cis-4-tert-butylcyclohexyl acetate

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

bioaccumulation: aquatic / sediment

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

Run on 2013-04

Reliability:

1 (reliable without restriction)

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

Remarks:

The bioconcentration factor (BCF) of the substance was evaluated with the most recent model from BCFBAF model v3.01 from EPI Suite v4.1, which fulfilled all OECD principles. The substance is within the domain of the Arnot-Gobas BCFBAF model based on the fragments present in the BCFBAF database.

Justification for type of information:

1. SOFTWARE
EPISUITE v4.1

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

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC(=O) OC1CCC(CC1)C(C)(C)C
log Pow: 4.8 (experimental result performed on a read-across substance, Givaudan 1996)

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF
- Defined endpoint: Bioconcentration Factor (BCF) and Bioaccumulation Factor (BAF).
- Unambiguous algorithm: BCFBAF v3.01 contains two methods for estimating BCFs. In this endpoint study record, the more relevant method is presented.
This method has been expanded to calculate both BCF as well as BAF for three general trophic levels of fish. This method is based on the multiple-linear regression-derived equation which is used by the BCFBAF program to estimate the kM Biotransformation Half-Life.
- Defined domain of applicability: The estimation domain for BCF is based on the number of instances given for each correction factor in any of the training set compounds, and the minimum and maximum values for molecular weight and log Kow.
- Appropriate measures of goodness-of-fit and robustness and predictivity: Arnot-Gobas BCF and BAF statistics for the kM biotransformation half-life of the training dataset are; Number = 421 / r² = 0.821 / std deviation = 0.494 / avg deviation = 0.383. For the kM validation dataset; Number = 211 / r² = 0.734 / std deviation = 0.602 / avg deviation = 0.446.
- Mechanistic interpretation: no data

5. APPLICABILITY DOMAIN
See attached QPRF

6. ADEQUACY OF THE RESULT
See attached QPRF

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSARs R.6, May 2008

Deviations:

no

Principles of method if other than guideline:

See QMRF and QPRF in "Attached background material" and in "Any other information on materials and methods incl. tables" (the QMRF is only available for the former version of the QSAR model).

GLP compliance:

no

Specific details on test material used for the study:

- log Pow: 4.8 (experimental result performed on a read-across substance, Givaudan 1996)

Radiolabelling:

no

Details on sampling:

Not applicable

Details on preparation of test solutions, spiked fish food or sediment:

Not applicable

Test organisms (species):

no data

Details on test organisms:

Not applicable

Test type:

other: QSAR

Water / sediment media type:

not specified

Hardness:

Not applicable

Test temperature:

Not applicable

pH:

Not applicable

Dissolved oxygen:

Not applicable

TOC:

Not applicable

Salinity:

Not applicable

Details on test conditions:

Not applicable

Nominal and measured concentrations:

Not applicable

Reference substance (positive control):

no

Details on estimation of bioconcentration:

Not applicable

Type:

BCF

Value:

234 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Arnot-Gobas method, including biotransformation rate estimates, upper trophic. log BCF = 2.369

Type:

BCF

Value:

309.2 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Arnot-Gobas method, including biotransformation rate estimates, mid trophic. log BCF = 2.490

Key result

Type:

BCF

Value:

334.6 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Arnot-Gobas method, including biotransformation rate estimates, lower trophic. log BCF = 2.524

Details on kinetic parameters:

Not applicable

Metabolites:

Not applicable

Results with reference substance (positive control):

Not applicable

Details on results:

Based on the biodegradation potential of the substance, it's more relevant to consider the result including biotransformation rate estimates instead of the result assuming a biotransformation rate of zero.

