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Bioaccumulation: aquatic / sediment

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Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Remarks:
The substance is not fully compliant with the applicability domain of the model. However, this calculation is used in a weight of evidence approach, in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2. It is adequately documented and justified: the prediction is evaluated on the basis of the model performance on similar substances. For more details see section `overall remarks, attachments´.
Justification for type of information:
1. SOFTWARE
EPI Suite v4.11 Estimation Programs Interface Suite™ for Microsoft® Windows v 4.11. US EPA, United States Environmental Protection Agency, Washington, DC, USA.

2. MODEL (incl. version number)
BCFBAF v3.01, Arnot-Gobas method

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached information on the model provided by the developer. Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables"

5. APPLICABILITY DOMAIN
See attached information and information as provided in "Any other information on results incl. tables".

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.
Qualifier:
according to guideline
Version / remarks:
REACH Guidance on QSARs R.6
Principles of method if other than guideline:
- Software tool(s) used including version: EPI Suite v4.11
- Model(s) used: BCFBAF v3.01

Full reference and details of the used formulas can be found in:
1. Arnot JA, Gobas FAPC. 2003. A generic QSAR for assessing the bioaccumulation potential of organic chemicals in aquatic food webs. QSAR and Combinatorial Science 22: 337-345.
- Model description: see field 'Justification for non-standard information', 'Attached justification' and 'any other information on Material and methods'
- Justification of QSAR prediction: see field 'Justific ation for type of information', 'Attached justification' and/or 'overall remarks'
GLP compliance:
no
Vehicle:
no
Test organisms (species):
other: fish
Route of exposure:
other: aqueous and dietary
Test type:
other: calculation
Water / sediment media type:
natural water: freshwater
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: EPI Suite v4.11, BCFBAF v3.01
- Result based on measured log Pow of: 5.70
- Water solubility: 2.86 mg/L
Type:
BCF
Value:
399.9 L/kg
Basis:
whole body w.w.
Remarks on result:
other: constituent 1
Remarks:
including biotransformation, upper trophic
Type:
BCF
Value:
421.7 L/kg
Basis:
whole body w.w.
Remarks on result:
other: constituent 2
Remarks:
including biotransformation, upper trophic
Type:
other: log BCF
Value:
2.602 dimensionless
Basis:
whole body w.w.
Remarks on result:
other: constituent 1
Remarks:
including biotransformation, upper trophic
Type:
other: log BCF
Value:
2.625 dimensionless
Basis:
whole body w.w.
Remarks on result:
other: constituent 2
Remarks:
including biotransformation, upper trophic

For detailed information on the results please refer to the attached report.

Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Remarks:
The substance is not fully compliant with the applicability domain of the model. However, this calculation is used in a weight of evidence approach, in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2. It is adequately documented and justified: the prediction is evaluated on the basis of the model performance on similar substances. For more details see section `overall remarks, attachments´.
Justification for type of information:
1. SOFTWARE
EPI Suite v4.11 Estimation Programs Interface Suite™ for Microsoft® Windows v 4.11. US EPA, United States Environmental Protection Agency, Washington, DC, USA.

2. MODEL (incl. version number)
BCFBAF v3.01, regression-based method

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached information on the model provided by the developer. Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables"

5. APPLICABILITY DOMAIN
See attached information and information as provided in "Any other information on results incl. tables".

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.
Principles of method if other than guideline:
- Software tool(s) used including version: EPI Suite v4.11
- Model(s) used: BCFBAF v3.01

Full reference and details of the used formulas can be found in:
1. Meylan, W.M., Howard, P.H, Aronson, D., Printup, H. and S. Gouchie.  1997.  "Improved Method for Estimating Bioconcentration Factor (BCF) from Octanol-Water Partition Coefficient", SRC TR-97-006 (2nd Update), July 22, 1997; prepared for: Robert S. Boethling, EPA-OPPT, Washington, DC; Contract No. 68-D5-0012; prepared by: ; Syracuse Research Corp., Environmental Science Center, 6225 Running Ridge Road, North Syracuse, NY 13212.
2. Meylan,WM, Howard,PH, Boethling,RS et al. 1999.  Improved Method for Estimating Bioconcentration / Bioaccumulation Factor from Octanol/Water Partition Coefficient.Environ. Toxicol. Chem. 18(4): 664-672 (1999).
- Model description: see field 'Justification for non-standard information', 'Attached justification' and 'any other information on Material and methods'
- Justification of QSAR prediction: see field 'Justific ation for type of information', 'Attached justification' and/or 'overall remarks'
GLP compliance:
no
Test organisms (species):
other: fish
Route of exposure:
aqueous
Test type:
other: calculation
Water / sediment media type:
natural water: freshwater
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF v3.01
- Result based on measured log Kow of: 5.70
- Water solubility: 2.86 mg/L
Type:
BCF
Value:
10 L/kg
Basis:
whole body w.w.
Remarks on result:
other: constituent 1
Type:
other: log BCF
Value:
1 dimensionless
Basis:
whole body w.w.
Remarks on result:
other: constituent 1
Type:
BCF
Value:
10 L/kg
Basis:
whole body w.w.
Remarks on result:
other: constituent 2
Type:
other: log BCF
Value:
1 dimensionless
Basis:
whole body w.w.
Remarks on result:
other: constituent 2

For detailed information on the results please refer to the attached report.

Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Remarks:
The substance is not fully compliant with the applicability domain of the model. However, this calculation is used in a weight of evidence approach, in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2. It is adequately documented and justified. For more detail see field `overall remarks, attachments´.
Justification for type of information:
1. SOFTWARE
Vega version 1.1.3

2. MODEL (incl. version number)
CAESAR v 2.1.14

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached information on the model provided by the developer. Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables"

5. APPLICABILITY DOMAIN
See attached information and information as provided in "Any other information on results incl. tables".

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.
Qualifier:
according to guideline
Version / remarks:
REACH Guidance on QSARs R.6
Principles of method if other than guideline:
- Software tool(s) used including version: Vega v1.1.3
- Model(s) used: CAESAR BCF Model version 2.1.14

Full reference and details of the used formulas can be found in:
Zhao, C., Boriani, E., Chana, A., Roncaglioni,A., Benfenati, E. A new hybrid system of QSAR models for predicting bioconcentration factors (BCF). Chemosphere (2008), 73, 1701-1707.
Lombardo A, Roncaglioni A, Boriani E, Milan C, Benfenati E. Assessment and validation of the CAESAR predictive model for bioconcentration factor (BCF) in fish. Chemistry Central Journal (2010), 4 (Suppl 1).
Todeschini R. and Consonni V., Molecular Descriptors for Chemoinformatics, Wiley-VCH, (2009).
- Model description: see field 'Justification for non-standard information', 'Attached justification' and 'any other information on Material and methods'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and/or 'overall remarks'
GLP compliance:
no
Vehicle:
no
Test organisms (species):
other: fish
Route of exposure:
aqueous
Justification for method:
minimised test method used to support BCF estimates based on QSAR
Test type:
other: calculation
Water / sediment media type:
natural water: freshwater
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: Vega version 1.1.3, CAESAR v 2.1.14
- Result based on calculated log Pow (default) of: 5.02 and 4.57
Type:
BCF
Value:
11 L/kg
Basis:
whole body w.w.
Remarks on result:
other: constituent 1
Type:
BCF
Value:
17 L/kg
Basis:
whole body w.w.
Remarks on result:
other: constituent 2
Type:
other: log BCF
Value:
1.03 dimensionless
Basis:
whole body w.w.
Remarks on result:
other: constituent 1
Type:
other: log BCF
Value:
1.23 dimensionless
Basis:
whole body w.w.
Remarks on result:
other: constituent 2
Type:
BAF
Value:
411.7 L/kg
Basis:
whole body w.w.
Remarks on result:
other: Arnot-Gobas including biotransformation, upper trophic
Remarks:
constituent 1
Type:
BAF
Value:
435.5 L/kg
Basis:
whole body w.w.
Remarks on result:
other: Arnot-Gobas including biotransformation, upper trophic
Remarks:
constituent 2

For detailed information on the results please refer to the attached report.

Description of key information

BCF = 10 – 421.7 L/kg wet-wt (EPI Suite v4.11 and VEGA v1.2.3)

log BCF = 1.0 – 2.625 (EPI Suite v4.11 and VEGA v1.2.3)

Key value for chemical safety assessment

BCF (aquatic species):
421.7 L/kg ww

Additional information

Experimental data for the bioaccumulation potential of Reaction mass of N-(1-oxooctadecyl)sarcosine and N-hexadecanoyl-N-methylglycine (EC 947-850-7) is not available. The log D values (used for ionisable substances instead of log Kow) are 5.06 - 6.06 at pH 4, 2.40 to 3.40 at pH 7 and 1.53 to 2.54 at pH 9 (SPARC v4.6, calculated for the two main constituents of the substance, Stearoyl sarcosine (CAS 142-48-3) and Palmitoyl sarcosine (CAS 2421-33-2).

