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Partition coefficient

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Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05/2017 - 06/2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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 - HPLC Method)
GLP compliance:
yes (incl. QA statement)
Type of method:
HPLC method
Partition coefficient type:
octanol-water
Analytical method:
high-performance liquid chromatography
Key result
Type:
log Pow
Partition coefficient:
< 0.23
Temp.:
20 °C
pH:
7
Conclusions:
The aim of this study was the determination of the n-octanol/water partition coefficient of TDI-Uron 80 by high performance liquid chromatography (HPLC) method according to EC method A.8 and OECD guideline 117.
The analysis was performed on an analytical column packed with a solid phase containing long hydrocarbon chains chemically bound onto silica (Luna 5µ C18(2) 100A; 250 x 3.0 mm). A mixture of 60 % methanol and 40 % ultra-pure grade water was used as mobile phase and the column temperature was 20 °C ± 1 °C.
As the determination of the test item leads to two signals the weighted average log Pow was calculated using the relative area and the Pow value of each single signal.

The average log Pow is < 0.23

The two measurements made under identical conditions and using the same set of reference items fall within a range of ± 0.1 log units. The requirements of OECD guideline 117 concerning the quality criteria are fulfilled.
Executive summary:

The aim of this study was the determination of the n-octanol/water partition coefficient of TDI-Uron 80 by high performance liquid chromatography (HPLC) method according to EC method A.8 and OECD guideline 117.

The analysis was performed on an analytical column packed with a solid phase containing long hydrocarbon chains chemically bound onto silica (Luna 5µ C18(2) 100A; 250 x 3.0 mm). A mixture of 60 % methanol and 40 % ultra-pure grade water was used as mobile phase and the column temperature was 20 °C ± 1 °C.

As the determination of the test item leads to two signals the weighted average log Pow was calculated using the relative area and the Pow value of each single signal.

The results are listed below:

weighted average

mean weighted average

Absolute

Number of signals

log Pow

log Pow of two runs

deviation

in chromatogram

First run

< 0.23°

< 0.23°

0.00

2

Second run

< 0.23°

 

 

 

°: extrapolated, below the log Pow of the lowest reference standard (log Pow of the lowest reference standard 2-Butanone is 0.3) but within the determination limit of the method (0.0 according to OECD 117 and EC method A.8)

The two measurements made under identical conditions and using the same set of reference items fall within a range of ± 0.1 log units. The requirements of OECD guideline 117 concerning the quality criteria are fulfilled.

Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Study period:
January 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Remarks:
QSAR
Justification for type of information:
QSAR calculation using three different models: SPARC v4.6, KOWWIN v1.67, and ACD/Labs, ACD/LogP (AB/LogP v2.0).
Principles of method if other than guideline:
The n-octanol/water partition coefficient (Kow) is a key physico-chemical parameter for chemical safety assessment (CSA), classification and labelling (C&L), and PBT assessment. It is used in various estimation models and algorithms for environmental partitioning, sorption, bioavailability, bioconcentration/bioaccumulation and also human- and ecotoxicity.
The generation of a Kow value is required at all tonnage bands (i.e. > 1 t/y; Annex VII - IX).
According to the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.7.1.8.1, the Kow can be determined either by laboratory tests, or by appropriate computational (in silico) estimation methods based on the molecule’s structure.
For organic substances experimentally derived Kow values are preferred over other determinations of Kow. However, when no experimental reliable data are available, validated quantitative structure activity relationships (QSARs) for the determination of the log Kow may be used. Such validated QSARs may be used if they are restricted to chemicals for which their applicability is well characterised. As there is a broad availability of free as well as commercial QSAR prediction models, a consistency check can be made between predicted Kow values from different softwares (SPARC v4.6, KOWWIN v1.67, and ACD/Labs, ACD/LogP (AB/LogP v2.0)).
GLP compliance:
no
Type of method:
other: QSAR calculation using three different models: SPARC v4.6, KOWWIN v1.67, and ACD/Labs, ACD/LogP (AB/LogP v2.0).
Partition coefficient type:
octanol-water
Key result
Type:
log Pow
Partition coefficient:
0.69
Remarks on result:
other: Information on temperature and pH cannot be provided as this is a QSAR estimation.
Details on results:
As several valid models were used, the agreement between the QSARs was compared. As all three values are in the same range (0.64-0.77) and are in good agreement, the average number was selected as most representative. The average number of all three log Kow values is 0.69.
The calculated values are very low and far from the critical regulatory cut off point of log Kow = 3, even taking into account the percentage of predicted within 0.5 log unit and respective standard error (see Table 1). The impact of errors on model predictions for a low log Kow value (<1) is usually less critical. Therefore, the average Log Kow of 0.69 is accepted and no further testing is required.
Conclusions:
The log Kow for TDI-Urone was calculated to be < 1 (0.69). The prediction should be used for classification and risk assessment.
Executive summary:

The n-octanol/water partition coefficient (Kow) is a key physico-chemical parameter for chemical safety assessment (CSA), classification and labelling (C&L), and PBT assessment. It is used in various estimation models and algorithms for environmental partitioning, sorption, bioavailability, bioconcentration/bioaccumulation and also human and eco-toxicity. The generation of a Kow value is required at all tonnage bands (i.e. > 1 t/y; Annex VII - IX).

According to the ECHA guidance on information requirements and chemical safety assessment, chapter R.7.1.8.1, the Kow can be determined either by laboratory tests, or by appropriate computational (in silico) estimation methods based on the molecule’s structure. For organic substances experimentally derived Kow values are preferred over other determinations of Kow. However, when no reliable experimental data are available, validated quantitative structure activity relationships (QSARs) for the determination of the log Kow may be used. Such validated QSARs may be used if they are restricted to chemicals for which their applicability is well characterised. As there is a broad availability of free as well as commercial QSAR prediction models, a consistency check can be made between predicted Kow values from different softwares.

The values that were calculated for TDI-Urone using KOWWIN, SPARC and ACD/Labs are log Kow = 0.77, 0.66, and 0.64, respectively, and are very low. All values are far from the critical regulatory cut-off point of log Kow = 3, even taking into account the percentage of predicted within 0.5 log unit and respective standard error. The impact of errors on model predictions for a low log Kow value (< 1) is usually less critical. Therefore, the average Log Kow of 0.69 is taken forward to the chemical safety assessment and no further testing is required.

Description of key information

The Log Kow of TDI-Urone is 0.23, determined by HPLC-Method.

Key value for chemical safety assessment

Log Kow (Log Pow):
0.23
at the temperature of:
20 °C

Additional information

The n-octanol/water partition coefficient (Kow) is a key physico-chemical parameter for chemical safety assessment (CSA), classification and labelling (C&L), and PBT assessment. It is used in various estimation models and algorithms for environmental partitioning, sorption, bioavailability, bioconcentration/bioaccumulation and also human and eco-toxicity. The generation of a Kow value is required at all tonnage bands (i.e. > 1 t/y; Annex VII - IX).

According to the ECHA guidance on information requirements and chemical safety assessment, chapter R.7.1.8.1, the Kow can be determined either by laboratory tests, or by appropriate computational (in silico) estimation methods based on the molecule’s structure. For organic substances experimentally derived Kow values are preferred over other determinations of Kow.

An experimantal study has been performed. The QSAR-calculation is taken as supporting study.