1-acetyl-4-(3-dodecyl-2,5-dioxo-1-pyrrolidinyl)-2,2,6,6-tetramethylpiperidine

Adsorption / desorption

Link to relevant study record(s)

Reference

Endpoint:

adsorption / desorption: screening

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

November 2017

Reliability:

1 (reliable without restriction)

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

Remarks:

Results from two relevant supporting models corroborate key model result.

Justification for type of information:

See attached QPRF and QMRF section "Attached justification".

Guideline:

other: ECHA Guidance on Information Requirements and Chemical Safety Assessment. Chapter R.6: QSARs and grouping of chemicals

Version / remarks:

2008

Guideline:

other: ECHA Practical guide How to use and report (Q)SARs

Version / remarks:

2016

Principles of method if other than guideline:

Key model:
The organic carbon normalized adsorption coefficient (Koc) was calculated by KOCWIN v. 2.00 included in EPI Suite TM v4.1 (EPA, 2011) developed by the US-EPA. It was estimated using a
weight of evidence including two valid models, the first order molecular connectivity index (MCI) based method as published (Meylan et al., 1992) and the log Kow based method.

Supporing models used are implemented in Chemical Properties Estimation Software System (ChemProp) version 6.5 (UFZ, 2016). ChemProp includes different methods for calculation of the
organic carbon normalized adsorption coefficient (Koc). It includes applicability domain checks specific for the respective models. As such, not all implemented models for Koc calculation
could be used for the submission substance.

Supporting model (1):
Model by Huuskonen (e-states; 2003b). The log Koc is estimated based on first order molecular connectivity index (MCI) and the sums Si of particular electrotopological states.

Supporting model (2):
Model by Huuskonen (Sw or Kow; 2003a). The log Koc is estimated based on log Kow, molecular weight, and structural determinants (number of aromatic 5 or 6 rings; number of rotational bonds;
presence of carboxylic acid residue).

Supporting model (3):
Model by Poole and Poole (LSER; 1999). Koc is calculated from linear solvation energy relationship (LSER) parameters.

References:

- EPA, Environmental Protection Agency (2011)
Estimation Programs Interface Suite™ for Microsoft® Windows, v 4.10.
Online: http://www.epa.gov/oppt/exposure/pubs/episuite.htm, Druckdatum: 2011
U.S. Environmental Protection Agency, Washington, DC, USA

- Huuskonen, J. (2003a)
Prediction of soil sorption coefficient of a diverse set of organic chemicals from molecular structure
Journal of Chemical Information and Computer Sciences, 43, 1457-1462

- Huuskonen, J. (2003b)
Prediction of soil sorption coefficient of organic pesticides from the atom-type electrotopological state indices
Environmental Toxicology and Chemistry, 22, 816-820

- Meylan, W.; Howard, P.H.; Boethling, R.S. (1992)
Molecular topology/fragment contribution method for predicting soil sorption coefficients
Environmental Science & Technology, 26, 1560-1567

- Poole, S.K.; Poole, C.F. (1999)
Chromatographic models for the sorption of neutral organic compounds by soil from water and air
Journal of Chromatography A, 845, 381-400

- UFZ, Department of Ecological Chemistry (2016)
ChemProp 6.5
http://www.ufz.de/ecoc

GLP compliance:

no

Type of method:

other: QSAR

Remarks:

For the key model KOCWIN v. 2.00, major data source was original soil adsorption data (Batch Equilibrium Method) rather data derived from HPLC screening method (OECD 121).

Media:

soil

Specific details on test material used for the study:

• CAS number: 106917-31-1
• EC number: 411-930-5
• IUPAC name / common name: 1-(1-Acetyl-2,2,6,6-tetramethylpiperidin-4-yl)-3-dodecylpyrrolidine-2,5-dione / Hostavin 3058
• Structural formula: C27-H48-N2-O3.
• Canonical SMILES: CCCCCCCCCCCCC1CC(=O)N(C1=O)C2CC(N(C(C2)(C)C)C(=O)C)(C)C
• Partition coefficient n-octanol water, log Kow: 7.439 (slow stirring method according to OECD 123; Noack, 2016) at 25°C and pH 5.7

Test temperature:

Not applicable, QSAR

Details on sampling:

Not applicable, QSAR

Details on matrix:

Not applicable, QSAR

Details on test conditions:

Not applicable, QSAR

Computational methods:

For key model calculation via US EPA KOCWIN v. 2.00 included in EPI Suite TM v4.1 (EPA, 2011), see attached QMRF and QPRF!
For supporting estimations using models included in Chemical Properties Estimation Software System (ChemProp) version 6.5 (UFZ, 2016), see below section "Any other information on materials and
methods including tables"!

Key result

Sample No.:

#1

Type:

log Koc

Remarks:

QSAR

Value:

4.967 dimensionless

Matrix:

Soil

Remarks on result:

other: Key model: US EPA KOCWIN v. 2.00 - BCF was estimated using a weight of evidence based on two valid models (MCI; log Kow) included (for details, see QPRF). Value from log Kow method.

