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EC number: 479-930-8
CAS number: 613222-52-9
SIKA Hardener LH rapidly hydrolyses upon
contact with water. Further, the hydrolysis reaction is catalysed in an
acid environment. Calculated partition coefficient logPow is 14.22 and
estimated water solubility is 5.5E-11 mg/L.
The estimated partition coefficient
indicates that the compound is not likely to penetrate skin. However,
even if dermally absorbed, its toxicity is very low. Although no acute
dermal toxicity study was carried out, the compound was assessed in a
skin irritation and skin sensitisation study. In the skin irritation
study, using rabbits, no local effects or systemic toxicity were noted,
following topical application of Sika Hardener LH. A guinea pig
maximisation test did not reveal any signs of toxicity either and the
compound was classified a non-sensitiser. Furthermore, the aldehyde
hydrolysis product did not cause any systemic toxicity, following dermal
application (LD50 > 2000 mg/kg bw) nor did any of the polyamines formed
(LD50 > 2000 mg/kg bw, BASF correspondence and IUCLID-data).
Due to its high reactivity, orally ingested
Sika Hardener LH will undergo spontaneous hydrolysis upon reaching the
stomach, especially as the hydrolysis reaction is acid catalysed. The
portion of Sika Hardener LH not hydrolysed immediately will, most
probably, not solubilise in the stomach, due to its low solubility.
Consequently, Sika Hardener LH is not likely to cross GI-tract
membranes. Taken together, absorption of Sika Hardener LH and
consequently bioavailability is rather unlikely.
The products of Sika Hardener LH
decomposition are the aldehyde 2,2-dimethyl-3-lauroyloxy-propanal and
respective polyamine (Hexamethylenediamine). The aldehyde is not stable
in water-based systems and further degrades, forming carbonic acid and
several short-chain polar compounds. The polyamines formed might also be
transformed further, most likely in enzyme catalysed metabolism. Even
though the Sika Hardener LH degradation products might be absorbed and
become bioavailable, they are of low toxicity .
One of the most important pathway of
aldehyde metabolism is oxidation to carboxylic acids by aldehyde
dehydrogenases (Vasiliou et al., 2000). The enzymes involved in these
detoxification reactions most probably belong to the category of
aldehyde dehydrogenases, known to be relatively substrate unspecific,
but effective in protecting organisms from potentially harmful
xenobiotics (Sladek, 2003). Other phase I metabolic reactions may
include cytochrome P450 mediated transformations such as aldehyde
reductions or aldehyde scissions. Following phase I metabolic reactions
or chemical decomposition, the formed metabolites are rendered more
polar by phase II metabolism. Most likely the carboxylic acid
metabolites are ultimately conjugated with glycine or glutamine and
excreted in urine or bile.
Any polyamines, formed by hydrolysis of Sika
Hardener LH, that reach the body’s systemic circulation are probably
either excreted in unchanged form or metabolised by the cytochrome P450
system or by amine oxidases. Phase I metabolism of polyamines is likely
to be followed by phase II metabolism, possibly rendering molecules even
more polar. Likely conjugation compounds are glycine and glutamine,
preceding the metabolites eventual elimination in urine or bile.
Toxicokinetic assessment of
hexamethylenediamine, used as a model compound, revealed that the amine
is rapidly distributed systemically following i.v. administration to
rats, and completely excreted within 72 hours, via urine (47 %), faces
(27 %) and respiration (20 %). Similar excretion can be assumed for all
polyamine degradation products.
Excretion analysis in humans following oral
administration, using the same model compound hexamethylenediamine,
revealed that more than 90 % is eliminated in urine, during the first 10
hours post administration, either unchanged or metabolised to
6-aminohexanoic acid. A human inhalation study revealed that 90 % were
eliminated within the first 28 hours following exposure to 25 μg/m3. In
a second human inhalation study and exposure to 30 μg/m3, 90 %
hexamethylenediamine was eliminated via the urine within the first three
hours. For the human inhalation studies the renal half-life of
hexamethylenediamine was determined to be 1.4 hours and 1.2 hours,
respectively. A similar excretion pattern can be assumed for all
polyamine degradation products in humans.
It is unlikely that metabolism will render
neither the parent compound nor its degradation products more toxic.
This assumption is supported by results obtained in an in vitro Ames
test and a chromosome aberration test. In both assays no significant
increases in toxicity were noted, in the presence of a rodent microsomal
S9-fraction. This clearly indicates that formation of reactive
metabolites is unlikely.
Based on the reactive nature of Sika
Hardener LH and its limited stability in water-based systems,
bioaccumulation is not likely to occur. Orally consumed hardener is most
rapidly hydrolysed to aldehyde and polyamine, with the reaction being
acid catalysed. Thus, absorption of SIKA Hardener LH is most unlikely.
Although the results of the sub chronic toxicity reveal alterations in
the spleen in females in form of macroscopically enlargement associated
with increases in spleen weight accompanied by splenic hyperplasia after
exposure with Sika Hardener LH, this effect is most likely attributed to
the hydrolysis product Aldehyde L (see disseminated dossier published on
the ECHA homepage, submitted by Incorez Ltd.). Splenic
alterations were fully reversible after exposure with SIKA Hardener LH
or Aldehyde L; however, changes in the spleen weight were detected at
the end of the recovery period.
Even though the degradation products might
be absorbed and become bioavailable, toxicity is low bioconcentration
rather unlikely. Absorbed or bioavailable degradation products are
probably excreted, either in original form or further metabolised, prior
to elimination via urine or bile. Formation of toxic metabolites is
unlikely, based on the results of the sub acute toxicity study and two
in vitro studies using isolated S9 fractions as well as the
reversibility of the spleen alterations in the sub chronic toxicity
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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