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:
key study
Study period:
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:
OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)
Version / remarks:
18 June, 2019
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous

In vitro test system

Test system:
human skin model
Remarks:
EPISKIN SM™
Source species:
human
Details on animal used as source of test system:
The EPISKIN-SMTM tissues are provided as kits (SkinEthic), consisting of the following components relevant for this study:
1x EPISKIN-SM™ plate containing 12 reconstructed epidermis units (area: 0.38 cm2); each reconstructed epidermis is attached to the base of a tissue culture insert with an O-ring set and maintained on nutritive agar for transport (Lot: 19-EKIN-046 for main experiment, 19-EKIN-041 for killed tissue controls)
1x 12-well assay plate
1x flask of sterile maintenance medium (basic medium for incubations, Lot: 19MAIN3052)
1x flask of sterile assay medium (basic medium for use in MTT assays, Lot: 19ESSC048)
Validity controls as provided by the supplier (SkinEthic):
Vehicle:
unchanged (no vehicle)
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Duration of treatment / exposure:
3min, 60min, 4h
Number of replicates:
2

Results and discussion

In vitro

Resultsopen allclose all
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
3min
Value:
81.2
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
60min
Value:
75.4
Negative controls validity:
other: not relevant
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
4h
Value:
30.6
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Other effects / acceptance of results:
The test item showed non-specific MTT-reducing potential. Therefore, additional killed tissue controls were treated with the test item to determine the non-specific reduction of MTT (NSMTT) and the results were corrected to the true MTT metabolic conversion (TODTT). The test item showed no water-colouring potential.
The controls confirmed the validity of the study. The mean OD570 of the two negative control tissues was between 0.6 and 1.5 for each exposure period, excepted for the 60 minute time point (1,651). This do not influence the outcome of the test because the corrosivity was shown with the 4 hours’ time point and the outcome of the test would not change. The mean relative tissue viability (% negative control) of the positive control was  20% (3.2%) after 4 h treatment. The maximum inter tissue viability difference of replicate tissues of all dose groups was  30% (0.1% - 25.3%).

Applicant's summary and conclusion

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
In this study under the given conditions the test item showed corrosive effects. The relative mean tissue viability after 4 h treatment was decreased below 35%. Additionally, the relative mean tissue viability was decreased to not more than 35% after 60 min treatment. The test item is therefore classified as “corrosive“ in accordance with a combination of optional sub-categories 1B and 1C.
Executive summary:

In the present study the skin corrosivity potential of cyclic Glucamide C8-C10 was analysed. Since corrosive chemicals are cytotoxic after a short time exposure to the stratum corneum of the epidermis the cytotoxic effects of the test item on EPISKIN-SM™, a reconstituted three-dimensional human epidermis model, were determined. Hereby, the test item was applied topically. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT after a 3 min, 60 minand 4 hexposure period and compared to those of the concurrent negative controls.

The test item showed non-specific MTT-reducing potential. Therefore, additional killed tissue controls were treated with the test item to determine the non-specific reduction of MTT (NSMTT) and the results were corrected to the true MTT metabolic conversion (TODTT). The test item showed no water-colouring potential.

The test item showed corrosive effects. The mean relative tissue viability (% negative control) was reduced below 35% (30.6%, NSMTT-corrected) after 4 h treatment and to not more than 35% (75.4%, NSMTT-corrected) after 60 min treatment. Relative mean tissue viability was reduced to 81.2%, NSMTT-correctedafter 3 min treatment.

The controls confirmed the validity of the study. The mean OD570of the two negative control tissues was between 0.6 and 1.5 for each exposure period, excepted for the 60 minute time point (1,651). This do not influence the outcome of the test because the corrosivity was shown with the 4 hours’ time point and the outcome of the test would not change. The mean relative tissue viability (% negative control) of the positive control was£ 20% (3.2%) after 4 h treatment. The maximum inter tissue viability difference of replicate tissues of all dose groups was£ 30% (0.1% - 25.3%).

In this study under the given conditions the test item showed corrosive effects. The relative mean tissue viability after 4 h treatment was decreased below 35%. Additionally, the relative mean tissue viability was decreased to not more than35%after 60 min treatment. The test item is therefore classified as “corrosive“ in accordance witha combination of optional sub-categories 1B and 1C.