Sample No.:

#2

Type:

log Koc

Remarks:

QSAR

Value:

3.86 dimensionless

Matrix:

Soil

Remarks on result:

other: Supporting model 1: Model by Huuskonen (e-states; 2003b) - Model implemented in ChemProp v. 6.5 (UFZ, 2016)

Sample No.:

#3

Type:

log Koc

Remarks:

QSAR

Value:

4.82 dimensionless

Matrix:

Soil

Remarks on result:

other: Supporting model 2: Model by Huuskonen (Sw or Kow; 2003a) - log Koc estimated based on log Kow, MW, and structural determinants; model implemented in ChemProp v. 6.5 (UFZ, 2016)

Sample No.:

#4

Type:

log Koc

Remarks:

QSAR

Value:

5.01 dimensionless

Matrix:

Soil

Remarks on result:

other: Supporting model 3: Model by Poole and Poole (LSER; 1999) - log Koc calculated from linear solvation energy relationship (LSER) parameters; model implemented in ChemProp v. 6.5 (UFZ, 2016)

Details on results (HPLC method):

Not applicable, QSAR

Adsorption and desorption constants:

Not applicable, QSAR

Recovery of test material:

Not applicable, QSAR

Concentration of test substance at end of adsorption equilibration period:

Not applicable, QSAR

Concentration of test substance at end of desorption equilibration period:

Not applicable, QSAR

Details on results (Batch equilibrium method):

Not applicable, QSAR

Statistics:

Not applicable, QSAR

Result from KOCWIN Calculation (Key Model)

The organic carbon normalized adsorption coefficient (Koc) was calculated by KOCWIN v. 2.00 included in EPI Suite TM v4.1 (EPA, 2011) developed by the US-EPA. It was estimated using a weight of evidence including two valid models, the first order molecular connectivity index (MCI) based method and the log Kow based method. Independently of the model, for polar compounds the log Koc value is first calculated based on a regression equation not considering structure-based molecular descriptors for polar functional groups or special chemical classes used for assigning correction factors (non-corrected log Koc). In a second step – also independently of the model - identity and number of occurrence of structure-based molecular descriptors are determined. The value for each correction factor assigned to a certain descriptor is then dependent on the model and is multiplied by its frequency of occurrence in the molecule and contributes (summation with the non-corrected log Koc) to the final estimate for log Koc – for details, see QMRF and QPRF attached to this registration dossier.

Because the model fulfils the OECD principles for QSAR-models with algorithm and used experimental data for model build and validation being freely available (see QMRF); because the submission substance is in the applicability domain of the model and relevant functional groups are well represented in the structural descriptors library for assignment of correction factors (see QPRF); and because two different methods (in a weight of evidence considering fragment counts for the MCI model) result in equivalent values (see QPRF), this increases the confidence in the estimated value for the submission substance according to ECHA guidance chapter R.6 (ECHA, 2008), section R.6.1.5.3. As such, the estimated value for the organic carbon normalized adsorption coefficient (Koc) resulting from the log Kow based method implemented in KOCWIN v. 2.00 is adequate for environmental exposure and risk assessment for the submission substance.

log Koc (KOCWIN v. 2.00): 4.9669 (Koc: 92660 L/kg)

For further information, please see corresponding QMRF and QPRF attached to this document.

Results from supporting models using ChemProp v. 6.5 (UFZ, 2016)

Results

The following results were obtained using the three different models implemented in ChemProp v. 6.5 as outlined in section "Any other information on materials and methods including tables:"

•       log Koc = 3.86 with Huuskonen (e-states) model

•       log Koc = 4.82 with Huuskonen (Sw or Kow) model

•       log Koc = 5.01 with Poole and Poole (LSER) model

 

 Discussion on supporting model results

The resulting Koc values from supporting models are between log Koc 3.86 to log Koc 5.01. According to the classification by McCall et al. (1981) compounds with Koc above 5000 (log KOC ≥ 3.7) are regarded as immobile in soil. As such, all three values are in agreement with regard to the overall behaviour of the submission substance in soil.

Judging from the respective published information on test and training sets as well as statistical measures for prediction accuracy (see section "Any other information on materials and methods including tables"), the model Huuskonen (Sw or Kow) provides more accurate predictions and is based on a much larger training set (n= 403, ca. 3 times larger compared to e-states model) and validation set (n= 165, ca. 4 times larger compared to e-states model). Importantly, the compound set contained a large fraction of pesticides with diverse structures including amides (the submission substance contains amide functional groups). Thus, the value of log Koc of 4.82 is regarded to be most relevant with regard to the two Huuskonen models.

The value according to Poole and Poole (1999) based on LSER of log Koc 5.01 is very close to the most relevant value of 4.82 according to Huuskonen (Kow).

