Registration Dossier

Administrative data

Description of key information

Both studies performed to no specified methods, however written with clear and concise study plans. 
Not irritating to the skin or eye.

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:
Not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted to no specified methods
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
other: not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Three male and 3 female New Zealand White rabbits (obtained from H.A.R.E. Rabbits far Research, Hewitt, New Jersey) were used for this study. The rabbits weighed from 2302 to 2529 grams at the beginning of the study. They were individually housed in hanging wire-mesh cages in temperature and humidity controlled quarters. They were maintained in accordance with the recommendations contained in H.E.W. Publication No. 74-23 (N.I.H.) entitled "Guide for the Care and Use of Laboratory Animals" and were conditioned for a minimum of 25 days prior to study initiation. Water and Purina Rabbit Chow were available ad libitum.
Type of coverage:
occlusive
Preparation of test site:
abraded
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
Five hundred milligrams of the test material were applied to the back of each rabbit under a one inch square gauze patch.
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
3 male
3 female
Details on study design:
The hair was removed from the back of each rabbit (20-30% of the body surface) with an electric clipper. The skin of 3 of the rabbits was abraded with a scalpel blade. The abrasions penetrated the stratum corneum, but were not deep enough to cause bleeding.
Five hundred milligrams of the test material were applied to the back of each rabbit under a one inch square gauze patch. The application sites were then covered with gauze bandaging and overwrapped with Saran Wrap. The entire application area was then wrapped with several layers of 75 mm Elastoplast tape. A collar was also applied. Following 24 hours of application, the bandages and collars were removed and the sites were washed with tepid tap water and examined for skin irritation. The examinations were repeated at 72 hours.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours
Score:
> 0 - < 1
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
other: Intact skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: Intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: Intact skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours
Score:
> 0 - < 1
Max. score:
1.5
Reversibility:
fully reversible
Remarks on result:
other: Abraded skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: Abraded skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: Abraded skin
Irritant / corrosive response data:
Not specified

Number of Animals Exhibiting Signs with scoring Value/Number Dosed

 

Intact Skin

Abraded Skin

Hours

Hours

Observations

Value

24

72

24

72

Erythema, Eschar Formation

0

1/3

3/3

2/3

3/3

1

2/3

 

1/3

 

2

 

 

 

 

3

 

 

 

 

4

 

 

 

 

Edema Formation

0

3/3

3/3

3/3

3/3

1

 

 

 

 

2

 

 

 

 

3

 

 

 

 

4

 

 

 

 

 

Primary Skin Irritation – Individual Rabbit Scores and Score Calculation

Intact Skin

 

Erythema

Edema

 

Observation Period (Hours)

Observation Period (Hours)

Animal No./Sex

24

72

24

72

33339, Male

1.0

 

0

0

33367, Male

0

0

0

0

33354, Female

0.5

0

0

0

Total

1.5

0

0

0

Abraded Skin

 

Erythema

Edema

 

Observation Period (Hours)

Observation Period (Hours)

Animal No./Sex

24

72

24

72

33813, Male

0

0

0

0

33368, Male

0

0

0

0

33376, Female

1.5

0

0

0

Total

1.5

0

0

0

Calculation for Primary Skin Irritation Score (Score = The average of all the erythema scores plus the average of all the edema score): (3.0 ÷ 12) + (0.0 ÷ 12) = 0.3

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Primary Irritation Score = 0.3
Executive summary:

Primary Irritation Score = 0.3.

Based upon the data obtained and in accordance with the require­ments of the regulations of the Federal Hazardous Substances Act, the test material would not be considered a primary skin irritant.

