Bis(5-oxo-L-prolinato-N1,O2)copper

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

key study

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

2. MODEL (incl. version number)
KOWWIN v1.68

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES Copper PCA is : C1CC(=O)NC1C(=O)[O-].C1CC(=O)NC1C(=O)[O-].[Cu+2] and was not recognized by software, in consequence, it was chosen to use acid pidolic data as Copper PCA is an ionized structure of pidolic acid. The calculation is based on the pidolic acid SMILES as following :
C1CC(=O)N[C@@H]1C(=O)O


4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Partition coefficient n-octanol/water : Log Kow i.e. identical to OECD 117.
- Unambiguous algorithm: provided in KOWWIN v1.68 Help, including bibliographic references and all equations.
- Defined domain of applicability: Partition coefficient n-octanol/water estimation domains are detailed in KOWWIN v1.68 Help.
- Appropriate measures of goodness-of-fit and robustness and predictivity: Partition coefficient n-octanol/water estimation domains are detailed in KOWWIN v1.68 Help.
- Mechanistic interpretation: Partition coefficient n-octanol/water or octanol-water partition coefficient is a physical property used extensively to describe a chemical's lipophilic or hydrophobic properties. It is the ratio of a chemical's concentration in the octanol-phase to its concentration in the aqueous phase of a two-phase system at equilibrium.


5. APPLICABILITY DOMAIN
- Descriptor domain: Molecular weight of Copper PCA belongs to [18;720]. Considering, the molecular structure, copper PCA is a ionized molecule in the pH interval [2;8] of the experimental study of OECD 117 but KOWWIN includes some “corrections” for ionisable and zwitterionic substances to refine the low predictivity for these substances.
- Structural and mechanistic domains: Fragment number with and without correction is in accordance with KOWWIN annex D.
- Similarity with analogues in the training set: within the training set, 3 molecules with a proline structure can be considered close to the test item in terms of structure, and their estimated log Kow values (Est) are in very good accordance with the experimental values (Exp):
CAS Number Mol Formula Chem Name Experimental Log Kow Kowwin Estimate
Hydroxyproline: CAS:51-35-4; Formula: C5H9N1O3; Log Kow(exp): -3,17; Log Kow(est) -2,69
Proline: CAS: 147-85-3; Formula: C5H9N1O2; Log Kow(exp): -2,54; Log Kow(est): -2,15
Proline,N-acetyl N'-MeAmino-amide: CAS: 24847-46-9; Formula: C8H14N2O2; Log Kow(exp): -1,19; Log Kow(est) -1,22

6. ADEQUACY OF THE RESULT
The prediction fits the purpose of classification/labelling and PBT/vPvB assessment: Log Kow appears as a criterion in:
- CLP or GHS criteria, to define the long-term aquatic classification of poorly degradable substances. The log Kow cut-off cited is 4: it is possible to conclude with certainty that this cut-off is not reached for this substance which has a very low calculated log Kow.
- Screening criteria for B/vB assessment in ECHA’s Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.11. The log Kow cut-off for possible Bioaccumulative properties is 4.5: it is possible to conclude with certainty that this cut-off is not reached for this substance which has a very low calculated log Kow.
The prediction fits the purpose of risk assessment: in this dossier, no CSA (exposure and risk assessment) is required, so a calculated Log Kow value is sufficient.

Data source

Reference

Reference Type:

other: (Q)SAR report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: ECHA’s Practical guide : How to use and report (Q)SARs Version 3.1 – July 2016

Principles of method if other than guideline:

KOWWIN uses a "fragment constant" methodology to predict log P. In a "fragment constant" method, a structure is divided into fragments (atom or larger functional groups) and coefficient values of each fragment or group are summed together to yield the log P estimate. KOWWIN’s methodology is known as an Atom/Fragment Contribution (AFC) method. Coefficients for individual fragments and groups were derived by multiple regression of 2447 reliably measured log P values.

GLP compliance:

no

Type of method:

calculation method (fragments)

Partition coefficient type:

octanol-water

Test material

Test material information

Constituent 1

Reference substance name:

Bis(5-oxo-L-prolinato-N1,O2)copper

EC Number:

239-471-4

EC Name:

Bis(5-oxo-L-prolinato-N1,O2)copper

Cas Number:

15454-74-7

Molecular formula:

C10H12CuN2O6

IUPAC Name:

bis(5-oxo-L-prolinato-N1,O2)copper

Specific details on test material used for the study:

TMI is not applicable, QSAR inputs are listed below:
- CAS and chemical name were used to retrieve any experimental data from the QSAR database: no corresponding chemical found.
- Boiling point: no input (see IUCLID § 4.3, the result was decomposition)
- SMILES: C1CC(=O)N[C@@H]1C(=O)O NB: the corresponding MW value is 129.11

Results and discussion

Partition coefficient

Key result

Type:

log Pow

Partition coefficient:

-0.72

Remarks on result:

other: T°C and pH not applicable for QSAR

Applicant's summary and conclusion

Executive summary:

KOWWIN v1.68 and the conservative nature of this prediction (the salt being more soluble in water) enabled to estimate a value of Copper PCA log Kow as -0.72, with a very good reliability and fit for purpose of classification/labelling and PBT/vPvB/risk assessments.

This value is representative of the neutral form (pidolic acid, non dissociated). At environmental pH (5-9) there is an equilibrium between this neutral form and the dissociated form, and the latter is expected to be more soluble in water and less in octanol, due to ionic charges. Therefore, it is likely that the modelled log Kow (neutral form) is an upper limit of the actual log Kow (actual mix of neutral and ionic forms).