1,1,3,3-tetramethyl-1,3-divinyldisiloxane

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The study was conducted according to an appropriate national standard method, with acceptable restrictions. The restrictions were that there was no depuration and there was some variability in concentration in fish between replicates at later sampling points.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 305 C (Bioaccumulation: Test for the Degree of Bioconcentration in Fish)

Principles of method if other than guideline:

The test was performed according to the "Method for Testing the Degree of Accumulation of Chemical Substances in Fish Body" stipulated in the "Testing Methods for New Chemical Substances" (July 13, 1974, Kempgyo No 5, Planning and Coordination Bureau, Environment Agency, Yakuhatu No 615, Pharmaceutical Affairs Bureau, Ministry of Health and Welfare, and 49 Kikyoko No 392, Basic Industries Bureau, Ministry of International Trade and Industry, Japan). The test method is essentially the same as that in the OECD Guidelines for Testing of Chemicals, "305C, Bioaccumulation: Degree of Bioconcentration in Fish" (May 12, 1981)

GLP compliance:

yes

Details on sampling:

- Sampling intervals/frequency for test organisms: Concentration of test substance in fish for both level 1 and 2 were analysed 4 and 5 times for each , in weeks 2, 4, 6, and 8 for level 1 and 2, 4, 6, 8 and 10 for level 2 (n = 2). Control fish analysed at start and termination of exposure (n = 2).

- Sampling intervals/frequency for test medium samples: Concentration of test substance in water for both level 1 and 2 were analysed 16 times, twice a week intervals (n = 1).

- Details on sampling and analysis of test media samples (e.g. sample preparation, analytical methods): Aliquot test water: 8ml (level 1); 80 mL (level 2). Pre-treatment: Sodium chloride added and vessel sealed and shaken for 10 min. Gas layer sampled for GC-MS.

Details on sampling and analysis of test organisms (e.g. sample preparation, analytical methods): Test fish taken. Weight and length measured. Acetonitrole addition. Homogenisation. Centrifugation. Filtrate filtered. Sodium chloride added. Shaking 10 min. Gas layer sampled for GC-MS.

Details on preparation of test solutions, spiked fish food or sediment:

Dispersants used in stock solution: N, N-Dimethylformamide (DMF) and HCO-20
The test substance and 5-fold its volume of HCO-20 were dissolved in DMF to obtain a 50 g/l test substance solution. This solution was diluted with deionised water to prepare a 1000 mg/l stock solution.
High exposure level: 32 mg/l stock solution was prepared by diluting 1000 mg/l solution with dionised water.
Low exposure level: 3.2 mg/l stock solution was prepared by diluting 1000 mg/l solution with dionised water.

Test organisms (species):

Cyprinus carpio

Details on test organisms:

TEST ORGANISM
- Common name: Carp

- Source: Sugishima fish farm, Kumamoto, Japan

- Length at study initiation (lenght definition, mean, range and SD): 10.5 cm average

- Weight at study initiation (mean and range, SD): 31.4 g average

- Lipid content: 4.3% (average at test initiation)

- Health status: Checked visually at delivery - fish demonstarting any abnormalities removed.

- Description of housing/holding area: Reared for 1 d in flow through system following external disinfection.

- Feeding during test

- Food type: Pelleted feed for carp

- Amount: 2% total body weight twice a day in halves. On day before fish sampling no feed given.



ACCLIMATION
- Acclimation period: After rearing, fish were medicated to eliminate parasites and trasferred to acclimatizing aquarium. 45d.

- Health during acclimation (any mortality observed): Fish demonstrating any abnormalities were removed and reared for 46d.

Route of exposure:

aqueous

Test type:

flow-through

Water / sediment media type:

natural water: freshwater

Total exposure / uptake duration:

10 wk

Test temperature:

25 ± 2 °C

Dissolved oxygen:

5.1 - 6.5 mg/L (high exposure)
5.2 - 7.0 mg/L (low exposure)
6.8 - 7.5 mg/L (control)

Details on test conditions:

TEST SYSTEM
- Test vessel: Glass tank of 100 litres volume.

