Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
April 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019
Report date:
2019

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)
Version / remarks:
Jul 2016 version
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
3a,4,7,7a-tetrahydro-1H-indene
EC Number:
221-260-3
EC Name:
3a,4,7,7a-tetrahydro-1H-indene
Cas Number:
3048-65-5
Molecular formula:
C9H12
IUPAC Name:
3a,4,7,7a-tetrahydro-1H-indene
Constituent 2
Chemical structure
Reference substance name:
4-vinylcyclohexene
EC Number:
202-848-9
EC Name:
4-vinylcyclohexene
Cas Number:
100-40-3
Molecular formula:
C8H12
IUPAC Name:
4-vinylcyclohexene
Constituent 3
Chemical structure
Reference substance name:
Cyclopentadiene
EC Number:
208-835-4
EC Name:
Cyclopentadiene
Cas Number:
542-92-7
Molecular formula:
C5H6
IUPAC Name:
cyclopenta-1,3-diene
Constituent 4
Chemical structure
Reference substance name:
cis-1,2-Divinylcyclobutane
Cas Number:
2422-85-7
Molecular formula:
C8H12
IUPAC Name:
cis-1,2-Divinylcyclobutane
Constituent 5
Chemical structure
Reference substance name:
Ethylbenzene
EC Number:
202-849-4
EC Name:
Ethylbenzene
Cas Number:
100-41-4
Molecular formula:
C8H10
IUPAC Name:
ethylbenzene
Constituent 6
Chemical structure
Reference substance name:
5-vinylnorborn-2-ene
EC Number:
221-259-8
EC Name:
5-vinylnorborn-2-ene
Cas Number:
3048-64-4
Molecular formula:
C9H12
IUPAC Name:
5-vinylbicyclo[2.2.1]hept-2-ene
Constituent 7
Chemical structure
Reference substance name:
Cycloocta-1,5-diene
EC Number:
203-907-1
EC Name:
Cycloocta-1,5-diene
Cas Number:
111-78-4
Molecular formula:
C8H12
IUPAC Name:
cycloocta-1,5-diene
Constituent 8
Chemical structure
Reference substance name:
3a,4,7,7a-tetrahydro-4,7-methanoindene
EC Number:
201-052-9
EC Name:
3a,4,7,7a-tetrahydro-4,7-methanoindene
Cas Number:
77-73-6
Molecular formula:
C10H12
IUPAC Name:
3a,4,7,7a-tetrahydro-4,7-methanoindene,
Constituent 9
Chemical structure
Reference substance name:
3a,4,7,7a-tetrahydro-4-methyl-1H-indene
EC Number:
231-021-5
EC Name:
3a,4,7,7a-tetrahydro-4-methyl-1H-indene
Cas Number:
7413-02-7
Molecular formula:
C10H14
IUPAC Name:
4-methyl-3a,4,7,7a-tetrahydro-1H-indene
impurity 1
Chemical structure
Reference substance name:
Combination of: 6-(cyclohex-3-en-1-yl)bicyclo[2.2.1]hept-2-ene 2-vinyl-1,2,3,4,4a,5,8,8a-octahydro-1,4-methanonaphthalene 6-vinyl-1,4,4a,5,6,7,8,8a-octahydro-1,4-methanonaphthalene 2-vinyl-1,2,3,4,4a,5,8,8a-octahydro-1,4:5,8-dimethanonaphthalene 2,2'-bi(bicyclo[2.2.1]heptane-5,5'-diene) 3a,4,4a,5,8,8a,9,9a-octahydro-1H-5,8-methanocyclopenta[b]naphthalene 4,4a,4b,5,8,8a,9,9a-octahydro-1H-1,4-methanofluorene
Molecular formula:
C13H18 to C14H18
IUPAC Name:
Combination of: 6-(cyclohex-3-en-1-yl)bicyclo[2.2.1]hept-2-ene 2-vinyl-1,2,3,4,4a,5,8,8a-octahydro-1,4-methanonaphthalene 6-vinyl-1,4,4a,5,6,7,8,8a-octahydro-1,4-methanonaphthalene 2-vinyl-1,2,3,4,4a,5,8,8a-octahydro-1,4:5,8-dimethanonaphthalene 2,2'-bi(bicyclo[2.2.1]heptane-5,5'-diene) 3a,4,4a,5,8,8a,9,9a-octahydro-1H-5,8-methanocyclopenta[b]naphthalene 4,4a,4b,5,8,8a,9,9a-octahydro-1H-1,4-methanofluorene
Constituent 10
Chemical structure
Reference substance name:
4,4a,4b,5,8,8a,9,9a-octahydro-1H-1,4-methanofluorene OR 4,4a,4b,5,8,8a,9,9a-octahydro-1H-1,4:5,8-dimethanofluorene
Molecular formula:
C14H18 to C15H18
IUPAC Name:
4,4a,4b,5,8,8a,9,9a-octahydro-1H-1,4-methanofluorene OR 4,4a,4b,5,8,8a,9,9a-octahydro-1H-1,4:5,8-dimethanofluorene
Constituent 11
Chemical structure
Reference substance name:
3a,4,4a,5,8,8a,9,9a-octahydro-4,9:5,8-dimethano-1H-benz[f]indene
EC Number:
230-512-1
EC Name:
3a,4,4a,5,8,8a,9,9a-octahydro-4,9:5,8-dimethano-1H-benz[f]indene
Cas Number:
7158-25-0
Molecular formula:
C15H18
IUPAC Name:
3a,4,4a,5,8,8a,9,9a-octahydro-1H-4,9:5,8-dimethanocyclopenta[b]naphthalene
Constituent 12
Reference substance name:
Tetramers of cyclopentadiene and 1,3-butadiene
Molecular formula:
C16H24 to C20H24
IUPAC Name:
Tetramers of cyclopentadiene and 1,3-butadiene
Test material form:
liquid
Details on test material:
Light brown liquid.
Batch number 776809

