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There are no in vivo test data on the toxicokinetics of 2,4,6,8,10-pentamethylcyclopentasiloxane (HD5).

The following summary has therefore been prepared based on the physicochemical properties of the substance itself and its hydrolysis products and using these 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 2,4,6,8,10-pentamethylcyclopentasiloxane, reasonable predictions or statements may be made about its potential absorption, distribution, metabolism and excretion (ADME) properties.

In aqueous solution 2 ,4,6,8,10-pentamethylcyclopentasiloxane reacts very rapidly (half-life 4.2 min at 22.5°C). The end products of the hydrolysis may vary depending on conditions. Both silanols and polymers may be formed under conditions relevant for human health exposure. Methylsilanetriol is the end product of hydrolysis at low concentrations and is considered representative of other small molecule silanols that could form. The expected intermediate products of hydrolysis are linear siloxanes and methylsilanediol; hydrogen gas is produced as a by-product of the reaction.

Human exposure can occur to the parent and hydrolysis products by the inhalation or dermal routes.



Significant human exposure by the oral route is not expected for this substance.

In an in vitro study conducted to assess the rate and extent of hydrolysis and condensation reactions of 2, 4, 6, 8 -tetramethylcyclotetrasiloxane (HD4) and 2, 4, 6, 8, 10-pentamethylcyclopentasiloxane (HD5) in

simulated rat gastric conditions (DCC, 2014) no reaction products were observed after up to 4 hours with >99% of the original concentration of HD4 or HD5 remaining. Although this result would appear to indicate that after oral administration in the rat the substance does not hydrolyse at a the predicted rate, further analysis of the methodology used shows that as the concentrations used far exceed the solubility of the substance (particularly at the high concentration employed), the result is not unexpected. This is because it was noted that the test substance and buffer solutions had formed two distinct layers so only a small proportion of the test substance was in contact with the aqueous medium and therefore subject to hydrolysis. However, regardless of the very low soluble fraction at these concentrations, some hydrolysis would have occurred resulting in the formation of the hydrolysis product, methylsilanetriol. Furthermore, as a result of the lipophilic nature of the substance, intestinal absorption via micellular uptake would occur and once into the more aqueous systemic environment at lower concentrations, hydrolysis would occur.


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. With a log Kow of 6.33 and water solubility of 0.11 mg/l, absorption of 2,4,6,8,10-pentamethylcyclopentasiloxane across the skin is unlikely as it does not possess the required properties.

The high water solubility (1E+06 mg/l) of the final hydrolysis product, methylsilanetriol, is favourable for absorption across the skin but the log Kow of -2.4 is not. Therefore absorption across the skin is not likely to occur as the substance is likely to be too hydrophilic to cross the lipid-rich environment of the stratum corneum. However, the possible intermediate hydrolysis products have log Kow values in or close to the favourable range and are water soluble so absorption across the skin is potentially possible for them.

There are no dermal studies to check for evidence of absorption.


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 for 2,4,6,8,10-pentamethylcyclopentasiloxane results in a blood:air coefficient of approximately 0.3:1 meaning that, if lung exposure occurred there may be some uptake in to the systemic circulation of the parent substance. The high water solubility of the final hydrolysis product, methylsilanetriol, results in a very high blood:air partition coefficient (approximately 7.9E+07:1) 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 methylsilanetriol may lead to some of it being retained in the mucus of the lungs so absorption is then likely to slow down. Similarly, the possible intermediate hydrolysis products also have high blood:air partition coefficients so systemic exposure to them is also likely.

In an acute inhalation study no effects were noted.


For blood:tissue partitioning a QSPR algorithm has been developed by DeJongh 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. Although systemic exposure to 2,4,6,8,10-pentamethylcyclopentasiloxane via inhaled or dermal routes is unlikely to occur as described above, should it occur then a qualitative comparison of the predicted coefficients suggests it will distribute primarily into fat and to a much lesser extent into the other main body compartments.

For the final hydrolysis product, methylsilanetriol, distribution into the main body compartments would be minimal with tissue:blood partition coefficients of less than 1 for all major tissues (approaching zero for fat). The possible intermediate hydrolysis products would be predicted to distribute primarily into fat but to a lesser extent than the parent substance.


 Table 1: Tissue:blood partition coefficients


Log Kow
























There are no data on the metabolism of 2,4,6,8,10-pentamethylcyclopentasiloxane. Genetic toxicity tests in vitro showed no observable differences in effects with and without metabolic activation.


A determinant of the extent of urinary excretion is the soluble fraction in blood. QPSRs as developed by DeJongh 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 2,4,6,8,10-pentamethylcyclopentasiloxane is <0.001% however the corresponding figure for the final hydrolysis product, methylsilanetriol, is > 99%.The soluble fraction of the intermediate hydrolysis products range from approximately 5 to 95% but as they are hydrolytically unstable they are expected to be eliminated in the form of the final hydrolysis product methylsilantriol. Therefore although long duration systemic exposure to the parent substance is unlikely, should it occur, it will rapidly hydrolyse and the final hydrolysis product will be effectively eliminated via the kidneys in urine so accumulation will not occur.


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.

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.