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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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
1. SOFTWARE
EpiSuite v4.11, US EPA, 2012

2. MODEL (incl. version number)
BCFBAF v3.01

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
OC(CCC(O)(CC(C)C)C)(C)CC(C)C

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: BCF
- Unambiguous algorithm:
The BCFBAF method classifies a compound as either ionic or non-ionic. Ionic compounds include carboxylic acids, sulfonic acids and salts of sulfonic acids, and charged nitrogen compounds (nitrogen with a +5 valence such as quaternary ammonium compounds). All other compounds are classified as non-ionic.

Training Dataset Included:
466 Non-Ionic Compounds
61 Ionic Compounds (carboxylic acids, sulfonic acids, quats)

Methodology for Non-Ionic was to separate compounds into three divisions by Log Kow value as follows:
Log Kow < 1.0
Log Kow 1.0 to 7.0
Log Kow > 7.0

For Log Kow 1.0 to 7.0 the derived QSAR estimation equation is:

Log BCF = 0.6598 Log Kow - 0.333 + Σ correction factors
(n = 396, r2 = 0.792, Q2 = 0.78, std dev = 0.511, avg dev = 0.395)

The previous BCFWIN equation:
Log BCF = 0.77 Log Kow - 0.70 + Σ correction factors

For Log Kow > 7.0 the derived QSAR estimation equation is:

Log BCF = -0.49 Log Kow + 7.554 + Σ correction factors
(n = 35, r2 = 0.634, Q2 = 0.57, std dev = 0.538, avg dev = 0.396)

For Log Kow < 1.0 the derived QSAR estimation equation is: All compounds with a log Kow of less than 1.0 are assigned an estimated log BCF of 0.50

- Defined domain of applicability:
Currently there is no universally accepted definition of model domain. However, users may wish to consider the possibility that bioconcentration factor estimates are less accurate for compounds outside the MW and logKow ranges of the training set compounds, and/or that have more instances of a given correction factor than the maximum for all training set compounds. It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no fragment coefficient was developed; and that a compound has none of the fragments in the model’s fragment library. In the latter case, predictions are based on molecular weight alone. These points should be taken into consideration when interpreting model results.

Training Set (527 Compounds):

Molecular Weight:
Minimum MW: 68.08 (Furan)
Maximum MW: 991.80 Ionic: (2,7-Naphthalenedisulfonic acid, 4-amino-5-hydroxy-3,6-
bis[[4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt)
Maximum MW: 959.17 Non-Ionic: (Benzene, 1,1 -oxybis[2,3,4,5,6-pentabromo-)
Average MW: 244.00

Log Kow:
Minimum LogKow: -6.50 Ionic: (2,7-Naphthalenedisulfonic acid, 4-amino-5-hydroxy-3,6-bis[[4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt)
Minimum LogKow: -1.37 Non-Ionic: (1,3,5-Triazine-2,4,6-triamine)
Maximum LogKow: 11.26 (Benzenamine, ar-octyl-N-(octylphenyl)-)

- Appropriate measures of goodness-of-fit and robustness and predictivity:
Accuracy of the Training Set:
n=527
r²=0.833
SD=0.502
Average deviation=0.382

Accuracy of the Validation Set:
n=158
r²=0.82
SD=0.59
Average deviation=0.46


5. APPLICABILITY DOMAIN
- Descriptor domain: The components of the substance are within the molecular weight range of the training set compounds, and all fragments are represented in the training set. Thus, it is concluded, that the substance is within the applicability domain.
- Similarity with analogues in the training set: several linear and branched alkanes and alkenes, which are considered to be similar, are present in the training set.

6. ADEQUACY OF THE RESULT
The QSAR prediction is valid and of good reliability. Thus, the result is adequate for chemical safety assessment.
Principles of method if other than guideline:
estimation using EpiSuite v4.11, BCFBAF v3.01, US EPA, 2012
GLP compliance:
no
Remarks:
not applicable for in silico study
Type:
BCF
Value:
149 L/kg
Basis:
whole body w.w.
Calculation basis:
steady state

SMILES : OC(CCC(O)(CC(C)C)C)(C)CC(C)C

CHEM  :

MOL FOR: C14 H30 O2

MOL WT : 230.39

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

Summary Results:

 Log BCF (regression-based estimate): 2.17 (BCF = 149 L/kg wet-wt)

 Biotransformation Half-Life (days) : 0.425 (normalized to 10 g fish)

 Log BAF (Arnot-Gobas upper trophic): 2.15 (BAF = 142 L/kg wet-wt)

 

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

BCF (Bioconcentration Factor):

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

Log Kow (estimated) : 4.32

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 3.80 (user entered)

 

Equation Used to Make BCF estimate:

  Log BCF = 0.6598 log Kow - 0.333 + Correction

 

     Correction(s):                   Value

      No Applicable Correction Factors

 

  Estimated Log BCF = 2.174 (BCF = 149.4 L/kg wet-wt)

 

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

Whole Body Primary Biotransformation Rate Estimate for Fish:

