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EC number: 617-969-6 | CAS number: 87135-01-1
- 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
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Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
Key value for chemical safety assessment
Additional information
The only in vivo data on the toxicokinetics of the registered substance is an acute oral gavage study carried out in rats to determine the systemic availability of 1,6-bis(trimethoxysilyl)hexane or its hydrolysis products. To support the assessment of the toxicokinetics of the substance, the following summary has been prepared. It is based on validated predictions of the physicochemical properties of the substance itself and its hydrolysis products and using this data in algorithms that are the basis of many computer-based physiologically based pharmacokinetic or toxicokinetic (PBTK) prediction models. The main input variable for the majority of these algorithms is log Kow so by using this, and other where appropriate, known or predicted physicochemical properties of 1,6-bis(trimethoxysilyl)hexane or its hydrolysis products, reasonable predictions or statements may be made about their potential ADME properties.
In contact with water 1,6-bis(trimethoxysilyl)hexane reacts rapidly (half-life 5.2 hours at pH 7, 0.08 hours at pH 5, 0.15 hours at pH 9 and 25°C) to produce 1,6-bis(trihydroxysilyl)hexane and methanol. Human exposure can occur via the inhalation or dermal routes. Relevant inhalation exposure would be to the parent and hydrolysis products.
The toxicokinetics of methanol have been reviewed in other major reviews and are not considered further here.
Absorption
Oral
When oral exposure takes place it is necessary to assume that except for the most extreme of insoluble substances, that uptake through intestinal walls into the blood takes place. Uptake from intestines must be assumed to be possible for all substances that have appreciable solubility in water or lipid. Other mechanisms by which substances can be absorbed in the gastrointestinal tract include the passage of small water-soluble molecules (molecular weight up to around 200) through aqueous pores or carriage of such molecules across membranes with the bulk passage of water (Renwick, 1993).
Although significant oral exposure is not expected for 1,6 -bis(trimethoxysilyl)hexane, should it occur then with a solubility of 526 mg/l it is reasonable to assume some systemic exposure may occur also.
For the hydrolysis product, 1,6 -bis(trihydroxysilyl)hexane, oral exposure to humans following hydrolysis in the gastro-intestinal tract or via the environment may be relevant. With a higher solubility (1.0E+06 mg/l) than the parent, then should oral exposure to1,6-Bis(trihydroxysilyl)hexane occur then it is reasonable to assume systemic exposure will occur also and to a greater extent than the parent.
The repeated dose oral toxicity studies show evidence of absorption as adverse systemic effects were observed. This is supported by a well reported non-guideline toxicokinetic study which found that single oral doses of the test substance given to rats resulted in the presence of silicon in the blood sampled at 2 and 5 hours after dosing (Dow Corning Corporation, 2009d). Blood silicon concentrations were between two-fold and six-fold higher at 2 h than at 5 h, and higher in males than females. A dose-response relationship was observed, which was more marked at 2h than at 5h. No other toxicokinetic evaluations were made. Based upon the dose concentrations, significant condensation and polymerisation of the hydrolysis product would be expected. The results of this study suggest that absorption of silicon containing substance can occur.
Dermal
The fat solubility and therefore potential dermal penetration of a substance can be estimated by using the water solubility and log Kow values. Substances with log Kow values between 1 and 4 favour dermal absorption (values between 2 and 3 are optimal) particularly if water solubility is high.
The water solubility (526 mg/l) and log Kow(1.7) of the parent substance are therefore favourable for dermal absorption, but this will be limited by the hydrolysis of this substance. For the hydrolysis product, although the water solubility is high (1.0E+06 mg/l), the log Kow(-3.5) is far from the ideal range so dermal penetration would be unlikely.
Therefore once hydrolysis has occurred on the skin, absorption is likely to be reduced.
The available reliable skin irritation study did not provide evidence of absorption as there were no systemic clinical effects reported.
Inhalation
There is a QSPR to estimate the blood:air partition coefficient for human subjects as published by Meulenberg and Vijverberg (2000). The resulting algorithm uses the dimensionless Henry coefficient and the octanol:air partition coefficient (Koct:air) as independent variables.
Using these values for1,6-bis(trimethoxysilyl)hexane results in a high blood:air coefficient of approximately 23000:1 meaning that, if lung exposure occurred there would be uptake in to the systemic circulation. The high water solubility of the hydrolysis product,1,6-bis(trihydroxysilyl)hexane, results in a markedly higher blood:air partition coefficient (approximately 3.8E+15:1) so once hydrolysis has occurred, as it would be expected to in the lungs, then significant uptake would be expected into the systemic circulation. However, the high water solubility of 1,6-bis(trihydroxysilyl)hexane may lead to some of it being retained in the mucus of the lungs so once hydrolysis has occurred, absorption is likely to slow down
Distribution
For blood:tissue partitioning a QSPR algorithm has been developed by De Jongh et al. (1997) in which the distribution of compounds between blood and human body tissues as a function of water and lipid content of tissues and the n-octanol:water partition coefficient (Kow) is described. Using this value for1,6-Bis(trimethoxysilyl)hexane predicts that, should systemic exposure occur, distribution would primarily be into fat, with potential distribution into liver, muscle, brain and kidney but to a much lesser extent.
For the hydrolysis product,1,6-Bis(trihydroxysilyl)hexane, distribution would be minimal with tissue:blood partition coefficients of less than 1 for all tissues (zero for fat).
Table 1: tissue:blood partition coefficients
|
Log Kow |
Kow |
Liver |
Muscle |
Fat |
Brain |
Kidney |
1,6-Bis(trimethoxysilyl) |
1.7 |
50.12 |
1.8 |
1.4 |
32.3 |
1.5 |
1.2 |
1,6-Bis(trihydroxysilyl) |
-3.5 |
3.16E-04 |
0.6 |
0.7 |
0.0 |
0.7 |
0.8 |
Metabolism
There are no data regarding the metabolism of 1,6 -bis(trimethoxysilyl)hexane. Genetic toxicity tests in vitro showed no observable differences in effects with and without metabolic activation for1,6 -bis(trimethoxysilyl)hexane.
Excretion
A determinant of the extent of urinary excretion is the soluble fraction in blood. QPSRs as developed by De Jongh et al. (1997) using log Kow as an input parameter, calculate the solubility in blood based on lipid fractions in the blood assuming that human blood contains 0.7% lipids.
Using this algorithm, the soluble fraction of 1,6-bis(trimethoxysilyl)hexane in blood is approximately 74% while the corresponding value for the hydrolysis product,1,6-bis(trihydroxysilyl)hexane, is > 99%. Therefore these figures suggest that both the parent and the hydrolysis product are likely to be effectively eliminated via the kidneys in urine and accumulation is therefore unlikely.
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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