Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 221-950-4 | CAS number: 3290-92-4
- 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
![](https://echa.europa.eu./o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Endpoint summary
Administrative data
Link to relevant study record(s)
- Endpoint:
- basic toxicokinetics, other
- Remarks:
- G.I. human passive 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 (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source
- Objective of study:
- absorption
- Guideline:
- other: REACH Guidance on QSARs R.6
- Principles of method if other than guideline:
- Model to predict either high or low fraction absorbed for an orally administered, passively transported substance on the basis of a new absorption parameter. The model includes only two inputs: the octanol-water partition coefficient (Kow) and the dimensionless oversaturation number (OLumen). The latter is the ratio of the concentration of drug delivered to the gastro-intestinal (GI) fluid to the solubility of the compound in that environment.
- Specific details on test material used for the study:
- SMILE = C(=O)(C(=C)C)OCC(CC)(COC(=O)C(=C)C)COC(=O)C(=C)C
- Species:
- other: Human
- Route of administration:
- oral: unspecified
- Type:
- absorption
- Results:
- Absorption from gastrointestinal tract for 1 mg dose: 100%
- Type:
- absorption
- Results:
- Absorption from gastrointestinal tract for 1000 mg dose: 90%
- Conclusions:
- According to the Danish QSAR database, the oral absorption of TMPTMA is between 100% and 95%.
- Endpoint:
- basic toxicokinetics, other
- Remarks:
- in silico
- Type of information:
- (Q)SAR
- Adequacy of study:
- other information
- 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 adequate and reliable documentation / justification
- Justification for type of information:
- See enclosed files
- Objective of study:
- absorption
- distribution
- excretion
- metabolism
- Qualifier:
- according to guideline
- Guideline:
- other: REACH Guidance on QSARs R.6
- Qualifier:
- according to guideline
- Guideline:
- other: REACH Guidance on IR&CSA, Chapter R.14, Occupational exposure assessment Update to change the scope of the guidance from exposure estimation to exposure assessment
- Version / remarks:
- August 2016
- Principles of method if other than guideline:
- pkCSM uses graph-based signatures to develop predictive models of central ADME properties. pkCSM performs as well or better than current methods.
- Specific details on test material used for the study:
- SMILE: O=C(OCC(CC)(COC(=O)C(=C)C)COC(=O)C(=C)C)C(=C)C
- Radiolabelling:
- no
- Type:
- absorption
- Results:
- Intestinal absorption (human): 98%
- Type:
- distribution
- Results:
- VDss (human) (log L/kg): -0.22
- Type:
- distribution
- Results:
- Fraction unbound (human) : 0.436
- Type:
- distribution
- Results:
- BBB permeability (log BB): -0.815
- Type:
- distribution
- Results:
- CNS permeability (log PS): -2.889
- Type:
- excretion
- Results:
- Total Clearance (log ml/min/kg): 1.259
- Type:
- excretion
- Results:
- Renal OCT2 substrate: no
- Details on absorption:
- According to the model "Intestinal absorption (human)", 98% of the substance is absorbed after oral exposure.
- Details on distribution in tissues:
- According to the model "VDss (human)", the volume of distribution (VD, i.e. theoritical volume that the total dose of a drug would need to be uniformly distributed to give the same concentration as in blood plasma) is low (Log below -0.15).
According to the model "Fraction unbound (human)", 43.6% of the absorbed dose is unbound in the plasma.
According to the model "BBB permeability", the substance is poorly distributed to the brain (Log BB near to -1).
According to the model "CNS permeability", it is not possible to predict if the substance is unable or not to penetrate the CNS (-3 - Details on excretion:
- According to the model "Renal OCT2 substrate", the substance is not a OCT2 substrate. The substance is not transported by this renal transporter.
According to the model "Total clearance" , the predicted total clearance (hepatic & renal clearance) is of 18 ml/min/kg (log(ml/min/kg) 1.245) corresponding to the high clearance (between 14 and 30 ml/min/kg). - Metabolites identified:
- not measured
- Details on metabolites:
- the substance is not likely to be metabolized by either P450 cytochrome, and not likely going to be a cytochrome P450 inhibitor.
