2-(1-(3',3'-dimethyl-1'-cyclohexyl)ethoxy)-2-methyl propyl propanoate

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:

1994-04-20 to 1994-06-02

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The study was conducted according to an internationally recognised method. Purity is specified, however batch number is not identified, so the isomers composition could not be retrieved from the notifier. Moreover, the result is slightly above the recommended range. Therefore full validation cannot apply.

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

GLP compliance:

yes (incl. QA statement)

Remarks:

UK GLP compliance programme (inspected on 31 January 1994 / signed on 16 March 1994)

Type of method:

flask method

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

Storage condition of test material: metal canister at 4°C in the dark.

Analytical method:

gas chromatography

Type:

Pow

Partition coefficient:

47 500

Temp.:

22.5 °C

pH:

>= 6.5 - <= 7.3

Key result

Type:

log Pow

Partition coefficient:

4.68

Temp.:

22.5 °C

pH:

>= 6.5 - <= 7.3

The preliminary assessment determined the partition coefficient to be greater than 2500 (log Kow > 3.4).

The peak height of the standard and sample solutions in organic and aqueous phases are detailed in the experimental report.

Sample number	Volume of n-octanol (mL)	Volume of water (mL)	Total weight (mg)	n-octanol phase		Water phase
				Analysed concentration (mg/L)	Total weight (mg)	Analysed concentration (mg/L)	Total weight (mg)	pH
1	25	200	62.3	2.57 x 10^3	64.2	4.38 x 10^-2	8.76 x 10^-3	7.3
2	25	200	62.3	2.51 x 10^3	62.6	5.58 x 10^-2	1.12 x 10^-2	7.0
3	50	200	125	2.54 x 10^3	127	4.81 x 10^-2	9.62 x 10^-3	6.7
4	50	200	125	2.58 x 10^3	129	6.49 x 10^-2	1.30 x 10^-2	6.6
5	100	200	249	2.46 x 10^3	246	5.67 x 10^-2	1.14 x 10^-2	6.6
6	100	200	249	2.49 x 10^3	249	5.49 x 10^-2	1.10 x 10^-2	6.5

Temperature = 22.5 +/-0.5°C

pH of n-octanol saturated water = 7.4

Calculations

Sample number	n-octanol / water volume ratio	Partition coefficient	Log10 Kow	Mean partition coefficient
1	1:8	5.86 x 10^4	4.77	5.18 x 10^4
2	1:8	4.49 x 10^4	4.65
3	1:4	5.29 x 10^4	4.72	4.63 x 10^4
4	1:4	3.98 x 10^4	4.60
5	1:2	4.33 x 10^4	4.64	4.44 x 10^4
6	1:2	4.54 x 10^4	4.66

Mean = 4.75 x 10⁴, Log₁₀Kow = 4.68, standard deviation = 6.93 x 10³

Conclusions:

The substance has potential to bioaccumulate in the environment, according to CLP classification criteria for aquatic chronic toxicity (log Kow >4).
It shall also be taken into account for PBT assessment (log Kow >4.5).

Executive summary:

The partition coefficient of the test substance was measured according to the EU A8 guideline, flask method.

Three ratio were prepared in duplicate, and each phase was analysed by GC. The sample chromatographed with 4 peaks, but only two were integrated for the aqueous phase. The mean result from the 6 samples was retained.

The partition coefficient (log Kow) of the test substance has been determined to be 4.68 (at 22.5°C and pH ca 7).

Reference 2

Endpoint:

partition coefficient

Type of information:

experimental study

Remarks:

Experimental result on the transformation product (C6 isomers) of the registered substance.

Adequacy of study:

supporting study

Study period:

2008-10-21

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Remarks:

The study was conducted according to an internationally recognised method. Substance identification is sufficient for purpose. However some minor restrictions apply due to missing informations.

