2-Propenoic acid, 2-methyl-, 7-oxabicyclo[4.1.0]hept-3-ylmethyl ester

Skin irritation / corrosion

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: ISO 10993-10 Annex D: 2010 "Biological evaluation of medical devices - Part 10"

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

{7-oxabicyclo[4.1.0]heptan-3-yl}methyl 2-methylprop-2-enoate

EC Number:

688-147-2

Cas Number:

82428-30-6

Molecular formula:

C11 H16 O3

IUPAC Name:

{7-oxabicyclo[4.1.0]heptan-3-yl}methyl 2-methylprop-2-enoate

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".