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EC number: 221-800-8
CAS number: 3238-40-2
A toxicokinetic assessment was performed based on the available data of the substance.
A substance can enter the body via the
gastrointestinal tract, the lungs, and the skin. To determine the
absorption rate, the different routes are assessed individually. In
general, a compound needs to be dissolved before it can be taken up from
the gastrointestinal tract after oral administration. The low molecular
weight of FDCA (approximately 156) favors uptake via passive diffusion.
FDCA is slightly soluble in water (0.899 g/L), therefore the substance
will dissolve into the gastrointestinal fluids to some extent and can
potentially be taken up. FDCA contains two ionisable carboxylgroups, and
it is therefore expected to ionize as soon as it dissolves in the fluids
of the gastro-intestinal tract. It is generally assumed that ionized
substances do not readily diffuse across biological membranes, although
the absorption of ionic substances (i.e. acids and bases) is influenced
by the varying pH of the GI tract. This is also reflected in the Pow,
which varies at different pH values: at pH 1.9, a log Pow of 0.56 was
measured, which decreases to -1.43 at neutral pH. This indicates that
the Pow will vary at different sites of the gastrointestinal tract. At
neutral pH, the substance will be more hydrophilic, which will hamper
passive diffusion. At lower pH, the log Pow is expected to be moderate
which is favourable for absorption by passive diffusion. Although its
low molecular weight and moderate Pow at low pH favour passive
absorption, its hydrophilicity at neutral pH, its low water solubility,
the size of the particles and the ionic dissociation are expected to
hamper optimal uptake, therefore, for risk assessment purposes oral
absorption of FDCA is set at 50%. The oral toxicity data do not provide
reason to deviate from the proposed oral absorption factor. Once
absorbed, wide distribution of the substance throughout the body is
expected to be limited based on its low water solubility. Absorbed FDCA
is most likely excreted via urine. Based on its moderate to low
partition coefficient -1.43 to 0.56), it is very unlikely that FDCA will
accumulate in adipose tissue. The low vapour pressure (5.6*10-10 Pa at
25°C) indicates that it is not likely that FDCA will reach the
nasopharyncheal region or subsequently the tracheo/bronchial/pulmonary
region via inhalation of vapour. The mean particle size is above 100 μm,
with 50% below 439 μm and 10% of the particles smaller than 164 μm. In
humans, particles with aerodynamic diameters below 100 μm have the
potential to be inhaled. For FDCA, this fraction is about 4.66%.
Particles with aerodynamic diameters below 50 μm may reach the thoracic
region and those below 15 μm the alveolar region of the respiratory
tract (for FDCA these fractions were found to be approximately 1.9% and
0.4% respectively). However, once FDCA reaches the tracheobronchial
region, it is likely to dissolve within the mucus lining the respiratory
tract and to get absorbed. Based on the above data, for risk assessment
purposes the inhalation absorption of FDCA is set at 100%.
FDCA is a powder. When it comes in contact
with the skin without additional water, uptake will be limited. However,
it may dissolve into the surface moisture of the skin. The first layer
of the skin, the stratum corneum, is a barrier for hydrophilic
compounds. FDCA has a moderate to low log Pow. Since the pH of the skin
is in the acidic range (between pH 4.0 to 7.0), which means that the Pow
of the substance will be above 0 and is likely to be sufficiently
lipophilic to cross the stratum corneum. However, as for oral absorption
also for skin absorption the ionisable structure might negatively
influence adsorption. According to the criteria given in the REACH
Guidance, 10% dermal absorption will be considered in case MW >500 andlog
Pow <-1 or >4, otherwise 100% dermal absorption should be used. As the
physical/chemical properties of FDCA do not meet the criteria for
limited dermal absorption (MW 156 and log Pow between -1.43 and 0.56 at
physiological pH range), for risk assessment purposes dermal absorption
should be set at 100%. However, as it is generally accepted that dermal
absorption does not exceed oral absorption, 50% dermal absorption of
FDCA is considered a more realistic dermal absorption factor for risk
assessment purposes. The results of the toxicity studies do not provide
reasons to deviate from this proposed dermal absorption factor.
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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