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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 29 January 2019 to 6 February 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
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:
OECD Test Guideline 431 (reconstructed human epidermis
(RHE) Test Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
4,4’-isopropylidenediphenol, reaction products with 1-chloro-2,3-epoxypropane, mono, di and triesters with acrylic acid
EC Number:
948-054-2
Molecular formula:
not applicable - the substance is an UVCB
IUPAC Name:
4,4’-isopropylidenediphenol, reaction products with 1-chloro-2,3-epoxypropane, mono, di and triesters with acrylic acid
Test material form:
liquid

In vitro test system

Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Details on animal used as source of test system:
N/A
Justification for test system used:
The EpiDerm TM skin model and assay for skin corrosion testing is endorsed by OECD TG 431.
Vehicle:
unchanged (no vehicle)
Details on test system:
RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiDermTM (EPI-200) Reconstructed Human Epidermis
- Tissue batch number(s): 28682
- Delivery date: 05/02/2019
- Date of initiation of testing: 05/02/2019

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37°C

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: not specified
- Incubation time: pre-incubated at 37°C for 1 hour
- Spectrophotometer: BMG LabTech FluoStar Optima
- Wavelength: 570 nm (no reference filter)

FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: 2.049 ± 0.023 OD. PASS.
- Barrier function: 5.3hrs. PASS.
- Morphology: 12 layers present, 101.2 µm tissue thickness. PASS.
- Contamination: No contamination. PASS.

NUMBER OF REPLICATE TISSUES: n=3

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
- Prior to the assay, the test item was checked for interference (water colouration or MTT interference) and found not to interfere.

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 3

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered to be corrosive to skin if the viability after 3 minutes exposure is less than 50%, or if the viability after 3 minutes exposure is greater than or equal to 50 % and the viability after 1 hour exposure is less than 15%.
- Justification for the selection of the cut-off point(s) if different than recommended in TG 430: In accordance with TG 431.
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25 mg
- Concentration (if solution): neat
- Application: push-pin applicator

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 50 µl
- Concentration (if solution): neat

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 50 µl
- Concentration (if solution): 8.0N
Duration of treatment / exposure:
3 and 60 minutes
Number of replicates:
3

Results and discussion

In vitro

Resultsopen allclose all
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
3 minutes
Value:
111.3
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
60 minutes
Value:
95.24
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Other effects / acceptance of results:
- OTHER EFFECTS:
- Colour interference with MTT: Checked, no interference.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: mean OD570 must be >0.8. - PASSED
- Acceptance criteria met for positive control: mean of the positive control relative percentage viability, after 1hour exposure must be < 15% of the mean of the negative control. - PASSED
- Acceptance criteria met for variability between replicate measurements: In the range between 20% and 100% viability, the coefficient of variation (CV) is an additional acceptance criterion. It should not exceed 0.3 (30%). - PASSED

Any other information on results incl. tables

see attached background documents.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
4,4’-isopropylidenediphenol, reaction products with 1-chloro-2,3-epoxypropane, mono, di and triesters with acrylic acid was evaluated for skin corrosion. The substance did not meet the criteria for classification as corrosive to the skin.
Executive summary:

A GLP-compliant in-vitro skin corrosion study was carried out on 4,4’-isopropylidenediphenol, reaction products with 1-chloro-2,3-epoxypropane, mono, di and triesters with acrylic acid using the EpiDermTM Reconstructed Human Epidermis (RHE) tissue model. The study was performed following OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test). The aim of the test was establish whether 4,4’-isopropylidenediphenol, reaction products with 1-chloro-2,3-epoxypropane, mono, di and triesters with acrylic acid has or does not have a corrosive effect on skin, and to what extent. This was done for the purposes of providing a rational basis for a risk assessment.

A single topical application of 25mg of neat test item and 50µl of each reference item were applied to the surface of the EpiDermTM skin models using push-pin applicators. This was left for 3 and 60 minutes under the following conditions: 37°C, 5% CO2, ≥95% Relative Humidity. Three tissues were used per condition.

The results were that the mean tissue viability of the reconstructed human epidermis remained above 50% at 3 minutes (111.30%) and 15% at 60 minutes (95.24%). The substance did not meet the criteria for classification as corrosive to the skin in accordance with Regulation (EC) No.1272/2008.