- Type of flow-through (e.g. peristaltic or proportional diluter): Continuous flow system

- Renewal rate of test solution (frequency/flow rate): Flow rate 2mL/min for stock solution and 1600 mL/min for dilution water.

- No. of organisms per vessel: 16 (5 for control)

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: Underground water from the premises of Kurume Research Laboratories

Nominal and measured concentrations:

Nominal: Level 1 (high exposure) 40 µg/l; Level 2 (low exposure) 4 µg/l.
Measured: Level 1 39.7 µg/l (average at high exposure); Level 2.4 µg/l (average at low exposure).

Reference substance (positive control):

no

Type:

BCF

Value:

1 290 - 2 410 L/kg

Remarks on result:

other: Result as stated in original study report

Remarks:

Conc.in environment / dose:40 µg/l (nominal)

Type:

BCF

Value:

776 - 1 660 L/kg

Remarks on result:

other: Result as stated in original study report

Remarks:

Conc.in environment / dose:4 µg/l (nominal)

Type:

BCF

Value:

1 684 L/kg

Calculation basis:

steady state

Remarks on result:

other: (empirical average BCF calculated by the registrant from the experimental data)

Remarks:

Conc.in environment / dose:40 µg/l (nominal)

Type:

BCF

Value:

1 181 L/kg

Calculation basis:

steady state

Remarks on result:

other: (empirical average BCF calculated by the registrant from the experimental data)

Remarks:

Conc.in environment / dose:4 µg/l (nominal)

Type:

BCF

Value:

1 958 L/kg

Calculation basis:

steady state

Remarks on result:

other: (lipid-normalised empirical average BCF calculated by the registrant from the experimental data)

Remarks:

Conc.in environment / dose:40 µg/l (nominal)

Type:

BCF

Value:

1 374 L/kg

Calculation basis:

steady state

Remarks on result:

other: (lipid-normalised empirical average BCF calculated by the registrant from the experimental data)

Remarks:

Conc.in environment / dose:4 µg/l (nominal)

Type:

BCF

Value:

1 695 L/kg

Calculation basis:

kinetic

Remarks on result:

other: (growth-corrected kinetic BCF calculated by registrant from the experimental data using first-order fish uptake/depuration model)

Remarks:

Conc.in environment / dose:40 µg/l (nominal)

Type:

BCF

Value:

1 420 L/kg

Calculation basis:

kinetic

Remarks on result:

other: (growth-corrected kinetic BCF calculated by registrant from the experimental data using first-order fish uptake/depuration model)

Remarks:

Conc.in environment / dose:4 µg/l (nominal)

Type:

BCF

Value:

1 971 L/kg

Calculation basis:

kinetic

Remarks on result:

other: (lipid-normalised growth-corrected kinetic BCF calculated by registrant from the experimental data using first-order fish uptake/depuration model)

Remarks:

Conc.in environment / dose:40 µg/l (nominal)

Type:

BCF

Value:

1 652 L/kg

Calculation basis:

kinetic

Remarks on result:

other: (lipid-normalised growth-corrected kinetic BCF calculated by registrant from the experimental data using first-order fish uptake/depuration model)

Remarks:

Conc.in environment / dose:4 µg/l (nominal)

Details on results:

No abnormality in appearance or behavior was noted.

Table 1: Bioconcentration factors at different time points and concentrations in water

	Duration of exposure	2weeks	4 weeks	6 weeks	8weeks	10 weeks
High concentration level	Concentration in the water (µg/l; average concentration at this time from start of exposure)	33.7	38.0	38.5	39.7	-
	Concentration infish (ng/g; two samples)	72800; 73800	79000; 59400	92800; 49900	51700; 51200	-
	Bioconcentration factor	2160; 2190	2080; 1560	2410; 1300	1300; 1290	-
Low concentration level	Concentration in the water(µg/l; average concentration at this time from start of exposure)	2.55; 2.55	2.27; 2.27	2.29; 2.29	2.40; 2.40	2.43; 2.43
	Concentration infish (ng/g; two samples)	1980; 2100	2010; 2100	2570; 2530	4000; 2930	2030; 2890
	Bioconcentration factor	776; 826	885; 926	1120; 1100	1660; 1220	836; 1190

 

Conclusions:

