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EC number: 945-910-7 | 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:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2016
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study performed under GLP. Relevant validity criteria were met with acceptable amendment to allow for partition coefficient screening beyond the traditional guideline range.
- Remarks:
- Specific constitutents with Log P < 3.0 were reviewed by the applicant, separately.
- 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
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 830.7570 (Partition Coefficient, n-octanol / H2O, Estimation by Liquid Chromatography)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- inspected: September 2015; signature: November 2015
- Type of method:
- HPLC method
- Remarks:
- using UPLC system
- Partition coefficient type:
- octanol-water
- Analytical method:
- liquid chromatography
- photometric method
- other: UPLC
- Type:
- log Pow
- Partition coefficient:
- 7.1
- Temp.:
- 35 °C
- pH:
- 7
- Remarks on result:
- other: Refers to constituents 1 and 2
- Conclusions:
- The partition coefficient of the test substance was determined to be log Pow = 7.1 at 35 °C and pH 7.0 with oxydipropanol constituents beyond the guideline range Log P < 0 (zero).
- Executive summary:
The n-octanol-water partition coefficient was determined using the HPLC method of EU Method A.8, OECD Method 117 and OPPTS 830.7570. The partition coefficient of the substance was determined to be log Pow = 7.1 at 35 °C and neutral pH. Applicant assessment indicates the oxydipropanol constituent is beyond the range of the HPLC method (calculated Log P = -0.64, US EPA, KOWWIN v1.68). Peak 1 is one of two known hydrolysis degradation products which has limit values of: Log P = 2.85 (measured and predicted). The main constituents have log P > 6.0 and were measured by a scientifically acceptable amendment to the OECD TG 117 guideline by interpolation using benzo[ghi]perylene (Log P = 7.2).
- Endpoint:
- partition coefficient
- Type of information:
- (Q)SAR
- Adequacy of study:
- key study
- Study period:
- 2017
- 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
- Justification for type of information:
- 1. SOFTWARE
EPISUITE v4.1
2. MODEL (incl. version number)
KOWWIN v1.68 - November 2012 (model publication)
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See attached QPRF attached: ‘QPRF Title: Reaction mass of methyl 2-[[(E)-(2,4-dimethylcyclohex-3-en-1-ylidene)methyl]amino]benzoate and methyl 2-[[(Z)-(2,4-dimethylcyclohex-3-en-1-ylidene)methyl]amino]benzoate and oxydipropanol using the model KOWWIN v1.68 for the endpoint: Partition Coefficient (Log Kow)’ version 1.0; 30 May 2017 which has been newly compiled.
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
QMRF named ‘QMRF Title: KOWWIN v1.68 : n-Octanol/Water Partition Coefficient (Log Kow)’ version 1.01, 01 September 2015
5. APPLICABILITY DOMAIN
See ‘any other information on results incl. tables’.
6. ADEQUACY OF THE RESULT
See ‘any other information on results incl. tables’ and ‘overall remarks, attachments’. The results are adequate when taken under consideration of REACH Regulation (EC) 1907/2006 in a weight of evidence. - Guideline:
- other:
- Version / remarks:
- REACH Guidance on QSARs R.6, May/July 2008
- Principles of method if other than guideline:
- - Software tool(s) used including version: EPISUITE v4.1
- Model(s) used: KOWWIN v1.68
- Model description: 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 1.01; 01 September 2015. There has been no model updates in the intervening period since the QMRF was prepared.
The model applies the following methodology to generate predictions: Fragment based (group contribution) QSAR; based on multivariate 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:
1. Shake Flask method (OECD TG 107)
2. HPLC method (OECD TG 117)
3. 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.
- Justification of QSAR prediction: Supporting information within weight of evidence due to test item properties and guideline method limitations. - Specific details on test material used for the study:
- Detailed information on the 'test material identity' is provided in the attached QSAR Prediction Reporting Format (QPRF) document including information on individual constituents.
- Type:
- log Pow
- Partition coefficient:
- -0.64
- Temp.:
- 25 °C
- pH:
- 7
- Remarks on result:
- other: Oxydipropanol
- Type:
- log Pow
- Partition coefficient:
- 2.26
- Temp.:
- 25 °C
- pH:
- 7
- Remarks on result:
- other: hydrolysis product 1
- Type:
- log Pow
- Partition coefficient:
- 2.85
- Temp.:
- 25 °C
- pH:
- 7
- Remarks on result:
- other: hydrolysis product 2
- Type:
- log Pow
- Partition coefficient:
- 6.23
- Temp.:
- 25 °C
- pH:
- 7
- Remarks on result:
- other: constituent 1 and 2
- Conclusions:
- The results are adequate for the regulatory purpose.
