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EC number: 700-956-5 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Partition coefficient
Administrative data
Link to relevant study record(s)
- Endpoint:
- partition coefficient
- Type of information:
- (Q)SAR
- Adequacy of study:
- key study
- Study period:
- 2015
- Reliability:
- 2 (reliable with restrictions)
- Justification for type of information:
- 1. SOFTWARE
Estimation Programme Interface (EPI) Suite programme for Microsoft Windows v4.11
Contact EPISuite:
U.S. Environmental Protection Agency
1200 Pennsylvania Ave.
N.W. (Mail Code 7406M)
Washington, DC 20460
2. MODEL (incl. version number)
KOWWIN v1.68
September 2010 (model development); November 2012 (model publication)
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
The SMILES and input parameters plus the predicted values are provided within the QPRF attached: ‘QPRF Title: Substance: Reaction mass of (3E)-4-(2,6,6-trimethylcyclohex-2-en-1-yl)but-3-en-2-one and 4-(dodecylsulfanyl)-4-(2,6,6-trimethylcyclohex-1-en-1-yl)butan-2-one and 4-(dodecylsulfanyl)-4-(2,6,6-trimethylcyclohex-2-en-1-yl)butan-2-one using the model WATERNT v1.01 for the endpoint: Water Solubility’ version 1.0; 01 September 2015.
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Full details of the method are provided in the attached QMRF named ‘QMRF Title: KOWWIN v1.68 : n-Octanol/Water Partition Coefficient (Log Kow)’ version 1.02; date: 01 September 2015; updated 24 January 2018.
5. APPLICABILITY DOMAIN
Information provided within the QPRF attached: ‘QPRF Title: Reaction mass of (3E)-4-(2,6,6-trimethylcyclohex-2-en-1-yl)but-3-en-2-one and 4-(dodecylsulfanyl)-4-(2,6,6-trimethylcyclohex-1-en-1-yl)butan-2-one and 4-(dodecylsulfanyl)-4-(2,6,6-trimethylcyclohex-2-en-1-yl)butan-2-one using the model KOWWIN v1.68 for the endpoint: Partition Coefficient (Log Kow))’ version 1.0; 01 September 2015.
6. ADEQUACY OF THE RESULT
1) QSAR model is scientifically valid. 2) The substance falls within the applicability domain of the QSAR model. 3) The prediction is fit for regulatory purpose (see below).
To address the information requirement for REACH Regulation (EC) 1907/2006: Annex VII – Section 7.8 (Partition Coefficient) and contribute to the assessment for Classification and Labelling: part 4 Environmental Hazards; under CLP Regulation (EC) 1272/2008 as amended. Provision of measured experimental log Kow for all constituents has been determined as not technically possible under guideline OECD TG 117 HPLC method. It is also potentially not possible by other methods such as OECD TG 123 slow stir method due to the high log Kow predicted and the limitations of the methods that may be employed. Therefore, in accordance with the tonnage driven information requirements: the calculated method for log Kow has been adopted. - Guideline:
- other: REACH Guidance on QSARs R.6, May/July 2008
- Principles of method if other than guideline:
- Full details of the method are provided in the attached QMRF named ‘QMRF Title: KOWWIN v1.68 : n-Octanol/Water Partition Coefficient (Log Kow)’ version 1.02; date: 01 September 2015; updated 24 January 2018.
- The model applies the following methodology to generate predictions:
Fragment based (group contribution) QSAR; based on multiple linear-regression modelling
- The model and the training and validation sets are published by US Environmental Protection Agency (USA).
The experimental Log Kow values in the training set and validation set were measured using one or more methods equivalent or similar to the following guidelines:
- Shake Flask method (OECD TG 107)
- HPLC method (OECD TG 117)
- Slow Stirring method (OECD TG 123)
Plus relevant EU (1992 as amended) and US EPA OPPTS (1982 as amended) and ASTM (1993) methods may be also used where appropriate.
A full list of experimental Log Kow reference citations is provided in the KOWWIN help menu with additional reference citations. - Partition coefficient type:
- octanol-water
- Type:
- log Pow
- Partition coefficient:
- ca. 3.85
- Temp.:
- 25 °C
- pH:
- ca. 7
- Remarks on result:
- other: Value represents the Log P for constituent 1
- Type:
- log Pow
- Partition coefficient:
- >= 9.64 - <= 9.77
- Temp.:
- 25 °C
- pH:
- ca. 7
- Remarks on result:
- other: Value represents range of Log P for constituents 2 and 3
- Conclusions:
- The results are adequate for the for the regulatory purpose.