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

GLP compliance:

no

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

- Storage condition of test material: Refrigerator (between 0 and 10°C under nitrogen)

Analytical method:

high-performance liquid chromatography

Type:

log Pow

Partition coefficient:

4.33

Temp.:

30 °C

pH:

5.5

Remarks on result:

other: extrapolated

Preliminary estimate: log Kow = 4.01

Standards

Component	Retention time (min)	log Kow
injection peak (dead time = t0)	3.08	---
Anisole	6.17	2.1
Ethyl benzoate	7.24	2.6
Toluene	8.32	2.7
Ethyl benzene	10.71	3.2
Isopropylbenzene	13.51	3.7
Biphenyl	15.99	4.0

slope = 3.0886

intercept = 2.0860

correlation coefficient (r) = 0.9914

Sample

Component	Retention time (min)	log Kow
injection peak (dead time = t0)	3.08	---
Test substance	19.50	4.33

Conclusions:

The substance has potential to bioaccumulate in the environment, according to CLP classification criteria for aquatic chronic toxicity (log Kow >4).
No difference between isomers.

Executive summary:

The partition coefficient of the test substance was measured according to the OECD 117/EU A8 guideline, HPLC method.

The system was calibrated with 6 reference substances, and the result for the sample was extrapolated from the linear regression.

LogKow of C6 transformation product = 4.33

Reference 3

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Remarks:

QSAR result on the transformation product (C7 isomers) of the registered substance.

Adequacy of study:

supporting study

Study period:

2016-04-01 to 2016-04-04

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

Remarks:

Calculation method using QSAR value. The substance falls into applicability domains of the QSAR model used.

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

not applicable

Remarks:

QSAR model

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)

Deviations:

not applicable

Remarks:

QSAR model

Principles of method if other than guideline:

A Quantitative Structure-Property Relationship (QSPR) model was used to calculate the n-octanol/water partition coefficient of the test item. This QSPR model has been validated as a QSAR model to be compliant with the OECD recommendations for QSAR modeling (OECD, 2004) and predicts the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following Guideline for Testing of Chemicals No. 107, "Partition Coeficient (n-octanol/water): Shake Flask Method" and No. 123 "Partition Coeficient (n-octanol/water): Slow Stirring Method”.
See attached QMRF and QPRF.

GLP compliance:

no

Type of method:

calculation method (fragments)

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

4.4

All the required fragment contribution values were available from the iSafeRat® log Kow module. Since no missing fragments were identified, the test substance is within the structural fragment domain of the model.

Conclusions:

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

Executive summary:

A QSAR prediction was performed to assess the partition coefficient of the test item.

This model has been validated to be compliant with the OECD recommendations for QSAR modelling (OECD, 2004) and predicts the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following Guideline for Testing of Chemicals No. 107, "Partition Coeficient (n-octanol/water): Shake Flask Method" and No. 123 "Partition Coeficient (n-octanol/water): Slow Stirring Method”. The criterion predicted was the log Kow (also known as log Pow).

The determination was performed using a fragment based approach in which the molecule is divided into large and small fragments and each fragment is related to a specific log Kow which may be positive or negative. The final log Kow is determined by simple addition of the fragments.

Calculation was performed from the input SMILES. The substance falls within the applicability domain of the model as demonstrated in the QPRF.

The log Kow of C7 transformation product was determined to be 4.4.

Description of key information

Partition coefficient (log Kow) = 4.68 (experimental) for all isomers.

For the transformation product, log Kow = 4.33 (exp) for the C6 isomers, and 4.4 for C7 (calc).

The log Kow indicates a preliminary alert that substance may have potential to bioaccumulate in the environment, according to CLP classification criteria for aquatic chronic toxicity (log Kow >4).

It shall also be taken into account for PBT assessment.

Key value for chemical safety assessment

Log Kow (Log Pow):

4.68

at the temperature of:

22.5 °C

Additional information

A reliable experimental study, conducted according to a recognized EC method and under GLP, is available. Despite restrictions due to substance identification (isomers composition unknown), it is considered as a key study.

Moreover, as the parent substance is likely to degrade, supporting information is provided also on the log Kow of the transformation products, which are the relevant species for the environmental risk assessment.

The worst-case value, i.e. parent substance, is retained as key data for purpose of CSA.