Dihexyl ether

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

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 adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
EPISuite v4.11
2. MODEL (incl. version number)
BCBAF v3.01
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES: O(CCCCCC)CCCCCC

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
EPISuite and its modules (including BCFBAF) has been utilized by the scientific community for prediction of phys/chem properties and environmental fate and effect properties since the 1990’s. The program underwent a comprehensive review by a panel of the US EPA’s independent Science Advisory Board (SAB) in 2007. The SAB summarized that the EPA used sound science to develop and refine EPISuite. The SAB also stated that the property estimation routines (PERs) satisfy the Organization for Economic Cooperation and Development (OECD) principles established for quantitative structureactivity relationship ((Q)SAR) validation. The EPISuite modules (including BCFBAF) have been incorporated into the OECD Toolbox. Inclusion in the OECD toolbox requires specific documentation, validation and acceptability criteria and subjects EPISuite to international use, review, providing a means for receiving additional and on-going input for improvements. BCFBAF is listed as one of the
QSARs for use in predicting bioaccumulation values in the Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance. In summary, the EPISuite modules (including BCFBAF) have had their scientific validity established repeatedly.

5. APPLICABILITY DOMAIN
According to the BCFBAF documentation, there is currently no universally accepted definition of model domain. However, the documentation does provide information for reliability of the calculations. Estimates will possibly be less accurate for compounds that 1) have a MW and log Kow outside the ranges of the training set compounds and 2) 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. The molecular weight of dihexyl ether is 186.34 which falls within the range of the training set (68.08 to 959.17) and it’s log Kow
(4.98) also falls within the training set’s range (-1.37 to 11.26). In addition, the BAF calculations clearly show that all fragments of the substance were analysed:
Whole Body Primary Biotransformation Rate Estimate for Fish:
===========================================================
------+-----+--------------------------------------------+---------+---------
TYPE | NUM | LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION | COEFF | VALUE
------+-----+--------------------------------------------+---------+---------
Frag | 2 | Linear C4 terminal chain [CCC-CH3] | 0.0341 | 0.0682
Frag | 1 | Aliphatic ether [C-O-C] | -0.0232 | -0.0232
Frag | 2 | Methyl [-CH3] | 0.2451 | 0.4902
Frag | 10 | -CH2- [linear] | 0.0242 | 0.2419
L Kow| * | Log Kow = 4.98 (KowWin estimate) | 0.3073 | 1.5299
MolWt| * | Molecular Weight Parameter | | -0.4778
Const| * | Equation Constant | | -1.5371
============+============================================+=========+=========
RESULT | LOG Bio Half-Life (days) | | 0.2921
RESULT | Bio Half-Life (days) | | 1.959
NOTE | Bio Half-Life Normalized to 10 g fish at 15 deg C |
============+============================================+=========+=========

As a result dihexyl ether would not be considered outside the estimation domain.

6. ADEQUACY OF THE RESULT
The results are adequate for the purpose of classification and labelling and/or risk assessment:
BCFBAF calculated the regression based BCF from the following equation: Log BCF = 0.6598 log Kow - 0.333 + Correction
Correction Value for Alkyl chains (8+ -CH2- groups): -1.374
The BCFBAF model had the following statistics: Training Set number = 527 correlation coef (r2) = 0.833 Validation Set number = 158 correlation coef (r2) = 0.82
These correlation coefficients indicate the BCFBAF model calculates results that are equivalent to those generated experimentally and are, hence, adequate for the purpose of classification and labelling and/or risk assessment.

Documentation of the BCFBAF model is provided in the following references:
Arnot JA, Mackay D, Bonnell M. 2008b. Estimating metabolic biotransformation rates in fish from laboratory data. Environmental Toxicology and Chemistry 27: 341-351.
Arnot JA, Gobas FAPC. 2003. A generic QSAR for assessing the bioaccumulation potential of organic chemicals in aquatic food webs. QSAR and Combinatorial Science 22: 337-345.
Arnot, J.A. and F.A.P.C. Gobas. 2006. A review of bioconcentration factor (BCF) and bioaccumulation factor (BAF) assessments for organic chemicals in aquatic organisms. Environmental reviews 14(4): 257-297.
Arnot JA, Meylan W, Tunkel J, Howard PH, Mackay D, Bonnell M, Boethling RS. 2009. A QSAR for predicting metabolic biotransformation rates for organic chemicals in fish. Environmental Toxicology and Chemistry. 28: in press.
Meylan, W.M., Howard, P.H, Aronson, D., Printup, H. and S. Gouchie. 1997. "Improved Method for Estimating Bioconcentration Factor (BCF) from Octanol-Water Partition Coefficient", SRC TR-97-006
(2nd Update), July 22, 1997; prepared for: Robert S. Boethling, EPA-OPPT, Washington, DC; Contract No. 68-D5-0012; prepared by: ; Syracuse Research Corp., Environmental Science Center, 6225 Running Ridge Road, North Syracuse, NY 13212.
Meylan,WM, Howard,PH, Boethling,RS et al. 1999. Improved Method for Estimating Bioconcentration /Bioaccumulation Factor from Octanol/Water Partition Coefficient. Environ. Toxicol. Chem. 18(4): 664-672 (1999).ECHA (2012) “Guidance on information requirements and chemical safety assessment Chapter R.7b: Endpoint specific guidance”.
McFarland, M. et al. 2007. “Science Advisory Board (SAB) Review of the Estimation Programs Interface Suite (EPI SuiteTM)”.