- Executive summary:
KOWWIN v1.68 (model publication: November 2012)
Log Kow range (all constituents): 3.85 and 9.64 to 9.77
Constituent 1: 3.85 (experimental reference within the prediction model validation set)
Constituents 2 and 3: 9.64 to 9.77
Adequacy of the QSAR:
1) QSAR model is scientifically valid. 2) The substance falls within the applicability domain of the QSAR model. 3) The prediction is fit for regulatory purpose.
The prediction is adequate for the Classification and Labelling or risk assessment of the substance as indicated in REACH Regulation (EC) 1907/2006: Annex XI Section 1.3. The assessment indicates that the prediction is suitable for the regulatory conclusion in accordance with the tonnage driven information requirements specifically when combined with further information available such as environmental toxicity and environmental fate testing.
- Endpoint:
- partition coefficient
- Data waiving:
- study technically not feasible
- Justification for data waiving:
- other:
- Justification for type of information:
- JUSTIFICATION FOR DATA WAIVING
In accordance with REACH Regulation (EC) 1907/2006 Annex XI, section 2: the study is technically not possible in that the substance possesses constituents outside the applicable range for guideline tests. Such as OECD TG 117 HPLC method (0.0 > Log P < 6.0) and OECD TG 123 slow stirring method adapted to OECD, 2003 (limit for hydrophobic substances: log P < 8.3). The applicant completed the OECD TG 117 and confirmed the test method inapplicability. A calculated value for log P meeting the requirements of REACH Regulation (EC) 1907/2006 Annex XI, section 1.3 is provided. The applicant adapts the information requirement by providing a calculated value for log P. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.1.8.4, July 2017) the study does not need to be conducted. Further testing for partition coefficient is not justified. - Endpoint:
- partition coefficient
- Type of information:
- experimental study
- Adequacy of study:
- disregarded due to major methodological deficiencies
- Study period:
- 2013
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Guideline study performed under GLP; supporting information provided. Not all constituents were within the test guideline calibration range. Choice of reference substances was not optimal for determining the Log P of specific constituents less than 4.0 screening criteria. Only one reference substance had log P < 4.0 leading to poor calibration in this range.
- Qualifier:
- according to guideline
- Guideline:
- EU Method A.8 (Partition Coefficient)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- inspected: November 2011; signature: March 2012
- Type of method:
- HPLC method
- Partition coefficient type:
- octanol-water
- Analytical method:
- high-performance liquid chromatography
- Type:
- log Pow
- Partition coefficient:
- 4.11
- Temp.:
- 30 °C
- pH:
- 5.5
- Remarks on result:
- other: Constituent 1; mean log Pow
- Conclusions:
- The partition coefficient of the test substance could not be determined as not all constituents eluted within the calibration range. Constituent 1 was determined to be log Pow = 4.11 at 30 °C and pH 5.5. Constituents 2 and 3 were outside the calibration range.
- Executive summary:
The n-octanol-water partition coefficient was evaluated using the HPLC method of EU Method A.8 and OECD Method TG 117 under GLP. The partition coefficient of the test substance could not be fully determined since not all constituents eluted within the calibration range. Constituent 1 was determined to have log Pow = 4.11 at 30 °C and pH 5.5. Applicant reassessment of the data indicates this constituent is poorly calibrated for due to choice of reference substances. Comparison with calculated values (KOWWIN v1.67) presented within the study report and apparent consistency between HPLC result (log P = 4.11) and the calculated value (log P = 4.29) did not consider that the constituent was present as an experimental literature value within the model dataset. Constituent 2 and 3 had calculated log P = 9.77 and 9.64, respectively.
Referenceopen allclose all
1. Defined Endpoint:
QMRF 1. Physical Chemical Properties
QMRF 1.6. Octanol-water partition coefficient (Kow)
Reference to type of model used and description of results:
KOWWIN v1.68; integrated within the Estimation Programme Interface (EPI) Suite programme for Microsoft Windows v4.11; September 2010 (model development); November 2012 (model publication)
2. Description of results and assessment of reliability of the prediction:
The predicted values are provided within the QPRF attached: ‘QPRF Title: Reaction mass of (3E)-4-(2,6,6-trimethylcyclohex-2-en-1-yl)but-3-en-2-one and 4-(dodecylsulfanyl)-4-(2,6,6-trimethylcyclohex-1-en-1-yl)butan-2-one and 4-(dodecylsulfanyl)-4-(2,6,6-trimethylcyclohex-2-en-1-yl)butan-2-one using the model KOWWIN v1.68 for the endpoint: Partition Coefficient (Log Kow))’ version 1.0; 01 September 2015.
