1-Butanone, 3-(dodecylthio)-1-[(1R,2S)-2,6,6-trimethyl-3-cyclohexen-1-yl]-, rel-

Partition coefficient

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 08 November 2011 to 15 February 2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Study conducted with three different methods similar to guideline, but validation information missing. Purity of test sustance specified but not isomers composition. Therefore reliability applies with restrictions.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)

Deviations:

yes

Remarks:

reference substances out of guideline range

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 123 (Partition Coefficient (1-Octanol / Water), Slow-Stirring Method)

Deviations:

yes

Remarks:

analytical data lacking

Principles of method if other than guideline:

Three methods have been applied to measure or estimate the logP of the test substance. One was a direct measurement using a modified slow stir method. This gave an estimation of the logP of the test substance. The two others were indirect measurements based on the retention of the test substance on non-polar C18 stationary phase when eluting in a polar solvent (methanol + water in reversed phase HPLC or in reversed phase TLC) using an extended calibration range obtained using highly hydrophobic reference compounds selected from existing databases.

GLP compliance:

no

Type of method:

other: three methods reported: slow-stirring, RP-HPLC and RP-TLC

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

other: TLC

Type:

log Pow

Partition coefficient:

9.4

Remarks on result:

other: TLC

Type:

log Pow

Partition coefficient:

9.6

Remarks on result:

other: HPLC

Type:

log Pow

Partition coefficient:

> 9.2

Remarks on result:

other: slow-stirring

RP-TLC measurement:

Experiment No.	Solvent system (MeOH/H2O)	r^2	log P	average	SD
1	95/5	0.9816	9.7
2	95/5	0.9604	9.8	9.7	0.1
3	95/5	0.9814	9.5
4	98/2	0.9375	8.7
5	98/2	0.9638	9.2
6	98/2	0.9790	9.6	9.4	0.3
global				9.6

Experiment 4 has been discarded, since there was obviously an issue during the experiment (inadequate positioning of the plate in the solvent system is hypothesized).

HPLC measurement:

Experiment No.1	tr (mean of 3)	log k	log P
MeC16	2.25	0.39	7.38
MeC20	5.01	0.83	9.30
MeC22	7.81	1.04	10.20
internal 1	0.95	-0.33	4.7 - 5.46
internal 2	1.28	-0.01	5.83 - 6.88
Test substance	5.40	0.86	9.4

Experiment No.2	tr (mean of 6)	log k	log P
MeC16	2.25	0.39	7.38
MeC18	3.27	0.60	8.35
MeC20	5.00	0.83	9.30
MeC22	7.90	1.05	10.20
internal 1	0.95	-0.34	4.7 - 5.46
internal 2	1.28	-0.01	5.83 - 6.88
Test substance	5.42	0.87	9.4

Leave-one-out type of validation has been done on internal reference compounds used. For each of these two compounds, calibration curve has been recalculated after the target compound being removed from the reference compounds dataset. The logP of these two compounds has been deduced from their retention time using these specific calibration curves. The bias was less than 3%.

Slow-stirring measurement:

The turbidity of the 1-octanol saturated water solution was measured using a nephelometer, and was found to be 0.02NTU, equivalent to pure water. A true solution was consequently anticipated.

The quantity of the test substance in this water phase was found to be significantly different from a blank sample, but below the limit of quantification (0.5 ng/mL = 1.27 10^-12 mol/mL).

Since the amount of the test substance that diffused in the water phase was negligible compared to the initial concentration of the test substance in octanol, the ratio was calculated from these concentrations; the LOQ being considered as a maximum concentration in the water phase, log P is expressed as a limit value:

log P = log [c octanol]/[c water] = log (1.8 10^-3 / <1.27 10^-12)

log P > 9.2

Conclusions:

The partition coefficient of the test material has been determined to be greater than 9.2 (ca 9.5).

Executive summary:

Introduction. Three methods have been applied to measure or estimate the logP of the test substance.

Method. One was a direct measurement using a modified slow stir method. The concentration found in the water phase was <LOQ, giving a limit value for estimation of the logP of the test substance. The two others were indirect measurements based on the retention of the test substance on nonpolar C18 stationary phase when eluting in a polar solvent (MeOH/water), in reversed phase TLC or HPLC, using an extended calibration range obtained using highly hydrophobic reference compounds selected from existing databases.

Results & Conclusion. The three methods gave similar results, respectively log P >9.2, 9.4 and 9.6.

Reference 2

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

From 16 June 2004 to 03 August 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study in accordance with the Method A8 of Commission Directive 92/69/EEC. Purity and isomers composition specified.