- Conclusions:
- According to the model Intestinal absorption (human) from pkCSM (QSAR), 98% of the substance is absorbed after oral exposure.
According to the different models in pkCSM QSAR, 43.6% of the absorbed dose could be unbound in the plasma, and the substance is predicted to be poorly distributed into the brain; a high total clearance (hepatic & renal clearance) is predicted. - Endpoint:
- dermal absorption, other
- Remarks:
- Mathematical simulation
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source
- Guideline:
- other: REACH Guidance on QSARs R.6
- Principles of method if other than guideline:
- IH SkinPerm mathematical tool for estimating dermal absorption
- Time point:
- 8 h
- Dose:
- 100
- Parameter:
- percentage
- Absorption:
- 0 %
- Conclusions:
- According to the IH skin perm (QSAR), the dermal absorption of TMPTMA is low (<10%).
Referenceopen allclose all
Description of key information
There were no studies available in which the toxicokinetic properties of TMPTMA were investigated. However, as per REACH guidance document R7.C, information on absorption, distribution, metabolism and excretion may be deduced from the physicochemical properties and QSAR predictions.
Based on the available data, high oral and inhalation absorption are predicted, but low dermal absorption.²
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
- Absorption rate - oral (%):
- 100
- Absorption rate - dermal (%):
- 10
- Absorption rate - inhalation (%):
- 100
Additional information
No experimental toxicokinetic study is available on TMPTMA. However, as per REACH guidance document R7.C, information on absorption, distribution, metabolism and excretion may be deduced from the physicochemical properties and QSAR predictions.
The key physico-chemical parameters taken into accound for toxicokinetics assessment are the following:
-Mean molecular weight: 338 g/mol
-Water solubility: 20 mg/L
-Partition coefficient Log Kow: 4.19
-Vapour pressure: 0.003 Pa (20°C)
ABSORPTION
The high values of log Kow and the low water solubility are not favourable for oral absorption.
According to the Danish QSAR database, the oral absorption of TMPTMA is between 95 and 100%. According to the model Intestinal absorption (human) from pkCSM (QSAR), 98% of the substance is absorbed after oral exposure.
However, no systemic effects were observed after one single (2000 mg/kg), but adverse effects were observed in the oral 90d repeated administration at 1000 mg/kg in rats.
An oral absorption of 100% is taken into account for risk assessment.
The Log Kow > 4, the low solubility in water are not favourable to a high dermal absorption. However, the methacrylates are known to bind to skin components, and this binding decreases their dermal absorption.
According to the IH SkinPerm (QSAR), the dermal absorption of TMPTMA is estimated to be low (< 10%).
The low dermal absorption can be confirmed in the dermal acute toxicity study, where no systemic effect or mortality was observed in rats treated with 2000 mg/kg bw, and TMPTMA is not a skin sensitizer.
A dermal absorption of 10% is taken into account for risk assessment.
Based on the low value of the vapour pressure (<0.01 Pa), TMPTMA is not a volatile substance.
An absorption of 100% after inhalation exposure is taken into account for risk assessment.
DISTRIBUTION
No specific data is available on the distribution of TMPTMA.
According to the different models in pkCSM QSAR, 43.6% of the absorbed dose could be unbound in the plasma, and the substance is predicted to be poorly distributed into the brain.
METABOLISM
No specific data is available on the metabolism of TMPTMA.
According to the pkCSM prediction (QSAR), the substance is not likely to be metabolized by either P450 cytochrome, and not likely going to be a cytochrome P450 inhibitor.
Hydrolysis calculation concluded the half-life of the substance at 25° C was 6.89 years at pH8 and 68.88 years at pH7.
ELIMINATION
Due to the low water solubility and a moderate molecular mass (between 200 and 1000 g/mol), the excretion of TMPTMA in the urines is not expected. An excretion via bile and faeces is possible.
According to the pkCSM prediction (QSAR), a high total clearance (hepatic & renal clearance) is predicted for TMPTMA.
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.
![ECHA](/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/echa_logo.png)