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EC number: 908-917-6
CAS number: -
Reaction mass of 2-hydroxyethyl laurate and ethylene dilaurate (EC
908-917-6) is a solid multi-constituent substance with two main
constituents. The substance will be hydrolysed within the
gastrointestinal tract. The hydrolysis products (mainly the respective
C12 fatty acid and ethylene glycol) are predicted to be readily absorbed
via the oral route. The major metabolic pathway for linear fatty acids
is the beta-oxidation pathway for energy generation or fatty acids can
be re-esterified to triglycerides after absorption and transported via
chylomicrons. The absorbed ethylene glycol is expected to be readily
distributed throughout the organism and bio-transformed in liver and
kidney. Absorption via inhalation and dermal route is expected to be
low. The excretion will mainly be as carbon dioxide in expired air; with
a smaller fraction of urinary excretion. No bioaccumulation is expected.
In the following the term “Reaction mass” is used as abbreviation
for: Reaction mass of 2-hydroxyethyl laurate and ethylene dilaurate (EC
908-917-6). In accordance with Annex VIII, Column 1, Section 8.8.1, of
Regulation (EC) No. 1907/2006 and with Guidance on information
requirements and chemical safety assessment Chapter R.7c: Endpoint
specific guidance (ECHA, 2017), assessment of the toxicokinetic
behaviour of the Reaction mass is conducted to the extent that can be
derived from the relevant available information. This comprises a
qualitative assessment of the available substance specific data on
physico-chemical and toxicological properties according to Guidance on
information requirements and chemical safety assessment Chapter R.7c:
Endpoint specific guidance (ECHA, 2017) and taking into account further
available information on structural analogue substances.
There are no studies available in which the toxicokinetic
behaviour of the Reaction mass has been investigated.
The substance Reaction mass is a well-defined multi-constituent
substance with the two main constituents, 2-hydroxyethylaurate
(Molecular Formula C14H28O3) and ethylene dilaurate (Molecular Formula
C26H50O4). Both constituents are fatty acid esters belonging to the
subgroup of glycol esters. 2-hydroxyethyl laurate is a monoester with
ethane-1,2-diol and lauric acid. Ethylene dilaurate is a diester with
ethane-1,2-diol and lauric acid.
The constituent 2-hydroxyethyl laurate has a molecular weight of
244.37 and a calculated log Pow of 4.31. The constituent ethylene
dilaurate has a molecular weight of 426.67 and calculated log Pow of
Reaction mass is a solid at 20°C which has a molecular weight
ranging from 244.37 – 426.67 g/mol. Experimental data for water
solubility were not available at the time of dossier submission (see
IUCLID section 4.8). The calculated log Pow value was in the range of
4.25 to 10.23 (Episuite calculation, 2017) and the vapour pressure was
calculated to be between 0.018-0.153 Pa at 25°C (Episuite calculation,
Absorption is a function of the potential for a substance to
diffuse across biological membranes. The most useful parameters
providing information on this potential are the molecular weight, the
octanol/water partition coefficient (log Pow) value and the water
solubility. The log Pow value provides information on the relative
solubility of the substance in water and lipids (ECHA, 2017).
In general, molecular weights below 500 and log Pow values between
-1 and 4 are favourable for absorption via the gastrointestinal (GI)
tract, provided that the substance is sufficiently water soluble (> 1
mg/L). Lipophilic compounds may be taken up by micellar solubilisation
by bile salts, but this mechanism may be of particular importance for
highly lipophilic compounds (log Pow > 4), in particular for those that
are poorly soluble in water (≤ 1 mg/L) as these would otherwise be
poorly absorbed (Aungst and Shen, 1986; ECHA, 2017).
When assessing the potential of Reaction mass to be absorbed in
the gastrointestinal (GI) tract, it has to be considered that fatty acid
esters will undergo to a high extent hydrolysis by ubiquitous GI enzymes
(Long, 1958; Lehninger, 1970; Mattson and Volpenhein, 1972). The
hydrolysis represents the first chemical step in the absorption,
distribution, metabolism and excretion (ADME) pathways likely to be
similarly followed by all glycol esters. The hydrolysis is catalysed by
classes of enzymes known as carboxylesterases or esterases (Heymann,
1980). Due to the hydrolysis the predictions based on the
physico-chemical characteristics of the intact parent substance alone
may no longer apply but also the physico-chemical characteristics of the
breakdown products of the ester; the alcohol propylene glycol and the
corresponding fatty acids (mainly C12). Ethylene glycol is rapidly
absorbed from the gastrointestinal tract and subsequently undergoes
rapid biotransformation in liver and kidney (IPCS, 2001; WHO, 2002;
ATSDR, 2010). The lipophilic fatty acids are absorbed by micellar
solubilisation. Within the epithelial cells, fatty acids are
(re)-esterified with glycerol to triglycerides.
