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Description of key information

Skin irritation and skin corrostion of the test substance was tested employing an artificial human skin model as test subject, according to the OECD test guidelines 439 and 431, employing exposure times of 20 minutes(OECD 439) and 3 minutes or 1 hour (OECD 431), respectively. 
Eye irritation/corrosion of the test substance was tested employing an in-vivo test using rabbits as test subjects, according to the OECD test guideline 405, employing exposure time of 24 hours.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
other: Human Skin Model
Strain:
other: EST-1000 (CellSystems® Biotechnology GmbH)
Details on test animals or test system and environmental conditions:
TEST ANIMALS
No test animals used, In-vitro test

ENVIRONMENTAL CONDITIONS
n/a

Type of coverage:
other: as specified in guidelines
Preparation of test site:
other: as specified in guidelines
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30 µL IPETC were applied to the skin model with a surface area of 0.6 cm2
- Concentration (if solution): 95.7

VEHICLE
- Amount(s) applied (volume or weight with unit): no vehicle used
Duration of treatment / exposure:
20 minutes
Observation period:
n/a
Number of animals:
n/a
Details on study design:
Negative control: phosphate buffered saline (D-PBS)
Positive control: 5% aqueous sodium dodecyl sulphate (SDS)
Irritation / corrosion parameter:
other: other: Percent Viability of cells exposed to test item
Value:
ca. 10.2
Remarks on result:
other:
Remarks:
Basis: mean Mean of 3 tissue sample responces in percent. Time point: 20 minutes. Max. score: 2.8. Reversibility: other: Not tested. Remarks: This is an in-vitro test with other irritation parameters than a traditional in-vivo test. (migrated information)
Irritant / corrosive response data:
Summarized results (Mean±SD):

Optical density 20 minutes
Extinction# (n=3 tissues) % Extinction compared to control

Negative kontrol(D-PBS) 0.459±0.008
IPETC (test substance) 0.047±0.039 10.2
Positive kontrol(SDS) 0.014±0.007 3.1
Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the present test conditions IPETC , tested at an exposure time of 20 minutes, was cytotoxic and, hence, irritant to skin in an experiment employing an artificial three-dimensional model of human skin.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
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
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: LPT Laboratory of Pharmacology and Toxicology GmbH & Co. KG branch Löhndorf, 24601 Löhndorf/Post Wankendorf, Germany
- Age at study initiation: 6.5-7.5 months
- Weight at study initiation: At dosing
Animal no. 1: 2.8 kg
Animal no. 2: 2.5 kg
Animal no. 3: 2.5 kg
At Termination of test
Animal no. 1: 2.8 kg
Animal no. 2: 2.6 kg
Animal no. 3: 2.5 kg

- Housing: Singly in 380mm*425mm*600mm cages
- Diet (e.g. ad libitum): ssniff ® K-H V2333 ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: minimum 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 h light / 12 h dark

IN-LIFE DATES: From: July 12, 2012 To: July 21, 2012
Vehicle:
unchanged (no vehicle)
Controls:
other: left eye served as control, right eye as test eye
Amount / concentration applied:
0.1 mL of the test item was administered into one eye each of three animals.
Duration of treatment / exposure:
24 hours after instillation the eyes were rinsed with 20 mL NaCl solution. For 8 hours following test item application, the animals were kept singly in restrain¬ers which allowed free movement of the head but prevented a complete body turn, wiping of the eyes with the paws and excluded irritation of the eye by excre¬ments and urine.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with NaCl solution
- Time after start of exposure: 24

SCORING SYSTEM:

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 hourss after dosing
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 72 Hours
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 hours after dosing
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
(redness, palpebra/bulbar conjunctivae; excl. cornea/iris)
Basis:
mean
Time point:
other: 60 minutes after dosing
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Remarks:
(swelling, refers to lids and/or nictitating membrane)
Basis:
mean
Time point:
other: 60 minutes after dosing
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Irritant / corrosive response data:
Under the present test conditions, a single instillation of 0.1 mL IPETC per animal into the conjunctival sac of the right eye of three rabbits caused the following changes:
Corneal opacity (grade 1) was observed in animal nos. one and three 24 and 48 hours after instillation.
The fluorescein test performed 24 hours after instillation revealed corneal staining in animal nos. 1 and 3 (up to 1/4 of the surface).
Irritation of the iris (grade 1) was observed in animal no. one 24 hours after instillation.
Conjunctival redness (grade 1) was observed in all animals 60 minutes and in animal nos. 1 and 3 up to 24 hours after instillation.
Chemosis (grade 1) was observed in all animals 60 minutes after instillation.
There were no systemic intolerance reactions.
All symtoms were fully reversible within 72 hours after exposure.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the present test conditions, under the criteria set up in EC-Commission directive 67/548/EEC and EC-Regulation 1272/2008, the test item is concluded to be non-irritating to eyes
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

All three tests (Skin irritation, OECD 439, Skin corrosion, OECD 431 and Eye irritation/corrosion OECD 405) demonstrated adverse effect upon exposure to the test substance. These effects were all irritative in nature, not corrosive and at least for the in-vivo test mere minor and temporary in nature., all symptomps done within 72 hours after exposure.


Justification for selection of skin irritation / corrosion endpoint:
Two studies were made on the skin irritative/corrosive properties of this substance, one irritation study following the OECD guideline 439 and one irritation study following the OECD guideline 431, both studies employing an artificial human skin model as test subject. Both studies showed demostrated the adverse effects of the test substance on the artificial human skin, but the corrosivity study not enough effect to classify as corrosive. The irritation study did show suficient effect to classify the substance as irritative in category 2 according to the CLP classification criteria. The corrosive study, does not give grounds for classification of the test substance as an irritant, thus redenring the irritation study the only of the 2 tests to have given grounds for classification.

Justification for selection of eye irritation endpoint:
Only endpoint study available

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

The skin irritation test (OECD 439) was the only of the 3 performed skin/eye irritation/corrosion tests that produced sufficient effects equivalent to the classification criteria that justifies classification of the substance as irritating to skin in category 2, in accordance with Regulation (EC) No 1272/2008 (CLP).

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