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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Description of key information

BCF: 14900 l/kg (lipid normalised, kinetic)
BMF 0.47 (lipid-normalised steady-state);
Depuration rate constants from BCF study: 0.0613 d-1

Key value for chemical safety assessment

BCF (aquatic species):
14 900 L/kg ww
BMF in fish (dimensionless):

Additional information

A steady-state BCF value of 12400l/kg(0.26 µg/l measured) and a kinetic BCF value of 13400l/kg(0.26 µg/l measured) were determined 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 (DCC, 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 BCFss= 9700 l/kg, BCFk= 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 BCFkis 14900 l/kg.

A GLP flow-through bioconcentration study in common carp (Cyprinus carpio) (yearling fish; weight ~10 – 20 g) conducted according to OECD Guideline 305 is also available (CERI, 2007). Steady-state BCF (BCFss) values were calculated to be 3128.8 and 3000.4 for the 2.52 µg/l and 0.22 µg/l treatment groups, respectively. Lipid content of the fish was 3.18% before initiation, 5.36% (higher treatment group) – 6.56% (lower treatment group) on day 1 of depuration and 4.22% at test termination. Lipid normalisation was not carried out by the authors of the study report. Given the variation in lipid content measured, and the proximity to the 5% value to which normalisation is carried out, this is considered acceptable.

The depuration half-life was estimated as 8.8 days for the 2.52 µg/l treatment group and 6.5 days for the 0.22 µg/l group. Uptake and depuration rates do not appear to be reported, and a kinetic BCF is not presented.

A second study (only available in Japanese) appears to be a GLP flow-through bioconcentration study in common carp (Cyprinus carpio) conducted according to OECD Guideline 305 (CERI, 2010). Steady-state BCF (BCFss) values were calculated to be 3329.4 and 3967.2 for the 2.40 µg/l and 0.23 µg/l treatment groups, respectively. The lipid content in the fish appears to be presented as 4.15% – 6.43%. Given the proximity to the 5% standard lipid value, lipid normalisation is not carried out.

The depuration half-life was estimated by the authors as 7.0 days for the2.40 µg/l treatment group and 8.2 days for the 0.23 µg/l. Uptake and depuration rates do not appear to be reported by the authors of the study, and a kinetic BCF is not presented.

There was significant fish growth during the uptake phase of this study, with the mean fish weight increasing by a factor of two for both treatment groups. Kinetic data from the uptake phase is therefore unreliable, and a kinetic BCF is not calculated by the authors of the current report. Fish weights appear to remain constant during the depuration phase.

A fish feeding study is also available. The BMFSS, 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 BMFSSLwas 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. BMFKg) 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.

A second GLP dietary accumulation test using D4 was carried out in carp (Cyprinus carpio) and conducted according to OECD TG 305 dietary exposure test (draft version 10 of August 31st2010). The full study report (CERI, 2011) is currently available only in Japanese but the reported BMF values and rate constants can be verified from the raw data reported.Steady-state does not appear to have been reached during the 13 day uptake phase. Steady-state BMF values are not reported by the authors.

The uptake rates (k1) and depuration rates (k2) and kinetic BMF values were determined using Berkeley Madonna software, to fit the data using a first order one-compartment model.

A k1value of 0.0162 day-1 and k2value of 0.1115 day-1 were calculated. The kinetic BMF (BMFK) value was calculated to be 0.145. The lipid normalised, kinetic BMF value was calculated to be 0.405.

The kinetic BMF values and uptake rates (k1) and depuration rates (k2) were also determined using the OECD test guideline (OECD TG 305 Draft, 2010). A k1value of 0.01047 day-1and k2value of 0.0797 day-1were calculated. The kinetic BMF (BMFK) value was calculated to be 0.131. The lipid normalised, kinetic BMF value was calculated to be 0.367.

