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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Reference
Endpoint:
bioaccumulation: aquatic / sediment
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
2010
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 adequate and reliable documentation / justification
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Guideline:
other: BCFBAFWIN v3.00
Principles of method if other than guideline:
Estimation of fish BCF based on input structure of DIBK, its impurities, and structural analogs.
GLP compliance:
no
Specific details on test material used for the study:
The substance and its impuritieswere entered into the estimation software using the following SMILES
notations:
2,6-dimethylheptan-4-one
C(=O)(CC(C)C)CC(C)C
2,6-dimethylheptan-4-ol
C(C)(C)CC(O)CC(C)C
2,4-dimethylheptan-2-ol
C(C)(=O)CC(C)CC(C)C


Details on properties of test surrogate or analogue material (migrated information):
Surrogate substances (analogous ketones), having measured fish BCF values and log Pow values bracketing those of the test substance/impurities, were entered into the estimation software using the following SMILES notations:


18-pentatriacontanone, CAS 504-53-0
C(=O)(CCCCCCCCCCCCCCCCC)CCCCCCCCCCCCCCCCC
Benzophenone CAS 119-61-9
c1(C(=O)c2ccccc2)ccccc1
Methyl Styryl ketone CAS 122-57-6
C(C)(=O)C={t}Cc1ccccc1
2-hydroxy-4-methoxybenzophenone AS 131-57-7
O=C(c(cccc1)c1)c(c(O)cc(OC)c2)c2
Radiolabelling:
no
Details on sampling:
not applicable
Details on preparation of test solutions, spiked fish food or sediment:
not applicable
Details on test organisms:
the estimation programs predict fish BCF values (L/kg) on whole fish, wet wt. basis
Details on estimation of bioconcentration:
BCFBAFWIN v3.00 (2009): The fish BCF is estimated using established correlation with log Pow, and corrected for certain structural features (e.g., molecular size) and metabolism:
Log BCF = 0.6598 log Kow - 0.333 + Correction Factors

The Base-line BCF V01.02 (2010) predicts a maximum BCF value (BCFmax) from correlation with log Kow, then corrects this value (BCFcorr) for mitigating factors such as molecular size, ionization (amines, acids, phenols), water solubility, and metabolism.
Type:
BCF
Value:
130 L/kg
Remarks on result:
other: Predicted BCF for DIBK (BCFBAF v3.00)
Details on kinetic parameters:
not applicable
Metabolites:
The Catalogic v05.10.06 software, which provides the basis for correction of BCFmax due to mitigating factor of metabolism, predicts the following transformations:
1. Phase I: Reduction of ketone group to corresponding alcohol
2. Phase II: Glucoronidation at alcohol sites
Results with reference substance (positive control):
Results of predicted vs. measured BCF values for the four structural analogs are shown in Table 1.
Details on results:
The BCFBAF estimation predicts fish BCF with in a factor of 2 of the measured values for four stucturally-related ketone substances having log Pow values bracketing those of the DIBK substance and impurities. The Base-line BCF estimation predicted BCF values which were consistently much lower than the experimental values. Therefore, the BCFBAF-predicted values of BCF are reported as the estimated BCF values used in the chemical safety asessment.
Reported statistics:
BCFBAFWIN v3.00 produced estimated fish BCF values which fell within a factor of 2 of measured BCF values for four related ketone substances.

Table 1.   Summary of estimated and measured log Powand fish BCF values for 2,6-dimethyheptan-4-one, its associated impurities, and structural analogs

 

 

 

Substance Name

 

Measured

log Pow

KOWWIN

Estimated

log Pow

Measured – Estimated Log Pow

 

Measured BCF (L/kg)

BCFBAF

Estimated

BCF (L/kg)

Measured - Estimated

BCFBAF

Base-line BCF

Estimated

BCFcorr(L/kg)

Measured - Estimated

Base-line BCF

2,6-dimethylheptan-4-one

3.71*

2.56

1.15

-

128

-

3.8

-

2,6-dimethylh-4-heptanol

-

3.08

-

-

50

-

18

-

2,4-dimethylheptan-2-one

-

2.56

-

-

23

-

3.8

-

18-pentatriacontanone

-

15.48

-

12

3.2

8.8

7.6

4.4

Benzophenone

3.18

3.1

0.08

12

15

3.0

5.5

6.5

Methyl Styryl ketone

2.07

2.0

0.07

18

11

7

15

3

2-hydroxy-4-methoxybenzophenone

3.79

3.52

0.27

72

38

34

20

52

Mean Error =

0.38

 

13.2

 

16.5

*Estimated value using the OECD Guideline 117: HPLC Method

Conclusions:
Predicted BCF for DIBK is 130 L/kg (BCFBAF v3.00)
Predicted BCF for other components/impurities of the substance are 50 and 23 L/kg.

Predicted BCF using BCFBAF program are within a factor of 2 of experimental BCF values for other ketone substances having log Kow bracketing that of DIBK.
Executive summary:

The fish bioconcentration factor (BCF) was estimated for 2,6 -dimethylheptan-4 -one (DIBK) , two known impurties, and four analogous ketone substances having measured BCF values. The estimated BCF for DIBK is 130 L/kg (wet wt. basis), while that for the impurities is 50 and 23. The estimation methods were shown to produce estimated BCF values which differed by no more than a factor of 4 from measured BCF values, for four ketone substances having log Pow values which bracket those of DIBK and impurities. Considering the magnitude of these estimated BCF values, and the magnitude of absolute error for the estimates with structural analogs, the substances can be reliably regarded as having very low potential for bioaccumulation in the aquatic environment.

Description of key information

Predicted BCF for DIBK is 130 L/kg (BCFBAF v3.00)
Predicted BCF for other components/impurities of the substance are 50 and 23 L/kg.

Key value for chemical safety assessment

BCF (aquatic species):
130 L/kg ww

Additional information

The fish BCF values for DIBK and its two reported impurities were estimated using two accepted QSAR methods:

1. U.S. EPA BCFBAFWIN v3.00 software

2. OASIS CATALOGIC v05.10.06 running Base-line BCF model v01.02

The BCFBAFWIN software predicted fish BCF values within a factor of 4 for four structural analogs (ketones) having log Pow values which bracketed those of DIBK and its impurities. The Base-line BCF software consistently predicted BCF values which were significanlty lower than measured values. However, this software predicts two possible transformation steps which could mitigate bioconcentration by facilitating excretion of the substances from fish:

1) Phase I reduction of ketone groups to corresponding alcohols

2) Phase II glucoronidation at the alcohol groups

Using the estimations of BCFBAFWIN as the preferred values, the predicted BCF for DIBK is 130 L/kg (BCFBAF v3.00)

Predicted BCF for other components/impurities of the substance are 50 and 23 L/kg.