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If aquatic exposure occurs, polyol esters category members will be mainly taken up by ingestion and digested through common metabolic pathways providing a valuable energy source for the organisms as dietary fats. The category members are not expected to bioaccumulate in aquatic or sediment organisms and secondary poisoning does not pose a risk.
Experimental bioaccumulation data are not available for the
members of the polyol ester category. The high log Kow as an intrinsic
property of the category members indicates a potential for
bioaccumulation. But it does not reflect the behavior of the substance
in the environment and the metabolism in living organisms.
Due to ready biodegradability and high potential of adsorption,
the category members can be effectively removed in conventional STPs
either by biodegradation or by sorption to biomass. The low water
solubility and high estimated log Kow indicate the substance is highly
lipophilic. If released into the aquatic environment, the substance
undergoes extensive biodegradation and sorption on organic matter, as
well as sedimentation. The bioavailability of the substance in the water
column is reduced rapidly. The relevant route of uptake of polyol esters
in organisms is considered predominately by ingestion of particle
Metabolism of polyol esters
Should the substance be taken up by fish during the process of
digestion and absorption in the intestinal tissue, polyol esters are
expected to be initially metabolized via enzymatic hydrolysis in the
corresponding free fatty acids and the free alcohols such as
neopentylglycol (NPG), trimethylolpropane (TMP), pentaerythritol (PE)
and dipentaerythritol (DiPE). The hydrolysis is catalyzed by classes of
enzymes known as carboxylesterases or esterases (Heymann, 1980). The
most important of which are the B-esterases in the hepatocytes of
mammals (Heymann, 1980; Anders, 1989). Carboxylesterase activity has
been noted in a wide variety of tissues in invertebrates as well as in
fish (Leinweber, 1987; Suldano et al, 1992; Barron et al., 1999,
Wheelock et al., 2008). The catalytic activity of this enzyme family
leads to a rapid biotransformation/metabolism of xenobiotics which
reduces the bioaccumulation or bioconcentration potential (Lech & Bend,
1980). It is known for esters that they are readily susceptible to
metabolism in fish (Barron et al., 1999) and literature data have
clearly shown that esters do not readily bioaccumulate in fish (Rodger &
Stalling, 1972; Murphy & Lutenske, 1990; Barron et al., 1990). In fish
species, this might be caused by the wide CaE distribution, high tissue
content, rapid substrate turnover and limited substrate specificity
(Lech & Melancon, 1980; Heymann, 1980).
Metabolism of enzymatic hydrolysis products
Neopentylglycol (NPG), trimethylolpropane (TMP), pentaerythritol
(PE) and dipentaerythritol (DiPE) are the expected possible
corresponding alcohol metabolites from the enzymatic reaction of the
polyol ester category members. In general, the hydrolysis rate of fatty
acid esters and polyol ester in particular varies depending on the fatty
acid chain length, and grade of esterification (Mattson and Volpenhein,
1969; Mattson and Volpenhein, 1972a,b).
In the gastrointestinal GI tract(GIT), metabolism prior to
absorption via gut microflora or enzymes in the GI mucosa may occur. In
fact, after oral ingestion, fatty acid esters with glycerol (glycerides)
are rapidly hydrolized by ubiquitously expressed esterases and almost
completely absorbed (Mattson and Volpenhein, 1972a).The result of the
pancreatic digestion of one NPG ester shows a degradation of the ester
of almost 90% within 4 hours (Oßberger, 2012). In contrast with regard
to the Polyol esters it was shown that lower rate of enzymatic
hydrolysis in the GIT were showed for compounds with more than 3 ester
groups (Mattson and Volpenhein, 1972a,b). In vitro hydrolysis rate of
pentaerythritol ester was about 2000 times slower in comparison to
glycerol esters (Mattson and Volpenhein, 1972a,b).
When hydrolysis occurs the potential hydrolysis products are
absorbed and subsequently enter the bloodstream. Potential cleavage
products are stepwise degraded via beta–oxidation in the mitochondria.
Even numbered fatty acids are degraded via beta-oxidation to carbon
dioxide and acetyl-CoA, with release of biochemical energy. In contrast,
the metabolism of the uneven fatty acids results in carbon dioxide and
an activated C3-unit, which undergoes a conversion into succinyl-CoA
before entering the citric acid cycle (Stryer, 1994). Alternative
oxidation pathways (alpha- and omega-oxidation) are available and are
relevant for degradation of branched fatty acids.
The other cleavage products Polyols (NPG, TMP and PE) are easily
absorbed and can either remain unchanged (PE) or may further be
metabolized or conjugated (e.g. glucuronides, sulfates, etc.) to polar
products that are excreted in the urine (Gessner et al. 1960, Di Carlo
et al., 1964).
Lipids and their key constituent fatty acids are, along with
protein, the major organic constitute of fish and they play a major role
as sources of metabolic energy in fish for growth, reproduction and
movement, including migration (Tocher, 2003). In fishes, the fatty acids
metabolism in cell covers the two processes anabolism and catabolism.
The anabolism of fatty acids occurs in the cytosol, where fatty acids
esterified into cellular lipids that is the most important storage form
of fatty acids. The catabolism of fatty acids occurs in the cellular
organelles, mitochondria and peroxisomes via a completely different set
of enzymes. The process is termed beta-oxidation and involves the
sequential cleavage of two-carbon units, released as acetyl-CoA through
a cyclic series of reaction catalyzed by several distinct enzyme
activities rather than a multienzyme complex (Tocher, 2003).
As fatty acids are naturally stored in fat tissue and re-mobilized
for energy production is can be concluded that even if they
bioaccumulate, bioaccumulation will not pose a risk to living organisms.
