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Administrative data

Description of key information

- skin irritation: in 6 New Zealand rabbits, exposure of 2.5 cm x 2.5 cm skin to the test susbstance for 24 h, guideline study, non-GLP; 24/72h reading: erythema score >= 4.0

- eye irritation: in 6 New Zealand rabbits, 100µL instilled into the conjunctival sac, guideline study, non-GLP; reading time points 24/48/72h after treatment; moderate to severe effects on the eye, effect were mostly not reversible within 8 days

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to guideline
Guideline:
other: CFR, title 16, section 1500.41
GLP compliance:
no
Remarks:
study conducted prior to implementation of GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Lippische Versuchstierzucht, Extertal 1
- Weight at study initiation: 2.6 kg (average)
- Housing: each animal in separate cage
- Diet (e.g. ad libitum): mümmel z (sniff / Soest), ad libitum
- Water: ad libitum
- Acclimation period: 7-14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-18°C
- Humidity (%): 40% r.h.
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
occlusive
Preparation of test site:
other: shaved (left flank); shaved and scarified (right flank)
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 500 µL of liquid test substance Aktivator MO
Duration of treatment / exposure:
24 hours
Observation period:
30 min after end of exposure (24h) as well as 48 h (not reported in table of results) and 72 h after start of exposure, control observation on day 8 (not considered for scoring).
Number of animals:
6 males
Details on study design:
TEST SITE
- Area of exposure: 2.5x2.5cm on 8x8cm skin
- Type of wrap if used: double layer of substance saturated surgical dressing, covered with PVC-film, fixed with Leukoflex and wrapped with elastic bandage.

OBSERVATION TIME POINTS
24/48/72 hours, control observation on day 8
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
>= 0
Max. score:
4
Reversibility:
not specified
Remarks on result:
other:
Remarks:
grey/brown staining, later dry corrosion scab
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
>= 0
Max. score:
4
Reversibility:
not specified
Remarks on result:
other:
Remarks:
not scored
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
>= 0
Max. score:
4
Reversibility:
not specified
Remarks on result:
other:
Remarks:
grey/brown staining, later dry corrosion scab
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
>= 0
Max. score:
4
Reversibility:
not specified
Remarks on result:
other:
Remarks:
grey/brown staining, later dry corrosion scab
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Score:
>= 0
Max. score:
4
Reversibility:
not specified
Remarks on result:
other:
Remarks:
not scored
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
>= 0
Max. score:
4
Reversibility:
not specified
Remarks on result:
other:
Remarks:
grey/brown staining, later dry corrosion scab
Irritant / corrosive response data:
grey/brown staining within 24 hours, first with soft and later hard and dry corrosion scab
Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
The test substance was corrosive in the in vivo skin irritation test under the experimental conditions described in this report.
Executive summary:

In a primary dermal irritation study performed in accordance with the Code of Federal Regulations, Title 16, Section 1500.41, adult male albino rabbits (strain New Zealand White) were dermally exposed to 500 µL of the test substance for 24 hours to 6.25-64 cm² body surface area. Animals then were observed for 8 days. Irritation could not be scored due to corrosive effects.

Corrosion occurred during the observation period.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Skin Corr. 1 (H314: Causes severe skin burns and eye damage) is justified.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

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:
guideline study without detailed documentation
Qualifier:
according to guideline
Guideline:
other: CFR, title 16, section 1500.42
GLP compliance:
no
Remarks:
study conducted prior to implementation of GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Lippische Versuchstierzucht, Extertal 1
- Weight at study initiation: 2.6 kg (average)
- Housing: each animal in separate cage
- Diet (e.g. ad libitum): mümmel z (sniff / Soest), ad libitum
- Water: ad libitum
- Acclimation period: 7-14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-18°C
- Humidity (%): 40% r.h.
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 100 µL
Duration of treatment / exposure:
not applicable (eye was not rinsed after treatment)
Observation period (in vivo):
24/48/72 hours as well as 8 days after start of treatment.
Number of animals or in vitro replicates:
6 males
Details on study design:
SCORING SYSTEM:
Scoring according to "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, FDA, 1959, p.51".

TOOL USED TO ASSESS SCORE: ophthalmoscope 24/48/72 hours (fluorescein after 8 days; not considered for scoring)
Irritation parameter:
cornea opacity score
Basis:
animal: #1-#3,#6
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 48 hrs
Irritation parameter:
cornea opacity score
Basis:
animal: #4,#5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal: #1-#6
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.67
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal: #2,#4
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
not fully reversible within: 48 hrs
Irritation parameter:
conjunctivae score
Basis:
animal: #3,#5,#6
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal: #1,#2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3.33
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
not reversible
Irritant / corrosive response data:
Irritation effects were observed in all animals and at all irritation parameters. No effect was fully reversible and most effects were not reversible at all. Opthalmoscopic fluorescine observations on eyes rinsed with NaCl 8 days after treatment showed worsen cornea opacity score of 3.33 (average of animals #1-#6).

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

24 h

 2/2/2/1/1/2

 1/1/1/1/1/1

 2/3/2/3/2/2

 2/2/2/3/3/2

48 h

 1/1/1/1/1/1

 1/1/1/1/1/1

 3/2/2/2/2/2

 2/2/3/3/3/3

72 h

 1/1/1/1/1/1

 1/1/1/1/1/1

 3/2/2/2/2/2

 2/2/3/3/4/2

Average 24h, 48h, 72h

 1.33/1.33/1.33/1/1/1.33

 1/1/1/1/1/1

 2.67/2.33/2/2.33/2/2

 2/2/2.67/3/3.33/2.33

Reversibility*)

 n.c./n.c./n.c./n./n./n.c.

n./n./n./n./n./n.

 n./n.c./n./n.c./n./n.

 n./n./n./n./n./n.

Average time (unit) for reversion

 48 hrs

 --

 --

 --

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
In this study, the test substance showed irreversible effects on the eyes.
Executive summary:

In a primary eye irritation study performed in accordance with the Code of Federal Regulations, Title 16, Section 1500.42 (Test for eye irritants), the test substance was instilled into the right eye’s conjunctival sac of adult male albino rabbits (strain New Zealand White) followed by lid close for 1 second. The treated eyes were not washed after treatment. The left untreated eyes served as controls.

Animals then were observed for 8 days with score relevant observations being carried out at 24/48/72 hours after treatment.  Irritation was scored by the method described in “The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, FDA, 1959, p.51”.

Irritation effects were observed in all animals and at all irritation parameters. No effect was fully reversible and most effects were not reversible at all. Opthalmoscopic fluorescine observations on eyes rinsed with NaCl 8 days after treatment showed worsen cornea opacity score of 3.33 (average of animals #1-#6). In this study, the test substance is a strong eye irritant (GHS Cat 1).

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Eye Damage 1 (H318: Causes serious eye damage) is justified.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Skin irritation

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Skin Corr. 1 (H314: Causes severe skin burns and eye damage) is justified.

Eye irritation

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Eye Damage 1 (H318: Causes serious eye damage) is justified.

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