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EC number: 926-191-9 | CAS number: 1181221-96-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
Based on the physicochemical properties systemic availability of the UVCB substance itself
may be limited but cannot be completely excluded following oral intake. Moreover,
hydrolysis may enhance the chemical’s overall absorption properties. Due to hydrolysis of the
alkyloxysilane groups free methanol is formed which will be readily taken up through the
walls of the GI tract. However, the absence of any specific effects in the toxicity studies
indicates that only negligible amounts of methanol emerge from hydrolysis reactions.
Although the physicochemical properties do not favour transdermal absorption, the
immunological response observed in a LLNA provides evidence that at least small amounts of
the UVCB substance itself or its respective hydrolysis products become systemic available
following dermal administration. Considering the low vapour pressure no relevant amounts of
the UVCB substance are expected to be inhalable under normal use conditions. Based on the
physicochemical properties and the calculated BCF values neither the parent molecule nor its
hydrolysis products are considered to be bioaccumulative.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
1 Physicochemical Data on Hexamethylene diisocyanate, oligomers, reaction products with N-(3-trimethoxysilyl)propylbutylamine and Bis-(Trimethoxysilylpropyl)amine
The UVCB substance Hexamethylene diisocyanate, oligomers, reaction products with N-(3-
trimethoxysilyl)propylbutylamine and Bis-(Trimethoxysilylpropyl)amine appears as a viscous,
clear liquid at standard ambient temperature and pressure. The molecular weight of the UVCB
substance will be found in the range of approximately > 500 to 1800 g/mol.
The substance has a very low vapour pressure of 1x 10^-4 Pa at 20°C which can be regarded as
negligible for the present assessment. The UVCB substance has a very low water solubility
and is considered to be practically insoluble in aqueous solutions. Depending on the different
structures the respective logPow values, estimated by Epiwin, are expected to be in the range
of 3 to 10. The BCF values for the UVCB substance, as estimated by scientifically accepted
calculation models (CATALOGIC v5.11.2, and EPI suite v3.20), fall in the range of 2.35 to
60.67. The UVCB substance is reactive with water. More specifically, when placed in an
aqueous solution (e.g. in the body), the isocyanate end groups will readily hydrolyse to yield
carbamic acid, which decarboxylates to produce CO2 and an amine end group. Furthermore
the alkyloxysilane groups will readily become hydroxylated and form free methanol. Due to
the slow reaction, hydrolysis of the urea groups are not considered to play an important role
with regard to this assessment.
2 Toxicokinetic Analysis of Hexamethylene diisocyanate, oligomers, reaction products
with N-(3-trimethoxysilyl)propylbutylamine and Bis-(Trimethoxysilylpropyl)amine
Absorption
Oral route:
In order to be absorbed into the systemic circulation, chemicals have to dissolve into the
gastro-intestinal (GI) fluids and make contact with the mucosal surface. Hence, the poor water
solubility of the UVCB substance may drastically reduce the amount available for uptake into
the systemic circulation.
Moreover, the molecular weight of the reaction products itself (> 500 g/mol) does not favour
absorption into the systemic circulation via the GI tract. However, once the water reactive
chemicals come in contact with the digestive fluids of the stomach, hydrolysis reactions will
enhance the overall absorption properties. In addition, smaller more polar compounds are
formed. More specifically hydrolysis of the alkyloxysilane groups will yield small amounts of
free methanol which are known to be readily absorbed from the GI tract (Barceloux et al.,
2002).
With regards to toxicological data, an acute oral systemic toxicity studies in rats (OECD 423)
conducted with the UVCB substance determined the respective LD50 value to be greater
2000 mg/kg (limit dose). Besides local effects in the GI tract of a single animal, no systemic
effects were observed. Similarly no definite signs of systemic toxicity were observed in a 14
day dose range finding study with rats. Here, slightly lower body weights, protein and
albumin levels at the highest testing dose of 1000 mg/kg bw/day, were regarded as secondary
effects induced by local irritation of the GI system. No further effects were noted.
In a combined repeated dose toxicity study with the reproduction/developmental toxicity
screening test in rats (OECD 422) one female animal died spontaneously due to severe
ulceration of the forestomach after receiving the high dose of 750 mg/kg bw/day. Also a
decreased body weight gain in males was noted which was regarded as a secondary effect
resulting from local irritation of the forestomach. No further effects were observed in the
parental animals. Conclusively, the systemic NOAEL was determined to be 750 mg/kg
bw/day while the NOAEL for local toxicity was set to 75 mg/kg bw/day due to the observed
GI tract irritation. No effects on reproduction and offspring development were noted and the
respective NOAELs were determined to be 750 mg/kg bw/day.
Overall, based on the physicochemical properties and the results obtained in the toxicity
studies, systemic availability of the UVCB substance itself seems to be limited but cannot be
completely excluded following oral intake. Hydrolysis reactions acting on the reaction
products may enhance the overall absorption properties. As indicated above, free methanol is
formed by hydrolysis reactions which in turn is readily absorbed through the walls of the GI
tract. However, the absence of any specific effects in the toxicity studies indicates that only
minor amounts of methanol emerge by hydrolysis.
Inhalation route:
Considering the low vapour pressure and the resulting low volatility, it is unlikely that the
UVCB substance will become bioavailable via inhalation when handled at room temperature.
