Registration Dossier

Administrative data

Description of key information

Skin corrosion (equivalent to OECDTG404): not corrosive, no corrosive effects were observed in the in vivo skin irritation study.

Skin irritation (equivalent to OECDTG404): irritating

Eye irritation (equivalent to OECDTG405): irritating

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
Study period:
January 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Reliability has been presented as 2 because a protocol similar to OECD Guideline has been followed but pre-GLP.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
No further info on test animals or environmental conditions were provided.
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:
24 hours
Observation period:
7 days
Number of animals:
6
Details on study design:
OBSERVATION TIME POINTS: Erythema and edema after 4, 24, 48 and 72 hours and 7 days.
- Method of calculation: final irritation score was calculated as the average of iritation scores at 24 and 72 hours.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
animal #1
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
animal #2
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
animal #3
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
animal #4
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
animal #5
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
animal #6
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
animal #1
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
animal #2
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
animal #3
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
animal #4
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
animal #5
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
animal #6
Irritant / corrosive response data:
- Individual erythema scores for each animal were 2, 4, 3 and 3 for t=4, 24, 48 and 72 hours respectively.
- Individual edema scores for animal #1 were 2, 4, 3 and 3 for t=4, 24, 48 and 72 hours respectively. Individual edema scores for animal #2, #3, #4, #5 and #6 were 2, 3, 3 and 3 for t=4, 24, 48 and 72 hours respectively.
- All adverse effects were fully reversible within 7 days.

Other effects:
- A defatting effect was observed: skin sloughed off in ten to fourteen days. There was no in depth injury.

Interpretation of results:
other: Skin irritant Category 2
Remarks:
according to Regulation (EC) No 1272/2008 and its amendments.
Conclusions:
The substance was tested in a skin irritation study. Based on the results, the substance is considered to be a skin irritant.
Executive summary:

The substance was tested in a skin irritation study, equivalent to OECD TG 404. Six rabbits were exposed to the substance for 24 hours (instead of the normal 4h). Individual erythema scores for each animal were 4, 3 and 3 for t= 24, 48 and 72 hours respectively. Individual edema scores for animal #1 were 4, 3 and 3 for t=24, 48 and 72 hours respectively, and individual edema scores for animal #2, #3, #4, #5 and #6 were 3, 3 and 3 for t=24, 48 and 72 hours respectively. This resulted in a mean erythema score of 3.3 in all animals and a mean edema score of 3.3 and 3 for animal #1 and animals #2, #3, #4, #5 and #6 respectively (average of scores at 24, 48 and 72 hours). These effects had fully reversed within 7 days. A defatting effect was observed: skin sloughed off in ten to fourteen days, and no in depth injuries were observed. Based on these results, the substance is considered to be a skin irritant.