The range of constituents log Kow was: 3.85 to 9.77
Constituent 1 had log Kow = 3.85 (experimental reference within the prediction model validation set). Constituents 2 and 3 have predictions for log Kow = 9.77 and 9.64 respectively.
It is noted by the applicant there is no universally acknowledged applicability domain for the model. However, assessment of the substance within the applicability domains recommended by the developers is documented within the corresponding QMRF named ‘QMRF Title: KOWWIN v1.68 : n-Octanol/Water Partition Coefficient (Log Kow)’ version 1.02 – section 5:
Indicates the substance (constituents):
(i) All constituents fall within the Molecular Weight range domain.
(ii) No constituents have functional groups or features not in the training set of the model and/or for which no fragment constants and correction factors available. No constituents contain multiple fragment instances than the maximum of the training set (see QMRF title section 9.3 for more information).
It was however acknowledged, that predictions for log Kow > 8.0 need to be treated with additional caution due to the limited number of substances with measured values in that range in the validation set.
3. Uncertainty of the prediction and mechanistic domain:
The training set of the model has the following statistics and coefficients of determination:
Total Training Set Statistics: number in dataset = 2447 ; correlation coef (r2) = 0.982 ; standard deviation = 0.217 ; absolute deviation = 0.159 and avg Molecular Weight = 199.98
The model has been externally validated on a set of 10,946 substances and the following statistics and coefficients of determination are presented:
Total Validation Set Statistics: number in dataset = 10946 ; correlation coef (r2) = 0.943 ; standard deviation = 0.479 ; absolute deviation = 0.356 ; avg Molecular Weight = 258.98
Data for the training set are available via external validation (see attached QMRF prepared by the applicant for full citations).
There is no overt mechanistic basis for the model. The model correlates thermodynamic relationships of surrogates to chemical activity. The KOWWIN v1.68 run in standalone mode allows Log Kow to be estimated based on measured values of analogues within the training set (if available). Then the model applies by adding/subtracting fragment constants and correction factors from the measured value. This therefore improves prediction since calculations are based on structural differences between target and analogue. The model domain ideally has at least one or more structurally similar substances to target substances on which to then apply AFC methodology. Whilst there appears to be no direct analogues within the training set. The model has been has been extensively validated externally (using > 10,000) substances with a correlation coefficient (r2) = 0.943. The model is non-proprietary and the training sets and validation sets can be downloaded from the internet. A summary of this information is presented by the applicant. Expert review of the data on relevant structural analogues in the validation dataset indicate that in general they over predict log Kow compared to measured data. Model predictivity could be improved by the assignment of additional substances into the training set. Inclusion of additional structural fragments and expansion of sub-structure correction factors and related rules. In addition, rules for stereochemical effects could feasibly improve modelling. Constituent 1 was present within the validation set as an experimental reference. This result was by expert assessment preferentially selected over the model prediction for this constituent. Supported by reliable measured data which was available to the applicant on relevant structural analogues: with corresponding structural features and in the same Mw range (180 – 200) which indicate that log Kow < 4.0 is supported for this constituent. The discrepancy between prediction and experimental reference it was felt could be due to non-optimised measured data in the OECD TG 117 guideline within the dataset in this range of log Kow. In so far as poor selection of reference substances and optimisation of the method could yield erroneous results > 4.0. As previously mentioned, the model tends to over predict log Kow as indicated in the present substance predictions comparison with analogues.
Preliminary test
A preliminary assessment of the partition coefficient was made based by the KOWWIN calculation method (Epiwin® v3.10, Microsoft Windows c/William Meylan, 1990 -2000) using the structure of the test material.
