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EC number: 219-835-9 | CAS number: 2549-53-3
- 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)
Description of key information
There are no test data for tetradecyl methacrylate on bioaccumulation available.
Read across from structural analogue substance dodecyl methacrylate CAS: 142 -90 -5:
Short description of key information on bioaccumulation potential result:
As indicated in a dermal absorption study, the structural analogue
dodecyl methacrylate CAS: 142-90-5 is metabolised during penetration of
the skin and not expected to enter the circulation as the parent ester.
Gastro intestinal-, respiratory- and dermal absorption to a major extent
are not expected due to physico-chemical properties and in vitro dermal
absorption studies, where methacrylate esters of molecular weight equal
to or greater than butyl methacrylate were not detected in the receptor
fluid and are not expected to enter the circulation as the parent ester.
Short description of key information on absorption rate:
Structural analogue dodecyl methacrylate appears to be absorbed through
rat skin and epidermis to a low extent, 0.26 % in 24 hrs.
It is fully metabolized to methacrylic acid during the passage
(first-pass effect).
As indicated by a PB-PK model used in this study, human skin is 14 times
less permeable to dodecyl methacrylate than rat skin.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
- Absorption rate - dermal (%):
- 0.26
Additional information
Non-human information
Physico-chemical properties of the substance will enable qualitative judgements of the toxicokinetic (TK) behaviour (Guidance on information requirements and chemical safety assessment Chapter R.7.c, R.7.12 Guidance on Toxicokinetics):
In general with a calculated log Pow of 7.66 of tetradecyl methacrylate absorption into the blood form gastrointestinal (GI) absorption, respiratory absorption or skin is not expected. (log Pow values between -1 and 4 are favourable for absorption). With a water solubility of < 1 µg/l the substance is poorly soluble. The molecular weight is 282 g/mol and the substance is not a skin sensitizer.
Experimental in vitro studies of the toxicokinetics of the structural analogue dodecyl methacrylate are only available for dermal absorption. Experimental in vitro studies with the structurally related substance ethylhexyl methacrylate are used to assess the metabolism of tetradecyl methacrylate.
Absorption
GI absorption
No experimental data are available for GI absorption.
Substances with a molecular weight below 500, high water solubility and a log Pow between -1 and 4 are favourable for absorption. With log Pow > 4 passive diffusion through membranes is not expected but the substance may form micelles and be absorbed into the lymphatic system. However, due to the very poor water solubility of < 1 µg/l, only very low concentrations of the substance are bioavailable. Therefore, the substance is be absorbed poorly. Accordingly, no signs of systemic toxicity indicating that absorption has occurred were seen in an acute oral toxicity test up to 5000 mg/kg bw.
GI absorption is not the favoured route of absorption. Only few amounts of the substance may be absorbed by micellular solubilisation due to its very poor water solubility.
Respiratory absorption – Inhalation
No experimental data are available for respiratory absorption.
The vapour pressure of structural analogue dodecyl methacrylate is only 0.06 Pa@ 20 °C and therefore the volatility is too low for inhalation (substances with low volatility have a vapour pressure of less than 0.5 kPa).
Inhalation is not a relevant route of absorption.
Dermal absorption
Tetradecyl methacrylate is a liquid substance with a molecular weight between 100 and 500 Dalton which would favour dermal uptake, but with a very low water solubility of 1 µg/l dermal uptake from the stratum corneum into the epidermis is likely to be too low. With log Pow > 6 the rate of transfer between the stratum corneum and the epidermis will be slow and will limit absorption across the skin. Uptake into the stratum corneum itself is expected to be slow.
Although tetradecyl methacrylate has a skin binding structure (methacrylate), the structural analogue dodecyl methacrylate was not sensitizing in in vivo tests in mice and guinea pigs The substance is not skin irritating or corrosive, so that the substance itself will not enhance penetration through damaged skin. No signs of systemic toxicity indicating absorption were observed in an acute dermal toxicity study on dodecyl methacrylate with doses up to 3000 mg/kg bw.
