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Bioaccumulation: aquatic / sediment

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Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
For details see any other information on material and methods incl. tables.
Principles of method if other than guideline:
Calculation based on BCFBAF v3.01, Estimation Programs Interface Suite™ for Microsoft® Windows v 4.11. US EPA, United States Environmental Protection Agency, Washington, DC, USA.
GLP compliance:
no
Test organisms (species):
other: aqueous and dietary
Test type:
other: calculation
Water / sediment media type:
natural water: freshwater
Details on test conditions:
For further detailed description on the model and its applicability, see "Any other information on materials and methods incl. tables" and attached model background information in "Overall remarks, attachments".
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF v3.01
- Result based on measured log Pow of: 10.1
- Result based on calculated log Pow of: 12.42 (estimated, KOWWIN v.1.68)
Type:
BCF
Value:
60.74 L/kg
Basis:
whole body w.w.
Remarks on result:
other: Arnot-Gobas, upper trophic including biotransformation rate
Details on results:
For detailed description on on the prediction see "Any other information on results".

SMILES: BrCC(Br)(C)COc1c(Br)cc(C(C)(C)c2cc(Br)c(OCC(Br)(C)CBr)c(Br)c2)cc1Br

MOL FOR: C23 H24 Br8 O2

MOL WT: 971.68

--------------------------------- BCFBAF v3.01 --------------------------------

Summary Results:

Log BCF (regression-based estimate): 2.60 (BCF = 403 L/kg wet-wt)

Biotransformation Half-Life (days) : 3.74e+003 (normalized to 10 g fish)

Log BAF (Arnot-Gobas upper trophic): 5.47 (BAF = 2.96e+005 L/kg wet-wt)

 

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 10.10 (user entered)

 

Equation Used to Make BCF estimate:

Log BCF = -0.49 log Kow + 7.554 + Correction

 

Correction(s):                   Value

No Applicable Correction Factors

 

Estimated Log BCF = 2.605 (BCF = 402.7 L/kg wet-wt)

 

===========================================================

Whole Body Primary Biotransformation Rate Estimate for Fish:

===========================================================

------+-----+--------------------------------------------+---------+---------

TYPE | NUM | LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION | COEFF | VALUE

------+-----+--------------------------------------------+---------+---------

Frag | 4 | Aliphatic bromide  [-Br]                | 0.2734 | 1.0936

Frag | 4 | Aromatic bromide  [-Br]                 | 0.3964 | 1.5854

Frag | 3 | Carbon with 4 single bonds & no hydrogens | -0.2984 | -0.8953

Frag | 2 | Aromatic ether [-O-aromatic carbon]     | -0.0694 | -0.1388

Frag | 4 | Aromatic-H                               | 0.2664 | 1.0655

Frag | 4 | Methyl [-CH3]                           | 0.2451 | 0.9804

Frag | 4 | -CH2- [linear]                          | 0.0242 | 0.0967

Frag | 2 | o-Chloro / Mono-aromatic ether           | 0.7828 | 1.5656

Frag | 2 | Benzene                                  | -0.4277 | -0.8555

L Kow| * | Log Kow = 10.10 (user-entered  )       | 0.3073 | 3.1042

MolWt| * | Molecular Weight Parameter               |        | -2.4917

Const| * | Equation Constant                        |        | -1.5371

============+============================================+=========+=========

RESULT  |       LOG Bio Half-Life (days)           |        | 3.5732

RESULT  |           Bio Half-Life (days)           |        |   3743

NOTE    | Bio Half-Life Normalized to 10 g fish at 15 deg C  |

============+============================================+=========+=========

 

Biotransformation Rate Constant:

kM (Rate Constant): 0.0001852 /day (10 gram fish)

kM (Rate Constant): 0.0001041 /day (100 gram fish)

kM (Rate Constant): 5.856e-005 /day (1 kg fish)

kM (Rate Constant): 3.293e-005 /day (10 kg fish)

 

Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):

