N-(2-{[C16-18 (even numbered) alkanoyl]amino}ethyl)-N-(2-hydroxyethyl)[C16-18 (even numbered) alkylamide

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Endpoint:

bioaccumulation in aquatic species: fish

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
Estimation Programme Interface (EPI) Suite programme for Microsoft Windows v4.11.


2. MODEL (incl. version number)
BCFBAF v3.01


3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL

SMILES notation:
1) N-(2-hydroxyethyl)-N-(2-tetradecanamidoethyl)hexadecanamide - O=C(N(CCNC(CCCCCCCCCCCCC)=O)CCO)CCCCCCCCCCCCCCC
2) N-(2-hydroxyethyl)-N-(2-pentadecanamidoethyl)hexadecanamide - O=C(N(CCNC(CCCCCCCCCCCCCC)=O)CCO)CCCCCCCCCCCCCCC
3) N-(2-hydroxyethyl)-N-(2-hexadecanamidoethyl)hexadecanamide - O=C(N(CCNC(CCCCCCCCCCCCCCC)=O)CCO)CCCCCCCCCCCCCCC
4) N-(2-hydroxyethyl)-N-(2-pentadecanamidoethyl)octadecanamide - O=C(N(CCNC(CCCCCCCCCCCCCC)=O)CCO)CCCCCCCCCCCCCCCCC
5) N-(2-hydroxyethyl)-N-(2-hexadecanamidoethyl)octadecanamide - O=C(N(CCNC(CCCCCCCCCCCCCCC)=O)CCO)CCCCCCCCCCCCCCCCC
6) N-(2-hydroxyethyl)-N-(2-heptadecanamidoethyl)octadecanamide - O=C(N(CCNC(CCCCCCCCCCCCCCCC)=O)CCO)CCCCCCCCCCCCCCCCC
7) N-(2-hydroxyethyl)-N-(2-octadecanamidoethyl)octadecanamide - O=C(N(CCNC(CCCCCCCCCCCCCCCCC)=O)CCO)CCCCCCCCCCCCCCCCC
8) Stearic acid - O=C(O)CCCCCCCCCCCCCCCCC
9) Palmitic acid - CCCCCCCCCCCCCCCC(=O)O
10) Myristic acid - CCCCCCCCCCCCCC(O)=O
11) Aminoethylethanolamine - OCCNCCN
12) Urea - NC(N)=O


4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Please refer to attached justification.


5. APPLICABILITY DOMAIN
Please refer to attached justification.


6. ADEQUACY OF THE RESULT
Please refer to attached justification.

Qualifier:

according to guideline

Guideline:

other: ECHA's Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals

Version / remarks:

May 2008

Deviations:

no

Principles of method if other than guideline:

The determination of the bioconcentration factor (BCF) was performed by the BCFBAF model (v3.01) within EpiSuite (v4.1). The model is based on the relationship between the octanol/water partition coefficient and the bioconcentration factor of the training set. In order to improve the performance of the model correction factors for certain structural fragments were applied. Octanol can be viewed as a reasonable surrogate phase for lipids and biological organisms.

The predicted BCF value has been validated against experimental studies using the OECD 305 guideline or equivalent.

GLP compliance:

no

Remarks:

Not applicable, (Q)SAR prediction.

Specific details on test material used for the study:

1) N-(2-hydroxyethyl)-N-(2-tetradecanamidoethyl)hexadecanamide - O=C(N(CCNC(CCCCCCCCCCCCC)=O)CCO)CCCCCCCCCCCCCCC
2) N-(2-hydroxyethyl)-N-(2-pentadecanamidoethyl)hexadecanamide - O=C(N(CCNC(CCCCCCCCCCCCCC)=O)CCO)CCCCCCCCCCCCCCC
3) N-(2-hydroxyethyl)-N-(2-hexadecanamidoethyl)hexadecanamide - O=C(N(CCNC(CCCCCCCCCCCCCCC)=O)CCO)CCCCCCCCCCCCCCC
4) N-(2-hydroxyethyl)-N-(2-pentadecanamidoethyl)octadecanamide - O=C(N(CCNC(CCCCCCCCCCCCCC)=O)CCO)CCCCCCCCCCCCCCCCC
5) N-(2-hydroxyethyl)-N-(2-hexadecanamidoethyl)octadecanamide - O=C(N(CCNC(CCCCCCCCCCCCCCC)=O)CCO)CCCCCCCCCCCCCCCCC
6) N-(2-hydroxyethyl)-N-(2-heptadecanamidoethyl)octadecanamide - O=C(N(CCNC(CCCCCCCCCCCCCCCC)=O)CCO)CCCCCCCCCCCCCCCCC
7) N-(2-hydroxyethyl)-N-(2-octadecanamidoethyl)octadecanamide - O=C(N(CCNC(CCCCCCCCCCCCCCCCC)=O)CCO)CCCCCCCCCCCCCCCCC
8) Stearic acid - O=C(O)CCCCCCCCCCCCCCCCC
9) Palmitic acid - CCCCCCCCCCCCCCCC(=O)O
10) Myristic acid - CCCCCCCCCCCCCC(O)=O
11) Aminoethylethanolamine - OCCNCCN
12) Urea - NC(N)=O

Key result

Value:

>= 11.93 - <= 83.96 L/kg

Remarks on result:

other: Constituent 1 - 7

Remarks:

Remaining constituents not deemed relevent.