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

UK GLP Compliance Programme (inspected on December 02, 2002 / signed on February 13, 2003)

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

- Storage condition of test material: approximately 4°C in the dark under nitrogen

Analytical method:

other: HPLC-UV; 240nm for standards, 205nm for sample

Type:

log Pow

Partition coefficient:

> 6.2

Temp.:

30 °C

pH:

7.1

Details on results:

See "Remarks on results including tables and figures"

Preliminary estimate

The partition coefficient of the test material was estimated to be log10Pow= 9.51.

 

Definitive test

Calibration

The retention times of thiourea and the retention times, capacity factors (k) and log10Powvalues for the reference standards are shown in the following tables:

 

Dead time	Retention time (mins)		Mean Retention Time (mins)
	Injection 1	Injection 2
Thiourea	2.585	2.580	2.583

 

Standard	Retention Time (mins)		Mean retention time (mins)	Capacity Factor (k)	Log10k	Log10Pow
	Injection 1	Injection 2
Benzonitrile	3.447	3.447	3.447	0.335	-0.475	1.6
Toluene	4.946	4.947	4.947	0.915	-.03839	2.7
Naphthalene	5.528	5.530	5.529	1.141	0.05727	3.6
Phenanthrene	8.029	8.034	8.032	2.110	0.324	4.5
Triphenylamine	12.490	12.498	12.494	3.838	0.584	5.7
DDT	15.462	15.471	15.467	4.989	0.698	6.2

 

Partition coefficient of sample

 

The retention times, capacity factors and log10Pow values determined for the sample are shown in the following table:

Injection	Retention Time (mins)	Capacity Factor (k)	Log10k	Log10Pow
1	42.786	> 15.568	> 1.192	> 6.20
2	42.785	> 15.567	> 1.192	> 6.20

 

Mean log10Pow: > 6.20

Partition coefficient: > 1.59 x 10⁶

Conclusions:

The partition coefficient of the test material has been determined to be greater than 1.59 x 10EXP6, log10 Pow >6.20.

Executive summary:

Introduction. Partition Coefficient of the test substance was determined using the HPLC method, Method A8 or Council Regulation (EC) No 440/2008 dated 30 May 2008.

Method.A preliminary assessment of the partition coefficient was made based on the KowWin calculation method (Epiwin v3.10) using the structure of the test material; an estimated logP of 9.51 was calculated using this QSAR. The definitive test was carried out using the HPLC method at a neutral pH, the test material containing no dissociating functional groups.

Results & Conclusion.The partition coefficient of the test material has been determined to be P > 1590000, logPow > 6.20

Reference 3

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

run on 2013-02-26

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Remarks:

The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, is well documented with regard to validation parameters according to OECD principles. Moreover, the substance is fully characterised towards the applicability domain.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

QSAR estimation

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

3.36

Remarks on result:

other: unionised form

Type:

log Pow

Partition coefficient:

-0.45

Remarks on result:

other: ionised (Na salt)

Temperature and pH values are not considered in this model.

The definition of log Kow relates to the non-ionised form of the molecule. It should be noted that the substance has an estimated pKa of 3.56 (please refer to section 4.21), therefore it will be mainly under its ionised form at environmental pH, and ionised species are known to have lower bioaccumulation potential, as confirmed by the estimated value for Na salt.

No Experimental Value Adjustment was made.

The molecular weight of DD-ma is 284 g/mol, hence within the estimation domain of the validation set (27.03 -991.15 g/mol), all the functional groups are included in the list of descriptors, and the occurence of each fragment is below the maximum number in the training/validation sets (Appendix D).

Conclusions:

The substance has low potential to bioaccumulate in the environment, according to CLP classification criteria for aquatic chronic toxicity (log Kow <4).
Moreover, bioaccumulation is further limited by ionisation at environmental pH.
No concern for PBT assessment.

Executive summary:

The partition coefficient of delta-Damascone mercapto acetate (DD-ma) was estimated using the recommended QSAR model KOWWIN v1.68, based on Atom/Fragment Contribution (AFC) method. The substance is within the applicability domain (MW, descriptors).

The calculated result is log Kow = 3.36, with a standard deviation provided by the model of 0.48.

The substance being ionisable, log D will decrease with pH.