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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
Study period:
January 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Reliability has been presented as 2 because a protocol similar to OECD Guideline has been followed but pre-GLP.
Qualifier:
equivalent or similar to
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:
No further info on test animals and enivronmental conditions were provided.
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: animal #1
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: animal #2
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: animal #3
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: animal #4
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: animal #5
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: animal #6
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: animal #1
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: animal #2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: animal #3
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: animal #4
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: animal #5
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: animal #6
Irritation parameter:
conjunctivae score
Remarks:
redness, similar to chemosis
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.83
Max. score:
3.5
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: animal #1
Remarks:
No discrimination could be made between redness and chemosis.
Irritation parameter:
conjunctivae score
Remarks:
redness, similar to chemosis
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.17
Max. score:
3.5
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: animal #2
Remarks:
No discrimination could be made between redness and chemosis.
Irritation parameter:
conjunctivae score
Remarks:
redness, similar to chemosis
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.83
Max. score:
3.5
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: animal #3
Remarks:
No discrimination could be made between redness and chemosis.
Irritation parameter:
conjunctivae score
Remarks:
redness, similar to chemosis
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
3.5
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: animal #4
Remarks:
No discrimination could be made between redness and chemosis.
Irritation parameter:
conjunctivae score
Remarks:
redness, similar to chemosis
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.67
Max. score:
3.5
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: animal #5
Remarks:
No discrimination could be made between redness and chemosis.
Irritation parameter:
conjunctivae score
Remarks:
redness, similar to chemosis
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.67
Max. score:
3.5
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: animal #6
Remarks:
No discrimination could be made between redness and chemosis.
Irritation parameter:
chemosis score
Remarks:
chemosis, similar to redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.83
Max. score:
3.5
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: animal #1
Remarks:
No discrimination could be made between redness and chemosis.
Irritation parameter:
chemosis score
Remarks:
chemosis, similar to redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.17
Max. score:
3.5
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: animal #2
Remarks:
No discrimination could be made between redness and chemosis.
Irritation parameter:
chemosis score
Remarks:
chemosis, similar to redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.83
Max. score:
3.5
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: animal #3
Remarks:
No discrimination could be made between redness and chemosis.
Irritation parameter:
chemosis score
Remarks:
chemosis, similar to redness
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
3.5
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: animal #4
Remarks:
No discrimination could be made between redness and chemosis.
Irritation parameter:
chemosis score
Remarks:
chemosis, similar to redness
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.67
Max. score:
3.5
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: animal #5
Remarks:
No discrimination could be made between redness and chemosis.
Irritation parameter:
chemosis score
Remarks:
chemosis, similar to redness
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.67
Max. score:
3.5
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: animal #6
Remarks:
No discrimination could be made between redness and chemosis.
Irritant / corrosive response data:
For individual eye irritation scores as presented in the report, see table 1 in Any other information on results incl. tables.
Observations were as follows at different time points:
Immediate: slight discomfort
10 minutes: moderate erythema, copious discharge
1 hour: severe erythema, slight edema, copious discharge
24 hours: areas of barely percetible to slight corneal cloudiness, iris reaction to light was sluggish in three instances, slight to moderate erythema, very slight edema, copious discharge containing whitish exudate.
48-72 hours: gradual improvement
120 hours: all animals scored 0

FHSA method seems to make use of a modified Draize method. As in the report following is presented: mean score (x/110) and the maximum score in the Draize scoring system is also 110 it is assumed that this scoring system has been used. Though the scores used in the study are different from CLP criteria, the scores are recalculated resulting in the values presented in table 2, under Any other information on result incl. tables.

Tabel 1 Individual eye irritation scores

Animal

No.

1 hours

24 hours

48 hours

72 hours

120 hours

168 hours

C

I

CJ

C

I

CJ

C

I

CJ

C

I

CJ

C

I

CJ

C

I

CJ

1

0

0

16

10

5

12

5

0

6

0

0

4

0

0

0

0

0

0

2

0

0

16

20

5

12

10

5

8

5

0

6

0

0

0

0

0

0

3

0

0

16

10

0

12

5

0

6

0

0

4

0

0

0

0

0

0

4

0

0

16

20

5

12

10

0

8

5

0

4

0

0

0

0

0

0

5

0

0

16

10

0

10

5

0

6

5

0

4

0

0

0

0

0

0

6

0

0

16

10

0

12

5

0

6

5

0

2

0

0

0

0

0

0

Mean

16.0

27.5

14.1

7.3

0.0

0.0

C = Cornea
I = Iris
CJ = Conjunctivae

Table 2: Recalculated scores

Animal no.

Cornea

Cornea

Cornea

Cornea

Iris

Iris

Iris

Iris

Conjunctiva

Conjunctiva

Conjunctiva

Conjunctiva

 

24h

48h

72h

Average (24, 48, 72)

24h

48h

72h

Average (24, 48, 72)

24h

48h

72h

Average (24, 48, 72)

1

2

1

0

1

1

0

0

0.33

3

1.5

1

1.83

2

4

2

1

2.33

1

1

0

0.67

3

2

1.5

2.17

3

2

1

0

1

0

0

0

0

3

1.5

1

1.83

4

4

2

1

2.33

1

0

0

0.33

3

2

1

2

5

2

1

1

1.33

0

0

0

0

2.5

1.5

1

1.67

6

2

1

1

1.33

0

0

0

0

3

1.5

0.5

1.67

Draize uses following caluclations:

Cornea = Opacity score x Area score x 5

Iris = Iris score x 5

Conjunctiva = (Redness score + Chemosis score + Discharge score) x 2

Based on the Draize calculations, cornea and iris values as presented in Table 1 are divided by 5 to recalculate the scores to be used under CLP. Conjunctiva scores are divided by 2 and though 3 effects are included in the Draize score (Redness, Chemosis and Discharge) the values are further divided by 2 considering two effects (Redness and Chemosis) and thus being conservative.

