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EC number: 205-521-9 | CAS number: 142-09-6
- 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
Dermal absorption
Administrative data
- Endpoint:
- dermal absorption in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Reference
- Reference Type:
- other: thesis
- Title:
- Using physiologically based pharmacokinetic modelling to predict the pharmacokinetics and toxicity of methacrylate esters
- Author:
- Jones O
- Year:
- 2 002
- Bibliographic source:
- A Thesis submitted to Univ. of Manchester for the degree of Doctor of Philosophy
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 428 (Skin Absorption: In Vitro Method)
- Principles of method if other than guideline:
- A physiologically based pharmacokinetic model has been formulated to predict the pharmacokinetics and systemic disposition of alkylmethacrylate esters in rats and humans.
- GLP compliance:
- no
Test material
- Reference substance name:
- hexyl 2-methylprop-2-enoate
- EC Number:
- 205-521-9
- Cas Number:
- 142-09-6
- Molecular formula:
- C10H18O2
- IUPAC Name:
- hexyl 2-methylprop-2-enoate
- Test material form:
- liquid
Constituent 1
- Radiolabelling:
- no
Test animals
- Species:
- other: rat and human
- Strain:
- other: Wistar/Fischer F344/ not applicable
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Epidermal membrane absorption studies
Skin was used from male rats of the Wistar-derived strain (supplied by Charles River UK Ltd, Margate, Kent, UK.) aged 28 days ± 2 days
Whole skin absorption studies
Skin was taken from male Fisher F344 (supplied by Harlan Olac) rats weighing between 200 and 250 g.
Human epidermal membrane absorption studies
Extraneous tissue was removed from human abdominal whole skin samples obtained post mortem in accordance with local ethical guidelines
Administration / exposure
- Type of coverage:
- open
- Vehicle:
- unchanged (no vehicle)
- Duration of exposure:
- 48 h
- Doses:
- 100 µL/cm²
- No. of animals per group:
- 3 (human: 2)
- Details on in vitro test system (if applicable):
- The absorption of nHMA was evaluated through rat and human epidermis and through rat whole skin in an in vitro system.
Results and discussion
- Signs and symptoms of toxicity:
- not examined
- Dermal irritation:
- not examined
- Conversion factor human vs. animal skin:
- Human epidermis appears to be several times less permeable to the test substances than rat epidermis.
Any other information on results incl. tables
The results of the whole-skin penetration studies and the model predictions for
other methacrylate esters are presented in the table.
Table: Summary of the results for the peak rates of absorption of MAA & alkylmethacrylate esters through rat & human epidermis
|
Rat epidermis |
Human epidermis |
|||||||
Ester |
Peak rate of absorption (μg cm-2hr-1) ±SEM |
Period of peak absorption rate (hours) |
% age of applied dose absorbed over x hours |
Peak rate of absorption (μg cm-2hr-1) ±SEM |
Period of peak absorption rate (hours) |
% age of applied dose absorbed over x hours |
|||
MAA |
23825±2839 |
0.5-4 |
93% / 24h |
812 |
- |
- |
|||
MMA |
5888±223 |
2-8 |
46% / 16h |
453±44.5 |
4-24 |
10% / 24h |
|||
EMA |
4421 |
- |
- |
253 |
- |
- |
|||
i-BMA |
1418 |
- |
- |
80 |
- |
- |
|||
n-BMA |
1540±69 |
0-6 |
18% / 24h |
76.7±9.8 |
0-24 |
2% / 24h |
|||
HMA |
147 |
- |
- |
25 |
- |
- |
|||
2EHMA |
234±4.8 |
0-30 |
7.8% / 30h |
22.7 ±3.7 |
3-24 |
0.6% / 24h |
|||
OMA |
159±15 |
0-24 |
- |
7.8 |
- |
- |
Ester
Peak = rate of appearance of the parent ester (µg/cm2/hr)
MAA
Peak = rate of appearance of the hydrolysis product, MAA (µg/cm2/hr)
Period Peak Absorp. = Time (hours) after application for peak absorption
% Applied Dose = total % absorbed
** Predicted rates of MAA from model estimates.
Summary of the peak rates of absorption of MAA & alkyl-methacrylate esters through whole rat and human skin
Substance |
Molecular volume |
Rat whole rat |
Human whole skin |
|||
Peak rate of appearance (µg*cm-2*h-1)+- SEM |
Period of peak absorption rate (hours) |
% age of applied dose absorbed over x hours |
Rate of absorption of ester/MAA (μg*cm-2 *hr-1) |
|||
Ester |
MAA |
|||||
MAA |
78.96 |
|
4584 ± 344 |
5-8 |
70%/24 |
327 |
MMA |
93.1978 |
360± 20.9 |
108± 4.59 |
2.5-24 |
11.3%/24 |
33.4** |
EMA |
107.436 |
|
190** |
|
|
13.6** |
iBMA |
135.646 |
|
56** |
|
|
4** |
nBMA |
135.856 |
|
40± 9.4 |
2-10 |
0.4%/10 |
2.9** |
6HMA |
164.277 |
|
20** |
|
|
1.4** |
2EHMA |
191.66 |
|
9** |
|
|
0.6** |
OMA |
192.696 |
|
10.3 ± 0.65 |
8-24 |
0.24%/24 |
0.7** |
12LMA |
249.536 |
|
11.8 ± 2.11 |
8-24 |
0.26%/24 |
0.8** |
The values in normal type were obtained experimentally, whilst those in italics are predicted values.
** Values are predicted rates of appearance of total chemical including parent ester and metabolite
Applicant's summary and conclusion
- Conclusions:
- Prediction due to the experimental results of analogue substances (n-BMA and 2-EHMA): HMA readily absorbs through rat and human epidermis. Human epidermis appears to be several times less permeable to HMA than rat epidermis.
Human epidermis appears to be 10 times less permeable to 2-EHMA than rat epidermis and 20 times less permeable to n-BMA than rat epidermis. - Executive summary:
The in vivo and in vitro investigations as well as the PBPK models developed from the data showed that alkyl-methacrylate esters are rapidly absorbed and are hydrolyzed at exceptionally high rates to methacrylic acid by high capacity, ubiquitous carboxylesterases. Further, the removal of the hydrolysis product, methacrylic acid, also is very rapid (minutes).
The absorption of HMA was evaluated through rat and human epidermis in an in vitro system. The technique measures the rate of absorption of HMA across the epidermis. Glass diffusion cells are employed to measure the amount of HMA that is received into a receptor chamber with respect to time, following the application of 100 µl/cm² of HMA to the epidermal surface. The mean rate of absorption was 147
µg cm-2 hr-1
respectively. HMA appears readily absorbed through rat and human epidermis, but human epidermis is several times less permeable to HMA than rat epidermis due to the experimental results of analogue substances (n-BMA and 2-EHMA). Human epidermis appears to be 10 times less permeable to 2-EHMA than rat epidermis and 20 times less permeable to n-BMA than rat epidermis.
However, measuring the rate of absorption through rat and human epidermis provides a quantitative estimate for inter-species differences; however, because only the epidermal layer is used, no measure of metabolism during skin absorption is possible.
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