Estimated Log BCF (upper trophic) = 1.783 (BCF = 60.74 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 5.471 (BAF = 2.957e+005 L/kg wet-wt)

Estimated Log BCF (mid trophic)  = 1.961 (BCF = 91.43 L/kg wet-wt)

Estimated Log BAF (mid trophic)  = 5.107 (BAF = 1.279e+005 L/kg wet-wt)

Estimated Log BCF (lower trophic) = 2.016 (BCF = 103.7 L/kg wet-wt)

Estimated Log BAF (lower trophic) = 4.824 (BAF = 6.672e+004 L/kg wet-wt)

 

Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):

Estimated Log BCF (upper trophic) = 1.829 (BCF = 67.48 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 5.528 (BAF = 3.374e+005 L/kg wet-wt)

Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
20 Jul - 08 Aug 2012
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
An aqueous exposure (instead of dietary) took place although the substance is very insoluble in water. Concentrations tested were higher than the water solubility, therefore a solvent was used. Solvent was too high concentrated. No determination of a steady state, no determination of depuration, no correction of the results for a lipid content. The results cannot be evaluated with certainty but include relevant findings, which can be used in combination with other information in a weight of evidence approach for the bioaccumulation assessment.
Qualifier:
according to
Guideline:
OECD Guideline 305 (Bioconcentration: Flow-through Fish Test)
Deviations:
yes
Remarks:
solvent was too high concentrated (25 ml/L instead of max 0.1 ml/L), no correction of the results for lipid content, no determination of a steady state for BCF and no determination of depuration alternatively.
GLP compliance:
yes
Details on sampling:
- Sampling intervals/frequency for test organisms: fish lipid was analysed at the start and at the end of the exposure period. The test substance in the fish (n = 4) was analyzed on days 9, 14, 28, 41 and 6.
- Sampling intervals/frequency for test medium samples: water samples from each concentration level were taken after 9, 14, 19, 28, 34, 41, 48, and 62 d of exposure
- Details on sampling and measurement of the lipid content: fish were weighed and cut into pieces, 6 fold of fish weight sodium sulfate anhydrous was added, mixture was homogenized and dehydrated for 30 min. 80 mL n-hexane were added, homogenized for 5 min at 8000 rpm, then filtered with suction through filter paper in a 60 mm Kiriyama funnel. 80 mL n-hexane was added again to the residue, homogenized for 3 min and 8000 rpm and filtered again. Residue was washed with 20 mL n-hexane. Filtrates and the washing were filled in a recovery flask, evaporated and concentrated to approx. 10 mL with a rotary evaporator at 45 °C. Suspension was transferred to a pre-weighed flask (previous flask was washed twice with 5 mL n-hexane in order to assure complete transfer). Evaporation followed as described above with subsequent desiccation in a vacuum chamber for 4 h. Lipids were then weighed.
Vehicle:
yes
Remarks:
Tetrahydrofuran 25 ppm (v/v)
Details on preparation of test solutions, spiked fish food or sediment:
PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Controls: tetrahydrofuran
- Chemical name of vehicle (organic solvent, emulsifier or dispersant): tetrahydrofuran
- Concentration of vehicle in test medium: 25 ppm (v/v)

PREPARATION OF SPIKED FISH FOOD
- Details on fish food (source, fat content as supplied, etc): see section `details on test conditions´
- Details of spiking: 2 feed solutions were prepared (with 40 and 400 mg test substance/L) with tetrahydrofuran added to the appropriate amount of test substance and filled up to 500 mL. Test substance is stable in the feed solution for 21 d under light shielded conditions.
- Chemical name of vehicle (organic solvent), if used: tetrahydrofuran
Test organisms (species):
Cyprinus carpio
Details on test organisms:
TEST ORGANISM
- Common name: Carp
- Source: Niikura Fish Farm, Kanagawa, Japan
- Age at study initiation: yearling fish
- Length at study initiation: 4 - 8 cm
- Weight at study initiation: approx. 5.5 g
- Lipid content at test initiation: 3.4% (n = 5, 2.8 - 3.9%)
- Lipid content at test end: 4.1% (n = 5, 3.5 - 5.3%)

