Registration Dossier

Administrative data

Description of key information

Skin irritation was tested in a guideline study according to OECD guideline 404 in rabbits. 24 hours up to three days after treatment, the skin did not show any sign of erythema or edema. Mean scores on all observation time points after application were 0 for the three animals.
Hostanox SE 10 was tested for its eye irritant properties in 3 New Zealand White rabbits.The study was performed according to OECD Guideline 405. Mild effects were observed in all animals 24, 48 and 72 hours after application. Swelling of the lids and redness of the conjunctiva and iris was observed one hour after application. These symptoms were reduced at 24 to 48 hours and disappeared by 7 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
Study period:
6 Apr - 9 Apr 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline conform GLP study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Chemisch pharmazeutische Fabrik, Dr. Karl Thomae GmbH, Biberach, Germany
- Age at study initiation: 3-5 months
- Weight at study initiation: 2.8-3.0 kg
- Housing: in fully air-conditioned rooms, separate cages (arranged in a battery)
- Diet (e.g. ad libitum): Altromin 2123 maintenance diet - rabbits (Altromin GmbH, Lage/Lippe), ad libitum and hay (approx. 15 g daily)
- Water (e.g. ad libitum): deionised, chlorinated water from automatic water dispenser, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18+/-3°C
- Humidity (%): 55+/-20%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 06.04.1993 To: 09.04.1993
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: PEG 400
Controls:
not required
Amount / concentration applied:
500 mg
Duration of treatment / exposure:
4 h
Then test substance was removed from the skin with warm tap water.
Observation period:
30 - 60 min. after removal of the patches
24, 48 and 72 hrs after removal of the patches
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: 100%
The moistened substance was applied over the whole surface of a 2.5 x 2.5 cm cellulose patch on a piece of surgical plaster (specially produced by Beiersdorf AG, Hamburg). The plaster was fixed to the prepared skinarea (ca. 25 cm2) and then covered with a semi-occlusive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with warm tap water
- Time after start of exposure: 4 h

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) to slight eschar formation (lesion in depth).........4

Oedema
No oedema...................................................................................................................................0
very slight oedema (barely perceptible)..................................................................................1
slight oedema (edges of area well defined by definite raising)............................................2
moderate oedema (raised approximately 1mm)....................................................................3
severe oedema (raised more than 1mm and extending beyond area of exposure.........4
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
No erthema/edema recorded
Other effects:
No
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No edema or erythema were recorded after 4 h exposure of 500 mg Hostanox SE to rabbit skin. Therefore, the test substance is considered to be not irritating.
Executive summary:

Skin irritation was tested in a guideline study according to OECD guideline 404 in rabbits. 24 hours up to three days after treatment, the skin did not show any sign of erythema or edema. Mean scores on all observation time points after application were 0 for the three animals.

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:
20 Apr - 4 May 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD Guideline 405 and in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Chemisch pharmazeutsche Fabrik Dr. Karl Thomae GmbH, Biberach, Germany
- Age at study initiation: 3-5 months
- Weight at study initiation: 3.3-3.6 kg
- Housing: n fully air-conditioned rooms, separate cages (arranged in a battery)
- Diet (e.g. ad libitum): Altromin 2123 maintenance diet - rabbits (Altromin GmbH, Lage/Lippe), ad libitum and hay (approx. 15 g daily)
- Water (e.g. ad libitum): deionised, chlorinated water from automatic water dispenser, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/-3°C
- Humidity (%): 55+/-20%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 20.04.1993 To: 04.05.1993
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
100 mg
Duration of treatment / exposure:
24 h
Observation period (in vivo):
The eyes were examined 1, 24, 48 and 72 hours, 7 days after application of the test substance.
At 24 and 72 hours the eyes were also examined for corneal lesions under UV light after instillation of one drop of 0.01 % fluorescein-sodium solution. Lesions in cornea, iris or conjunctivae were graded numerically.
Number of animals or in vitro replicates:
3
Details on study design:
24 hours after application and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein-sodium solution took place, the treated eyes were washed out thoroughly with physiological saline at approx. 37 °C.


SCORING SYSTEM:

CORNEA
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 invisible ..................................................................................................4

Affected area (Opactiy and fluorescein-test)
0 = no translucence
1 = punctiform up to 1/4
2 = more than 1/4 up to 1/2
3 = more than 1/2 up to 3/4
4 = more than 3/4 up t o 4/4

IRIS
Normal ......................................................................................................................... 0
Folds above normal , congestion, swelling, circumcorneal injection (any of 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


CONJUNCTIVAE

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

Chemosi s (refers to palpebral and bulbar conjunctivae)
No swelling .........................................................................................0
Any swelling above normal (includes nictitating membran) ..... 1
Obvious swelling with partial eversion of l i d s ...........................2
Swelling with lids about half closed ................................................3
Swelling with lids half closed to completely closed.......................4
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.1
Max. score:
4
Reversibility:
fully reversible
Remarks:
48 h
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.1
Max. score:
2
Reversibility:
fully reversible within: 48 h
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
1.2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
Swelling of the lids and redness of the conjunctiva and iris was observed one hour after application. These symptoms were reduced at 24 to 48 hours and dissappeared by 7 days.
The test substance is not considered irritating.

Swelling of the lids and redness of the conjunctiva and iris was observed one hour after application. These symptoms were reduced at 24 to 48 hours and dissappeared by 7 days. The test substance is not considered irritating.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
With reference the reported scores (reversibility of effects) Hostanox SE 10 does not have to be classified as irritant to the eyes according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).
Executive summary:

Hostanox SE 10 was tested for its eye irritant properties in 3 New Zealand White rabbits.The study was performed according to OECD Guideline 405. Mild effects were observed in all animals 24, 48 and 72 hours after application. Swelling of the lids and redness of the conjunctiva and iris was observed one hour after application. These symptoms were reduced at 24 to 48 hours and disappeared by 7 days.

With reference the reported scores (reversibility of effects) Hostanox SE 10 does not have to be classified as irritant to the eyes according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation: 1 key study available: not irritating

Eye irritation: 1 key study available: not irritating

 

There is one reliable study on the skin irritancy potential. Skin irritation was tested in a guideline study according to OECD guideline 404 in 3 New Zealand White rabbits. 24 hours up to three days after treatment, the skin did not show any sign of erythema or edema. Mean scores on all observation time points after application were 0 for the three animals.

There is one reliable study available on the eye irritancy potential. Dioctadecyl disulphide was tested for its eye irritant properties in 3 New Zealand White. This study was performed according to OECD Guideline 405. Mild effects were observed in all animals 24, 48 and 72 hours after application. Swelling of the lids and redness of the conjunctiva and iris was observed one hour after application. These symptoms were reduced at 24 to 48 hours and disappeared by 7 days.


Justification for selection of skin irritation / corrosion endpoint:
Guideline conform GLP study

Justification for selection of eye irritation endpoint:
The study was conducted according to OECD Guideline 405 and in compliance with GLP.

Justification for classification or non-classification

With reference the reported scoresDioctadecyl disulphidehas not to be classified as irritant to the skin according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

With reference the reported scores (reversibility of effects) Dioctadecyl disulphide does not have to be classified as irritant to the eyes according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).