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Diss Factsheets
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EC number: 952-791-5 | CAS number: -
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics, other
- Remarks:
- Physiologically-based pharmacokinetic (PBPK) modeling
- Type of information:
- calculation (if not (Q)SAR)
- Adequacy of study:
- key study
- Study period:
- March - April 2023
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- accepted calculation method
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 023
- Report date:
- 2023
Materials and methods
- Objective of study:
- absorption
- distribution
- toxicokinetics
- Principles of method if other than guideline:
- Physiologically Based Pharmacokinetic Models
The Simcyp Animal Simulator Version 22 Release 1 (Certara UK) was used for PBPK simulations (https://www.certara.com/software/simcyp-pbpk/ ). A whole body PBPK model, which allows for the addition of further specific organs, or a minimal PBPK model was used in simulations. (further details see attachment) - GLP compliance:
- no
Results and discussion
Main ADME results
- Type:
- absorption
- Results:
- see attachment results
Any other information on results incl. tables
In a first step a physiologically-based pharmacokinetic (PBPK) models for 2-ethylhexyl acrylate (2EHA) and 2-ethylhexanol (2EH) were developed in the rat. Tissue distribution was predicted using a mechanistic tissue composition method (Rodgers et al., 2005, Rodgers and Rowland 2006) (Simcyp method 2). The tissue distribution models were parameterised using estimates of the log of the octanol-water partition coefficient (LogP) and predicted values for fraction unbound (fu) and blood:plasma ratio (B/P). For 2EH, a minimal PBPK model was parameterised with a single adjusting compartment to capture the biphasic time course of the compound in blood and for 2EHA, a full body PBPK model was used.
Metabolism of 2EHA to 2EH was parameterised using in vitro metabolism data in rat liver microsomes and rat plasma. Clearance of total 2EH-related radioactivity was included in the model based on urinary and expired CO2-reported mass balance data after intravenous (IV) dosing. The developed 2EH PBPK model in the rat was able to show close agreement between observed and predicted plasma concentration-time data from orally administered 2EH (70.6 mg/kg body weight (BW)) when assuming administration as a solution with precipitation and first pass intestinal extraction (20%). Considering the high predicted permeability and observed high intrinsic solubility, predicted fraction absorbed (fa) was 1.00 and was insensitive to critical supersaturation ratio (CSR) and precipitation rate constant (PRC) values. The 2EH model was subsequently modelled as a primary metabolite of 2EHA following oral 2EHA administration (100 mg/kg BW). When simulated as a solution with precipitation, considering intrinsic solubility of 2EHA, the CSR of 10 and a PRC of 0.3 1/h were found to capture observed fa (approximately 0.90) in line with in vivo data.
The same assumptions of absorption model settings were applied to 7 chemically related acrylate esters with varying chain lengths, lipophilicity, solubility and physical states. Chemicals with a solid physical state at 20°C were assumed to be administered as a solid (requiring the compound to dissolve in the intestine before absorption can take place). Predicted fa ranged from 0.0001 to 1.00. In general, the larger compounds (chain length >14) with higher log octanol/buffer partition coefficient (LogPo:w) (>8), lower intrinsic solubility (<2x10-6 mg/mL) and a solid physical state at 20oC resulted in lower predicted fa values.
Predicted fa in rat for a series of chemically related acrylate esters with varying chain lengths.
Absorption predictions were based on the settings utilised in a PBPK model built to describe absorption and exposure of 2-ethylhexyl acrylate and its metabolite 2-ethyl hexanol. :
Compound Name |
Side Chain Length |
LogPow |
Aqueous Solubility (mg/ml) |
Physical state at 20°C |
Predicted Rat fa |
Ethyl acrylate |
2 | 1.18 |
1.00E-02 |
Liquid |
1.00 |
2 -Ethylhexanol |
|
2.9 |
9.00E-01 |
Liquid |
1.00 |
2 -Ethylhexyl acrylate |
8 |
4 |
1.00E-02 |
Liquid |
0.91 |
Dodecyl acrylate |
12 |
6.13 |
2.00E-04 |
Liquid |
0.81 |
Tetradecyl acrylate |
14 |
7.11 |
2.00E-06 |
Liquid |
0.77 |
Hexadecyl acrylate |
16 |
8.09 |
1.19E-06 |
Solid paste |
0.0150 |
Octadecyl acrylate |
18 |
9.08 |
2.61E-10 |
Solid paste |
0.0001 |
Icosyl acrylate | 20 | 10.06 | 2.70E-08 | Solid paste | 0.0022 |
Docosyl acrylate | 22 | 11.04 | 1.50E-09 | Solid | 0.0006 |
Applicant's summary and conclusion
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.