1,1,5,5,5-hexamethyl-3,3-bis[(trimethylsilyl)oxy]trisiloxane

Bioaccumulation: aquatic / sediment

Description of key information

Bioaccumulation (aquatic) (read-across from tris(trimethylsiloxy)phenylsilane (PhM3T, CAS 2116-84-9)): Steady-state BCF values of 1011 l/kg (0.80 µg a. i. /l) and 384 (4.4 µg a. i. /l) and kinetic BCF values of 2992 l/kg (0.80 µg a. i. /l) and 1208 (4.4 µg a. i. /l). Lipid normalised (to 5%) values are: BCF_ss= 934 l/kg (0.80 µg a.i./l) and 255 l/kg (4.4 µg a.i./l) and BCF_k= 2765 l/kg (0.80 µg a.i./l) and 803 l/kg (4.4 µg a.i./l). A BCF value of 2765 is used in the key value as a worst-case. 

BMF (M4Q, CAS 3555-47-3): 0.37 (lipid normalised, kinetic); 0.16 (lipid normalised, steady state)

 

Key value for chemical safety assessment

BCF (aquatic species):

2 765 L/kg ww

BMF in fish (dimensionless):

0.37

Additional information

A non-guideline fish bioconcentration (BCF) study is available with the registered substance, 1,1,1,5,5,5-hexamethyl-3,3-bis[(trimethylsilyl)oxy]trisiloxane (M4Q, CAS 3555-47-3). In a study summary, a steady-state BCF value of 1300 l/kg at the approximate limit of solubility in water 1 µg/l is reported. The available documentation is limited, and the study is assigned Klimisch code 4. Consequently, good quality data for the structurally-related substance, tris(trimethylsiloxy)phenylsilane (PhM3T, CAS 2116-84-9) have been read across.

1,1,1,5,5,5 -Hexamethyl-3,3-bis[(trimethylsilyl)oxy]trisiloxane (M4Q, CAS 3555-47-3) and PhM3T are within the Reconsile Siloxane Category which have similar properties with regard to bioaccumulation. This Category consists of linear/branched and cyclic siloxanes which have a low functionality and a hydrolysis half-life at pH 7 and 25°C >1 hour and log K_ow>4. The Category hypothesis is that the bioaccumulation of a substance in fish (aquatic bioconcentration) is dependent on the octanol-water partition coefficient and chemical structure. In the context of the RAAF, Scenario 4 is applied.

Partitioning between the lipid-rich fish tissues and water may be considered to be analogous to partitioning between octanol and water. A review of the data available for substances in this Category indicates that BCF is dependent on log K_ow as well as on chemical structure.

The predicted log K_ow values of M4Q and PhM3T are both 9.0. M4Q and the source substance PhM3T are both branched siloxanes. M4Q is a quaternary-branched structure of five Si atoms, with four terminal Si atoms linked to a central Si atom by Si-O-Si bonds. Each of the four terminal Si atoms is substituted by three methyl groups. PhM3T is a tertiary-branched structure, with a central Si atom linked to three terminal Si atoms by Si-O-Si bonds and substituted with one phenyl group. The three terminal silicon atoms are fully methyl substituted. A comparison of the key physicochemical properties is presented in the table below. Both substances have negligible biodegradability and similar moderate hydrolysis rates.

Table 4.3.2 Key physicochemical properties of M4Q and surrogate substance PhM3T

Property	M4Q	PhM3T
Molecular weight	384.85	372.76
Log Kow	9.0 (QSAR)	9.0 (QSAR)
Log Koc	6.0 (QSAR)	6.0 (QSAR)
Water solubility (mg/l)	0.0001507 (at 23°C)	0.0066 (at 23°C)
Vapour pressure at 25°C (Pa)	15	0.09(QSAR)
Hydrolysis half- life at pH 7	>200-2000 h (QSAR)	>200 h (QSAR)
Hydrolysis products	Trimethylsilanol (4 moles) and silicic acid (1 mole)	Phenylsilanetriol (1 mole) and trimethylsilanol (3 moles)
Ready biodegradability	Not readily biodegradable	Not readily biodegradable

 

It is therefore considered valid to read-across the results for PhM3T to fill the data gap for the registered substance.