- Executive summary:
KOWWIN v1.68 (model publication: November 2012)
Log Kow range (all constituents): -0.64 to 6.23
Value represents range of Log P for impurities and hydrolysis degradation products and is based on a combination of measured and experimental reference citations.
Value also represents range for all constituents including model predictions.
Summary of individual predictions:
Oxidipropanol: Log Kow = -0.64 ;
Hydrolysis Product 1: 2.26 , experimental Log P: 1.88, Hansch, C et al. (1995)
Hydrolysis Product 2: 2.85
Constituent 1 and 2: 6.23
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:
- other justification
- Justification for data waiving:
- other:
- Justification for type of information:
- JUSTIFICATION FOR DATA WAIVING
In accordance with REACH Regulation (EC) No. 1907/2006 Annex VII, column 2 section 7.8 the study does not need to be conducted if the test cannot be performed (e.g. the substance decomposes). A calculated value for log P as well as details of the calculation method shall be provided. The test substance has been demonstrated to be hydrolytically unstable. The applicant confirms that Log P determination according to OECD TG 117 HPLC method was attempted however evidence of on-column degradation (hydrolysis) was observed. The applicant adapts the information by providing an endpoint study record for hydrolysis in conjunction to HPLC measurement of specific constituents with log P > 4.0 along with calculated values for log P. Testing according to the Flask Method OECD TG 107 or Slow Stirring Methods OECD TG 123 is inapplicable due to instability and physical properties of the test item. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.1.8.4, December 2016) the study does not need to be conducted.
Referenceopen allclose all
HPLC method
The results of the HPLC method are given in the Table 2 methanol/buffer pH 7 and Table 3 acetonitrile/buffer pH 7 as mobile phase, respectively.
methanol/buffer pH 7: The calibration curve of the log k’ of the reference substances as function of log Pow had an regression line represented by the equation: log k’ = 0.295 ´ log Pow – 0.644 (r = 0.998, n = 14)
acetonitrile/buffer pH 7: The calibration curve of the log k’ of the reference substances as function of log Pow had an regression line represented by the equation: k’ = 0.217 ´ log Pow – 0.524 (r = 0.995, n = 14).
Table 2. Pow of the substance - methanol/buffer pH 7
Substance |
tr,1 |
tr,2 |
mean tr |
log Pow |
Pow |
Formamide (t0) |
0.598 |
0.598 |
0.598 |
|
|
|
|
|
|
|
|
1,4-Dichlorobenzene |
1.918 |
1.925 |
1.922 |
3.4 |
|
Biphenyl |
2.574 |
2.585 |
2.580 |
4.0 |
|
1,2,4-Trichlorobenzene |
2.958 |
2.970 |
2.964 |
4.2 |
|
Dibenzyl |
4.282 |
4.301 |
4.292 |
4.8 |
|
Triphenylamine |
7.826 |
7.859 |
7.843 |
5.7 |
|
4,4’-DDT |
11.151 |
11.201 |
11.176 |
6.5 |
|
Benzo[ghi]perylene |
18.152 |
18.238 |
18.195 |
7.2 |
|
|
|
|
|
|
|
Peak1 |
0.934 |
0.933 |
0.934 |
1.3 #1 |
2.2´10^1 |
Peak2 |
16.684 |
16.693 |
16.689 |
7.0 |
1.1´10^7 |
Peak3 |
17.585 |
17.593 |
17.589 |
7.1 |
1.3´10^7 |
|
|
|
|
|
|
#1: Estimated value , calculated by extrapolation of the calibration curve.
Table 3. Pow of the substance - acetonitrile/buffer pH 7
Substance |
tr,1 |
tr,2 |
mean tr |
log Pow |
Pow |
Formamide (t0) |
0.553 |
0.553 |
0.553 |
|
|
|
|
|
|
|
|
1,4-Dichlorobenzene |
1.496 |
1.496 |
1.496 |
3.4 |
|
Biphenyl |
1.678 |
1.678 |
1.678 |
4.0 |
|
1,2,4-Trichlorobenzene |
1.995 |
1.994 |
1.995 |
4.2 |
|
Dibenzyl |
2.262 |
2.259 |
2.261 |
4.8 |
|
Triphenylamine |
3.700 |
3.694 |
3.697 |
5.7 |
|
4,4’-DDT |
4.741 |
4.742 |
4.742 |
6.5 |
|
Benzo[ghi]perylene |
6.586 |
6.586 |
6.586 |
7.2 |
|
|
|
|
|
|
|
Peak1 |
0.855 |
0.856 |
0.856 |
1.2 #1 |
1.6´10^1 |
Peak2 |
5.970 |
5.971 |
5.971 |
7.0 |
9.3´10^6 |
|
|
|
|
|
|
#1: Estimated value , calculated by extrapolation of the calibration curve.
