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EC number: 219-674-4 | CAS number: 2495-37-6
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2020
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 021
- Report date:
- 2021
Materials and methods
- Objective of study:
- metabolism
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Metabolic stability of the test item was analysed using pooled liver S9 fractions from male Sprague Dawley (SD) rats. Based on the knowledge gained during method development, in the present metabolic stability study of BNMA the following test conditions were used: 20 μM of BNMA were incubated in glass vials with 0.5 mg/ml S9 fractions and after 0, 2, 5,10,15 and 30 minutes samples were collected for analytical detection via LC-MS.
Two types of negative control (NC; n=3) i.e. heat-inactivated S9 fraction and pure assay buffer w/o S9 mix, respectively, were run in parallel to the experimental incubations to verify that any apparent loss of test article in the assay incubation was due to metabolism.
As positive control 1 μM verapamil was incubated in parallel to the test item (n=3), and the depletion of the compound was monitored to demonstrate the enzymatic activity of the S9 fractions. Positive control samples were taken after 0 and 30 minutes. - GLP compliance:
- no
Test material
- Reference substance name:
- Benzyl methacrylate
- EC Number:
- 219-674-4
- EC Name:
- Benzyl methacrylate
- Cas Number:
- 2495-37-6
- Molecular formula:
- C11H12O2
- IUPAC Name:
- benzyl methacrylate
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- Name of test material: Benzyl methacrylate
- Radiolabelling:
- no
Test animals
- Species:
- other: Rat liver S9 fractions
- Strain:
- Sprague-Dawley
- Sex:
- male
Administration / exposure
- Vehicle:
- DMSO
- Duration and frequency of treatment / exposure:
- sampling after 0, 2, 5,10,15 and 30 minutes
Doses / concentrations
- Dose / conc.:
- 20 other: µM
- Remarks:
- The final test concentration was determined during experimental development.
- No. of animals per sex per dose / concentration:
- not applicable; in vitro test
- Control animals:
- other: not applicable, in vitro test
- Positive control reference chemical:
- As positive control 1 μM verapamil was incubated in parallel to the test item (n=3), and the depletion of the compound was monitored to demonstrate the enzymatic activity of the S9 fractions. Positive control samples were taken after 0 and 30 minutes.
- Details on study design:
- - Dose selection rationale: based on experimantal method development (analytical detection)
- Details on dosing and sampling:
- TOXICOKINETIC / PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Time and frequency of sampling: after 0, 2, 5, 10, 15 and 30 minutes
METABOLITE CHARACTERISATION STUDIES
- Method type(s) for identification: Liquid chromatography – mass spectrometry (LC-MS)
- Limits of detection and quantification:
- Other: after incubation time samples were samples were processed for ACN precipitation and quantitative bioanalysis (addition of two volumes (i.e. 400 μl) stop solution (ACN containing the ISTD). - Statistics:
- Descriptive statistics were used, i.e., mean ± standard deviation. All calculations in the database were conducted using Microsoft Excel.
Results and discussion
Main ADME results
- Type:
- metabolism
- Results:
- The ester was rapidly converted into MAA and the respective alcohol. (<0.25 min)
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- Methacrylic acid (MAA) and benzyl alcohol
Any other information on results incl. tables
As shown in the Table 2, already at the first time point 0 min (+0.25 min), only 0.3 μM BNMA was detectable which corresponds to 1.5% of initial BNMA concentration. At the same time, the analytical measurements revealed the formation of the two metabolites Benzyl alcohol (Table 3) and Methacrylic acid (only qualitative detection of MAA). These findings clearly indicate that BNMA was rapidly metabolised within the first minute.
Table 2: Remaining BNMA (nominal initial concentration: 20 µM): measured concentration and calculated percentage of remaining test item after incubation with rat liver S9 fractions for different time points, (n=3)
Remaining BNMA concentration |
% remaining BNMA of initial concentration |
||||
Time [min] |
Mean (nM)[1] |
SD (nM) |
%CV[2] |
Time [min] |
Mean (%) |
0 |
301.4 |
120.0 |
39.8 |
0 |
1.5 |
2 |
0.0 |
0.0 |
n.a. |
2 |
0.0 |
5 |
0.0 |
0.0 |
n.a. |
5 |
0.0 |
10 |
0.0 |
0.0 |
n.a. |
10 |
0.0 |
15 |
0.0 |
0.0 |
n.a. |
15 |
0.0 |
30 |
0.0 |
0.0 |
n.a. |
30 |
0.0 |
Table 3: Measured concentration and calculated percentage of formed metabolite benzyl alcohol after incubation of BNMA (nominal initial concentration: 20 µM) with rat liver S9 fractions for different time points, (n=3)
Formed Benzyl alcohol concentration |
% formed Benzyl alcohol of initial concentration in BNMA |
||||
Time [min] |
Mean (nM) |
SD (nM) |
%CV |
Time [min] |
Mean (%) |
0 |
22385.6 |
2407.1 |
10.8 |
0 |
111.93 |
2 |
21714.8 |
2761.8 |
12.7 |
2 |
108.57 |
5 |
22218.3 |
1915.1 |
8.6 |
5 |
111.09 |
10 |
19567.2 |
423.3 |
2.2 |
10 |
97.84 |
15 |
20073.7 |
3283.2 |
16.4 |
15 |
100.37 |
30 |
23577.3 |
5884.2 |
25.0 |
30 |
117.89 |
[1]values were at or below quantification limit (LOQ 400 nM)
[2]Coefficient of variation expressed as percentage of SD divided by mean value
Taken all findings together it can be concluded that 20 μM BNMA was completely metabolized within very short time (< 0.25 min; at time point 0 min) in presence of 0.5 mg/ml rat liver S9 fractions (i.e. in presence of phase I and II enzymes). At time point 0 min already no BNMA was detectable and the formation of the primary metabolites could be shown as a proof of the very rapid enzymatic hydrolysis of BNMA. Due to the immediate cleavage of BNMA in presence of rat liver S9 fractions, half-life and intrinsic clearance could not be calculated.
Applicant's summary and conclusion
- Conclusions:
- Taken all findings together it can be concluded that 20 μM BNMA was completely metabolized within very short time (< 0.25 min; at time point 0 min) in presence of 0.5 mg/ml rat liver S9 fractions (i.e. in presence of phase I and II enzymes). At time point 0 min already no BNMA was detectable and the formation of the primary metabolites could be shown as a proof of the very rapid enzymatic hydrolysis of BNMA. Due to the immediate cleavage of BNMA in presence of rat liver S9 fractions, half-life and intrinsic clearance could not be calculated.
- Executive summary:
Taken all findings together it can be concluded that 20 μM BNMA was completely metabolized within very short time (< 0.25 min; at time point 0 min) in presence of 0.5 mg/ml rat liver S9 fractions (i.e. in presence of phase I and II enzymes). At time point 0 min already no BNMA was detectable and the formation of the primary metabolites could be shown as a proof of the very rapid enzymatic hydrolysis of BNMA. Due to the immediate cleavage of BNMA in presence of rat liver S9 fractions, half-life and intrinsic clearance could not be calculated.
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