In vitro test system

Test system:
human skin model
Source species:
human
Cell type:
other: epithelial
Cell source:
other: not specified
Vehicle:
unchanged (no vehicle)
Details on test system:
RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: Epiderm
- Tissue batch number(s): 28691
- Assay medium lot number: 040419MSC
- Delivery date: 9/4/19
- Date of initiation of testing: 10/4/19

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: Pre-incubation for 1hr at 37C (5% CO2)
- Temperature of post-treatment incubation (if applicable): 7C (5% CO2)

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: each tissue well rinsed with continuous stream of Dulbecco's phosphate bufffered saline for 40 seconds.
- Modifications to validated SOP: none required

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1mg/mL
- Incubation time: 3 hr
- Spectrophotometer: Labtech LT-2500 microplate reader
- Wavelength: 580nm
- Filter bandwidth: 10nm

NUMBER OF REPLICATE TISSUES: duplicate

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
- killed tissues
- Procedure used to prepare the killed tissues (if applicable): freezing
- N. of replicates : 2
- Method of calculation used: not required

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered to be non-corrosive to skin if the viability after 3 minutes exposure is greater than or equal to 50% and the viability after 1 hour exposure is greater than or equal to 15%.] The corrosivity potential of the test item is predicted from the relative mean tissue viabilities obtained after the 3 and 60-Minute exposure periods, compared to the mean of the negative control tissues (n=2) treated with sterile distilled water.
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50µL

VEHICLE
- None

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 50µL

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 50µL
- Concentration (if solution): 8N
Duration of treatment / exposure:
3 mins and 60 mins
Duration of post-treatment incubation (if applicable):
3 hours
Number of replicates:
2

Results and discussion

In vitro

Resultsopen allclose all
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
#1
Value:
ca. 92
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
#2
Value:
ca. 89.5
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system:
- Direct-MTT reduction:
- Colour interference with MTT:

DEMONSTRATION OF TECHNICAL PROFICIENCY:

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: viability 100%. Mean OD570 1.867 for 3 minute exposure and 1.933 for 60min exposure.
- Acceptance criteria met for positive control: 3min viability 3.7% and OD570 0.07 and 60min viabilty 3.5% and OD570 0.068.
- Acceptance criteria met for variability between replicate measurements: Yes
- Range of historical values if different from the ones specified in the test guideline: no information available in study report.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Executive summary:

In a guideline and GLP in vitro skin corrosivity study using the reconstructed human epidermis (EPIDERM) technique, the substance THI-TM was found to be non-corrosive. Classification is therefore not required for this end point.