References:

McCall, P.J.; Laskowski, D.A.; Swann, R.L.; Dishburger, H.J. (1981)

Measurement of sorption coefficients of organic chemicals and their use in environmental fate analysis

In: AOAC, Association of Official Analytical Chemists, Test Protocols for Environmental Fate & Movement of Toxicants, Proceedings of a Symposium Association of Official Analytical Chemists, 94th Annual Meeting, October 21, 22, 1980, Washington, DC, 89-109

Validity criteria fulfilled:

yes

Remarks:

with regard to OECD principles for (Q)SAR validation as well as ECHA guidance document R.6 (2008)

Conclusions:

The organic carbon normalized adsorption coefficient (Koc) was determined within a reliable QSAR study. Key values were determined using the valid (QMRF) key model KOCWIN v. 2.00 included in EPI Suite TM v4.1 (EPA, 2011) developed by the US EPA. Results were demonstrated to be reliable (QPRF) and were corroborated by 2 valid supporting models.
Overall, the following log Koc values were estimated:
Result:
log Koc = 4.97 (rounded)
Koc = 92660 L/kg

Executive summary:

The organic carbon normalized adsorption coefficient (Koc) was determined within a reliable QSAR study. Key values were determined using the valid (see QMRF attached to this dossier) key model KOCWIN v. 2.00 included in EPI Suite TM v4.1 (EPA, 2011) developed by the US EPA. The submission substance was shown to be in the applicability domain of the model and results were demonstrated to be reliable (see QPRF attached to this dossier) and were corroborated by 2 valid supporting models. 

Overall, the following log Koc values were estimated:

Key model:                                                                          4.97 (rounded, equivalent to Koc = 92660 L/kg)

Supporting model 1 (Huuskonen (Kow):                               4.82

Supporting model 2 (Poole and Poole (LSER):                     5.01

Both supporting models and their average (log Koc 4.92) are very close to the value calculated according to the key model KOCWIN v. 2.00 (log Koc 4.97) and thus in strong support of the key value used for environmental exposure and risk assessment.

In addition, a third model (Huuskonen, e-states) was applied, and a log Koc of 3.86 resulted from this model. According to the classification by McCall et al. (1981) compounds with Koc above 5000 (log KOC ≥ 3.7) are regarded as immobile in soil. As such, all three values from supporting models as well as the result from the key model are in agreement with regard to the overall behaviour of the submission substance in soil. With regard to the Huuskonen e-states model, judging from the respective published information on test and training sets as well as statistical measures for prediction accuracy, the model Huuskonen (Sw, Kow) provides more accurate predictions and is based on a much larger training set (n= 403, ca. 3 times larger compared to e-states model) and validation set (n= 165, ca. 4 times larger compared to e-states model). Importantly, the compound set contained a large fraction of pesticides with diverse structures including amides (the submission substance contains amide functional groups). Therefore, the Huuskonen (Kow) model being based on log Kow, molecular weight, and structural determinants as well as the Poole and Poole model based on linear solvation energy relationship (LSER) parameters were regarded as the relevant supporting models for the key model KOCWIN v.2.00.

Conclusion:

Relevant organic carbon normalized adsorption coefficient (Koc):

Koc = 92660 L/kg

 

Reference:

McCall, P.J.; Laskowski, D.A.; Swann, R.L.; Dishburger, H.J. (1981)

Measurement of sorption coefficients of organic chemicals and their use in environmental fate analysis

In: AOAC, Association of Official Analytical Chemists, Test Protocols for Environmental Fate & Movement of Toxicants, Proceedings of a Symposium Association of Official Analytical Chemists, 94th Annual Meeting, October 21, 22, 1980, Washington, DC, 89-109

Description of key information

The organic carbon normalized adsorption coefficient (Koc) was determined within a reliable QSAR study.

Key values were determined using the valid (QMRF) key model KOCWIN v. 2.00 included in EPI Suite TM v4.1 (EPA, 2011) developed by the US EPA. Results were demonstrated to be reliable (QPRF) and were corroborated by 2 valid supporting models.

Result:

log Koc = 4.97 (rounded)

Koc = 92660 L/kg

Key value for chemical safety assessment

Koc at 20 °C:

92 660

Additional information

The organic carbon normalized adsorption coefficient (Koc) was determined within a reliable QSAR study. Key values were determined using the valid (see QMRF attached to this dossier) key model KOCWIN v. 2.00 included in EPI Suite TM v4.1 (EPA, 2011) developed by the US EPA. The submission substance was shown to be in the applicability domain of the model and results were demonstrated to be reliable (see QPRF attached to this dossier) and were corroborated by 2 valid supporting models.  

Overall, the following log Koc values were estimated:

Key model:                                                        4.97 (rounded, equivalent to Koc = 92660 L/kg)

Supporting model 1 (Huuskonen (Kow):             4.82

Supporting model 2 (Poole and Poole (LSER):    5.01

Both supporting models and their average (log Koc 4.92) are very close to the value calculated according to the key model KOCWIN v. 2.00 (log Koc 4.97) and thus in strong support of the key value used for environmental exposure and risk assessment.

Conclusion:

Relevant organic carbon normalized adsorption coefficient (Koc):

Koc = 92660 L/kg

[LogKoc: 4.9669]