Guideline:

other: REACh guidance on QSARs R 6, May/July 2008

Principles of method if other than guideline:

General model for BCF: regression-based estimate ,
calculation of BCF from calculated log Kow = 4.98 (KOWWIN)

GLP compliance:

no

Specific details on test material used for the study:

SMILES : O(CCCCCC)CCCCCC
CHEM : Hexane, 1,1 -oxybis-
MOL FOR: C12 H26 O1; MOL WT : 186.34
The calculated logKow of 4.98 was used for estimating the BCF.

Details on estimation of bioconcentration:

The BCFBAF version 3.01 programme of the EPI Suite software (EPIWEB 4.11) was used to predict the BCF regression-based estimate estimate.

Key result

Type:

BCF

Value:

37.8 L/kg

Basis:

whole body w.w.

Calculation basis:

other: calculation with EPI suite

Remarks on result:

other: regression based estimate

Type:

BAF

Value:

756 L/kg

Basis:

whole body w.w.

Calculation basis:

other: calculation with EPI suite

Remarks on result:

other: Arnot-gobas upper trophic estimate

Details on results:

The BCFBAF version 3.01 programme of the EPI Suite software (EPIWEB 4.11) was used to predict either a log BCF of 1.58 (BCF of 37.8 L/kg ww) based on a regression estimate or a log BAF of 2.88 (BAF of 756 L/kg ww) based on the Arnot-Gobas upper trophic model both using the calculated LogKow of 4.98 (KOWWIN).

The BCF and BAF of dihexyl ether are predicted to be 37.8 L/kg and 756 L/kg using the regression-based and Arnot-Gobas upper trophic approach, respectively, using the calculated logKow of 4.98(KOWWIN).

Validity criteria fulfilled:

yes

Conclusions:

A reliable QSAR model was used to calculate the bioaccumulation potential of dihexyl ether. BCF values were calculated using the BCFBAF v3.01 module embedded within the EPISuite v4.11 computer model. The calculated BCF (regression-based model) was 38 L/kg wet-wt., while the BAF (Arnot-Gobas upper trophic) was 756 L/kg wet-wt.

Executive summary:

The BCFBAF version 3.01 programme of the EPI Suite software (EPIWEB 4.11) was used to predict a log BCF of 1.58 (BCF of 37.8) based on a regression estimate using an calculated Log Kow of 4.98.

Description of key information

A reliable QSAR model was used to calculate the bioaccumulation potential of dihexyl ether. BCF values were calculated using the BCFBAF v3.01 module embedded within the EPISuite v4.11 computer model.

The calculated BCF (regression-based model) was 37.8 L/kg wet-wt., while the BAF (Arnot-Gobas upper trophic) was 756 L/kg wet-wt.

Considering the readily biodegradability, which makes exposure of the aquatic compartment unlikely, a bioaccumulation study in fish would most likely not contribute to the assessment of the substance. Therefore, the respective vertebrate study is considered to be scientifically not justified.

Key value for chemical safety assessment

BCF (aquatic species):

37.8 L/kg ww

Additional information

Bioaccumulation in fish has been calculated the validated BCFBAF model (see http://www.epa.gov/oppt/exposure/pubs/episuite.htm). The BCF and BAF have been determined to be 38 and 756 L/kg wet-wt according to the regression and Arnot-Gobas method, respectively. As the registered substance falls within the applicability domain of the model, the result is considered reliable and valid.

Experimental data of the structurally related substance di-n-butylether showing BCF values of 30-144 fit to the values of 61 and 98 for the regression and Arnot-Gobas methods, respectively, calculated by the same model of EPISuite.

Considering this BCF, the readily biodegradability, which makes exposure of the aquatic compartment unlikely, and the low toxicity to fish, a bioaccumulation study in fish would most likely not contribute to the assessment of the substance. Therefore, the respective vertebrate study is considered to be scientifically not justified.