Furthermore, results obtained from an acute inhalation toxicity study (OECD 403) where rats
were exposed to a liquid aerosol form of the UVCB substance, indicate that even if the
substance becomes inhalable, no adverse systemic effects are to be expected. The respective
LD50 value was estimated to be 5.03 mg/L, a concentration which is above the limit dose.
Dermal route:
The physicochemical properties of the UVCB substance itself such as molecular weight and
water solubility, do not favour dermal absorption. Also the amount of methanol, produced by
hydrolysis reactions with air humidity, is regarded to be negligible for dermal exposure.
However, the immunological response observed in a local lymph node assay (LLNA) with
mice (OECD 429) provides evidence that at least small amounts of the UVCB substance itself
or its respective hydrolysis products become systemic available following dermal
administration.
Distribution
With regards to the physicochemical properties and the results achieved from the
comprehensive toxicity testing, it appears that the bioavailability of the UVCB substance
itself via the main entrance routes (i.e., oral, dermal and through inhalation) is limited but
cannot be excluded. If any amounts of the UVCB substance or its hydrolysis products become
systemically available, they will be most likely transported within the body via the blood
stream. Due to the absence of systemic effects in the oral toxicity studies, there are no hints
with regard to any potential target organ.
Once absorbed, the minor amounts of methanol formed by hydrolysis reactions will be
distributed within the body via the blood stream before being transported to the liver (Wu
Chen et al., 1985).
Metabolism
Because absorption of the UVCB substance itself into the interior part of the body cells is
considered to be limited, considerable contact of the substance with intracellular metabolising
enzymes is unlikely. However, in the event that the UVCB substance or its hydrolysis
products reach the systemic circulation it cannot be ruled out that they are metabolised by
Phase I enzymes while undergoing functionalisation reactions aiming to increase their
hydrophilicity. Furthermore, Phase II conjugation reactions may covalently link an
endogenous substrate to the chemicals or its Phase I metabolites in order to ultimately
facilitate excretion.
Following absorption, the hydrolysis product methanol is readily metabolised by alcohol
dehydrogenase to formaldehyde, which is further metabolised to formic acid. Formic acid
dissociates to formate and a hydrogen ion. Formate is metabolised to CO2 and water by a
folate-dependent mechanism.
Excretion
As mentioned before, it is expected that the bioavailability of the UVCB substance itself is
most likely to be limited and distribution into the body will be low. Thus it is expected that
following oral ingestion the vast majority of the chemicals is excreted with the faeces.
However, if a certain amount of the reaction product is absorbed, it will most likely be
excreted via the urine following potential metabolism reactions. Moreover, it is highly
unlikely that bioaccumulation within the body will occur according to the estimated BCF
values. Absorbed amounts of methanol will be either excreted as parent compound in the
urine or via expired air, or as formic acid metabolite in urine (Rowe and McCollister 1981).
3 Summary
Based on the physicochemical properties systemic availability of the UVCB substance itself
may be limited but cannot be completely excluded following oral intake. Moreover,
hydrolysis may enhance the chemical’s overall absorption properties. Due to hydrolysis of the
alkyloxysilane groups free methanol is formed which will be readily taken up through the
walls of the GI tract. However, the absence of any specific effects in the toxicity studies
indicates that only negligible amounts of methanol emerge from hydrolysis reactions.
Although the physicochemical properties do not favour transdermal absorption, the
immunological response observed in a LLNA provides evidence that at least small amounts of
the UVCB substance itself or its respective hydrolysis products become systemic available
following dermal administration. Considering the low vapour pressure no relevant amounts of
the UVCB substance are expected to be inhalable under normal use conditions. Based on the
physicochemical properties and the calculated BCF values neither the parent molecule nor its
hydrolysis products are considered to be bioaccumulative.
4 References
Barceloux D.G., Bond R., Krenzelok E.P., Cooper H,. Vale J.A. (2002) American Academy
of Clinical Toxicology Practice Guidelines on the Treatment of Methanol Poisoning. Ad Hoc
Committee. Journal of Toxicology - Clinical Toxicology; 40(4):415-46.
Bonse G., Metzler M. (1978) Biotransformation organischer Fremdsubstanzen. Thieme
Verlag, Stuttgart.
ECHA (2008) Guidance on information requirements and chemical safety assessment,
Chapter R.7c: Endpoint specific guidance.
Marquardt H., Schäfer S. (2004) Toxicology. Academic Press, San Diego, USA, 2nd Edition
688-689.
Mutschler E., Schäfer-Korting M. (2001) Arzneimittelwirkungen. Lehrbuch der
Pharmakologie und Toxikologie. Wissenschaftliche Verlagsgesellschaft, Stuttgart.
Renwick A.G. (1994) Toxicokinetics - pharmacokinetics in toxicology. In Hayes,A.W. (ed.)
Principles and Methods of Toxicology. Raven Press, New York, p 103.
Rowe V.K., McCollister S.B. (1981) Alcohols. In: Patty's Industrial Hygiene and Toxicology,
3rd ed. Vol. 2C, G.D. Clayton, F.E. Clayton, John Wiley & Sons, New York:4528-4541.
Rozman K.K., Klaassen C.D. (1996) Absorption, Distribution, and Excretion of Toxicants. In
Klaassen C.D. (ed.) Cassarett and Doull's Toxicology: The Basic Science of Poisons.
McGraw-Hill, New York.
Wu Chen N.B., Donoghue E.R., Schaffer M.I. (1985) Methanol intoxication: distribution in
postmortem tissues and fluids including vitreous humor. Journal of Forensic Sciences,
30(1):213-6.
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.
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