The dermal absorption (steady-state flux) of dodecyl methacrylate has been estimated by calculation using the principles defined in the Potts and Guy prediction model (Heylings JR, 2013)
Terms used for categorising absorption of chemicals through human skin:
Kp (cm/h)
|
Absorption Rate (µg/cm²/h)
|
Relative Absorption Rate Category
|
Predicted Absorption from Normal Exposure
|
1E-02 – 1E-01 |
>500 |
Very fast |
Very high |
1E-03 – 1E-02 |
100-500 |
Rapid - Fast |
High |
1E-04 – 1E-03 |
10-50 50-100 |
Slow - Moderate Moderate - Rapid |
Moderate |
1E-05 – 1E-04 |
0.1-10 |
Very slow - Slow |
Low |
1E-06 – 1E-05 |
0.001-0.1 |
Extremely - Very slow |
Minimal |
<1E-06 |
<0.001 |
Extremely slow |
Negligible |
Based on a molecular weight of 254.41 g/mol and a Kow of 6.68, the predicted flux of dodecyl methacrylate is 0.003 μg/cm²/h; the relative dermal absorption is minimal
Metabolism
No data are available on the metabolism of tetradecyl methacrylate in vivo.
If it is assumed that tetradecyl methacrylate will be absorbed through the skin, the prominent pathway for the metabolism of higher methacrylate esters starts with ester hydrolysis resulting in methacrylic acid and the corresponding alcohol (Jones, 2002); McCarthy and Witz, 1997). While the acid is further metabolised via the valine pathway of the citric acid cycle (ECETOC, 1995; European Union, 2002) the alcohol may be further metabolised by the two standard metabolic pathways for fatty alcohols (1. oxidation: fatty alcohol -> aldehyde -> acid, and subsequently CoA-mediated fatty acid metabolism - or - 2.: glucuronidation of the alcohol and excretion).
Alkyl esters of methacrylic acid up to C8(2-ethylhexyl methacrylate) showed rapid metabolism with half lives in rat blood of less than 30 min (Jones, 2002):
A series of in vitro and in vivo studies with a series of methacrylates were used to develop a PBPK model that accurately predict the metabolism and fate of these monomers. The studies confirmed that alkyl methacrylate esters are rapidly hydrolysed in the organism by ubiquitous carboxylesterases. First pass (local) hydrolysis of the parent esters has been shown to be significant for all routes of exposure. In vivo measurements of rat liver indicated this organ as with the greatest esterase activity. Similar measurements for skin microsomes indicated an approximately 20-fold lower activity than for liver. Nevertheless, this activity was substantial and capable of almost complete first-pass metabolism of the alkyl methacrylates applied on skin. For example, no parent ester penetrated whole rat skin in vitro for n-butyl methacrylate, octyl methacrylate or lauryl methacrylate. When tested experimentally, only methacrylic acid was identified in the receiving fluid. In addition, model predictions indicate that esters of ethyl methacrylate or larger would be completely hydrolysed before entering the circulation via skin absorption. This pattern is consistent with a lower rate of absorption for these esters indicating that the rate of metabolism is within the metabolic capacity of the skin. Parent ester also was hydrolyzed by S9 fractions from nasal epithelium and was predicted to be effectively hydrolysed following inhalation exposure.
These studies showed that any systematically absorbed parent ester will be effectively removed during the first pass through the liver (CL as % LBF, see table). In addition, removal of methacrylic acid from the blood also occurs rapidly (T50 %; see table).
Table:
Rate constants for the ester hydrolysis by rat-liver microsomes and predicted systemic fate kinetics from methacrylates following i.v. administration:
Ester |
Vmax |
Km |
CL (%LBF) |
T50%(min) |
Cmax(MAA) (mg L-1) |
Tmax(MAA) (min) |
MAA |
- |
- |
51.6% |
- |
- |
- |
MMA |
445.8 |
164.3 |
98.8% |
4.4 |
14.7 |
1.7 |
EMA |
699.2 |
106.2 |
99.5% |
4.5 |
12.0 |
1.8 |
i-BMA |
832.9 |
127.4 |
99.5% |
11.6 |
7.4 |
1.6 |
n-BMA |
875.7 |
77.3 |
99.7% |
7.8 |
7.9 |
1.8 |
HMA |
376.4 |
34.4 |
99.7% |
18.5 |
5.9 |
1.2 |
2EHMA |
393.0 |
17.7 |
99.9% |
23.8 |
5.0 |
1.2 |
OMA |
224.8 |
11.0 |
99.9% |
27.2 |
5.0 |
1.2 |
MAA = Methacrylic acid (CAS 79-41-4)
MMA = Methyl methacrylate (CAS 80-62-6)
EMA = Ethyl methacrylate (CAS 97-63-5)
i-BMA = Isobutyl methacrylate (CAS 97-86-9)
n-BMA = n-Butyl methacrylate (CAS 97-88-1)
HMA = Hexyl methacrylate (CAS 142-09-6)
2EHMA = 2-Ethylhexyl methacrylate (CAS 688-84-6)
OMA = Octyl methacrylate (CAS 2157-01-9)
DMA = Dodecyl methacrylate
Vmax (nM/min/mg) and Km (µM) from rat-liver microsomes (100 µg/ml) determinations; CL = clearance as % removed from liver blood flow, T50% = Body elimination time (min) for 50% parent ester, Cmax = maximum concentration (mg/L) of MAA in blood, Tmax = time (min) to peak MAA concentration in blood from model predictions.