In an acute oral gavage toxicity study (2017) according to OECD
guideline 420, no adverse toxic effects were seen in female Wistar rats
at a single dose of 2000 mg/kg bw.
There are no data available on dermal absorption or on acute
dermal toxicity of Reaction mass. On the basis of the following
considerations, the dermal absorption of the substance is considered to
No adverse toxic effects were found in two acute dermal toxicity
studies with the source substances Fatty acids, C18 and C18 unsatd.
epoxidized, ester with ethylene glycol (151661-88-0) and
1,2-Propandiol-mono/di-octanoat (CAS 31565-12-5). The acute LD50 value
was found to be > 2000 mg/kg bw in male and female rats in both studies.
To partition from the stratum corneum into the epidermis, a
substance must be sufficiently soluble in water. Thus, with a water
solubility <1 mg/L, dermal uptake of the substance is likely to be low.
In addition, for substances having an octanol/water partition
coefficient above 6, the rate of transfer between the stratum corneum
and the epidermis will be slow and thus limit absorption across the
skin. Furthermore, uptake into the stratum corneum itself may be slow.
In addition, as the test substance is a solid, hindered dermal
absorption has to be considered as dry particulates first have to
dissolve into the surface moisture of the skin before uptake vie the
skin is possible (ECHA, 2017).
The dermal permeability coefficient (Kp) can be calculated from
log Pow and molecular weight (MW) applying the following equation
described in US EPA (2012):
log(Kp) = -2.80 + 0.66 log Pow – 0.0056 MW
The Kp was calculated for the 2 main constituents of the substance
(please refer to Table 1). Retrieved dermal flux rates indicate only low
dermal absorption potential for the two main components of Reaction mass
(please refer to Table 1, Dermwin v2.02, EpiSuite 4.1; calculated in Feb
Table 1: Dermal absorption values for the constituents of Reaction
mass (calculated with Dermwin v 2.02, Epiweb 4.1)
Water solubility (mg/cm³)
Dermal absorption potential
C14 H28 O3
C26 H50 O4
If a substance shows skin irritating or corrosive properties,
damage to the skin surface may enhance penetration. If the substance has
been identified as a skin sensitizer then some uptake must have occurred
although it may only have been a small fraction of the applied dose
(ECHA, 2017) The irritation studies with the structurally related
substances ethane-1,2-diyl dioctadecanoate (CAS 627-83-8),
2-hydroxyethyl stearate (CAS 111-60-4) and Decanoic acid, mixed diesters
with octanoic acid and propylene (CAS 68583-51-7) showed no or only mild
irritating effects. No erythema or oedema was seen during an in vivo
skin sensitisation (Buehler) study in guinea pigs with the source
substance ethane-1,2-diyl dioctadecanoate (627-83-8) after 6 hours of
exposure to the undiluted test substance.
Overall, taking into account the physico-chemical properties of
2-hydroxyethylaurate (CAS 4219-48-1) and ethylene dilaurate (CAS
624-04-4) and the QSAR calculations, the dermal absorption potential of
the substance is predicted to be low.
In humans, particles with aerodynamic diameters below 100 μm have
the potential to be inhaled. Particles with aerodynamic diameters below
50 μm may reach the thoracic region and those below 15 μm the alveolar
region of the respiratory tract (ECHA, 2017).
Reaction mass is sold in solid form (solidified melt) and has a
very low calculated vapour pressure of 0.018-0.153, indicating low
volatility (Episuite calculation, 2017). Therefore, under normal use and
handling conditions, inhalation exposure and thus availability for
respiratory absorption of the substance in the form of vapours, gases,
or mists is not significant.
The potential for exposure via the inhalation route is considered
to be negligible.
Distribution and accumulation
As the glycol esters of Reaction mass are considered to be
hydrolysed before absorption, the distribution of the intact glycol
esters is less relevant than the distribution of the breakdown products
of intestinal hydrolysis.
Distribution of a compound within the body depends on the
physico-chemical properties of the substance; especially the molecular
weight, the lipophilic character and the water solubility. In general,
the smaller the molecule, the wider is the distribution. If the molecule
is lipophilic, it is likely to distribute into cells and the
intracellular concentration may be higher than extracellular
concentration, particularly in fatty tissues (ECHA, 2017).
The absorbed hydrolysis products, the free fatty acids and the
highly water-soluble alcohols can be distributed within the body.
Ethylene glycol has a low molecular weight (62.07 g/mol) and high water
solubility and will therefore be broadly distributed within the body
(ECHA Homepage; ATSDR, 2010; IPCS, 2001). Furthermore, substances with
high water solubility like ethylene glycol, do not have the potential to
accumulate in adipose tissue due to their low log Pow. Medium chain
fatty acids like those in the Reaction mass with fatty acid chain length
of C12, may be re-esterified with glycerol into triacylglycerides (TAGs)
and transported via chylomicrons after absorption in the GI tract. The
fatty acids are transported via the lymphatic system and the blood
stream to the liver and to extrahepatic tissue for storage e.g. in
adipose tissue (Stryer, 1994).
