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Description of key information

The substance was tested for its skin irritant properties using the three-dimensional human skin model Episkin-SM. The study was performed according to OECD Guideline 439. 10 mg of the test item and 5 µL distilled water were applied topically for 15 minutes. After 42 h post-incubation cytotoxic effects were determined via MTT reduction assay. The mean relative tissue viability (% negative control) was > 50%. The test item is therefore classified as "non-irritant" (EU CLP and UN GHS: No Category).
The substance was tested for its eye irritant properties in 3 New Zealand White rabbits.The study was performed according to OECD Guideline 405. Effects on conjunctivae (redness and swelling) were observed in all animals one hour after application. These signs decreased significantly within 72 hours and were fully reversible within 7 days. According to the findings in this study the substance does not meet the criteria for classification laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion
Remarks:
other: in vitro
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well performed guideline study according to GLP.
Qualifier:
according to guideline
Guideline:
other: EU Method B.46 (Skin Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
other: EpiSkin reconstructed human epidermis model (SkinEthic Laboratories)
Details on test animals or test system and environmental conditions:
organotypic reconstructed three-dimensional model of the human epidermis
Type of coverage:
other: direct application
Controls:
other: three tissues for negative control (10µL PBS) and positive control (10µL 5% SDS)
Amount / concentration applied:
10 mg + 5 µL aqua dest
Duration of treatment / exposure:
15 minutes
Observation period:
42 +/- 1 h
Number of animals:
three replicate tissues per dose group
Details on study design:
3 replicate tissues are dosed with the test item, the negative control (PBS) and the positive control (5% SDS), respectively. After 15 minutes treatment period at room temperature the test item and the controls are rinsed off with PBS and the tissues are post-incubated for 42 +/- 1 h. Then the tissues are stained via MTT for 3 hours. Isopropanol extracts are measured photometrically at 550 nm.
Irritation parameter:
other: mean relative tissue viability
Basis:
other: mean tissue viability of the negative control tissues
Time point:
other: 15 min treatment 42 h post-incubation
Score:
102
Max. score:
100
Remarks on result:
other: non-irritant; EU CLP and UN GHS: No Category
Irritant / corrosive response data:
If mean tissue viability is > 50% relative to the mean negative control, the test item is classified as non-irritant (EU CLP and UN GHS: No Category).
If mean tissue viability is <= 50% relative to the mean negative control, the test item is classified as irritant (EU CLP and UN GHS: Category 2).
In the in vitro skin irritation test using the EpiSkin human epidermis model 10 mg test item + 5 µL A. dest. were applied topically for 15 minutes. After 42 h post-incubation cytotoxic effects were determined via MTT reduction assay.
The mean relative tissue viability (% negative control) was > 50%.
The test item is therefore classified as "non-irritant" (EU CLP and UN GHS: No Category).
Other effects:
The test item showed no direct MTT reducing capability and no colouring potential.
Interpretation of results:
not classified
Remarks:
Migrated information non irritant Criteria used for interpretation of results: EU
Conclusions:
The substance is classified as "non-irritant" (No Category).
Executive summary:

The potential of the substance to induce skin irritation was analysed by using the three-dimensional human skin model EPISKIN-SM. In this study under the given conditions the substance showed no irritant effects. The substance is therefore classified as "non-irritant" in accordance with UN GHS and EU CLP "No Category".

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:
2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant guideline study
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
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK
- Age at study initiation: 12 -20 weeks
- Weight at study initiation: 2.26 -2.65 kg
- Housing: individually in suspended cages
- Diet (e.g. ad libitum): 2930C Teklad Global Rabbit diet (Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23°C
- Humidity (%): 30 -70%
- Air changes (per hr): at least 15/h
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2. 12. To: 16.12.2013
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (volume) which weighs approx. 67 mg

Duration of treatment / exposure:
eye were not rinsed
Observation period (in vivo):
1 hour post application
24 hours post application
48 hours post application
72 hours post application
7 days post application
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done

SCORING SYSTEM:

A. 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, ulzeration ..............................................................................4

Area of Cornea involoved (most dense area used)
One quarter (or less) but not zero.............................................................................1
Greater than one quarter but less than half............................................................ 2
Greater than half but less than three quarters........................................................3
Greter than three quarters, up to whole area..........................................................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
A. Redness
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

B. 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

C. Discharge
No discharge...............................................................................................................................0
Any discharge above normal....................................................................................................1
Discharge with moistening of the lids and hairs just adjacent to lids................................2
Discharge with moistening of the lids and hairs a considerable area around the eye....3


TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
No corneal effects were noted during the study. Iridial inflammation was noted in two treated eyes one hour after treatment. Moderate conjunctival irritation was noted in all treated eyes one hour after treatment. Moderate conjunctival irritation was noted in two treated eyes and minimal conjunctival irritation was noted in one treated eye at the 24-hour observation. Moderate conjunctival irritation was noted in one treated eye with minimal conjunctival irritation noted in two treated eyes at the 48-hour observation. Minimal conjunctival irritation was also noted in two treated eyes at the 72-hour observation.
One treated eye appeared normal at the 72-hour observation and two treated eyey appeared normal at the 7-day observation.
No corrosive effects were noted during the study. The test item did not induce significant or irreversible damage to the rabbit eye.
Other effects:
No clinical signs of toxicity were noted during the study. All animals showed expected gain in body weight during the study.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the findings in this study the substance does not meet the criteria for classification laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).
Executive summary:

The substance was tested for its eye irritant properties in 3 New Zealand White rabbits. The study was performed according to OECD Guideline 405. Effects on conjunctivae (redness and swelling) were observed in all animals one hour after application. These signs decreased significantly within 72 hours and were fully reversible within 7 days.

According to the findings in this study the substance does not meet the criteria for classification laid down 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, 1 supporting study available: not corrosive

Eye irritation: 1 key study available: not irritating, 1 supporting study available: mildly irritating

 

There is one fully reliable study available on the skin irritancy potential. The substance was tested for its skin irritant properties using the three-dimensional human skin model Episkin-SM. The study was performed according to OECD Guideline 439. 10 mg of the test item and 5 µL distilled water were applied topically for 15 minutes. After 42 h post-incubation cytotoxic effects were determined via MTT reduction assay. The mean relative tissue viability (% negative control) was > 50%. The test item is therefore classified as "non-irritant" (EU CLP and UN GHS: No Category). In an additionally performed skin corrosivity assay using the Epiderm model (according to OECD Guideline 431) the substance proved to be non corrosive.

There is one fully reliable study available on the eye irritancy potential. The substance was tested for its eye irritant properties in 3 New Zealand White rabbits. The study was performed according to OECD Guideline 405. Effects on conjunctivae (redness and swelling) were observed in all animals one hour after application. These signs decreased significantly within 72 hours and were fully reversible within 7 days.
The eye irritancy potential of the substance was also investigated in the bovine corneal opacity and permeability in vitro assay. The substance was classified as mild irritant due to its mean in vitro score of 16.65.


Justification for selection of skin irritation / corrosion endpoint:
Well performed guideline study in accordance with GLP.

Justification for selection of eye irritation endpoint:
Well performed guideline study in accordance with GLP.

Justification for classification or non-classification

With reference to the reported results of an in vitro skin irritation study and an in vitro skin corrosion study the substance has not to be classified as irritant to the skin according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

With reference the reported scores and the reversibility of the observed effects the substance does not have to be classified as irritant to the eyes according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).