Reported statistics:

Not applicable

Arnot-Gobas BCF model (Whole body Primary Biotransformation Rate estimate for fish):

TYPE	NUM	LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION	COEFF	VALUE
Frag Frag Frag Frag Frag L Kow MolWt Const	1 1 4 4 2 * * *	Ester [-C(=O)-O-C] Carbon with 4 single bonds & no hydrogens Methyl [-CH3] -CH2- [cyclic] -CH- [cyclic] Log Kow = 4.80 (user-entered) Molecular Weight Parameter Equation Constant	-0.7605 -0.2984 0.2451 0.0963 0.0126 0.3073	-0.7605 -0.2984 0.9804 0.3850 0.0252 1.4752 -0.5085 -1.5058
RESULT RESULT NOTE		Log Bio Half-life (days) Bio Half-life (days) Bio Half-life Normalized to 10 g fish at 15°C		-0.2387 0.5772

Biotransformation rate constant:kM (rate constant) = 1.201 / day (10 gram fish).

Arnot-Gobas BCFBAF Methods (including biotransformation rate estimates):

Estimated Log BCF (upper trophic) = 2.369 (BCF = 234 L/Kg wet-wt).

Estimated Log BCF (mid trophic) = 2.490 (BCF = 309.2 L/Kg wet-wt).

Estimated Log BCF (lower trophic) = 2.524 (BCF = 334.6 L/Kg wet-wt).

Arnot-Gobas BCFBAF Methods (assuming a biotransformation rate of zero):

Estimated Log BCF (upper trophic) = 3.742 (BCF = 5515 L/Kg wet-wt).

Validity criteria fulfilled:

yes

Conclusions:

The worst case Arnot-Gobas BCF for the substance is estimated at 334.6 L/Kg wet-wt (log BCF = 2.524), for the lower trophic, including biotransformation rate estimates.

Executive summary:

The bioconcentration factor (BCF) of the substance was evaluated with the most recent model from BCFBAF model v3.01 from EPI Suite v4.1, which fulfilled all OECD principles. The substance is within the domain of the BCFBAF model based on the fragments present in the BCFBAF database.

Based on the biodegradation potential of the substance, it's more relevant to consider the result obtain with Arnot-Gobas Method, including biotransformation rate estimates instead of the result assuming a biotransformation rate of zero. The worst case Arnot-Gobas BCF for the substance is estimated at 334.6 L/Kg wet-wt (log BCF = 2.524), for the lower trophic, including biotransformation rate estimates.

Reference 2

Endpoint:

bioaccumulation: aquatic / sediment

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

Not applicable

Reliability:

1 (reliable without restriction)

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
OASIS Catalogic v5.13.1.156

2. MODEL (incl. version number)
BCF base-line model v.03.10

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC(=O)OC1CCC(C(C)(C)C)CC1
log Pow: 4.8 (experimental result performed on a read-across substance, Givaudan 1996)

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF

5. APPLICABILITY DOMAIN
See attached QPRF

6. ADEQUACY OF THE RESULT
See attached QPRF

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSARs R.6, May 2008

Deviations:

no

Principles of method if other than guideline:

BCF calculated using BCF base-line model.
See attached QMRF and QPRF.

GLP compliance:

no

Specific details on test material used for the study:

- log Pow: 4.8 (experimental result performed on a read-across substance, Givaudan 1996)

Radiolabelling:

no

Details on sampling:

Not applicable

Details on preparation of test solutions, spiked fish food or sediment:

Not applicable

Details on test organisms:

Not applicable

Test type:

other: QSAR

Water / sediment media type:

not specified

Hardness:

Not applicable

Test temperature:

Not applicable

pH:

Not applicable

Dissolved oxygen:

Not applicable

TOC:

Not applicable

Salinity:

Not applicable

Details on test conditions:

Not applicable

Nominal and measured concentrations:

Not applicable

Reference substance (positive control):

no

Details on estimation of bioconcentration:

Not applicable

Key result

Type:

BCF

Value:

102 L/kg

Basis:

whole body w.w.

Remarks on result:

other: BCF corrected with mitigating factors

Type:

BCF

Value:

3 741 L/kg

Basis:

whole body w.w.