Additional information is given in a supporting report (PFA, 2017at) attached in Section 13 of the IUCLID dossier.

The BCF values determined for PhM3T were as follows:

Steady-state BCF values of 1011 l/kg (0.80 µg a. i. /l) and 384 (4.4 µg a. i. /l) and kinetic BCF values of 2992 l/kg (0.80 µg a. i. /l) and 1208 (4.4 µg a. i. /l). Lipid normalised (to 5%) values are: BCF_ss= 934 l/kg (0.80 µg a.i./l) and 255 l/kg (4.4 µg a.i./l) and BCF_k= 2765 l/kg (0.80 µg a.i./l) and 803 l/kg (4.4 µg a.i./l).

A reliable fish feeding study is also available with M4Q. A lipid-normalised steady-state BMF value of 0.16 and lipid-normalised kinetic BMF value of 0.37 were determined in a reliable study conducted in compliance with GLP. The food in this study was very highly dosed (500 µg/g of ¹⁴C-M4Q nominal; 411 µg/g mean measured), which may limit the applicability of the values obtained.

Fish bioconcentration (BCF) studies are most validly applied to substances with log K_ow values between 1.5 and 6. Practical experience suggests that if the aqueous solubility of the substance is low (i.e. below ~0.01 to 0.1 mg/l) (REACH Guidance R.11; ECHA, 2014), fish bioconcentration studies might not provide a reliable BCF value because it is very difficult to maintain exposure concentrations. Dietary bioaccumulation (BMF) tests are practically much easier to conduct for poorly water-soluble substances, because a higher and more constant exposure to the substance can be administered via the diet than via water. In addition, potential bioaccumulation for such substances may be expected to be predominantly from uptake via feed, as substances with low water solubility and high K_oc will usually partition from water to organic matter.

However, there are limitations with laboratory studies such as BCF and BMF studies with highly lipophilic and adsorbing substances. Such studies assess the partitioning from water or food to an organism within a certain timescale. The studies aim to achieve steady-state conditions, although for highly lipophilic and adsorbing substances such steady-state conditions are difficult to achieve. In addition, the nature of BCF and BMF values as ratio values, means that they are dependent on the concentration in the exposure media (water, food), which adds to uncertainty in the values obtained.

For highly lipophilic and adsorbing substances, both routes of uptake are likely to be significant in a BCF study, because the substance can be absorbed by food from the water. 

Dual uptake routes can also occur in a BMF study, with exposure occurring via water due to desorption from food, and potential egestion of substance in the faeces and subsequent desorption to the water phase. Although such concentrations in water are likely to be low, they may result in significant uptake via water for highly lipophilic substances.

The OECD 305 advocates for calculating a growth dilution correction for kinetic BCF and BMF values, where the growth rate constant (i.e. k_g) can be subtracted from the overall depuration rate constant (k₂).  In short, the uptake rate constant is divided by the growth-corrected depuration rate constant to give the growth corrected kinetic BCF or BMF value.  However, recent scientific discourse on this topic has pointed out that correcting for growth in the depuration phase and not likewise accounting for the effects of lack of growth in the uptake phase (i.e. with regards to reduced feeding rate or respiration rate for a non-growing fish), results in an equation where the laws of mass balance are violated (Gobas et al., 2019).  Essentially, the uptake parameters of the kinetic BCF or BMF calculation (i.e. k₁) are those of a growing fish, but the depuration parameters are altered to reflect no growth (i.e. k₂- k_g).  Based on this criticism of the growth dilution correction, these calculations are not considered best practice for the assessment of bioaccumulation (Gobas et al., 2019).

Goss et al. (2013) put forward the use of elimination half-life as a metric for the bioaccumulation potential of chemicals. Using the commonly accepted BMF and TMF threshold of 1, the authors derive a threshold value for k_elimination of >0.01 d^-1 (half-life 70d) as indicative of a substance that does not bioaccumulate.

Depuration rates from BCF and BMF studies, being independent of exposure concentration and route of exposure, are considered to be a more reliable metric to assess bioaccumulation potential than the ratio BCF and BMF values obtained from such studies.

