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Description of key information

The registered substance was not irritant in in-vivo skin and eye irritation studies


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Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: 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:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 28 JUN 2006 to 13 JUL 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD TG 404)
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Netherlands BV, Horst, The Netherlands
- Age at study initiation: 11-12 weeks
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet (batch no. 24/06; provided by Provimi Kliba AG, CH-4303 Kaiseraugst); ad libitum
- Water: Community tap water from Füllinsdorf, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g/animal
VEHICLE
- Amount applied: 0.5 mL/animal
Duration of treatment / exposure:
4 h
Observation period:
10 days
Number of animals:
3 (1 male, 2 females)
Details on study design:
TEST SITE
- Area of exposure: 4 cm x 4 cm

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

SCORING SYSTEM:
Grading of Skin Reactions according to COMMISSION DIRECTIVE 2004/73/EC, APRIL 29, 2004
ERYTHEMA AND ESCHAR FORMATION
No erythema................................................................................................0
Very slight erythema..................................................................................1
Well-defined erythema...............................................................................2
Moderate to severe erythema...................................................................3
Severe erythema (beef 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 mm).........................3
Severe oedema (raised more than 1 mm and extending
beyond the area of exposure)....................................................................4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritant / corrosive response data:
individual animal data 1h / 24h / 48h / 72h / 7 days / 10 days after removal of patch for animal #1-#3 :

erythema: 0/0/0/0/0/0, 1/0/0/0/0/0, 1/0/0/0/0/0

edema: 0/0/0/0/0/0, 0/0/0/0/0/0, 0/0/0/0/0/0
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item did not reveal any remarkable irritation potential on the skin of rabbits, tested in this study according to OECD test guideline no. 404 and GLP conditions.
Executive summary:

The primary skin irritation potential of the test item was investigated according to OECD test guideline no 404.The test item (0.5 g moistened with 0.5 ml purified water) was applied to the intact skin of three New Zealand White rabbits under semi-occlusive conditions for four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours as well as 7 and 10 days after removal of the test item.

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred. A light yellow staining was produced by the test item on the treated skin of the three rabbits. This persisted up to the 48-hour reading or up to day 7. A very slight erythema was noted in two animals at the 1-hour reading but was no longer present on the following day. Therefore, all scores are 0.

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

Eye irritation

Link to relevant study records

Referenceopen allclose all

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:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 12 JUL 2006 to 20 JUL 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD TG 405)
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: 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: Harlan Netherlands BV, Horst, The Netherlands
- Age at study initiation: 11-14 weeks
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet (batch no. 24/06; provided by Provimi Kliba AG, CH-4303 Kaiseraugst); ad libitum
- Water: Community tap water from Füllinsdorf, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
72 h (single application / treated eyes were not rinsed after instillation)
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3 (1 male, 2 females)
Details on study design:
SCORING SYSTEM:
Grading of Ocular Lesions according to COMMISSION DIRECTIVE 2004/73/EC, APRIL 29, 2004; comparable to Draize system

CORNEA
Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity.......................................................................................................0
Scattered or diffuse areas of opacity (other than slight dulling of normal
luster), details of iris clearly visible.....................................................................................1
Easily discernible translucent area, details of iris slightly obscured.............................2
Nacreous area, no details of iris visible, size of pupil barely discernible......................3
Opaque cornea, iris not discernible through the opacity................................................4

IRIS
Normal.....................................................................................................................................0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal
hyperemia, or injection, any of these or combination of any thereof, iris still
reacting to light (sluggish reaction is positive).................................................................1
No reaction to light, hemorrhage, gross destruction (any or all of these)...................2

CONJUNCTIVAE
Redness (refers to most severe reading of palpebral and bulbar conjunctivae
when compared with control eye)
Blood vessels normal..............................................................................................................0
Some blood vessels definitely hyperemic (injected)..........................................................1
Diffuse, crimson color, individual vessels not easily discernible....................................2
Diffuse beefy red......................................................................................................................3

Chemosis: lids and/or nictitating membranes
No swelling................................................................................................................................0
Any swelling above normal (including nictitating membranes)........................................1
Obvious swelling with partial eversion of lids.....................................................................2
Swelling with lids about half-closed......................................................................................3
Swelling with lids more than half-closed..............................................................................4

TOOL USED TO ASSESS SCORE:
Eye examinations were made with a Varta Cliptrix diagnostic-lamp (Roth AG, Reinach/Switzerland).
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: at the 1 hour reading very slight opacity affecting the whole area in 2 animals
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-48-72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility not applicable
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Time point:
other: mean of 24-48-72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Time point:
other: mean of 24-48-72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible
Remarks:
72 h
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Time point:
other: mean of 24-48-72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible
Remarks:
72 h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item did not reveal any remarkable irritation potential on the eyes of rabbits, tested in this study according to OECD test guideline no. 405 and GLP conditions.
Executive summary:

The test item was applied by instillation of 0.1 g into the left eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test item instillation. The instillation of the test item into the eye resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae. These effects were reversible and were no longer evident 72 houres after treatment, the end of the observation period for all animals. In two animals a slight corneal opacity affecting the whole area was noted at the 1-hour reading but was no longer present on the following day.

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.67, 0.67 and 0.33 for reddening and 0.00 for chemosis for all animals, respectively.

No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed and no clinical signs were observed.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

No classifiction


The testmaterial did not cause irritant effects on skin or eyes in vivo.