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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March - April 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Deviations:
no
Qualifier:
according to
Guideline:
other: ISO 10993-10 Annex D: 2010 "Biological evaluation of medical devices - Part 10"
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name: 3,4-Epoxycyclohexylmethyl methacrylate
- Chemical Name: 2-Propenoic acid, 2-methyl-7-oxabicyclo[4.1.0]hept-3-ylmethyl ester
- CAS No.: 82428-30-6
- Physical State / Colour: liquid / light yellow, transparent
- Density: 1.079 g/mL at 20 °C
- Molecular Weight: 196.2 g/mol

In vitro test system

Test system:
human skin model
Remarks:
EPISKIN-SM (SkinEthic) (TM)
Source species:
human
Cell type:
non-transformed keratinocytes
Cell source:
other: normal (non-cancerous), adult human-derived epidermal keratinocytes (NHEK)
Source strain:
not specified
Vehicle:
unchanged (no vehicle)
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
10 µL (26.3 µL/cm2) direct application of undiluted test item atop the EPISKIN-SM (TM) tissue.
Duration of treatment / exposure:
15 min
Duration of post-treatment incubation (if applicable):
42 h
Number of replicates:
3

Results and discussion

In vitro

Results
Irritation / corrosion parameter:
% tissue viability
Remarks:
mean
Run / experiment:
test item 15 min treatment
Value:
11
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Remarks:
100.0
Positive controls validity:
valid
Remarks:
14.0
Other effects / acceptance of results:
The mixture of 10 µL test item per 2 mL MTT medium showed no reduction of MTT compared to the solvent. The mixture did not turn blue/purple.
The mixture of 10 µL of the test item per 90 µL aqua dest. showed no colouring detectable by unaided eye-assessment.

Any other information on results incl. tables

TEST RESULTS

The test item showed irritant effects. The mean relative tissue viability (% negative control) was <= 50 % (11 %) after 15 min treatment and 42 h post incubation.

The controls confirmed the validity of the study. The mean OD550 of the six blank values was< 0.1. The mean absolute OD550 of the three negative control tissues was >= 0.6 and <= 1.5. The mean relative tissue viability (% negative control) of the positive control was <= 40 % (14%). The maximum standard deviation of viability of replicate tissues of all dose groups was < 18 % (2.4 % - 11.0 %).

Negative Control

Positive Control

Test Item

mean OD550 (3 tissues)

1.057 *

0.148

0.117

SD OD550

0.104

0.029

0.051

mean relative tissue viability [%]

100.0

14.0 **

11.0

SD tissue viability [%] ***

11.0

2.4

5.4

CV [% viability]

11.0

17.0

48.6

* Corrected mean OD550 of the negative control corresponds to 100 % absolute tissue viability.

** Mean relative tissue viability of the 3 positive control tissues is <= 40 %.

*** The standard deviation (SD) obtained from the three concurrently tested tissues is < 18 %.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
In this study under the given conditions the test item showed irritant effects. The test item is therefore classified as "irritant" in accordance with UN GHS "Category 2".
Executive summary:

SUMMARY

In the present study the skin irritant potential of 3,4-Epoxycyclohexylmethyl methacrylate was analysed. The EPISKIN-Standard Model (EPISKIN-SM (TM)), a reconstituted three-dimensional human epidermis model, was used as a replacement for the Draize Skin Irritation Test (OECD TG 404) to distinguish between UN GHS "Category 2" skin irritating test substances and not categorized test substances ("No Category") which may be considered as non-irritant. 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 15 min exposure and 42 h post incubation period and compared to those of the concurrent negative controls.

In this study under the given conditions the test item showed irritant effects. The relative mean tissue viability after 15 min of exposure and 42 h post incubation was <= 50 %. The test item is therefore classified as "irritant" in accordance with UN GHS "Category 2".