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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
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EC number: 230-241-9 | CAS number: 6976-93-8
- 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
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Endpoint summary
Administrative data
Link to relevant study record(s)
- Endpoint:
- dermal absorption
- Type of information:
- (Q)SAR
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
- Justification for type of information:
- 2. MODEL (incl. version number)
Potts and Guy prediction model
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
The physicochemical parameters of MW, Log P and saturated aqueous solubility have been used. An output of predicted steady-state flux has been calculated.
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
QSPeRs are statistically-derived linear and non-linear relationships between the steady-state permeability of a compound, usually measured from water, and various physicochemical descriptors and/or structural properties of the molecule. Typically, the main input parameter is the octanol:water partition coefficient. The dermal absorption measurement that has been most commonly used in QSAR modelling is the permeability coefficient Kp, because it characterises the steady-state permeation rate of a chemical from a specific vehicle through a given membrane. Although Kp is not directly suitable for application in risk assessment, it can be used in conjunction
with measured (or estimated) solubility in the same vehicle (e.g. water) to predict a maximum flux through the skin. Also, it can be combined in mathematical models with partition coefficient values for the skin to estimate non-steady state or finite dose absorption (IPCS, 2006). The prediction model used in this investigation for a set of methacrylate chemicals is based on an established model (Potts and Guy, 1992), using data derived with human epidermal membranes.
Categorisation is based upon the dermal absorption database developed at the laboratory between 1992 and 2012.
5. APPLICABILITY DOMAIN
no data
6. ADEQUACY OF THE RESULT
In a risk assessment context, QSPeRs are often used to identify chemicals that need further testing to define their likely dermal absorption potential in man more accurately. For example, if a new chemical belongs to a class of compounds known to be toxic, a simple QSPeR assessment may identify whether the risk is likely to be greater or less than the standards that already have sound in vitro or in vivo toxicological assessments. This wouldn’t necessarily negate further testing, but it can be very useful to reduce the number of compounds that require the more costly and time-consuming studies to establish the systemic exposure following dermal application. - Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The physicochemical parameters of MW, Log P and saturated aqueous solubility have been used in the evaluation of 56 methacrylate compounds. An output of predicted steady-state flux was calculated using the principles defined in the Potts and Guy prediction model. (Potts RO and Guy RH (1992). Predicting Skin Permeability. Pharm. Res. 9(5): 663- 669)
- GLP compliance:
- no
- Details on test animals or test system and environmental conditions:
- not applicable; in silico modelling
- Type of coverage:
- other: not applicable; in silico modelling
- No. of animals per group:
- not applicable; in silico modelling
- Absorption in different matrices:
- predicted flux: 1.366 µg/cm²/h; the relative dermal absorption is low
- Conclusions:
- The dermal absorption of MTMA is predicted to be low; the predicted flux is 1.366 µg/cm²/h.
- Executive summary:
The dermal absorption (steady-state flux) of MTMA has been estimated by calculation using the principles defined in the Potts and Guy prediction model.
Based on a molecular weight of 144.08 g/mol and a log Kow of 1.00, the predicted flux of MTMA is 1.366 µg/cm²/h; the relative dermal absorption is low.
Reference
Based on a molecular weight of 144.08 g/mol and a log Kow of 1.00, the predicted flux of MTMA is 1.366 µg/cm²/h; the relative dermal absorption is low.
Description of key information
MTMA is likely to be absorbed by all routes. The ester is rapidly hydrolysed by carboxylesterases to methacrylic acid (MAA) and Methoxyethanol. MAA is subsequently cleared rapidly from blood by standard physiological pathways, with the majority of the administered dose being exhaled as CO2. Methoxyethanol can be oxidised to the corresponding carboxylic acid and excreted via the urine.
Based on physicochemical properties, no potential for bioaccumulation is to be expected.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
- Absorption rate - oral (%):
- 50
- Absorption rate - dermal (%):
- 50
- Absorption rate - inhalation (%):
- 100
Additional information
Absorption
Oral absorption
The physicochemical properties of MTMA (log P = 1.3) and the molecular weight of 144.08 g/mol are in a range suggestive of absorption from the gastro-intestinal tract subsequent to oral ingestion.
For chemical safety assessment an oral absorption rate of 100% is assumed as a worst case default value in the absence of other data.
Dermal absorption
Based on a QSAR Prediction of Dermal Absorption (extract from Heylings JR, 2013) MTMA is predicted on the basis of their molecular weight and lipophilicity to have a relatively low ability to be absorbed through the skin. The predicted flux was1.366 μg/cm²/h.
However, for chemical safety assessment, a dermal absorption rate of 100% was assumed as worst case default value.
Inhalation absorption
Due to the low vapour pressure of MTMA (22.3 Pa at 20°C), exposure via inhalation is unlikely. For chemical safety assessment an inhalation absorption rate of 100% is assumed as a worst case default value in the absence of other data. By default, twice as high absorption is assumed compared to oral absorption in accordance with th eGuidance on Information Requirements and Chemical Safety Assessment, R8 (Extrapolation oral to inhalation: AF=2).
Distribution
As a small molecule a wide distribution can be expected. No information on potential target organs is available.
Metabolism and excretion
Ester hydrolysis is the primary step in the metabolism of methacrylate esters. The esters are rapidly hydrolysed by carboxylesterases.Those are a group of non-specific enzymes that are widely distributed throughout the body and are known to show high activity within many tissues and organs, including the liver, blood, GI tract, nasal epithelium and skin. Those organs and tissues that play an important role and/or contribute substantially to the primary metabolism of the short-chain, volatile, methacrylate esters are the tissues at the primary point of exposure, namely the nasal epithelia and the skin, and systemically, the liver and blood.
The alcohol, Methoxyethanol can be oxidised to Methoxyacetic acid and excreted via the urine (Mebus et al, 1992; Miller RR, 1987).
Methacrylic acid is subsequently cleared rapidly from blood and, as indicated by studies with MMA, this metabolism is by standard physiological pathways, with the majority of the administered dose being exhaled as CO2.
As the esters will not survive first pass metabolism in the liver, excretion of the parent compound is of no relevance.
Reference
Mebus CA et al. (1992) 2-methoxyethanol metabolism in pregnant CD-1 mice and embryos. Toxicol Appl Pharmacol, 112, 87-94
Miller RR (1987). Metabolism and distribution of glycol ethers. Drug Metab Rev, 18(1), 1-22
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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