Glycol esters of Reaction mass are not assumed to bio-accumulate
in the body, as hydrolysis takes place before absorption and
distribution. However, accumulation of the fatty acids in triglycerides
in adipose tissue or the incorporation into cell membranes is possible.
At the same time, fatty acids may also be used for energy generation.
Metabolism of Reaction mass initially occurs via stepwise
enzymatic hydrolysis of the ester , resulting in the corresponding
monoester (ethylene glycol monolaurate), and via further metabolism the
free fatty acids (C12) and ethylene glycol.
Ethylene glycol is first metabolised by alcohol dehydrogenase to
glycoaldehyde, which is then further oxidised successively to glycolic
acid, glyoxylic acid, oxalic acids by mitochondrial aldehyde
dehydrogenase and cytosolic aldehyde oxidase (ATSDR, 2010; WHO, 2002).
The anabolism of fatty acids occurs in the cytosol, where fatty acids
esterified into cellular lipids that are the most important storage form
of fatty acids (Stryer, 1994). The catabolism of fatty acids occurs in
the cellular organelles, mitochondria and peroxisomes via a completely
different set of enzymes. The process is termed β-oxidation and involves
the sequential cleavage of two-carbon units, released as acetyl-CoA
through a cyclic series of reaction catalysed by several distinct enzyme
activities rather than a multi-enzyme complex (Tocher, 2003). In this
multi-step process, the fatty acids are at first esterified into
acyl-CoA derivatives and subsequently transported into cells and
mitochondria by specific transport systems. In the next step, the
acyl-CoA derivatives are broken down into acetyl-CoA molecules by
sequential removal of 2-carbon units from the aliphatic acyl-CoA
molecule. Further oxidation via the citric acid cycle leads to the
formation of water and carbon dioxide.
Glycol esters and the breakdown products will be metabolised in
the body to a high extent. The fatty acid components, will be
metabolised for energy generation or stored as lipid in adipose tissue
or used for further physiological properties e.g. incorporation into
cell membranes (Lehninger, 1970; Stryer, 1994). Therefore, the fatty
acid component is not expected to be excreted to a significant degree
via the urine or faeces but excreted via exhaled air as carbon dioxide
or stored as described above. As ethylene glycol will be highly
metabolised as well, the primary route of excretion will be via exhaled
air as carbon dioxide and as parent compound and glycolic acid in the
urine. High doses of ethylene glycol lead to the excretion of the
metabolite oxalate via the urine (ATSDR, 2010).
Agency for Toxic Substances and Disease Registry (ATSDR, 2010):
Toxicological Profile for Ethylene Glycol. US Department of Health and
Human Services. US.
Aungst B. and Shen D.D. (1986). Gastrointestinal absorption of
toxic agents. In Rozman K.K. and Hanninen O. Gastrointestinal
Toxicology. Elsevier, New York, US.
ECHA (2017). Guidance on information requirements and chemical
safety assessment, Chapter R.7c: Endpoint specific guidance. Version
3.0, June 2017.
Heymann, E. (1980): Carboxylesterases and amidases. In: Jakoby,
W.B., Bend, J.R. & Caldwell, J., eds., Enzymatic Basis of Detoxication,
2nd Ed., New York: Academic Press, 291-323.
International Programme on Chemical Safety (IPCS) (2001): Ethylene
Glycol. Poisons Information Monograph. PIM 227.
Lehninger, A.L. (1970). Biochemistry. Worth Publishers, Inc.
Long, C.L. et al. (1958). Studies on absorption and metabolism of
propylene glycol distearate. Arch Biochem Biophys, 77(2):428-439.
Mattson F.H. and Volpenhein R.A. (1968). Hydrolysis of primary and
secondary esters of glycerol by pancreatic juice. J Lip Res 9, 79-84.
Mattson F.H. and Nolen G.A. (1972). Absorbability by rats of
compounds containing from one to eight ester groups. J Nutrition, 102:
Stryer, L. (1994): Biochemie. 2nd revised reprint, Heidelberg;
Berlin; Oxford: Spektrum Akad. Verlag.
Tocher, D.R. (2003): Metabolism and Functions of Lipids and Fatty
Acids in Teleost Fish. Reviews in Fisheries Science 11(2), 107-184.
US EPA (2012). Estimation Programs Interface Suite™ for Microsoft®
Windows, v 4.11. United States Environmental Protection Agency,
Washington, DC, USA. Downloaded from:
WHO (2002): Ethylene Glycol: Human Health Aspects. Concise
International Chemical Assessment Document 45.
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.
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