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

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

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

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

 Frag | 2 | Carbon with 4 single bonds & no hydrogens | -0.2984 | -0.5969

 Frag | 6 | Methyl [-CH3]                           | 0.2451 | 1.4706

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

 Frag | 2 | -CH-  [linear]                          | -0.1912 | -0.3825

 L Kow| * | Log Kow =  3.80 (user-entered  )       | 0.3073 | 1.1679

 MolWt| * | Molecular Weight Parameter               |        | -0.5908

 Const| * | Equation Constant                        |        | -1.5371

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

  RESULT  |       LOG Bio Half-Life (days)           |        | -0.3719

  RESULT  |           Bio Half-Life (days)           |        | 0.4247

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

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

 

Biotransformation Rate Constant:

 kM (Rate Constant): 1.632 /day (10 gram fish)

 kM (Rate Constant): 0.9178 /day (100 gram fish)

 kM (Rate Constant): 0.5161 /day (1 kg fish)

 kM (Rate Constant): 0.2902 /day (10 kg fish)

 

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

  Estimated Log BCF (upper trophic) = 2.151 (BCF = 141.5 L/kg wet-wt)

  Estimated Log BAF (upper trophic) = 2.151 (BAF = 141.5 L/kg wet-wt)

  Estimated Log BCF (mid trophic)  = 2.196 (BCF = 157 L/kg wet-wt)

  Estimated Log BAF (mid trophic)  = 2.197 (BAF = 157.3 L/kg wet-wt)

  Estimated Log BCF (lower trophic) = 2.199 (BCF = 158.1 L/kg wet-wt)

  Estimated Log BAF (lower trophic) = 2.204 (BAF = 160 L/kg wet-wt)

 

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

  Estimated Log BCF (upper trophic) = 2.820 (BCF = 661.2 L/kg wet-wt)

  Estimated Log BAF (upper trophic) = 3.079 (BAF = 1199 L/kg wet-wt)

 

Conclusions:
The BCF of 2,4,7,9-tetramethyldecane-4,7-diol was estimated to be 149 L/kg wet-wt (EpiSuite v4.11, BCFBAF v3.01).
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:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because
- they are manufactured from similar precursors under similar conditions
- they share structural similarities with common functional groups: both substances start with an acetylene group as core structure, however, in the target substance this acetylene group has been fully hydrogenated during the manufacturing process; geminal hydroxyl groups on the alpha carbon atoms; distal to the geminal hydroxyl groups is an isobutyl group (methyl isopropyl)
- they have similar physicochemical properties and thus, show a similar toxicokinetic behaviour
- they are expected to undergo similar metabolism: oxidation of the terminal methyl groups to result in alcohol, aldehyde and finally the corresponding acid

Since the central acetylene group in the source substance is sterically shielded by the neighbouring functional groups, this structural difference does not lead to major differences in reactivity and/or toxicity, which is demonstrated based on the available toxicological data.

Therefore, read-across from the existing toxicity studies on the source substance is considered as an appropriate adaptation to the standard information requirements of REACH regulation.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see “Justification for read-across” attached to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
see “Justification for read-across” attached to IUCLID section 13

4. DATA MATRIX
see “Justification for read-across” attached to IUCLID section 13
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Details on sampling:
The test substance in test water was analyzed according to the following procedure:
High conentration level:
0.5 ml of test water was filled up with acetonitrile to 5 mL (dilution ratio: 10)
Vehicle:
yes
Test organisms (species):
Cyprinus carpio
Details on test organisms:
Niikura Fish Farm
Lot# 09-K-1102
total length: 8 +/- 4 cm
Approximately 7 g
Age: approx. one year after hatching
Route of exposure:
feed
Test type:
flow-through
Water / sediment media type:
natural water: freshwater
Total exposure / uptake duration:
28 d
Test temperature:
24 +/- 2°C
pH:
6.0 - 8.5
Dissolved oxygen:
> 60 % of the saturation (> 5 mg/L at 24°C)
Reference substance (positive control):
yes
Remarks:
Dimethylsulfoxide DMSO
Lipid content:
> 2.4 - < 6.8 %
Time point:
start of exposure
Remarks on result:
other: 5.1 % (n=3)
Lipid content:
> 2.7 - < 3.3 %
Time point:
end of exposure
Remarks on result:
other: 3.0 % (n=3)
Key result
Type:
BCF
Value:
< 24 dimensionless
Validity criteria fulfilled:
yes
Conclusions:
The BCF was determined to be < 24. Based on these results, the test substance was judged not to have high bioconcentration potential.

Description of key information

The BCF of 2,4,7,9-tetramethyldecane-4,7-diol was estimated to be 149 L/kg wet-wt (EpiSuite v4.11, BCFBAF v3.01).

The BCF of the structurally related 2,5,8,11-tetramethyldodec-6-yne-5,8-diol was determined to be < 24. Based on these results, the test substance was judged not to have high bioconcentration potential. A justification for read-across is attached to iuclid section 13.

Key value for chemical safety assessment

BCF (aquatic species):
24 L/kg ww

Additional information