Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 825-814-0
CAS number: 222721-94-0
The water solubility of target substance 1,2,3-Propanetricarboxylic
acid, 2-hydroxy-, tri-C14-15-alkyl esters and the source substances is
very low (< 1 mg/L), therefore dissolution is regarded to be the rate
limiting step for gastrointestinal absorption. The similar substance
stearyl citrate is hydrolysed readily to stearyl alcohol and citric acid
in dogs, and to a lesser extent, in rats. Stearyl citrate, predominantly
as distearyl citrate, added to the fee of rats at a concentration of
2.5-10 % was poorly absorbed . These data that the intact substance is
not likely to be absorbed, but will be hydrolysed by gastro-intestinal
esterases. Hydrolysis in the rat is readily saturated and is
insignificant at high levels of exposure, whereas a higher level of
hydrolysis (~50%) is seen in the dog at high dose levels. The limited
absorption seen with the test material used in this study is likely to
be due largely to the mono-citrate, the results therefore indicate that
the absorption of the registered substance (which consists of tri-esters
only) will be even more limited in the rat.
Dermal absorption of the substances is not predicted based on its
physicochemical properties. Inhalation exposure to the substance is not
predicted based on its physicochemical properties.
Systemic distribution of the intact substances are not predicted.
Following gastrointestinal hydrolysis, absorption and subsequent
distribution of the hydrolysis product citric acid is likely. Citric
acid is a normal metabolic intermediate; citric acid resulting from
hydrolysis of the target substances and the Source substances and will
be distributed systemically but will be indistinguishable from the large
amounts of citric acid normally present in the body.
Orally administered the metabolite citric acid is well absorbed and
largely metabolized. Exogenous and endogenous citric acid can be
completely metabolized and serve as a source of energy. Citric acid is
an intermediate in the Krebs cycle. Citric acid completes the breakdown
of pyruvate, formed from glucose through glycolysis, and it liberates
carbon dioxide. Approximately 2 kg of citric acid are formed and
metabolized every day in humans. Ten to 35 % of filtered citrate is
excreted in the urine. The normal blood citrate level in humans is
approximately 25 mg/L.
The initial step in the mammalian metabolism of primary alcohols is the
oxidation to the corresponding carboxylic acid, with the corresponding
aldehyde being a transient intermediate. These carboxylic acids are
susceptible to further degradation via acyl-CoA intermediates by the
mitochondrial ß-oxidation process. This mechanism removes C2 units in a
stepwise process and linear acids are more efficient in this process
than the corresponding branched acids. In the case of unsaturated
carboxylic acids, cleavage of C2-units continues until a double bond is
reached. Since double bonds in unsaturated fatty acids are in the
cis-configuration, whereas the unsaturated acyl-CoA intermediates in the
ß-oxidation cycle are trans, an auxiliary enzyme, enoyl-CoA isomerase
catalyses the shift from cis to trans. Thereafter, ß-oxidation continues
as with saturated carboxylic acids.
An alternative metabolic pathway for aliphatic acids exists through
microsomal degradation via omega-or omega–1 oxidation followed by
β-oxidation. This mechanism provides an efficient stepwise
chain-shortening pathway for branched aliphatic acids.
The acids formed from the longer chained aliphatic alcohols can also
enter the lipid biosynthesis and may be incorporated in phospholipids
and neutral lipids. A small fraction of the aliphatic alcohols may be
eliminated unchanged or as the glucuronide conjugate.
With regards to the blood-brain barrier a chain-length dependent
absorption potential exists with the lower aliphatic alcohols and acids
more readily being taken up than aliphatic alcohols/acids of longer
chain-length. Taking into account the efficient biotransformation of the
alcohols and the physico-chemical properties of the corresponding
carboxylic acids the potential for elimination into breast milk is
considered to be low.
The long chain aliphatic carboxylic acids are efficiently eliminated and
aliphatic alcohols are therefore not expected to have a tissue retention
or bioaccumulation potential. Longer chained aliphatic alcohols within
this category may enter common lipid biosynthesis pathways and will be
indistinguishable from the lipids derived from other sources (including
A comparison of the linear and branched aliphatic alcohols shows a high
degree of similarity in biotransformation. For both sub-categories the
first step of the biotransformation consists of an oxidation of the
alcohol to the corresponding carboxylic acids, followed by a stepwise
elimination of C2 units in the mitochondrial β-oxidation process. The
metabolic breakdown for both the linear and mono-branched alcohols is
highly efficient and involves processes for both sub-groups of alcohols.
The presence of a side chain does not terminate the β-oxidation process,
however in some cases a single Carbon unit is removed before the C2
elimination can proceed.
In summary, long chained alcohols are generally highly efficiently
metabolised and there is limited potential for retention or
bioaccumulation for the parent alcohols and their biotransformation
The high log Pow value of the both target substances implies that they
have the potential to accumulate in adipose tissue. However, as they
undergo esterase-catalysed hydrolysis, the accumulation potential of the
cleavage products has to be considered. Substances with high water
solubility, like the alcohol, do not have the potential to accumulate in
adipose tissue due to their low log Pow. Overall, the available
information indicates that no significant bioaccumulation in adipose
tissue is anticipated.
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.
Ce site web utilise des cookies afin de vous garantir la meilleure expérience possible sur nos sites web.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again