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:
Not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted to no specified methods
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
other: Not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Three male and 3 female New Zealand White rabbits (obtained from H.A.R.E. Rabbits for Research, Hewitt, New Jersey) were used for this study. The rabbits weighed from 2300 to 2813 grams at the beginning of the study. The rabbits were individually housed in hanging wire-mesh cages in temperature and humidity controlled quarters. They were maintained in accordance with the recommendations contained in H.E.W. Publication No. 74-23 (N.I.H.) entitled "Guide for the Care and "Ose of Laboratory Animals". The animals were conditioned for a period of 20 days prior to study initiation. Water and Purina Rabbit Chow were available ad libitum.
Vehicle:
not specified
Controls:
other: left eye untreated
Amount / concentration applied:
The rabbits received 100 milligrams of the test material
Duration of treatment / exposure:
Not specified
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3 males
3 females
Details on study design:
Prior to test material administration, the eyes of each rabbit were examined with ultraviolet light following instillation of one drop of a 2.0 percent sodium fluorescein solution. Rabbits exhibiting corneal lesions were discarded.
The rabbits received 100 milligrams of the test material. The test material was placed into the cupped conjunctival sac of the right eye of each rabbit following which the eyelids were gently held together for one second. The left eye served as the untreated control for each rabbit. None of the rabbits received a washout.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1 hour
Score:
0
Max. score:
0
Remarks on result:
other: Opacity
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 hours
Score:
> 0 - < 1
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
other: Opacity
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 48, 72 hours & 7 days
Score:
0
Max. score:
0
Remarks on result:
other: Opacity
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1 hour
Score:
0
Max. score:
0
Remarks on result:
other: Area
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 hours
Score:
> 0 - < 1
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: Area
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 48, 72 hours & 7 days
Score:
0
Max. score:
0
Remarks on result:
other: Area
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1 hour
Score:
> 0 - < 1
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
other: Irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 hours
Score:
> 0 - < 1
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
other: Irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 48, 72 hours & 7 days
Score:
0
Max. score:
0
Remarks on result:
other: Irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1 hour
Score:
> 1 - < 2
Max. score:
1.5
Reversibility:
fully reversible
Remarks on result:
other: Redness
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 hours
Score:
> 1 - < 2
Max. score:
2.5
Reversibility:
fully reversible
Remarks on result:
other: Redness
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 48 hours
Score:
> 0 - < 1
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
other: Redness
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 72 hours
Score:
> 0 - < 1
Max. score:
0.5
Reversibility:
fully reversible
Remarks on result:
other: Redness
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 7 days
Score:
0
Max. score:
0
Remarks on result:
other: Redness
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1 hour
Score:
> 1 - < 2
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 hours
Score:
> 0 - < 1
Max. score:
1.5
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 48 hours
Score:
> 0 - < 1
Max. score:
0.5
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 72 hours & 7 days
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1 hour
Score:
> 1 - < 2
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: Discharge
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 hours
Score:
> 0 - < 1
Max. score:
1.5
Reversibility:
fully reversible
Remarks on result:
other: Discharge
Irritant / corrosive response data:
Not specified

Primary Eye Irritation Study in the Albino Rabbit – Group Observations

 

Observations

 

Examination Interval (No. Positive/No. Dosed)

Hours

Day

1

24

48

72

7

DRAIZE SCORING VALUES

Cornea

Cornea Normal

6/6

3/6

5/6

6/6

6/6

Dulling Normal Corneal Luster

 

2/6

1/6

 

 

Corneal Opacity

Very slight

 

1/6

 

 

 

Slight

 

 

 

 

 

Moderate

 

 

 

 

 

Marked

 

 

 

 

 

Iris

Iris Normal

5/6

4/6

6/6

6/6

6/6

Iridal Irritation

1/6

2/6

 

 

 

Conjunctivae

Redness

Normal

 

 

2/6

5/6

6/6

Very slight

 

3/6

2/6

1/6

 

Slight

6/6

2/6

2/6

 

 

Moderate

 

1/6

 

 

 

Marked

 

 

 

 

 

Chemosis

Normal

1/6

2/6

5/6

6/6

6/6

Very slight

4/6

4/6

1/6

 

 

Slight

1/6

 

 

 

 

Moderate

 

 

 

 

 

Marked

 

 

 

 

 

Discharge

Normal

 

5/6

6/6

6/6

6/6

Very slight

1/6

 

 

 

 

Slight

4/6

1/6

 

 

 

Moderate

1/6

 

 

 

 

Marked

 

 

 

 

 

SODIUM FLUORESCENT/ULTRA-VIOLET LIGHT EXAMINATION

 

Negative (normal)

 

---

---

---

6/6

6/6

Positive (corneal injury)

---

---

---

0/6

0/6

OTHER FINDINGS

Clear discharge

6/6

1/6

0/6

0/6

0/6

Blanching, conjunctivae

3/6

0/6

0/6

0/6

0/6

 

Primary Eye Irritation Study in the Albino Rabbit – Group Average Scores

Area

Average Scores (Range)

Period

Hours

Day

1

24

48

72

7

Cornea

A

0

0.2

(0 – 1.0)

0

0

0

B

0

0.5

(0 – 3.0

0

0

0

Score

0

0.5

0

0

0

Iris

A

0.2

(0 – 1.0)

0.3

(0 – 1.0)

0

0

0

Score

1.0

1.5

0

0

0

Conjunctivae

A

1.1

(1.0 – 1.5)

1.1

(0 – 2.5)

0.5

(0 – 1.0)

0.1

(0 – 0.5)

0

B

1.0

(0 – 2.0)

0.7

(0 – 1.5)

0.1

(0 – 0.5)

0

0

C

1.3

(0.5 – 2.0)

0.3

(0 – 1.5)

0

0

0

Score

6.8

4.2

1.2

0.2

0

 

Total scores

7.8

6.2

1.2

0.2

0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based upon the data obtained and in accordance with the requirements of the regulations of the Federal Hazardous Substances Act, the test material would not be considered a primary eye irritant
Executive summary:

Based upon the data obtained and in accordance with the requirements of the regulations of the Federal Hazardous Substances Act, the test material would not be considered a primary eye irritant

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

Additional information

Justification for selection of skin irritation / corrosion endpoint:
Study written with clear and concise study plan.

Justification for selection of eye irritation endpoint:
Study written with clear and concise study plan

Justification for classification or non-classification