Remarks on result:

other: BCF max, not accounting for mitigating factors

Details on kinetic parameters:

Not applicable

Metabolites:

Not applicable

Results with reference substance (positive control):

Not applicable

Details on results:

See details in "Any other information on results incl. tables".
The predicted value from the BCFMAX model determines practically the maximum possible bioconcentration factor (BCFMAX) if the only factor determining the water/organism equilibrium is lipophilicity. This outcome overestimates the bioconcentration potential for most of the chemicals because different chemical and organism properties (called mitigating factors) could reduce significantly the accumulation of substances, such as metabolism, ionization, molecular size, etc. 
Therefore the prediction to be retained is the one issued from the log BCF corrected 2.01 ± 2.32 L/kg wet, corresponding to a BCF corrected at 102 L/kg wet.

Reported statistics:

Not applicable

Predicted value (model result):

log BCF corrected 2.01 ± 2.32 L/kg wet, corresponding to a BCF corrected at 102 L/kg wet.

 

Concomitant predictions:

logBCFmax = 3.573 L/kg wet, corresponding to a BCF max at 3741 L/kg wet, when no mitigating factor is considered.

Here Metabolism is the major contributor to a lower bioaccumulation potential:

•       relative mitigating effect of Acids=  0.000

•       relative mitigating effect of Metabolism=  0.884

•       relative mitigating effect of Phenols=  0.000

•       relative mitigating effect of Size3=  0.1121

•       relative mitigating effect of Watersolubility=  3.31E-004

•       DiamMax Min value = 11.714 Å

•       DiamMax Max value = 13.022 Å

•       DiamMax Average = 12.275 Å

Validity criteria fulfilled:

yes

Conclusions:

The BCF for the substance, using the BCF base-line model v.03.10 available in OASIS Catalogic v5.13.1.156, is predicted at 102 L/kg using the log Kow measured of 4.8 on a source substance, and using mitigating factors that account for the reduction of the bioaccumulation potential of the chemical substance.

Executive summary:

The bioconcentration factor (BCF) of the substance was evaluated with BCF base-line model v.03.10 available in OASIS Catalogic v5.13.1.156, which fulfilled all OECD principles. The substance fulfils the general property requirements and can be considered within the parametric domain of the model, the substance is in the mechanistic domain of the model and in the interpolation structural space. The BCF for the substance is predicted at 102 L/kg using the log Kow measured of 4.8 on a source substance, and using mitigating factors that account for the reduction of the bioaccumulation potential of the chemical substance.

Also, the Maximum bioconcentration factor (BCFmax) is determined at 3 741 L/kg. This value determines practically the maximum possible bioconcentration factor if the only factor determining the water/organism equilibrium is lipophilicity. This outcome overestimates the bioconcentration potential for most of the chemicals because different chemical and organism properties (called mitigating factors) could reduce significantly the accumulation of substances, such as metabolism, ionization, molecular size, etc.  Therefore the prediction to be retained is the one issued from the log BCF corrected 2.01 ± 2.32 L/kg wet, corresponding to a BCF corrected at 102 L/kg wet.

The conclusion that the substance is not bioaccumulative can be used for CLP and PBT purposes.

Description of key information

Weight of Evidence approach, maximum predicted BCF value:

BCF = 335 L/kg.

The registered substance is not bioaccumulable according to CLP (BCF < 500) and PBT criteria (BCF < 2000).

Key value for chemical safety assessment

BCF (aquatic species):

335 L/kg ww

Additional information

A weight of evidence approach was used to assess the bioaccumulation potential of the registered substance, using QSAR predictions. Two QSAR models were used: BCF base-line model v03.10 available in OASIS Catalogic v5.13.1.156, and BCFBAF model v3.01 available in EPI Suite v4.11.

The relevant estimated BCF values for the registered substance were all comprised between 102 and 335 L/kg, calculated using the experimental log Kow value at 4.8, measured on a source substance. The result indicates that the registered substance is not bioaccumulable according to CLP (BCF < 500) and PBT criteria (BCF < 2000).