Comments: The substance possesses constituents with weak basic functional groups although at pH 7 the substance is considered to be typically in a non-ionised form of the substance. Therefore on this basis the HPLC test was conducted with appropriate buffer to pH 7.0. Additional buffers were deemed unnecessary.
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 methyl 2-[[(E)-(2,4-dimethylcyclohex-3-en-1-ylidene)methyl]amino]benzoate and methyl 2-[[(Z)-(2,4-dimethylcyclohex-3-en-1-ylidene)methyl]amino]benzoate and oxydipropanol using the model KOWWIN v1.68 for the endpoint: Partition Coefficient (Log Kow)’ version 1.0; 30 May 2017 which has been newly compiled.
The range of constituents Log Kow was: -0.64 to 6.23
Oxydipropanol: Log Kow = -0.64 ;
Hydrolysis Product 1: 2.26 , experimental Log P: 1.88, Hansch, C et al. (1995)
Hydrolysis Product 2: 2.85
Constituent 1 and 2: 6.23
The majority of constituents had log Kow = 6.23. All hydrolytic degradants and other constituents have predictions for log Kow < 4.0.
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 1.01, 01 September 2015 – section 5; indicates the substance (constituents):
(i) All constituents fall within the Molecular Weight range domain.
(ii) No substances 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 is however acknowledged that above Log P 6.0 to 7.0 there is lower numbers of substances in the training set although significant numbers of substances in the validation set. Above Log P 8.0 the model should be treated with additional caution. It is also acknowledged for the secondary amine constituents there are limited number of amine analogues within the training set. Which would improve the prediction. There is very good correlation between predictions and measured values on the ECHA REACH dissemination portal (checked 30 May 2017) for measured values of Log P for the hydrolysis products and oxydipropanol.
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 ACF 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.
Description of key information
Weight of evidence: Log Kow (all constituents) range: -0.64 to 7.1 at 25 °C and pH 7, 2017
Log Kow constituents at 25 °C:
Oxydipropanol: -0.64
Hydrolysis Product 1 / Impurity 1: 2.26
Hydrolysis Product 2 / Impurity 2: 2.85
Constituent 1 and 2 (isomers): 7.1
The above constituents are indicated by a combination of predicted (log Kow < 4.0) and measured (Log Kow > 4.0) methods in a weight of evidence approach.
Key value for chemical safety assessment
Additional information
In accordance with REACH Regulation (EC) No. 1907/2006 Annex VII, column 2 section 7.8 the study does not need to be conducted if the test cannot be performed (e.g. the substance decomposes). A calculated value for log P as well as details of the calculation method shall be provided. The test substance has been demonstrated to be hydrolytically unstable. The applicant confirms that Log P determination according to OECD TG 117 HPLC method was attempted however evidence of on-column degradation (hydrolysis) was observed. The applicant adapts the information by providing an endpoint study record for hydrolysis in conjunction to HPLC measurement of specific constituents with log P > 4.0 along with calculated values for log P. Testing according to the Flask Method OECD 107 or Slow Stirring Methods OECD TG 123 is inapplicable due to instability and physical properties of the test item. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.1.8.4, December 2016) the study does not need to be conducted.
Weight of evidence: Log Kow (all constituents) range: -0.64 to 7.1 at 25 °C and pH 7, 2017
Log Kow constituents at 25 °C:
Oxydipropanol: -0.64 (QSAR Prediction)
Hydrolysis Product 1 / Impurity 1: 2.26 (QSAR Prediction)
Hydrolysis Product 2 / Impurity 2: 2.85 (QSAR Prediction)
Constituent 1 and 2 (isomers): 7.1 (Measured)
The above constituents are indicated by a combination of predicted (log Kow < 4.0) and measured (Log Kow > 4.0) methods in a weight of evidence approach and using expert judgement.
References for further information:
1. QMRF Title: KOWWIN v1.68 : n-Octanol/Water Partition Coefficient (Log Kow) : version 1.01, 01 September 2015
2. QPRF Title: Reaction mass of methyl 2-[[(E)-(2,4-dimethylcyclohex-3-en-1-ylidene)methyl]amino]benzoate and methyl 2-[[(Z)-(2,4-dimethylcyclohex-3-en-1-ylidene)methyl]amino]benzoate and oxydipropanol using the model KOWWIN v1.68 for the endpoint: Partition Coefficient (Log Kow) : version 1.0, 30 May 2017
3. Experimental Study: Anon., OECD TG 117, 2016
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.