ACCLIMATION
- Acclimation period: 20 Jul – 08 Aug 2012
- Acclimation conditions (same as test or not): 24 ± 2 °C
- Type and amount of food: feeding with Babygold, Kyorin in an amount corresponding to 1.5% of the body weight. Feeding was discontinued for the 24 h before testing)
- Feeding frequency: daily
- Health during acclimation (any mortality observed): at the start of acclimation, abnormal fish were removed upon visual inspection. The remaining fish were placed in an aquarium with flowing water
Route of exposure:
aqueous
Test type:
flow-through
Water / sediment media type:
natural water: freshwater
Total exposure / uptake duration:
63 d
Hardness:
48 - 54 mg CaCO3/L
Test temperature:
24.3 - 24.6 °C
pH:
7 - 7.4
Dissolved oxygen:
>= 60% of the saturation (7.5 - 8.2 mg/L at 24 °C)
TOC:
14.18 - 15.88 mg/L (due to tetrahydrofuran solvent - theoretical TOC value is 16.7 mg/L)
Details on test conditions:
TEST SYSTEM
- Fill volume: 50 L
- Aeration: continuous
- Type of flow-through: continuous (800 L dilution water/d, 20 mL feed solution/d)
- No. of organisms per vessel: 36
- No. of organisms per control: 12
- No. of vessels per concentration (replicates): 1
- No. of vessels per control / vehicle control (replicates): 1

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: dechlorinated water treated with activated charcoal filter and sodium thiosulfate
- Intervals of water quality measurement: pH was measured at the start and the end of the exposure period. Total hardness of the test water was measured once during the exposure period. The TOC of the test water was measured once prior to the exposure and more than once about every 2 weeks during the exposure period. Dissolved oxygen and temperature were measured on test water sampling days.

OTHER TEST CONDITIONS
- Photoperiod: 16 h light
- Light intensity: Hf fluorescence lamp (400 - 700 nm)
- Overall daily feeding rate used in the study: 15% of the fish weight
- Number of feeds per day: 1 (Kyorin, Babygold®)

RANGE-FINDING / PRELIMINARY STUDY
- Other justification for choice of test concentrations: LC50 (96 h) was determined to be > 1 mg/L in a preliminary conducted acute toxicity test (OECD 203) with Oryzias latipes. Therefore following test concentrations for the BCF study were chosen: 0.001 mg/L (low) and 0.01 mg/L (high), which correspond to 1/100 and 1/1000 of the 96-h LC50 according to the guideline

Nominal and measured concentrations:
Control, 0.01 and 0.001 mg/L (nominal)
Reference substance (positive control):
no
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Determination limits of BCF: 7 and 66 for the high and the low concentration level, respectively
Lipid content:
3.4 %
Time point:
start of exposure
Lipid content:
4.1 %
Time point:
end of exposure
Conc. / dose:
0.01 mg/L
Type:
BCF
Value:
<= 45 dimensionless
Basis:
whole body w.w.
Conc. / dose:
0.001 mg/L
Type:
BCF
Value:
<= 94 dimensionless
Basis:
whole body d.w.
Details on results:
- Mortality of test organisms: no
- Behavioural abnormalities: no
- Observations on feeding behavior: no
- Other biological observations: no
- Other: the variations of mean BCF from three consecutive determinations separated by intervals of more than 48 h could not be confirmed to fall within ± 20 % at both concentration levels, BCFss could not be calculated mathematically
Reported statistics:
The mean concentrations in the test water and BCF were calculated according to the JIS Handbook "Guide to the handling of numbers".

The mean concentrations of the test substance in water during the exposure period were 0.00907 and 0.00117 mg/L for the high and low concentration levels, respectively.

Table 1: Mean measured concentiations of the test substance in the test water for the high and the low concentration level.

