N,N''-(4-methyl-m-phenylene)bis[N',N'-dimethylurea]

Partition coefficient

Link to relevant study record(s)

Reference

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  was calculated using KOWWIN, SPARC and ACD/Labs and resulted in values of log Kow = 0.77, 0.66, and 0.64, respectively. These 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. 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.

Key value for chemical safety assessment

Log Kow (Log Pow):

0.69

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. 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.