Interpretation of results:
other: Eye irritant, Category 2
Remarks:
According to Regulation (EC) No 1272/2008 and its amendments.
Conclusions:
Based on the results of this study the test substance is considered to be an eye irritant.
Executive summary:

The substance was tested in an eye irritation study equivalent to OECD TG 405. Six rabbits were exposed to the substance for 24 hours. Observations were made for 7 days. Mean irritation scores for cornea, iris and conjunctivae combined were 16.0, 27.5, 14.1 and 7.3 at respectively t=1, 24, 48 and 72 hours after application of the substance. This resulted in a mean overall irritation score (24, 48, 72 h) of 16.3. As the scores presented in the study are different form CLP criteria, the scores are recalculated per animal for cornea, iris and conjunctiva (average 24, 48 and 72h) resulting in the following scores: for cornea 1, 2.33, 1, 2.33, 1.33, and 1.33, for iris 0.33, 0.67, 0, 0.33, 0 and 0 and for conjunctiva 1.83, 2.17, 1.83, 2, 1.67 and 1.67 for animal 1, 2, 3, 4, 5 and 6 respectively. All adverse effects were fully reversed within 5 days. Based on these results, the substance is considered an eye irritant.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation:

The substance was tested in a skin irritation study, equivalent to OECD TG 404. Six rabbits were exposed to the substance for 24 hours (instead of the normal 4h). Individual erythema scores for each animal were 4, 3 and 3 for t= 24, 48 and 72 hours respectively. Individual edema scores for animal #1 were 4, 3 and 3 for t=24, 48 and 72 hours respectively, and individual edema scores for animal #2, #3, #4, #5 and #6 were 3, 3 and 3 for t=24, 48 and 72 hours respectively. This resulted in a mean erythema score of 3.3 in all animals and a mean edema score of 3.3 and 3 for animal #1 and animals #2, #3, #4, #5 and #6 respectively (average of scores at 24, 48 and 72 hours). These effects had fully reversed within 7 days. A defatting effect was observed: skin sloughed off in ten to fourteen days, and no in depth injuries were observed. Based on these results, the substance is considered to be a skin irritant.

Eye irritation:

The substance was tested in an eye irritation study equivalent to OECD TG 405. Six rabbits were exposed to the substance for 24 hours. Observations were made for 7 days. Mean irritation scores for cornea, iris and conjunctivae combined were 16.0, 27.5, 14.1 and 7.3 at respectively t=1, 24, 48 and 72 hours after application of the substance. This resulted in a mean overall irritation score (24, 48, 72 h) of 16.3. As the scores presented in the study are different form CLP criteria, the scores are recalculated per animal for cornea, iris and conjunctiva (average 24, 48 and 72h) resulting in the following scores: for cornea 1, 2.33, 1, 2.33, 1.33, and 1.33, for iris 0.33, 0.67, 0, 0.33, 0 and 0 and for conjunctiva 1.83, 2.17, 1.83, 2, 1.67 and 1.67 for animal 1, 2, 3, 4, 5 and 6 respectively. All adverse effects were fully reversed within 5 days. Based on these results, the substance is considered an eye irritant.

Justification for classification or non-classification

Based on the results of an in vivo skin irritation study and an in vivo eye irritation study, the substance is classified Category 2 for both skin irritation and eye irritation, H315: Causes skin irritation and H319: Causes serious eye irritation, according to EU CLP (EC No. 1272 /2008 and its amendments).

For GHS the substance needs to be classified as Category 2B mildly irritating to eyes, H320: Causes eye irritation.