0

0

1

0

0

0

1

0

1

0

0

1

1

0

0

0

0

0

0

Rabbits 7809, 7810 and 7811 had the treated eye rinsed with 30 cc of saline solution 30 seconds post-installation

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study the test material produced minimal irritation to both the unwashed and washed eyes.
Executive summary:

The eye irritation potential of the test material was investigated in a study which was broadly conducted in accordance with FHSA guideline16 CFR 1500.42. During the study 0.1 g of the test material was instilled into the left eye of six New Zealand white rabbits, with three of the treated eyes being rinsed after 30 seconds with saline. The animals were observed for three days and the eyes examined at 24, 48 and 72 hours. Irritation was scored according to the method of Draize.

 

Under the conditions of the study the test material produced minimal irritation to both the unwashed and washed eyes. No classification is required in accordance with EU criteria. 

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation

The primary skin irritation potential of the test material was investigated in a study which was broadly conducted in accordance with the FHSA guideline 16 CFR 1500.41. During the study 0.5 g of the test material was applied to both an intact and abraded site on each of six New Zealand White rabbits. The sites were occluded for 24 hours. The patches were then removed and the test sites wiped to prevent further exposure. Evaluation occurred 24 and 72 hours after exposure. All sites were clear of irritation during the test period and the Primary Dermal Irritation Index was determined to be 0.0.

Under the conditions of this study, the test material was not irritating to skin and requires no classification in accordance with the EU criteria.

 

Eye Irritation

The eye irritation potential of the test material was investigated in a study which was broadly conducted in accordance with FHSA guideline16 CFR 1500.42. During the study 0.1 g of the test material was instilled into the left eye of six New Zealand white rabbits, with three of the treated eyes being rinsed after 30 seconds with saline. The animals were observed for three days and the eyes examined at 24, 48 and 72 hours. Irritation was scored according to the method of Draize.

Under the conditions of the study the test material produced minimal irritation to both the unwashed and washed eyes. No classification is required in accordance with EU criteria. 


Justification for selection of skin irritation / corrosion endpoint:
Only one study available.
The key study was conducted broadly in accordance with the FHSA guideline 16 CFR 1500.41. This reference does not provide a full report with regard to the methods used in this study. However, as most basic key information is reported, the study can be judged as scientifically acceptable. As such, it was awarded a reliability score of 2 in accordance with the criteria of Klimisch (1997).

Justification for selection of eye irritation endpoint:
Only one study available.
The key study was conducted broadly in accordance with the FHSA guideline 16 CFR 1500.42. This reference does not provide a full report with regard to the methods used in this study. However, as most basic key information is reported, the study can be judged as scientifically acceptable. As such, it was awarded a reliability score of 2 in accordance with the criteria of Klimisch (1997).

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for irritation or corrosion to either the skin or eye.