Predicted value (model result):

Table 1:       Estimated Bioconcentration Factor of substance constituents.

Constituent		Estimated Log BCF	Estimated BCF (L/kg wet-wt)
1	N-(2-hydroxyethyl)-N-(2-tetradecanamidoethyl)hexadecanamide	1.924	83.96
2	N-(2-hydroxyethyl)-N-(2-pentadecanamidoethyl)hexadecanamide	1.683	48.24
3	N-(2-hydroxyethyl)-N-(2-hexadecanamidoethyl)hexadecanamide	1.443	27.72
4	N-(2-hydroxyethyl)-N-(2-pentadecanamidoethyl)octadecanamide	1.202	15.93
5	N-(2-hydroxyethyl)-N-(2-hexadecanamidoethyl)octadecanamide	1.558	36.14
6	N-(2-hydroxyethyl)-N-(2-heptadecanamidoethyl)octadecanamide	1.317	20.77
7	N-(2-hydroxyethyl)-N-(2-octadecanamidoethyl)octadecanamide	1.077	11.93
8	Stearic acid*	1.000	10.00
9	Palmitic acid*	1.750	56.23
10	Myristic acid*	1.750	56.23
11	Aminoethylethanolamine*	0.500	3.162
12	Urea*	0.500	3.162

*The highlighted constituents can all be described as unreacted starting materials. As these constituents cumulatively make up < 10 % (w/w) of the typical test item concentration and are structurally very different from the remaining > 90 % of the test item composition, the predicted BCF values for these constituents have been disregarded for the purposes of key value reporting and chemical safety assessment.

The predictions were generated by the following method using the model. Following classification of the constituent as either ionic or non-ionic; the model applies regression methodology using an appropriate algorithm: by applying fragment contribution and correction factor application where applicable. For non-ionic substances the model then sequentially calculates an estimate the log BCF from the log Kow using:

1. For log Kow – 1.0 to 7.0 the algorithm is as follows: Log BCF = 0.6598 x log Kow – 0.33 + Σ correction factors

2. For log Kow > 7.0 the algorithm is as follows: Log BCF = -0.49 x log Kow + 7.554 + Σ correction factors

3. All constituents with a log Kow of less than 1.0 are assigned an estimated log BCF of 0.5.

The full description of the methodology is described in the corresponding QMRF named ‘QMRF Title: BCFBAF v3.01 Bioconcentration Factor (BCF)’ version 1.02; 28 March 2018. There are no transformations of units however anti-logarithmic conversions are made to log BCF predictions to generate the BCF estimates. The result is then compared with the cut-off value given in Regulation (EC) 1272/2008 (CLP) for classification purposes. The predictions may then also be utilised in other endpoints related to environmental fate and/or toxicological endpoints to better predict the substance’s behaviour. Additional criteria may apply if appropriate when interpreting the result for relevant endpoints.

Conclusions:

The predicted BCF of the identified constituents of the test item range from ≥ 11.93 to ≤ 83.96 l/kg using BCFBAF v3.01 (EPI Suite V4.11). These predicted values were derived using partition coefficient values that were generated using the Log Koc method of KOCWIN v2.00 (EPI Suite V4.11).

Executive summary:

(Q)SAR –  The Bioconcentration Factor (BCF) of the test item was estimated using a procedure designed to be compatible with ECHA's Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals (May 2008).

SMILES notations were derived for each identified constituent.  The SMILES notation for a constituent was entered into BCFBAF v3.01 (EPI Suite V4.11) and the model was run. This was repeated for each identified constituent.  Subsequently, each identified constituent was assessed to see if they fell within the model’s applicability domain.  It was concluded that the BCF of each constituent could be predicted with an acceptable degree of accuracy.  As such the results of these estimations can be considered to be reliable given the limits of the training set.

A total BCF range of 3.16 - 83.96 l/kg was determined. However this range contains constituents that can be described as unreacted starting materials, which make up < 10 % (w/w) of the typical overall composition. As such the registrant believes that a value for BCF should be reported on the basis of the remaining > 90 % of the composition, which consists of species best described as reaction products.

Therefore, the test item was predicted to have a BCF of ≥ 11.93 to ≤ 83.96 l/kg.

Description of key information

Bioconcentration Factor: BCF ≥ 11.93 to ≤ 83.96 l/kg (EPI Suite v4.11, BCFBAF v3.01); ECHA's Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals (May 2008)

Additional information

(Q)SAR –  The Bioconcentration Factor (BCF) of the test item was estimated using a procedure designed to be compatible with ECHA's Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals (May 2008).

SMILES notations were derived for each identified constituent.  The SMILES notation for a constituent was entered into BCFBAF v3.01 (EPI Suite V4.11) and the model was run. This was repeated for each identified constituent.  Subsequently, each identified constituent was assessed to see if they fell within the model’s applicability domain.  It was concluded that the BCF of each constituent could be predicted with an acceptable degree of accuracy.  As such the results of these estimations can be considered to be reliable given the limits of the training set.

A total BCF range of 3.16 - 83.96 l/kg was determined. However this range contains constituents that can be described as unreacted starting materials, which make up < 10 % (w/w) of the typical overall composition. As such the registrant believes that a value for BCF should be reported on the basis of the remaining > 90 % of the composition, which consists of species best described as reaction products.

Therefore, the test item was predicted to have a BCF of ≥ 11.93 to ≤ 83.96 l/kg.