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EC number: 688-147-2 | CAS number: 82428-30-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Skin irritation: irritating | Human Skin Model | OECD 439 |
Eye irritation: irritation score >3 - <55 | Bovine Corneas | OECD 437 |
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- 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
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
- Deviations:
- no
- 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 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
- 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. - 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".
Reference
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 %.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- April 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Species:
- other: Bovine Corneas
- Strain:
- other: not applicable
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- 750 µL
- Duration of treatment / exposure:
- 10 min
- Duration of post- treatment incubation (in vitro):
- - 2 h (opacity measurement)
- 3.5 h total (determination of optical density) - Number of animals or in vitro replicates:
- 3 corneas
- Details on study design:
- - 3 corneas for the test item
- 3 corneas as negative controls treated with physiological saline 0.9% NaCl
- 3 corneas as positive control treated with ethanol 100%
- The BCOP assay is considered to be valid if the in vitro irritation score obtained with the positive control falls within the two standard deviations of the current historical mean. - Irritation parameter:
- in vitro irritation score
- Run / experiment:
- mean test item
- Value:
- 10.16
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Remarks:
- IVIS 2.08
- Positive controls validity:
- valid
- Remarks:
- IVIS 86.02
- Interpretation of results:
- other: Irritation score of 10.16 and histopathological findings indicate slight signs of irritation
- Remarks:
- Criteria used for interpretation of results: BCOP standard evaluation criteria
- Conclusions:
- No prediction can be made regarding the classification of the test substance 3,4-Epoxycyclohexylmethyl methacrylate according to the evaluation criteria. Further testing in another suitable method is required.
Under the conditions of this study, 3,4-Epoxycyclohexylmethyl methacrylate caused indicators for irritation consisting of slight multifocal apoptosis/necrosis associated with multifocal vacuolation in the epithelium of all specimen. - Executive summary:
The eye irritancy potential of 3,4-Epoxycyclohexylmethyl methacrylate was investigated in the bovine corneal opacity and permeability assay.
- Preparation of the test item: tested as provided by the sponsor
- Mean in vitro irritation score: 10.16
- Classification: No prediction can be made
The in vitro irritation score obtained with the positive control fell within the two standard deviations of the current historical mean and therefore this assay is considered to be valid.
Reference
RESULTS
Cornea No. | Test Item | Corr. Opacity | Corr. OD490 | IVIS |
1 | Neg. Control | 0.00 | 0.027 | |
2 | Neg. Control | 4.00 | 0.021 | |
3 | Neg. Control | 1.00 | 0.035 | |
mean | Neg. Control | 1.67 | 0.028 | 2.08 |
4 | Pos. Control | 50.33 | 1.919 | |
5 | Pos. Control | 64.33 | 2.053 | |
6 | Pos. Control | 53.33 | 2.031 | |
mean | Pos. Control | 56.00 | 2.001 | 86.02 |
7 | Test Item | 13.33 | -0.001 | |
8 | Test Item | 9.33 | -0.022 | |
9 | Test Item | 8.33 | -0.012 | |
mean | Test Item | 10.33 | -0.011 | 10.16 |
The following mean in vitro irritation score was calculated: 10.16
No prediction can be made regarding the classification of the test substance 3,4-Epoxycyclohexylmethyl methacrylate according to the evaluation criteria. Further testing in another suitable method is required.
The in vitro irritation score obtained with the positive control fell within the two standard deviations of the current historical mean and therefore this assay is considered to be valid.
HISTOPATHOLOGY
Negative control samples did not show any histological lesions.
In positive control samples, the main lesions consisted of vacuolated corneal epithelia and single cell apoptosis. In one sample (PK1), there was a marked epithelial flattening/height reduction associated with a focal chronic injury. This corneal sample is deemed to be affected before study start by an inflammatory/degenerative that is supported by the presence of brownish pigment (hemosiderin). In sample PK 3, there was a slight laceration of the cuboidal basal cell layer.
