Reaction mass of 1,1,1,5,5,5-hexamethyl-3-phenyl-3-((trimethylsilyl)oxy)trisiloxane and 1,1,1,7,7,7-hexamethyl-3,5-diphenyl-3,5-bis[(trimethylsilyl)oxy]tetrasiloxane and 1,1,1,9,9,9-hexamethyl-3,5,7-triphenyl-3,5,7-tris((trimethylsilyl)oxy)pentasiloxane

Bioaccumulation: aquatic / sediment

Description of key information

Bioaccumulation: aquatic: BCFss 1011 l/kg (0.80 µg a.i./l) and 384 (4.4 µg a.i./l) and BCFk 2992 l/kg (0.80 µg a.i./l) and 1208 (4.4 µg a.i./l), read-across from the monomer constituent of the registration substance, 1,1,5,5,5-hexamethyl-3-phenyl-3-[(trimethylsilyl) oxy]trisiloxane (PhM3T; CAS 2116 -84 -9).

Lipid normalised (to 5%) values are: BCFss 934 l/kg (0.80 µg a.i./l) and 255 l/kg (4.4 µg a.i./l) and BCFk 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 exposure assessment as a worst case.

Depuration rate constants: 0.161 d^-1(0.8 µg a.i./l); 0.0125 d^-1(4.4 µg a.i. l).

Key value for chemical safety assessment

BCF (aquatic species):

2 765 dimensionless

Additional information

There are no reliable bioaccumulation data available for phenyl silsesquioxanes, therefore good quality data for the structurally-related substance, 1,1,1,5,5,5-hexamethyl-3-phenyl-3-[(trimethylsilyl) oxy]trisiloxane (PhM3T, CAS 2116-84-9) have been read across. PhM3T (CAS 2116-84-9) is the monomer constituent (Constituent 1) of the registration substance.

Phenyl silsesquioxanes and PhM3T (CAS 2116-84-9) 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 analogue group indicates that BCF is dependent on log K_owas well as on chemical structure. 

The predicted log K_owvalues of phenyl silsesquioxanes (all constituents) and PhM3T are 9.0. Phenyl silsesquioxanes and the source substance PhM3T are structurally-similar substances, both are branched siloxanes with phenyl functionality. Phenyl silsesquioxanes is considered a multiconstituent substance, and is a reaction mass of the monomer, dimer and oligomers of phenyltris(trimethylsiloxy)silane. The linear oligomers of phenyl silsesquioxanes contain a siloxane chain, where the terminal Si atoms are fully methyl substituted, and the repeating unit contains a Si atom substituted with a phenyl and a trimethylsiloxy group. The major constituents comprise 70-80% of the linear oligomers n=1-5; the minor constituents comprise 10-20% cyclic (n=3-7) and linear (n=6-7) oligomers. The combined purity of both linear and cyclic oligomers is about 85-95%. The remaining impurities are higher polymerised material and alkoxy substituted oligomers. PhM3T (CAS 2116-84-9) is the monomer constituent (Constituent 1) of the registration substance. 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.

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, 2017) attached in Section 13 of the IUCLID dossier.

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) were determined for PhM3T in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.

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).

The BCF result for the monomer is considered to be a worst case value, as the other major linear constituents, and minor linear and cyclic constituents would be expected to have lower BCF values due to larger molecular size and lower solubility in water.

Fish bioconcentration (BCF) studies are most validly applied to substances with log K_owvalues 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, 2017), 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_ocwill 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 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 (Gobaset 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).

Gosset 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_eliminationof >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 are considered to be valid and to carry most weight for bioaccumulation assessment of phenyl silsesquioxanes. These rates are indicative of a substance which does not bioaccumulate.

Burkhard, L. P.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, L. P.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 the 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_lwis 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_lwvalues for siloxane substances is in progress. Initial laboratory work with olive oil as lipid substitute indicates that the assumption that K_lw= K_owis 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 PhM3T, using K_owfor K_lw.

 

Table: Calculated biota-water fugacity ratios for read-across substance PhM3T

Substance	Endpoint	Exposure concentration	BCF Value	Fbiota-water*
PhM3T	BCFss	0.80 µg a. i. /l	1011	2.35E-05
PhM3T	BCFss	4.4 µg a. i. /l	384	6.43E-06
PhM3T	BCFk	0.80 µg a. i. /l	2992	6.97E-05
PhM3T	BCFk	4.4 µg a. i. /l	1208	2.02E-05

*Using log K_ow9 for PhM3T

 

The fugacity-based BCFs 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 tends to be at a lower fugacity (or chemical activity) than in the water. It should be noted however, that the BCF studies may not have reached true steady-state in the timescale of the laboratory studies. The fugacity ratios indicate 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:

Gobas, F. A. P. C.et al.(2019). Growth‐Correcting the Bioconcentration Factor and Biomagnification Factor in Bioaccumulation Assessments.Environ Toxicol Chem 38: 2065-2072.

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. Environ Toxicol Chem 32: 1663-1671

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

ECHA (2017). European Chemicals Agency. Guidance on information requirements and chemical safety assessment Chapter R.11: PBT/vPvB assessment Version 3.0 – June 2017