BCF values of 1290 - 2410 l/kg (40ug/l); 776 - 1660 l/kg (4ug/l) have been determined with carp in separate exposures at two concentrations in a reliable study conducted according to an appropriate test protocol (Japanese Industrial Standard test method, essentially the same as OECD 305C), with acceptable restrictions. The restrictions were that there was no depuration and there was some variability in concentration in fish between replicates at later sampling points.
The study reports the range of BCF values at each exposure level; no steady state BCF (BCFss) values are reported.
Empirical average BCF values at each exposure level of 1684 l/kg (40 µg/l) and 1181 l/kg (4 µg/l) have been calculated by the registrant from the experimental data. Lipid-normalised empirical average BCF values (normalised to default fish lipid content of 5% wwt) are 1958 l/kg (40 µg/l) and 1374 l/kg (4 µg/l). Application of a first-order fish uptake/depuration model to the experimental data, by the registrant, produced an acceptable fit at both the low- and high-level HMDS exposures, with uptake rate constants ranging from 84 to 1000 l kg-1 day-1 and growth-corrected depuration rate constants ranging from 0.059 to 0.59 day-1. These values produce steady-state kinetic BCF (BCFk) values of 1420 and 1695 l/kg for the low- and high-level HMDS exposures, respectively; these values are consistent with the empirical BCF values, indicating that steady-state concentrations of HMDS were achieved in the carp. Lipid-normalised BCFk values are 1971 l/kg (40 µg/l) and 1652 l/kg (4 µg/l).
 
For further information refer to Dow Corning Corporation, 2014. DOW CORNING TECHNICAL REPORT Kinetic Modeling Interpretation of Hexamethyldisiloxane (CAS RN 107-46-0) Fish Bioconcentration Data with the Common carp (Cyprinus carpio)). 2014. Attached to the EPSR.

Reference 2

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Please refer to the endpoint summary for justification of read-across.

Reason / purpose for cross-reference:

read-across source

Type:

BCF

Value:

>= 1 290 - <= 2 410 L/kg

Remarks on result:

other:

Remarks:

Result as stated in original study report

Description of key information

Bioaccumulation: aquatic / sediment: BCF: 1290 - 2410 l/kg (40 µg/l); 776 - 1660 l/kg (4 µg/l) (national method equivalent to OECD 305 C), based on read-across from a structurally-related substance.
Empirical average BCF: 1684 l/kg (40 µg/l); 1181 l/kg (4 µg/l) (calculated by the registrant from the experimental data). 
Lipid-normalised empirical average BCF: 1958 l/kg (40 µg/l) and 1374 l/kg (4 µg/l) (calculated by the registrant from the experimental data).
Growth-corrected kinetic BCF: 1695 l/kg (40 µg/l); 1420 l/kg (4 µg/l) (calculated by registrant from the experimental data using first-order fish uptake/depuration model). 
Growth-corrected lipid-normalised kinetic BCF: 1971 l/kg (40 µg/l) and 1652 l/kg (4 µg/l) (calculated by registrant from the experimental data using first-order fish uptake/depuration model).
In exposure modeling (EUSES 2.1.2) the growth-corrected lipid-normalised kinetic BCF value of 1971 l/kg (40 µg/l) will be used as a worst case.

Key value for chemical safety assessment

BCF (aquatic species):

1 971 L/kg ww

Additional information

There are no reliable bioaccumulation data available for Vi2-L2, therefore good quality data for the structurally-related substance hexamethyldisiloxane, L2, (CAS 107-46-0), have been read across in a category approach.

Vi2-L2 and L2 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 category indicates that BCF is dependent on log K_owas well as on chemical structure.

Vi2 -L2 and the source substance L2 are both linear siloxanes with two silicon atoms linked by one oxygen atom. In L2, the Si atoms are fully methyl substituted, whereas in Vi2-L2 each Si atom is bonded to one vinyl group and two methyl groups.The vinyl groups of Vi2-L2 are not expected to have a significant effect on the bioaccumulation potential (BCFBAF (EPI Suite version 3.20) does not apply any correction factors for the vinyl group to the algorithm based on log K_ow). L2 and Vi2-L2 possess similar physicochemical properties.  A comparison of the key physico-chemical properties is presented in the table below. Both substances have negligible biodegradability and similar moderate hydrolysis rates.