In test item treated samples, there was slight multifocal apoptosis/necrosis in the epithelium of all specimens.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin irritation
In a two- step procedure (top- down approach), 3,4-epoxycyclohexylmethyl methacrylate was tested in vitro for skin corrosion and skin irritation. The first test, an OECD TG 431 study (GLP, Klimisch 1), revealed no corrosive potential of the test item. According to the second test, an OECD TG 439 (GLP, Klimisch 1), 3,4-epoxycyclohexylmethyl methacrylate has to be classified as irritant (GHS Skin Irrit. 2). Further information on the skin irritation potential can be obtained from the LLNA study conducted with mice. In this test, topical application of undiluted 3,4- epoxycyclohexylmethyl methacrylate led only to slight signs of irritation.
Eye Irritation
As first step, data available for structural homologues to 3,4-epoxycyclohexylmethyl methacrylate were evaluated. Both 1,2-epoxycyclohexane and methacrylic acid represent structural elements which are also contained in 3,4-epoxycyclohexylmethyl methacrylate. They are considered to be corrosive substances which in consequence bear also an eye damaging potential. The same conclusion was drawn for 2,3-epoxypropyl methacrylate, which contains glycidol instead of epoxycyclohexanol as alcoholic component. However, a corrosive potential did not become evident in the case of 3,4-epoxycyclohexylmethyl methacrylate on the basis of in vitro tests on skin irritation/corrosion and measurements of the skin irritation potential in the LLNA. Therefore, a conclusion to structural homologues with regard to irritating/corrosive effects seemed not to be appropriate. Nevertheless, the evidence from structural homologues supported the decision for a top-down approach to evaluate the eye irritation potential of 3,4-epoxycyclohexylmethyl methacrylate.
The BCOP was chosen as test system, since an OECD guideline is available for this method, and furthermore it addresses membrane lysis, which is the proposed mode of action for esters such as 3,4-epoxycyclohexylmethyl methacrylate (Scott, 2010). As an epoxide function is contained in the molecule as well, which is expected to induce actions on macromolecules, additional histological examinations were included in the BCOP test (Scott, 2010). The BCOP test was conducted according to OECD TG 437 (GLP, Klimisch 1). As result, an in vitro eye irritation score of 10.16 was obtained. Thus, the substance falls into the range of >3- <55 for which no prediction is possible. However, the histopathological examination revealed indications for irritation, consisting of slight multifocal apoptosis/necrosis associated with multifocal vacuolation in the epithelium of all specimen. The occurrence of these effects, which point to a low depth of injury, make it likely that 3,4- epoxycyclohexylmethyl methacrylate should be classified as eye irritant (GHS category 2). As no in vitro test has been validated for the identification of GHS category 2 eye irritants so far, further in vitro testing could not contribute to a better prediction and was therefore omitted at this stage.
Reference:
Scott, 2010. Scott, L., Eskes, C., Hoffmann, S., Adriaens, E.,
Alépée, N., Bufo, M., Clothier, R., Facchini, D., Faller, C., Guest, R.,
Harbell, J., Hartung, T., Kamp, H., Le Varlet, B., Meloni, M., McNamee,
P., Osborne, R., Pape, W., Pfannenbecker, U., Prinsen, M., Seaman, C.,
Spielman, H., Stokes, W., Trouba, K., Van den Berghe, C., Van Goethem,
F., Vassallo, M., Vinardell, P., and Zuang, V. (2010). A proposed eye
irritation testing strategy to reduce and replace in vivo studies using
Bottom- Up and Top- Down approaches. Toxicol. in Vitro 24:1- 9.
Effects on skin
irritation/corrosion: irritating
Effects on eye irritation: slightly irritating
Justification for classification or non-classification
The available data suggest a skin and eye irritation potential. Therefore, 3,4-epoxycyclohexylmethyl methacrylate has to be classified accordingly with "Skin Irrit. 2, H315; Eye Irrit. 2, H319 under the CLP regulation (Regulation (EC) 1272/2008).
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