Reference 4

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

run on 2013-02-26

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Remarks:

The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, but no documentation is available in the on-line calculator with regard to validation parameters according to OECD principles.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

QSAR estimation

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

3.66

Temp.:

25 °C

pH:

< 2

Remarks on result:

other: unionised form; pH-dependent

Ionic strength = 0

Log D (ratio of the equilibrium concentrations of all species, neutral and ionized) as a function of pH is calculated.

pH	Species
0.0	3.66
0.50	3.66
1.00	3.66
1.50	3.66
2.00	3.65
2.50	3.63
3.00	3.56
3.50	3.39
4.00	3.09
4.50	2.68
5.00	2.21
5.50	1.72
6.00	1.24
6.50	0.78
7.00	0.38
7.50	0.11
8.00	-0.04
8.50	-0.10
9.00	-0.12
9.50	-0.12
10.00	-0.12
10.50	-0.13
11.00	-0.13
11.50	-0.13
12.00	-0.13
12.50	-0.13
13.00	-0.13
13.50	-0.13
14.00	-0.13

Log D decreases with pH, consistent with anticipated ionisation (estimated pKa of 3.56; please refer to section 4.21).

Conclusions:

The substance has low potential to bioaccumulate in the environment, according to CLP classification criteria for aquatic chronic toxicity (log Kow <4).
Moreover, bioaccumulation is further limited by ionisation at environmental pH.
No concern for PBT assessment.

Executive summary:

The pH-dependent partition coefficient of delta-Damascone mercapto acetate (DD-ma) was estimated using the recommended QSAR model SPARC v4.6, based on Linear Solvation Energy Relationships. No data is available with regard to validation parameters according to OECD principles.

The calculated result is log Kow = 3.66 at 25°C, as unionised form. Log D will decrease with pH.

Reference 5

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

run on 2013-02-26

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification

Remarks:

The values are not experimental results, and no documentation is available in the on-line calculator with regard to validation parameters according to OECD principles.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

QSAR estimations

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

3.03

Remarks on result:

other: mean of 7; unionised form

The run displayed the following individual results:

Model	Value
ALOGPS	3.19
AC_logP	2.42
AB/LogP	(n/a)
MiLogP	(n/a)
ALOGP	2.92
MLOGP	2.61
KowWin	3.36
XLOGP2	3.48
XLOGP3	3.20
Average log P	3.03 (+/-0.39)

Temperature and pH values are not considered in this model.

The estimation is based on the non-ionised form of the molecule. It should be noted that the substance has an estimated pKa of 3.56 (please refer to section 4.21), therefore it will be mainly under its ionised form at environmental pH, and ionised species are known to have lower bioaccumulation potential.

However, VCClab models are not able to handle ionised forms, except KowWin (logD = -0.45).

Conclusions:

The substance has low potential to bioaccumulate in the environment, according to CLP classification criteria for aquatic chronic toxicity (log Kow <4).
Moreover, bioaccumulation is further limited by ionisation at environmental pH.
No concern for PBT assessment.

Executive summary:

The partition coefficient log Kow of substance delta-Damascone mercapto acetate (DD-ma) was estimated using the VCClab tool, providing calculations from nine different QSAR. No data is available with regard to validation parameters according to OECD principles.

Results ranged from 2.42 to 3.48, with an average log Kow = 3.03 (n=7), and a standard deviation of +/- 0.39 unit.

Reference 6

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

run on 2013-02-26

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Remarks:

The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, is well documented with regard to validation parameters according to OECD principles. Moreover, the substance is fully characterised towards the applicability domain.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

QSAR estimation

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

3.85

Remarks on result:

other: unionised form

Type:

log Pow

Partition coefficient:

0.04

Remarks on result:

other: ionised (Na salt)

Temperature and pH values are not considered in this model.

The definition of log Kow relates to the non-ionised form of the molecule. It should be noted that the substance has an estimated pKa of 4.33 (please refer to section 4.21), therefore it will be mainly under its ionised form at environmental pH, and ionised species are known to have lower bioaccumulation potential, as confirmed by the estimated value for Na salt.

No Experimental Value Adjustment was made.

The molecular weight of DD-mp is 298 g/mol, hence within the estimation domain of the validation set (27.03 -991.15 g/mol), all the functional groups are included in the list of descriptors, and the occurence of each fragment is below the maximum number in the training/validation sets (Appendix D).

Conclusions:

The substance has low potential to bioaccumulate in the environment, according to CLP classification criteria for aquatic chronic toxicity (log Kow <4).
Moreover, bioaccumulation is further limited by ionisation at environmental pH.
No concern for PBT assessment.

Executive summary:

The partition coefficient of delta-Damascone mercapto propionate (DD-mp) was estimated using the recommended QSAR model KOWWIN v1.68, based on Atom/Fragment Contribution (AFC) method. The substance is within the applicability domain (MW, descriptors).

The calculated result is log Kow = 3.85, with a standard deviation provided by the model of 0.48.