Fatty acids (typically C14 to C24 chain lengths) are also a major
component of biological membranes as part of the phospholipid bilayer
and therefore part of an essential biological component for the
integrity of cells in every living organism (Stryer, 1994).
Data from QSAR calculation
Additional information about this endpoint could be gathered
through BCF/BAF calculation using BCFBAF v3.01. The estimated BCF value
indicates a low bioaccumulation in organisms (BCF: 3.16 - 550 L/kg,
regression based). When including biotransformation rate constants a BCF
of 0.89 – 24.7 and a BAF of 0.89 – 24.7 L/kg resulted (Arnot-Gobas
estimate, including biotransformation, upper trophic). Even though the
members of the polyol ester category are outside the applicability
domain of the model they might be used as supporting indication that the
potential of bioaccumulation is low. The model training set is only
consisting of substances with log Kow values of 0.31 - 8.70. But it
supports the tendency that substances with high log Kow values (> 10)
have a lower potential for bioconcentration as summarized in the ECHA
Guidance R.11 and they are not expected to meet the B/vB criterion
Polyol esters are biotransformed to fatty acids and the
corresponding alcohol component by the ubiquitous carboxylesterase
enzymes in aquatic species. Based on the rapid metabolism it can be
concluded that the high log Kow, which indicates a potential for
bioaccumulation, overestimates the bioaccumulation potential of the
polyol ester category members. Taking all these information into
account, it can be concluded that the bioaccumulation potential of the
polyol ester category members is assumed to be low.
Anders, M.W. (1989): Biotransformation and bioactivation of
xenobiotics by the kidney. In: Hutson, D.H., Caldwell, J. & Paulson,
G.D., eds, Intermediary Xenobiotic Metabolism in Animals, New York:
Taylor & Francis, pp. 81-97.
Barron, M.G., Charron, K.A., Stott, W.T., Duvall, S.E. (1999):
Tissue carboxylesterase activity of rainbow trout. Environmental
Toxicology and Chemistry. 18(11), 2506-2511.
Barron, M.G., Mayes, M.A., Murphy, P.G., Nolan, R.J. (1990):
Pharmacokinetics and metabolism of triclopyr butoxyethyl ester in coho
salmon. Aquatic Tox., 16, 19-32.
Di Carlo F.J., Hartigan J.M. Jr., Couthino, C.B. and Phillips,
G.E. (1965): Absorption, distribution and excretion of Pentaerythritol
and Pentaerythritol Tetranitrate by mice. Proceedings of the Society for
Experimental Biology and Medicine. 118: 311-314.
ECHA (2012): Guidance on information requirements and chemical
safety assessment. Chapter R.11: PBT Assessment.
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, pp. 291-323.
Gessner PK, Parke DV, Williams RT (1960) Studies in detoxication. 80.
The metabolism of glycols Biochem J 74: 1-5.
Lech, J.J. & Bend, J.R. (1980): Relationship between
biotransformation and the toxicity and fate of xenobiotix chemicals in
fish. Environ. Health Perspec. 34, 115-131.
Lech, J., Melancon, M. (1980): Uptake, metabolism, and deposition
of xenobiotic chemicals in fish. EPA-600 3-80-082. U.S. Environmental
Protection Agency, Duluth, MN.
Leinweber, F.J. (1987): Possible physiological roles of carboxylic
ester hydrolases. Drug. Metab. Rev. 18: 379-439.
Mattson, F.H. and Volpenhein, R.A. (1969): Relative rates of
hydrolysis by rat pancreatic lipase of esters of C2 - C18 fatty acids
with C1 – C18 primary n-alcohols. J Lipid Res Vol(10): 271 – 276.
Mattson F.H. and Volpenhein R.A., 1972a: Hydrolysis of fully
esterified alcohols containing from one to eight hydroxyl groups by the
lipolytic enzymes of rat pancreatic juice. J Lip Res 13, 325-328.
Mattson F.H. and Volpenhein R.A., 1972b: Digestion in vitro of
erythritol esters by rat pancreatic juice enzymes. J Lip Res 13, 777-782.
Murphy, P.G., Lutenske, N.E. (1990): Bioconcentration of
haloxyfop-methyl in bluegill (Lepomis macrochirus Rafinesque). Environ.
Intern. 16, 219-230.
Oßberger, M., 2012:Investigation of the hydrolysis behaviour of
2,2-dimethyl-1,3-propandiolheptanoate. Report No. 3635-12. Croda Europe
Limited, Goole, UK.
Rodger, C.A., Stalling, D.L. (1972): Dynamics of an ester of 2,3-D
in organs of three fish species.Weed Sci. 20, 101-105.
Stryer, L. (1994): Biochemie. 2nd revised reprint, Heidelberg;
Berlin; Oxford: Spektrum Akad.Verlag.
Suldano, S., Gramenzi, F., Cirianni, M., Vittozzi, L. (1992):
Xenobiotic-metabolizing enzyme systems in test fish - IV. Comparative
studies of liver microsomal and cytosolic hydrolases. Comparative
Biochemistry and Physiology Part C: Comparative Pharmacology. 101(1),
Tocher, D.R. (2003): Metabolism and Function of Lipid and Fatty
Acids in Teleost Fish. Review in Fisheries Science. 11(2), 107-184.
Wheelock, C.E., Phillips, B.M., Anderson, B.S., Miller, J.L.,
Hammock, B.D. (2008): Applications of carboxylesterase activity in
environmental monitoring and toxicity identification evaluations (TIEs).
Reviews in Environmental Contamination and Toxicology 195:117-178.
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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