4-(α,α-dimethylbenzyl)phenol

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Endpoint:

bioaccumulation in aquatic species, other

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2014

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reliable and accepted model used to estimate BCF based on measured log Kow.

Justification for type of information:

A reliable QSAR model was used to calculate the bioaccumulation potential of p-Cumylphenol. 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 149 L/kg wet-wt., while the BAF (Arnot-Gobas upper trophic) was 173 L/kg wet-wt. The SMILES notation used for the predictions was:

Oc(ccc(c1)C(c(cccc2)c2)(C)C)c1

The BCFBAF predicted bioaccumulation values are considered valid and fit for purpose. A calculated value from a QSAR model is considered valid and fit for purpose if the following conditions are met: 1) Results are derived from a (Q)SAR model whose scientific validity has been established; 2) The substance falls within the applicability domain of the (Q)SAR model; 3) Results are adequate for the purpose of classification and labelling and/or risk assessment and 4) Adequate and reliable documentation of the applied method is provided.

1) Results are derived from a (Q)SAR model whose scientific validity has been established

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 structure-activity 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.

2) The substance falls within the applicability domain of the (Q)SAR model

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 p-Cumylphenol is 212.29 which falls within the range of the training set (68.08 to 959.17) and it’s log Kow (3.8) 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 | 1 | Aromatic alcohol [-OH] | -0.4727 | -0.4727
Frag | 1 | Carbon with 4 single bonds & no hydrogens | -0.2984 | -0.2984
Frag | 1 | Unsubstituted phenyl group (C6H5-) | -0.6032 | -0.6032
Frag | 9 | Aromatic-H | 0.2664 | 2.3974
Frag | 2 | Methyl [-CH3] | 0.2451 | 0.4902
Frag | 2 | Benzene | -0.4277 | -0.8555
L Kow| * | Log Kow = 3.80 (user-entered ) | 0.3073 | 1.1679
MolWt| * | Molecular Weight Parameter | | -0.5444
Const| * | Equation Constant | | -1.5371

As a result p-Cumylphenol would not be considered outside the estimation domain.

3) 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(s): Value
No Applicable Correction Factors

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.

4) Adequate and reliable documentation of the applied method is provided

Documentation of the BCFBAF model is provided in the following references:

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)”.

Qualifier:

no guideline required

Principles of method if other than guideline:

The BCFBAF v3.01 module embedded within the EPISuite v4.11) computer model was used.

Specific details on test material used for the study:

SMILES : Oc(ccc(c1)C(c(cccc2)c2)(C)C)c1, log Kow = 3.8

Test organisms (species):

other: fish

Route of exposure:

aqueous

Details on estimation of bioconcentration:

- Estimation software: EPISuite
- Result based on measured log Pow of: 3.8

Type:

BCF

Value:

149 L/kg

Basis:

other: wet weight

Type:

BAF

Value:

173 L/kg

Basis:

other: wet weight

BCFBAF Program (v3.01) Results:

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

SMILES : Oc(ccc(c1)C(c(cccc2)c2)(C)C)c1

CHEM   : Phenol, 4-(1-methyl-1-phenylethyl)-

MOL FOR: C15 H16 O1

MOL WT : 212.29

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

Summary Results:

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

 Biotransformation Half-Life (days) :  0.555  (normalized to 10 g fish)

 Log BAF (Arnot-Gobas upper trophic):  2.24  (BAF = 173 L/kg wet-wt)

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 |  1  |  Aromatic alcohol  [-OH]                   | -0.4727 | -0.4727

Frag |  1  |  Carbon with 4 single bonds & no hydrogens | -0.2984 | -0.2984

Frag |  1  |  Unsubstituted phenyl group (C6H5-)        | -0.6032 | -0.6032

Frag |  9  |  Aromatic-H                                |  0.2664 |  2.3974

Frag |  2  |  Methyl  [-CH3]                            |  0.2451 |  0.4902

Frag |  2  |  Benzene                                   | -0.4277 | -0.8555

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

MolWt|  *  |  Molecular Weight Parameter                |         | -0.5444

Const|  *  |  Equation Constant                         |         | -1.5371

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

  RESULT   |        LOG Bio Half-Life (days)            |         | -0.2558

  RESULT   |            Bio Half-Life (days)            |         |  0.5549

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

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

Biotransformation Rate Constant:

kM (Rate Constant):  1.249 /day (10 gram fish)

kM (Rate Constant):  0.7024 /day (100 gram fish)

kM (Rate Constant):  0.395 /day (1 kg fish)

kM (Rate Constant):  0.2221 /day (10 kg fish)

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

  Estimated Log BCF (upper trophic) =  2.239  (BCF = 173.4 L/kg wet-wt)

  Estimated Log BAF (upper trophic) =  2.239  (BAF = 173.4 L/kg wet-wt)

  Estimated Log BCF (mid trophic)   =  2.266  (BCF = 184.3 L/kg wet-wt)

  Estimated Log BAF (mid trophic)   =  2.267  (BAF = 184.8 L/kg wet-wt)

  Estimated Log BCF (lower trophic) =  2.262  (BCF = 182.9 L/kg wet-wt)

  Estimated Log BAF (lower trophic) =  2.268  (BAF = 185.4 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)

Validity criteria fulfilled:

yes

Conclusions:

A reliable QSAR model was used to calculate the bioaccumulation potential of p-Cumylphenol. 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 149 L/kg wet-wt., while the BAF (Arnot-Gobas upper trophic) was 173 L/kg wet-wt.

Executive summary:

A reliable QSAR model was used to calculate the bioaccumulation potential of p-Cumylphenol. 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 149 L/kg wet-wt., while the BAF (Arnot-Gobas upper trophic) was 173 L/kg wet-wt.

Description of key information

A reliable QSAR model was used to calculate the bioaccumulation potential of p-Cumylphenol. 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 149 L/kg wet-wt., while the BAF (Arnot-Gobas upper trophic) was 173 L/kg wet-wt. These values are supported by an experimental bioaccumulation study reported on the J-Check website with BCF values ranging from 69 to 190 L/kg.

Key value for chemical safety assessment

BCF (aquatic species):

149 L/kg ww