The depuration rate constants of 0.161 d^-1(0.8 µg a.i./l) and 0.0125 d^-1(4.4 µg a.i./l) obtained from the BCF study with PhM3T, and the depuration rate of 0.0245  d^-1 from the BMF study with M4Q, are considered to be valid and to carry most weight for bioaccumulation assessment of the substance. These rates are indicative of a substance which does not bioaccumulate.

Burkhard et al. (2012) has described fugacity ratios as a method to compare laboratory and field measured bioaccumulation endpoints. By converting data such as BCF and BSAF (biota-sediment accumulation factor) to dimensionless fugacity ratios, differences in numerical scales and unit are eliminated.

Fugacity is an equilibrium criterion and can be used to assess the relative thermodynamic status (chemical activity or chemical potential) of a system comprised of multiple phases or compartments (Burkhard et al., 2012). At thermodynamic equilibrium, the chemical fugacities in the different phases are equal. A fugacity ratio between an organism and a reference phase (e.g. water) that is greater than 1, indicates that the chemical in the organism is at a higher fugacity (or chemical activity) than the reference phase. The fugacity of a chemical in a specific medium can be calculated from the measured chemical concentration by the following equation:

f = C/Z

Where f is the fugacity (Pa), C is concentration (mol/m³) and Z is the fugacity capacity (mol(m³.Pa)).

The relevant equation for calculating the biota-water fugacity ratio (F_biota-water) is:

F_biota-water = BCF_WD/LW / K_lw x ρ_l/ ρ_B

where BCF_WD/LW is ratio of the steady-state lipid-normalised chemical concentration in biota (µg-chemical/kg-lipid) to freely dissolved chemical concentration in water (µg-dissolved chemical/l-water), K_lw  is the lipid-water partition coefficient and ρ_l is the density of lipid and ρ_B is the density of biota.

A study to determine storage lipid-air partition coefficients of cVMS has been carried out (Dow Corning Corporation, 2015c). The conclusion from that study is that partitioning of cVMS compounds between storage lipids and air or water is reasonably similar, but not identical, to octanol. K_{storage lipid-air} values for cVMS were systematically lower than K_octanol-air by 0.2 to 0.4 log units depending on temperature. K_{octanol-water} values may be expected to be similar.

Table 4.3.3 presents fugacity ratios calculated from the BCF data for PhM3T using log K_ow as a worst case approximation for log K_lw. BMF values do not require adjustments because these values are already equivalent to fugacity-based values.

Table 4.3.3 Calculated biota-water fugacity ratios for tris(trimethylsiloxy)phenylsilane

Substance	Endpoint	Exposure concentration	BCF Value	Fbiota-water*
Tris(trimethylsiloxy)phenylsilane	BCFss	0.80 µg a.i./l	1011	2.35E-05
Tris(trimethylsiloxy)phenylsilane	BCFss	4.4 µg a.i./l	384	6.43E-06
Tris(trimethylsiloxy)phenylsilane	BCFk	0.80 µg a.i./l	2992	6.97E-05
Tris(trimethylsiloxy)phenylsilane	BCFk	4.4 µg a.i./l	1208	2.02E-05

*Using log K_ow 9

The fugacity-based BCF directly reflect the thermodynamic equilibrium status of the chemical between the two media included in the ratio calculations. The fugacity ratios calculated are all below 1, indicating that the chemical in the organism is at a lower fugacity (or chemical activity) than in the water. It should be noted however, that the BCF study may not have reached true steady-state in the timescale of the laboratory studies. The fugacity ratio indicates that uptake may be less than expected on thermodynamic grounds, suggesting that elimination is faster than might be expected on grounds of lipophilicity alone.

References:

Dow Corning Corporation (2015c) Non-regulated study: Determination of storage lipid-to-air partition coefficients and their temperature dependence for Octamethylcyclotetrasiloxane (D4; CAS 556-67-2), Decamethylcyclopentasiloxane (D5; CAS 541-02-6) and Dodecamethylcyclohexasiloxane (D6; CAS 540-97-6). DOW CORNING CORPORATION HEALTH AND ENVIRONMENTAL SCIENCES (HES) TECHNICAL REPORT. HES Study No.: 17240-108. Report date: May 20, 2015.