Table: Key physico-chemical properties of Vi2-L2 and source substance L2

Property	Vi2 -L2 (2627 -95 -4)	L2 (107 -46 -0)
Molecular weight	186.4	162.38
Log Kow	5.4	5.06
Log Koc	3.2	3.0
Water solubility (mg/l)	2.1E-01(at 20°C)	9.3E-01 (at 23°C)
Vapour pressure at 25°C (Pa)	1.7E+03	5.5E+03
Hydrolysis half- life at pH 7 (h)	140	116

Given the similar properties and structural similarities, it is considered valid to read across bioaccumulation data from L2 to Vi2 -L2.

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

The BCF values for L2 were 1290 - 2410 l/kg (40 µg/l); 776 - 1660 l/kg (4 µg/l), determined with carp in separate exposures at two concentrations in a reliable study conducted according to an appropriate test protocol (Japanese Industrial Standard test method, essentially the same as OECD 305C), with acceptable restrictions. The restrictions were that there was no depuration and there was some variability in concentration in fish between replicates at later sampling points. It is noted that, in accordance with ECHA decision number SEV-2114279195 -41 -01/F , a further aqueous bioaccumulation study (OECD 305, aqueous exposure) is in progress and the study result will be read-across to the submission substance when available.

The existing study reports the range of BCF values at each exposure level; no steady state BCF (BCFss) values are reported.

Empirical average BCF values at each exposure level of 1684 l/kg (40 µg/l) and 1181 l/kg (4 µg/l) have been calculated by the registrant from the experimental data. Lipid-normalised empirical average BCF values (normalised to default fish lipid content of 5% wwt) are 1958 l/kg (40 µg/l) and 1374 l/kg (4 µg/l). Application of a first-order fish uptake/depuration model to the experimental data, by the registrant, produced an acceptable fit at both the low- and high-level L2 exposures, with uptake rate constants ranging from 84 to 1000 l kg-1 day-1 and growth-corrected depuration rate constants ranging from 0.059 to 0.59 day-1. These values produce steady-state kinetic BCF (BCFk) values of 1420 and 1695 l/kg for the low- and high-level L2 exposures, respectively; these values are consistent with the empirical BCF values, indicating that steady-state concentrations of L2 were achieved in the carp. Lipid-normalised BCFkvalues are 1971 l/kg (40 µg/l) and 1652 l/kg (4 µg/l). The carp had a measured lipid content of 4.3% and the estimated freely-dissolved fraction of L2 in water is 100%, resulting in a lipid-adjusted, freely-dissolved BCFLW/fd values of 3.30 E+04 and 3.94 E+04 l/kg-lipid, for the low- and high-level exposures, respectively. These values, expressed as a biota/water fugacity ratio, Fbiota/water, produces values for the low- and high-level L2 exposures of 0.29 and 0.34, respectively. Fugacity ratio values less than 1.0 are indicative of materials that do not pose a bioaccumulation/biomagnifications risk to aquatic organisms.  For further information refer to Dow Corning Corporation, 2014, attached to the Endpoint Study Record in the IUCLID 6 dataset.

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.

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 growth corrected depuration rate constants of 0.059 d^-1(4.0 µg/l) and 0.59 d^-1(40 µg/l) obtained from the BCF study for L2 are considered to be valid and to carry most weight for bioaccumulation assessment. 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 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 L2, using K_owfor K_lw.

Calculated biota-water fugacity ratiosfor read-across substance L2

Endpoint	Exposure concentration	BCF Value	Fbiota-water*
BCFss	4 µg/l	1181	2.2E-01
BCFss	40µg/l	1684	3.1E-01
BCFk	4µg/l	1420	2.6E-01
BCFk	40 µg/l	1695	3.1E-01

*Using log K_ow5.06

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 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

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.

Dow Corning Corporation, 2104. DOW CORNING TECHNICAL REPORT Kinetic Modeling Interpretation of Hexamethyldisiloxane (CAS RN 107-46-0) Fish Bioconcentration Data with the Common carp (Cyprinus carpio)). 2014.

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.

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