2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane

Bioaccumulation: aquatic / sediment

Description of key information

BCF: 14900 l/kg (lipid normalised, kinetic) - based on read-across.

BMF 0.47 (lipid-normalised steady-state);

- based on read-across.

Depuration rate constants from BCF study: 0.0613 d^-1

- based on read-across.

Key value for chemical safety assessment

BCF (aquatic species):

14 900 L/kg ww

BMF in fish (dimensionless):

0.47

Additional information

There are no bioaccumulation data available for 2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane (Vi4-D4), therefore good quality data for the structurally-related substance, D4 (CAS 556-67-2), have been read across.

There are no bioaccumulation data available for 2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane (Vi4-D4), therefore good quality data for the structurally-related substance, D4 (CAS 556-67-2), have been read across.

The registration substance has an average purity of >70% Vi4-D4, with <20% 2,4,6,8,10-pentamethyl-2,4,6,8,10-pentavinylcyclopentasiloxane (Vi5-D5; CAS 17704-22-2; Impurity 1) and <10% 2,4,6-trimethyl-2,4,6-trivinylcyclotrisiloxane (Vi3-D3; CAS 3901-77-7; Impurity 2) present as impurities. Read-across studies are in place as supporting studies, to consider the properties of the impurities. Data for Vi5-D5 are read-across from decamethylcyclopentasiloxane D5 (CAS 541-02-6). Bioaccumulation data are not relevant for Vi3-D3, as it hydrolysis rapidly; a data waiver is in place.

2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane (Vi4-D4) and octamethycyclotetrasiloxane (D4), and 2,4,6,8,10-pentamethyl-2,4,6,8,10-pentavinylcyclopentasiloxane (Vi5-D5) and decamethylcyclopentasiloxane (D5), 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_owvalue of Vi4-D4 and the measured value for D4 are6.47 and 6.49 respectively.D4 is a cyclic siloxane chain with four silicon atoms, connected by four oxygen atoms, in which the Si-O bonds are susceptible to hydrolysis. All silicon atoms present are fully substituted with methyl groups. Similarly, the submission substance is a cyclic siloxane chain with four silicon atoms, connected by four oxygen atoms, in which the Si-O bonds are susceptible to hydrolysis. All silicon atoms present are substituted with one methyl group and one vinyl group. The structural relationship between Vi5-D5 and D5 is analogous to Vi4-D4 to D4, however the cyclic chain consists of five silicon atoms connected by five oxygen atoms.A comparison of the key physicochemical properties is presented in the table below. All substances have negligible biodegradability and similar hydrolysis rates.

Table: Key physicochemical properties of Vi4-D4 and Vi5-D5 and surrogate substance D4 and D5

CAS Number	2554-06-5	556-67-2	17704-22-2	541-02-6
Chemical Name	2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane	Octamethylcyclotetrasiloxane	2,4,6,8,10-pentamethyl-2,4,6,8,10-pentavinylcyclopentasiloxane (Impurity 1 (Vi5-D5))	Decamethylcyclopentasiloxane (D5)
Ultimate Si hydrolysis product	Methylvinylsilanediol	Dimethylsilanediol	Methylvinylsilanediol	Dimethylsilanediol
Molecular weight (parent)	344.66	296.62	431	370.8
Molecular weight (hydrolysis product)	104.18	92.17	104.18	92.17
log Kow(parent)	6.47	6.49	9.0	8.07
Water sol (parent)	0.0073 – 0.0088 mg/l at 23°C	0.056 mg/l	9.1E-06 mg/l	0.017 mg/l
Vapour pressure (parent)	93.5 Pa	132 Pa	0.6 Pa	33 Pa
Hydrolysis t1/2at pH 7 and 25°C	approximately 63 hours	69-144 hours	1600 hours	1590 hours

 

It is therefore considered valid to read-across the results for D4 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 6 dossier.

A steady-state BCF value of 12400l/kg(0.26 µg/l measured) and a kinetic BCF value of 13400 l/kg(0.26 µg/l measured) were determined for the source substance, D4, in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP. No lipid data is reported in the original study report (Dow Corning Corporation, 1991). A value of 6.4% is reported in a published paper (Fackler et al., 1995) describing the preliminary and definitive phases of the same study. Lipid normalisation of the BCF values reported for the definitive phase of the study would indicate BCF_ss= 9700 l/kg, BCF_k= 10500 l/kg. In a re-analysis with a kinetic model, using all data from the preliminary and definitive BCF studies, a kinetic BCF value of 19000 l/kg was calculated (Smitet al.,2012). Normalised to 5% lipid content, the BCF_kis 14900 l/kg.

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.

A fish feeding study is also available with the read-across substance D4.. The BMF_SS, calculated as the concentration of D4 in the fish tissue divided by the concentration in the feed was 0.18. When normalized for the average lipid content in the fish and fish feed, the BMF_SSLwas calculated to be 0.47 (Dow Corning Corporation, 2007d). The kinetic BMF value, based on dividing the uptake rate (k₁)by the total depuration rate (k₂) was determined to be 0.34. When adjusted for lipid concentrations, the kinetic BMF is 0.863. The growth corrected kinetic BMF value (i.e. BMF_Kg) was calculated and reported to be 1.83 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/g of¹⁴C-D4 nominal; 457 µg/g mean measured), which may limit the applicability of the values obtained.

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 highlylipophilic and adsorbingsubstances, 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_eliminationof >0.01 d^-1(half-life<70 d) 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.

A growth corrected depuration rate constant (i.e. k₂– k_g) of 0.00649d^-1was obtained from the D4 BMF study (Dow Corning Corporation 2007d). This value may not be valid due to the very high loading of the food in this study had the potential to overload metabolic/elimination pathways. This depuration rate is therefore not taken into account in the assessment of bioaccumulation.

The depuration rate constant of 0.0613 d^-1(0.26 µg/l measured) obtained by Smitet al.(2012) in their re-analysis of the DCC (2001) BCF study is considered to be valid and to carry most weight for bioaccumulation assessment. This rate is 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/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_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 D4, using K_owfor K_lw.

Table: Calculated biota-water fugacity ratios for read-across substance D4

Endpoint	Exposure concentration	BCF Value	Fbiota-water*
BCFss	0.26 µg/l	12400	5.65E-02
BCFk	0.26 µg/l	13400	6.11E-02
BCFk, lipid normalised. Re-analysis of BCF­k from Smit et al.,2012)	0.26 µg/l	14900	8.66E-02

*Using log K_ow6.49

 

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 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:

Fackler P H, Dionne E, Hartley D A, and Hamelink J L, 1995, Bioconcentration by fish of a highly volatile silicone compound in a totally enclosed aquatic exposure system. Environmental Toxicology and Chemistry, 14, 1649–1656.

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. Integr Environ Assess Manag 8: 17-31.

Smit, C. E., Posthuma-Doodeman, C. J. A. M., Verbruggen, E. M. J., (2012). Environmental risk limits for octamethylcyclotetrasiloxane in water: A proposal for water quality standards in accordance with the Water Framework Directive. National Institue for Public Health and the Environment, P. O. Box 1, 3720 BA Bilthoven. Report no.: RIVM Letter report 601714020.

Gobas, F. A. P. C.et al.(2019). Growth –correcting the BCF and BMF in bioaccumulation assessments.Submitted for publication.

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.