The substance being ionisable, log D will decrease with pH.

Reference 7

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

run on 2013-02-26

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Remarks:

The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, but no documentation is available in the on-line calculator with regard to validation parameters according to OECD principles.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

QSAR estimation

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

3.68

Temp.:

25 °C

pH:

< 2.5

Remarks on result:

other: unionised form; pH-dependent

Ionic strength = 0

Log D (ratio of the equilibrium concentrations of all species, neutral and ionized) as a function of pH is calculated.

pH	Species
0.0	3.68
0.50	3.68
1.00	3.68
1.50	3.68
2.00	3.68
2.50	3.67
3.00	3.66
3.50	3.62
4.00	3.51
4.50	3.28
5.00	2.92
5.50	2.47
6.00	1.99
6.50	1.50
7.00	1.02
7.50	0.56
8.00	0.16
8.50	-0.11
9.00	-0.26
9.50	-0.31
10.00	-0.33
10.50	-0.34
11.00	-0.34
11.50	-0.34
12.00	-0.34
12.50	-0.34
13.00	-0.34
13.50	-0.34
14.00	-0.34

Log D decreases with pH, consistent with anticipated ionisation (estimated pKa of 4.33; please refer to section 4.21).

Conclusions:

The substance has low potential to bioaccumulate in the environment, according to CLP classification criteria for aquatic chronic toxicity (log Kow <4).
Moreover, bioaccumulation is further limited by ionisation at environmental pH.
No concern for PBT assessment.

Executive summary:

The pH-dependent partition coefficient of delta-Damascone mercapto propionate (DD-mp) was estimated using the recommended QSAR model SPARC v4.6, based on Linear Solvation Energy Relationships. No data is available with regard to validation parameters according to OECD principles.

The calculated result is log Kow = 3.68 at 25°C, as unionised form. Log D will decrease with pH.

Reference 8

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

run on 2013-02-26

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification

Remarks:

The values are not experimental results, and no documentation is available in the on-line calculator with regard to validation parameters according to OECD principles.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

QSAR estimations

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

3.29

Remarks on result:

other: mean of 7; unionised form

The run displayed the following individual results:

Model	Value
ALOGPS	3.56
AC_logP	2.88
AB/LogP	(n/a)
MiLogP	(n/a)
ALOGP	2.96
MLOGP	2.86
KowWin	3.85
XLOGP2	3.84
XLOGP3	3.10
Average log P	3.29 (+/-0.44)

Temperature and pH values are not considered in this model.

The estimation is based on the non-ionised form of the molecule. It should be noted that the substance has an estimated pKa of 4.33 (please refer to section 4.21), therefore it will be mainly under its ionised form at environmental pH, and ionised species are known to have lower bioaccumulation potential.

However, VCClab models are not able to handle ionised forms, except KowWin (logD = 0.04).

Conclusions:

The substance has low potential to bioaccumulate in the environment, according to CLP classification criteria for aquatic chronic toxicity (log Kow <4).
Moreover, bioaccumulation is further limited by ionisation at environmental pH.
No concern for PBT assessment.

Executive summary:

The partition coefficient log Kow of substance delta-Damascone mercapto propionate (DD-mp) was estimated using the VCClab tool, providing calculations from nine different QSAR. No data is available with regard to validation parameters according to OECD principles.

Results ranged from 2.86 to 3.85, with an average log Kow = 3.29 (n=7), and a standard deviation of +/- 0.44 unit.

Reference 9

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

run on 2013-03-25

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Remarks:

The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, is well documented with regard to validation parameters according to OECD principles. Moreover, the substance is fully characterised towards the applicability domain.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

QSAR estimation

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

4.16

Temperature and pH values are not considered in this model.

No ionisation (please refer to section 4.21), therefore no pH-dependency is anticipated for the molecule.

No Experimental Value Adjustment was made.

The molecular weight of DD is 192 g/mol, hence within the estimation domain of the validation set (27.03 -991.15 g/mol), all the functional groups are included in the list of descriptors, and the occurence of each fragment is below the maximum number in the training/validation sets (Appendix D).

Conclusions:

The substance has potential to bioaccumulate in the environment, according to CLP classification criteria for aquatic chronic toxicity (log Kow >4).

Executive summary:

The partition coefficient of delta-Damascone (DD) was estimated using the recommended QSAR model KOWWIN v1.68, based on Atom/Fragment Contribution (AFC) method. The substance is within the applicability domain (MW, descriptors).

The calculated result is log Kow = 4.16, with a standard deviation provided by the model of 0.48.