Day Mean concentration in water mg/L (at high concentration level) Mean concentration in water mg/L (at low concentration level)
0 0.01115 0.00120
9 0.01027 0.00123
14 0.00980 0.00122
19 0.00964 0.00117
28 0.00940 0.00116
34 0.00936 0.00115
41 0.00924 0.00116
48 0.00912 0.00116
62 0.00907 0.00117

Table 2: Calculated BCF values for the high and the low concentration levels of the test item.

High concentration level of the test item Low concentration level of the test item
Day Concentration in fish body (µg/g) Mean concentration in water mg/L BCF Mean BCF Concentration in fish body (µg/g) Mean concentration in water mg/L BCF Mean BCF
9 <0.092 0.01027 <9 NA <0.093 0.00123 <76 NA
9 0.106 0.01027 10 <0.093 0.00123 <76
14 0.118 0.0098 12 13 <0.093 0.00122 <77 NA
14 0.123 0.0098 13 <0.093 0.00122 <77
28 0.202 0.0094 22 20 <0.091 0.00116 <79 NA
28 0.171 0.0094 18 <0.091 0.00116 <79
41 0.275 0.00924 30 38 0.0902 0.00116 78 82
41 0.417 0.00924 45   0.0902 0.00116 86
62 0.279 0.00907 31 27 0.1034 0.00117 88 91
62 0.199 0.00907 22 0.11 0.00117 94

Description of key information

BCF (0.01 mg/L) : <9 to 45, BCF (0.001 mg/L): <76 to 94 (OECD 305)

BCF = 60.74 L/kg (BCFBAF v3.01, EPISUITE v 4.11)

Key value for chemical safety assessment

Additional information

One study is available testing the bioconcentration potential of Reaction mass of 1,1'-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)benzene] and 1,3-dibromo-2-(2,3-dibromo-2-methylpropoxy)-5-{2-[3,5-dibromo-4-(2,3,3-tribromo-2-methylpropoxy)phenyl]propan-2-yl}benzene in fish.

 

In the available study conducted according to OECD 305 (1996) Cyprinus carpio (carp) was exposed for 63 d to the test item (Shinde, 2013). Two concentration levels of 0.01 mg/L and 0.001 mg/L (nominal) and a control were tested. Tetrahydrofuran was used as a vehicle in a continuous flow-through dilution system. The solvent was higher concentrated than recommended by the guideline (25 ml/L instead of max 0.1 mL/L). Pre-treated samples were analytically measured by UPLC. The BCF was found to lie between <9 and 45 at the high concentration level of the test item and between <76 and 94 at the low concentration level. BCF steady state could however not be calculated and the bioconcentration factors were not corrected for lipid content.

 

Since the above described study shows certain limitations a QSAR (BCFBAF v3.01, EPISUITE v 4.11) calculation was additionally performed. The BC factor was calculated to be 60.74 L/kg for the upper trophic including a biotransformation rate of 0.0001852 /day (for 10 g fish). The substance does not meet completely the applicability domain of the model (log Kow > 9 and molecular weight > 959.17) and therefore results have to be observed with caution.

 

Physicochemical and toxicokinetic data were additionally taken into account and give further evidence about the bioaccumulative fate of Reaction mass of 1,1'-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)benzene] and 1,3-dibromo-2-(2,3-dibromo-2-methylpropoxy)-5-{2-[3,5-dibromo-4-(2,3,3-tribromo-2-methylpropoxy)phenyl]propan-2-yl}benzene. The high molecular weight and the very high log Kow of > 10 (OECD 117) indicate according to guideline (EC) No 1907/2006 low bioaccumulation possibility due to low bioavailability. This is further encouraged by the toxicokinetic assessment which can be read in detail in chapter 7.1.

 

Considering all above mentioned evidence Reaction mass of 1,1'-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)benzene] and 1,3-dibromo-2-(2,3-dibromo-2-methylpropoxy)-5-{2-[3,5-dibromo-4-(2,3,3-tribromo-2-methylpropoxy)phenyl]propan-2-yl}benzene is not expected to bioaccumulate in organisms.