Reaction mass of trimethyl(octadecyloxy)silane and octadecanol

Endpoint summary

Additional information

1.1.1   

There are no in vitro or in vivo data on the toxicokinetics of the registration substance, reaction mass of octadecan-1-ol and trimethyl(octadecyloxy)silane.

The following summary has therefore been prepared based on validated predictions of the physicochemical properties of the substance itself and its hydrolysis productsand using this data in algorithms that are the basis of many computer-based physiologically based pharmacokinetic or toxicokinetic (PBTK) prediction models.Although these algorithms provide a numerical value, for the purposes of this summary only qualitative statements or comparisons will be made.

The main input variable for the majority of these algorithms is log K_ow so by using this, and other where appropriate, other known or predicted physicochemical properties oftrimethyl(octadecyloxy)silanereasonable predictions or statements may be made about its potentialabsorption, distribution, metabolism and excretion (ADME) properties.

In contact with water, trimethyl(octadecyloxy)silanereacts at a moderate rate(predicted half-life of approximately 15 hours at pH 7) to generateoctadecan-1-ol and trimethylsilanol. Trimethyl(octadecyloxy)silane has a very low water solubility (2.2E-06 mg/L) which is expectedto limit the extent of hydrolysis in-vivo. Relevant human exposure is to the registration substance, reaction mass of octadecan-1-ol and trimethyl(octadecyloxy)silane, and can occur via the inhalation or dermal routes.

The toxicokinetics of octadecan-1-ol have been reviewed in other major reviews (OECD SIDS, 1993) and are not considered further here. The discussion that follows focuses on the toxicokinetics of trimethyl(octadecyloxy)silane, the main constituent of the registration substance.

 

Absorption

Oral

Significant oral exposure is not expected for this substance.

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).

Due to the molecular weight (342.69) and very low water solubility (2.2E-06 mg/L) of trimethyl(octadecyloxy)silane,should oral exposure occur significant systemic exposure to the parent substance is unlikely. 

Therepeat dose toxicity study via the oral route(Charles River (2017)) does not show evidence of absorption of substance-related material, as no adverse effects were observed.

 

Dermal

The fat solubility and therefore potential dermal penetration of a substance can be estimated by using the water solubility and log K_owvalues. Substances with log K_owvalues between 1 and 4 favour dermal absorption (values between 2 and 3 are optimal) particularly if water solubility is high.

Trimethyl(octadecyloxy)silane has a log K_owvalue (9.0) above the favourable range and low water solubility (2.2E-06mg/L) therefore absorption across the skin is not likely to occur and significant systemic exposure following dermal exposure is unlikely.

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 (K_oct:air) as independent variables.

Using these values for trimethyl(octadecyloxy)silane results in a blood:air partition coefficient of approximately 0.01:1 meaning that if lung exposure occurreduptake into the systemic circulation is not likely.

There are no inhalation data that could be reviewed for signs of systemic toxicity, and therefore absorption.

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 (K_ow) is described.

Usinga log Kow value of 9 for trimethyl(octadecyloxy)silane the algorithm predicts that, should systemic exposure occur, it will distribute into the main body compartments as follows: fat >> brain > liver ≈ kidney > muscle with tissue:blood partition coefficients of 113.9 for fat and 5.5 to 20.5 for the remaining tissues.

 

Table 1: tissue:blood partition coefficients

	Log Kow	Kow	Liver	Muscle	Fat	Brain	Kidney
trimethyl(octadecyloxy)silane	9	1.0E+09	8.9	5.5	113.9	20.5	8.4

 

Metabolism

There are no data regarding the metabolism of trimethyl(octadecyloxy)silane. Genetic toxicity tests in vitro showed no observable differences in effects with and without metabolic activation for trimethyl(octadecyloxy)silane. 

Excretion

A determinant of the extent of urinary excretion is the soluble fraction in blood. QPSR’s as developed by De Jongh et al. (1997) using log K_owas an input parameter, calculate the solubility in blood based on lipid fractions in the blood assuming that human blood contains 0.7% lipids.

 

Using the algorithm, the soluble fraction oftrimethyl(octadecyloxy)silane in blood is <<1%. Therefore, should systemic exposure occur trimethyl(octadecyloxy)silane would not be eliminated via the urine; however, it is possible that it may be partly excreted in urine as water soluble metabolites.In the available repeat dose toxicity studies, no adverse effects were noted in the kidneys.

 

References

Renwick A. G. (1993) Data-derived safety factors for the evaluation of food additives and environmental contaminants.Fd. Addit. Contam.10: 275-305.

Meulenberg, C.J. and H.P. Vijverberg, Empirical relations predicting human and rat tissue:air partition coefficients of volatile organic compounds. Toxicol Appl Pharmacol, 2000. 165(3): p. 206-16.

DeJongh, J., H.J. Verhaar, and J.L. Hermens, A quantitative property-property relationship (QPPR) approach to estimate in vitro tissue-blood partition coefficients of organic chemicals in rats and humans. Arch Toxicol, 1997.72(1): p. 17-25.

OECD (1993): Screening Information Data Set (SIDS) of 1-octadecanol (CAS No 112-92-5). OECD High Production Volume Chemicals Programme (1993).