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

Bioaccumulation: aquatic / sediment

Description of key information

Bioaccumulation: aquatic: BCFss 3870 l/kg (0.43 µg/l) and 1610 l/kg (5.3 µg/l), and BCFk 3830 l/kg (0.43 µg/l) and 1760 l/kg (5.3 µg/l), read-across from a structurally-related substance. Lipid normalised (to 5%) values are: BCFss 6910 l/kg (0.43 µg/l) and 2880 l/kg (5.3 µg/l), and BCFk 6840 l/kg (0.43 µg/l) and 3140 l/kg (5.3 µg/l). A BCF value of 6910 l/kg is used in the exposure assessment as a worst case. Depuration rate constants from BCF study: 0.211 d-1 (0.43 µg/l); 0.124 d-1 (5.3 µg/l).

Key value for chemical safety assessment

BCF (aquatic species):

6 910 L/kg ww

BMF in fish (dimensionless):

0.48

Additional information

A steady-state BCF value of 3500 l/kg (range 1500 l/kg to 9600 l/kg) is available for the substance itself. The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline, with acceptable restrictions. It was not compliant with GLP. The restrictions were that the concentration of test substance in water was higher than the measured water solubility (1.89 µg/l at 23°C) and concentrations in water dropped throughout the test and did not stabilise, the depuration period was short, no information on lipid content or growth rate is provided, and tables of results were not provided.

As the concentration of test substance exceeded the water solubility and the substance has a high log Koc, absorption onto organic matter within the test system is highly likely. It is therefore probable that the test fish were exposed via the food, as well as via dissolved substance in water, to a significant extent during the study.

There are therefore significant uncertainties in the interpretation of the results from the study.

Good quality data for the structurally-related substance decamethyltetrasiloxane, L4, (CAS 141 -62 -8), have been read across as additional weight of evidence for the bioaccumulation endpoint. The data for M3T and L4 are used as weight-of-evidence, but the data for L4 are used in the exposure assessment, due to the uncertainties in the interpretation of the results from the study with M3T.

M3T and L4 are members of the Reconsile Siloxanes Category. 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 analogue group indicates that BCF is dependent on log K_ow as well as on chemical structure. The log K_ow values of M3T and L4 are similar (8.2 and 8.21, respectively). M3T and the source substance L4 arestructural isomers; both are methylated siloxanes containing four Si atoms linked by oxygen. L4 is a linear chain with four silicon atoms linked by three oxygen atoms, whereas M3T is a branched structure of four Si atoms, the longest siloxane chain contains three silicon atoms and two oxygen atoms, with a Si-O branch on the central silicon atom in the chain. In both substances, the silicon atoms are fully substituted by methyl groups. Neither substance contains any other functional groups;both have a molecular weight of 311. A comparison of the key physicochemical properties is presented in the table below. Both substances have negligible biodegradability and similar moderate hydrolysis rates.

Key physicochemical properties of M3T and surrogate substance L4

	M3T	L4
Chemical name	1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane	decamethyltetrasiloxane
CAS	17928-28-8	141-62-8
Molecular weight (parent)	311	311
Log Kow (parent)	8.2 at 20°C (QSAR)	8.21 at 25.1°C
Water solubility (parent)	0.00189 mg/L at 23°C	0.00674 mg/L at 23°C
Vapour pressure (parent)	210 Pa at 25°C (QSAR)	73 Pa at 25°C
Henry’s Law Constant (parent)	1.61+07 Pa m^3mol^-1at 12°C	2.59E+06 Pa m^3mol^-1at 12°C
Log Koc (parent)	5.3 (QSAR)	5.16 at 23.7°C
Ready biodegradability	Not readily biodegradable	Not readily biodegradable
Hydrolysis t1/2at pH 7 and 25°C	630 h (QSAR)	728 h
Hydrolysis products	Trimethylsilanol (3 moles per mole of parent) and methysilanetriol (1 mole)	Trimethylsilanol (2 moles per mole of parent) and dimethylsilanediol (2 moles)

Given the similar properties and structural similarities, it is considered valid to read-across bioaccumulation data from L4 to M3T.

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

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The BCF values determined for L4 were as follows:

Steady-state BCF values of 3870 l/kg (0.43 µg/l) and 1610 l/kg (5.3 µg/l) and kinetic BCF values of 3830 l/kg (0.43 µg/l) and 1760 l/kg (5.3 µg/l). Lipid normalised (to 5%) values are: BCF_ss= 6910 l/kg (0.43 µg/l) and 2880 l/kg (5.3 µg/l) and BCF_k= 6840 l/kg (0.43 µg/l) and 3140 l/kg (5.3 µg/l).

Growth correction was not applied, though based on fish weight data reported the growth of the fish during the study was minimal.

A non-guideline fish feeding study for L4 is also available. A lipid-normalised steady-state BMF value of 0.44 was determined in a reliable study conducted in compliance with GLP. The growth corrected kinetic BMF value (i.e. BMF_Kg) was calculated and reported to be 3.8 in the study report; however, recent scientific discourse on the methodology to calculate growth corrected BCF and BMF values has revealed that these methods violate the rules of mass balance (Gobas et al., 2019). Therefore, the reported growth corrected values are not considered valid for the determination of bioaccumulation. The food in this study was very highly dosed (500 µg/g¹⁴C-L4 nominal; 534 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 adsorbed to 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 TG 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 andnotlikewise 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 0.211 d^-1(0.43 µg/l)and 0.124 d^-1(5.3 µg/l) obtained from the BCF study for the read-across substance L4 are considered to be valid. These rates are indicative of a substance which does not bioaccumulate.

Burkhardet 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_lwx ρ_l/ ρ_B

where BCF_WD/LWis 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_lis the density of lipid and ρ_Bis the density of biota.

It can be assumed that n-octanol and lipid are equivalent with respect to their capacity to store organic chemicals, i.e. K_lw= K_ow. For some substances with specific interactions with the organic phase, this assumption is not sufficiently accurate. Measurement of K_lw values for siloxane substances is in process. Initial laboratory work with olive oil as lipid substitute indicates that the assumption that K_lw= K_ow is appropriate (Reference: Dow Corning Corporation, personal communication). However, the calculated fugacity ratios presented here should be used with caution at this stage.

The table below presents fugacity ratios calculated from the BCF data for the read-across substance L4, using K_ow for K_lw. BMF values do not require adjustments because these values are already equivalent to fugacity-based values.

Table Calculated biota-water fugacity ratios

Endpoint	Exposure concentration	BCF Value	Fbiota-water*
BCFsteady-state	0.43 µg/l	3870	8.17E-04
BCFsteady-state	5.3 µg/l	1610	3.40E-04
BCFkinetic	0.43 µg/l	3830	8.08E-04
BCFkinetic	5.3 µg/l	1760	3.71E-04

*Using log K_ow8.21

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:

Burkhard, L. P., Arnot, J. A., Embry, M. R., Farley, K. J., Hoke, R. A., Kitano, M., Leslie, H. A., Lotufo, G. R., Parkerton, T. F., Sappington, K. G., Tomy, G. T. and Woodburn, K. B. (2012). Comparing Laboratory and Field Measured Bioaccumulation Endpoints. Integrated Environmental Assessment and Management 8, 17-31.

Goss, K-U., Brown, T. N. and Endo, S. (2013). Elimination half-life as a metric for the bioaccumulation potential of chemicals in aquatic and terrestrial food chains. Environmental Toxicology and Chemistry 32, 1663-1671.