Table: Summary of the peak rates of absorption of MAA and alkyl-methacrylate esters through whole rat and human skin.
|
|
Rat whole skin |
Human whole skin |
|||||
Ester |
Molec. Volume |
Peak rate of appearance |
Peak rate of appearance |
Period of peak abs. rate |
Absorbed dose |
Predicted rate of absorption |
||
|
|
µg cm-2h-1 |
±SEM |
µg cm-2h-1 |
±SEM |
h |
% of applied/ over x hours |
µg cm-2h-1 |
MAA |
78.96* |
|
|
4584** |
±344 |
5-8 |
70%/24 |
327.0** |
MMA |
93.198 |
360 |
±20.9 |
108** |
±4.59 |
2.5-24 |
11.3%/24 |
33.4** |
EMA |
107.436 |
|
|
190** |
- |
|
|
13.6** |
iBMA |
135.646 |
|
|
56** |
- |
|
|
4.0** |
nBMA |
135.856 |
|
|
40.9 |
±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** |
DMA |
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
GSH conjugation, the second potential pathway, has only been observed with small alkyl methacrylates (methyl methacrylate/MMA, ethyl methacrylate/EMA) but was no longer measurable with butyl methacrylate. Moreover, GSH conjugation was only detectable with MMA and EMA at high concentrations which are only achievable under laboratory conditions (Elovaara et al., 1983, Mc Carthy et al., 1994).
Distribution
As the bioavailability of structural analogue dodecyl methacrylate is very low that means neither GI- and respiratory absorption nor dermal absorption to a more than minimal extent are expected and complete metabolism is predicted, only a very low amount of the substance comes into consideration for distribution in blood or plasma and accumulation in organs and tissues.
In theory the lipophilic molecule is likely to distribute into cells and then the intracellular concentration may be higher than extracellular concentration particular in fatty tissues, but this is of secondary importance as the bioavailability of the substance is very low.
Accummulation
In principle, tetradecyl methacrylate should be absorbed accumulation in adipose tissue could be expected as the calculated log Pow is 7.66, but before that it is expected to be completely metabolised due to the rapid cleavage by esterases as described.
Excretion
As absorption is very low respectively not expected and complete metabolism is very fast, excretion of tetradecyl methacrylate is hardly relevant.
Human information
No human information available.
Summary and discussion of toxicokinetics
According to logP > 4, bioaccumulation of tetradecyl methacrylate is in principle expected. However, with < 1 µg/l the substance is poorly soluble in water. Therefore the bioavailablity of the substance is very low. QSAR modelling for dermal skin absorption predicted minimal absorption with a calculated flux of 0.003 µg/cm²/h for dodecyl methacrylate. In vitro studies with rat liver showed fast ester hydrolysis with alkyl methacrylates up to C8-methacrylates. The same rapid metabolism is predicted for tetradecyl methacrylate particularly as the available concentration in the body will be very low.
Experimental studies of the toxicokinetics of tetradecyl methacrylate are not available. There is only for the structural analogue dodecyl methactylate a study for dermal absorption. In these in vitro studies, the substance was not detected in the receptor fluid, only the metabolite methacrylic acid. Therefore, it is not expected to enter the circulation as the parent ester.
Discussion on absorption rate:
Dodecyl methacrylate appears to be absorbed through rat skin and epidermis to a low extent, 0.26 % in 24 hrs. It is fully metabolized to methacrylic acid during the passage (first-pass effect). As indicated by a PB-PK model used in this study, human skin is 14 times less permeable to dodecyl methacrylate than rat skin.
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