Log Pow estimate: 4.29 (constituent 1)
Definitive test
Calibration
The retention times, capacity factors (k) and log Pow values for the reference standards are shown in the following tables:
Table 1
Standard |
Tr1 |
Tr2 |
Tr3 |
Tr4 |
Tr5 |
Tr mean |
K |
Log K |
Log Pow |
|
2.92 |
2.92 |
2.92 |
2.92 |
2.92 |
2.92 |
0.00 |
- |
- |
Isopropylbenzene |
5.24 |
5.24 |
5.24 |
5.24 |
5.24 |
5.24 |
0.79 |
-0.100 |
3.70 |
Biphenyl |
6.66 |
6.66 |
6.66 |
6.66 |
6.66 |
6.66 |
1.28 |
0.107 |
4.00 |
n-Butylbenzene |
7.09 |
7.09 |
7.09 |
7.09 |
7.09 |
7.09 |
1.43 |
0.155 |
4.50 |
2,6-diphenylpyridine |
8.66 |
8.66 |
8.66 |
8.66 |
8.66 |
8.66 |
1.97 |
0.294 |
4.90 |
Triphenylamine |
11.95 |
11.96 |
11.95 |
11.95 |
11.96 |
11.95 |
3.09 |
0.490 |
5.70 |
DDT |
12.65 |
12.65 |
12.65 |
12.65 |
12.65 |
12.65 |
3.33 |
0.523 |
6.50 |
The retention times, capacity factors and log Pow values determined for the sample are shown in the following table:
Standard |
Tr1 |
Tr2 |
Tr3 |
Tr4 |
Tr5 |
Tr mean |
K |
Log K |
Log Pow |
To |
2.92 |
2.92 |
2.92 |
2.92 |
2.92 |
2.92 |
0.00 |
- |
- |
Constituent 1 |
6.28 |
6.29 |
6.29 |
6.29 |
6.29 |
6.29 |
1.153 |
0.062 |
4.11 |
|
|
|
|
|
|
|
|
|
|
* constituent 2 and 3 did not elute
Description of key information
Key value for chemical safety assessment
Additional information
QSAR Predictions KOWWIN v1.68 model, 2015 - Log Kow range (all constituents): ≥3.85 to ≤9.77, at 25 °C and ca. pH 7
Constituent 1: 3.85 (experimental reference within the prediction model validation set)
Constituents 2 and 3: 9.64 to 9.77
References for further information:
1. QMRF Title: KOWWIN v1.68 : n-Octanol/Water Partition Coefficient (Log Kow); version 1.02, dated: 01-09-2015; updated: 24-01-2018
2. QPRF Title: Reaction mass of (3E)-4-(2,6,6-trimethylcyclohex-2-en-1-yl)but-3-en-2-one and 4-(dodecylsulfanyl)-4-(2,6,6-trimethylcyclohex-1-en-1-yl)butan-2-one and 4-(dodecylsulfanyl)-4-(2,6,6-trimethylcyclohex-2-en-1-yl)butan-2-one using the model KOWWIN v1.68 for the endpoint: Partition Coefficient (Log Kow); version 1.0, dated: 01-09-2015
Disregarded study, EU Method A.8, 2013: The n-octanol-water partition coefficient was evaluated using the HPLC method of EU Method A.8 and OECD Method TG 117 under GLP. The partition coefficient of the test substance could not be fully determined since not all constituents eluted within the calibration range. Constituent 1 was determined to have log Pow = 4.11 at 30 °C and pH 5.5. Applicant reassessment of the data indicates this constituent is poorly calibrated for due to choice of reference substances. Comparison with calculated values (KOWWIN v1.67) presented within the study report and apparent consistency between HPLC result (log P = 4.11) and the calculated value (log P = 4.29) did not consider that the constituent was present as an experimental literature value within the model dataset. Constituent 2 and 3 had calculated log P = 9.64 and 9.77, respectively.
In accordance with REACH Regulation (EC) 1907/2006 Annex XI, section 2: the study is technically not possible in that the substance possesses constituents outside the applicable range for guideline tests. Such as OECD TG 117 HPLC method (0.0 > Log P < 6.0) and OECD TG 123 slow stirring method adapted to OECD, 2003 (limit for hydrophobic substances: log P < 8.3). The applicant completed the OECD TG 117 and confirmed the test method inapplicability. A calculated value for log P meeting the requirements of REACH Regulation (EC) 1907/2006 Annex XI, section 1.3 is provided. The applicant adapts the information requirement by providing a calculated value for log P. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.1.8.4, July 2017) the study does not need to be conducted. Further testing for partition coefficient is not justified.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.