Fish bioconcentration (BCF) studies are most validly applied to substances with log Kowvalues 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 Kocwill 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 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. kg) 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 caluculation (i.e. k1) are those of a growing fish, but the depuration parameters are altered to reflect no growth (i.e. k2- kg). Based on this criticisim 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 keliminationof >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.

Agrowth corrected depuration rate constant (i.e.k2– kg) 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.

Two further studies (Domoradzkiet al., 2015a and 2015b, in publication) report metabolism rates (km) for D4 and D5. In Domoradzkiet al., 2015a, a 96-h metabolism study was conducted in rainbow trout whereby a 15 mg [14C] D4 or [14C] D5/kg bw single bolus oral dose was administered via gavage. Of the administered dose, 79% (D4) and 78% (D5) was recovered by the end of the study; 82% and 25% of the recovered dose was absorbed based on the percentage of recovered dose in carcass (69% and 17%), tissues, bile and blood (12% and 8%) and urine (1%) for D4 and D5, respectively. A significant portion of the recovered dose (i.e. 18% for D4 and 75% for D5) was eliminated in faeces. Maximum blood concentrations were 1.6 and 1.4 µg D4 or D5/g blood at 24 h with elimination half-lives of 39 h (D4) and 70 h (D5). Modelling of parent and metabolite blood concentrations resulted in metabolism rate constants (km) of 0.15 day-1(D4) and 0.17 day-1(D5).

In Domoradzki et al., 2015b,Whole Body Autoradiography (WBA) was conducted in conjunction with dietary bioaccumulation studies with [14C] D4 and [14C] D5 to assess distribution and metabolism in rainbow trout. Comparison of radioactivity to D4 parent concentrations in liver extracts indicated the presence of one or more metabolites. WBA conducted during the depuration phase showed that the highest amounts of radioactivity were present in the gastrointestinal (GI) or digestive tract, liver and fat (adipose) tissue, with lesser amounts in other tissues. There was a significant amount of radioactivity in the gall bladder, with moderate amounts in the liver and contents of the digestive tract. Continued presence of parent D4 in the digestive tract contents at 42 days’ depuration demonstrates elimination of parent D4 via enterohepatic circulation. Similarly, a [14C] D5 bioaccumulation study analysis of radioactivity concentration and WBA provide evidence that D5 is metabolised and eliminated via the digestive tract over time. WBA findings support in vivo 96-h metabolism studies with rainbow trout.

A conservative kmvalue of ≥0.01 day-1may be estimated from these study data and is indicative of a substance that 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 units 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 (Burkhardet 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 (Fbiota-water) is:

Fbiota-water= BCFWD/LW/ Klwx ρl/ ρB

where BCFWD/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), Klw is the lipid-water partition coefficient, ρlis the density of lipid and ρBis 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. Klw= Kow. For some substances with specific interactions with the organic phase, this assumption is not sufficiently accurate. Measurement of Klw values for siloxane substances is in process. Initial laboratory work with olive oil as lipid substitute indicates that the assumption that Klw= Kow 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 D4, using Kow for Klw. BMF values do not require adjustments because these values are already equivalent to fugacity-based values.

Table4.3.2Calculated biota-water fugacity ratios


Exposure concentration

BCF Value



0.26 µg/l




0.26 µg/l



BCFk, lipid normalized. Re-analysis of BCF­k from Smitet al.,2012)

0.26 µg/l



*Using log Kow6.49

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.

Trophic Magnification Factors (TMF) values for D4 have been evaluated in several aquatic systems (Powell D. al. 2009 (Lake Pepin), Powell D. al. 2010 (Inner and Outer Oslofjord), Powellet al.,2012 (Tokyo Bay), Borgået al., 2012 (Lake Mjosa), McGoldricket al., 2014 (Lake Erie), Borgå al., 2013 (Lake Mjosa and Lake Randsfjorden), Jia, H.,et al.,2015 (Chinese Yellow Sea), NIVA 2016 (Inner Oslofjord). Further information and interpretation of the TMF data is available in Annex 4 of the CSR (see attached file).