Reference 10

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

run on 2013-03-25

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Remarks:

The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, but no documentation is available in the on-line calculator with regard to validation parameters according to OECD principles.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

QSAR estimation

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

3.64

Temp.:

25 °C

pH:

< 2

Remarks on result:

other: not pH-dependent

Ionic strength = 0

Log D (ratio of the equilibrium concentrations of all species, neutral and ionized) as a function of pH is calculated.

pH	Species
0.0	3.64
0.50	3.64
1.00	3.64
1.50	3.64
2.00	3.64
2.50	3.64
3.00	3.64
3.50	3.64
4.00	3.64
4.50	3.64
5.00	3.64
5.50	3.64
6.00	3.64
6.50	3.64
7.00	3.64
7.50	3.64
8.00	3.64
8.50	3.64
9.00	3.64
9.50	3.64
10.00	3.64
10.50	3.64
11.00	3.64
11.50	3.64
12.00	3.64
12.50	3.64
13.00	3.64
13.50	3.64
14.00	3.64

Log D does not vary with pH, consistent with no ionisation anticipated (please refer to section 4.21).

Conclusions:

The substance has low potential to bioaccumulate in the environment, according to CLP classification criteria for aquatic chronic toxicity (log Kow <4).

Executive summary:

The partition coefficient of delta-Damascone (DD) was estimated using the recommended QSAR model SPARC v4.6, based on Linear Solvation Energy Relationships. No data is available with regard to validation parameters according to OECD principles.

The calculated result is log Kow = 3.64 at 25°C, no pH-dependency is predicted.

Reference 11

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

run on 2013-03-25

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification

Remarks:

The values are not experimental results, and no documentation is available in the on-line calculator with regard to validation parameters according to OECD principles.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

QSAR estimations

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

3.55

Remarks on result:

other: mean of 7;

The run displayed the following individual results:

Model	Value
ALOGPS	3.95
AC_logP	3.10
AB/LogP	(n/a)
MiLogP	(n/a)
ALOGP	3.25
MLOGP	3.00
KowWin	4.16
XLOGP2	3.98
XLOGP3	3.41
Average log P	3.55 (+/-0.47)

Temperature and pH values are not considered in this model.

No ionisation (please refer to section 4.21), therefore no pH-dependency is anticipated for the molecule.

Conclusions:

The substance has low potential to bioaccumulate in the environment, according to CLP classification criteria for aquatic chronic toxicity (log Kow <4).

Executive summary:

The partition coefficient log Kow of substance delta-Damascone (DD) was estimated using the VCClab tool, providing calculations from nine different QSAR. No data is available with regard to validation parameters according to OECD principles.

Results ranged from 3.00 to 4.16, with an average log Kow = 3.55 (n=7), and a standard deviation of +/- 0.47 unit.

Description of key information

Parent substance Log Kow ca 9.5 (experimental). May be too high for bioaccumulation potential.

Metabolites are expected to have low potential for bioaccumulation, according to CLP classification criteria for aquatic chronic toxicity (log Kow <4):

- metabolites DD-ma and DD-mp respectively 3.1 and 3.3, and anticipated to ionise at environmental pH (>=5), i.e. lower LogD.

- metabolite DD log Kow ca 3.6.

Key value for chemical safety assessment

Log Kow (Log Pow):

9.5

Additional information

An experimental study on partition coefficient measurement of the substance was conducted under GLP, and considered as fully reliable. However, it could provide only a limit value. Another study, conducted for research purpose without full validation, provided consistent results with three different methods. The mean of the two non-limit values is retained as key data for purpose of CSA.

Moreover, as the parent substance is likely to degrade into DD-ma, DD-mp and DD, supporting information is provided also on the log Kow of the metabolites, which are the relevant species for the environmental risk assessment.

The log Kow was estimated using QSAR calculations. Three models, using different methodologies, were used, one was considered as valid, the two others not assignable. A total of 8 results per structure was obtained, within the range 2.42 to 3.66 for DD-ma, range 2.86 to 3.85 for DD-mp, and range 3.00 to 4.16 for DD. The arithmetical mean value will be retained, respectively 3.1 (+/-0.4), 3.3 (+/-0.4), 3.6 (+/-0.4).

However, according to SPARC model, dissociation constant pKa was estimated to be 3.56 for DD-ma and 4.33 for DD-mp (please refer to section 4.21), therefore both substances will be mainly or totally under their ionised form at environmental pH. The log D curve (pH-dependent partitioning) shows values below the lowest threshold of 3 (DSD criteria) from pH=5.0. This confirms that no bioaccumulation potential is anticipated from these metabolites under actual conditions.