Moreover, due to calculated Log Koc values (Log Koc of 2.17 – 4.08 (25 °C, pH 4 – pH 9, Franco, Fu and Trapp)), a low to moderate potential for adsorption to particles is expected in soil. Even if exposed to the soil the substance is readily biodegradable indicating that it will not be persistent in the environment. Furthermore, the substance has a low potential for bioaccumulation (see chapter 5.3.1), i.e. based on log D < 4.5, metabolisation and excretion and BCF values of 10 – 421.7 L/kg wet-wt (EPI Suite v4.11 and VEGA v1.2.3). Thus, the substance is not expected to bioaccumulate in terrestrial organism. 

Additionally, the information gathered on environmental behavior and metabolism, in combination with QSAR-estimated values, provide enough evidence (in accordance to the Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2), to cover the data requirements of Regulation (EC) No 1907/2006, Annex IX and to state that the substance is likely to show negligible bioaccumulation potential.

The substance is characterized by a water solubility of 2.86 mg/L (OECD 105) and ready biodegradability. According to the Guidance on information requirements and chemical safety assessment, Chapter R.7b, readily biodegradable substances can be expected to undergo rapid and ultimate degradation in most environments, including biological sewage treatment plants (STPs) (ECHA, 2016). Thus, only negligible concentrations of the substance are likely to be released into the environment through conventional STPs. In addition, if released into the environment, the substance will not persist.

Moreover, the calculated pka values of both molecules is 3.96 (SPARC v4.6), indicating that the ionized, charged anionic forms will predominate at environmentally relevant pH values in the range of 4 to 9, which is expected to increase the hydrophilicity of the substance.

(Q)SAR predictions provide further evidence for a low potential for bioaccumulation in aquatic organisms. For the assessment of the potential for bioaccumulation, the bioconcentration factor (BCF) was predicted for the two main constituents of the substance using the following three (Q)SAR models:

-         EPI Suite v4.11, BCFBAF v3.01, regression-based estimate

-         EPI Suite v4.11, BCFBAF v3.01, Arnot-Gobas including biotransformation for fish (upper trophic)

-         VEGA v1.2.3, CAESAR v2.1.14

The predicted BCF values obtained by the three different models are summarized in Table 1 below.
Though the substance fulfilled the descriptor and structural domains of the models, it did not fully fall within the applicability domains of the models, mainly because it is ionisable, which is a property the models do not account for. However, collectively, the predictions were considered sufficiently reliable for use in a weight-of-evidence approach (for more details see section “overall remarks, attachments” in the respective robust study summaries) in accordance with REACH regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2.

According to section 1 of Annex XIII to the REACH regulation (EC) No 1907/2006, a substance fulfills the bioaccumulation criterion (B) when the BCF in aquatic species is > 2000 L/kg and fulfills the ”very bioaccumulative” criterion (vB) when the BCF in aquatic species is > 5000 L/kg.

All models consistently predicted BCF values of clearly < 2000 L/kg, showing a low bioaccumulation potential for the substance. This conclusion is further supported by the VEGA assessment of threshold values for bioaccumulation, speciation and environmental fate considerations as well as toxickinetic data. The VEGA output states that the target compounds can be associated with conservative confidence intervals of 0.7 and 0.5 log units for safe classification on which basis both constituents can be safely classified as “not bioaccumulative” and “not very bioaccumulative”. Moreover, the VEGA report states that both constituents contain a carbonyl residue and a tertiary amine, which both were found to be present in a very large number of non-bioaccumulative compounds (112/28) with log Kow values higher than 3.0. Furthermore, both constituents contain a COOH polar group, which is known to increase hydrophilicity, which in turn is related to lower BCF values. This is in line with the calculated pKa of 3.96 for both constituents, which indicates that both main constituents are ionized at environmentally relevant pH values of 4 to 9. What is more, the substance is readily biodegradable and therefore not expected to persist in the aquatic environment. Hence, chronic exposure and bioaccumulation is unlikely.

 

Toxicokinetic considerations with regard to absorption, distribution, metabolisation and excretion of the substance provide further evidence for a low bioaccumulation potential. Based on a qualitative assessment of the physico-chemical properties of the substance as well as on available experimental mammalian studies with rats, absorption via dermal and inhalation routes is not expected but a systemic bioavailability after oral uptake is considered likely. However, the substance is not expected to distribute to a significant degree in the body and no bioaccumulation potential has been identified. While metabolisation of the substance is not anticipated, experimental studies with an analogue substance demonstrated rapid excretion of 82 to 89% of the tested substance via urine within 24 h. Urinary excretion is expected to be the main excretion route based on the behavior of structurally similar substances (i.e. N-acyl amino acids), which are known to undergo detoxification and excretion by xenobiotic carboxylates (Farrel, 2008). Further details are provided in the toxicokinetic statement in IUCLID section 7.1.

 

Taking all these information into account, such as metabolisation and excretion as well as BCF values, it can be concluded that bioaccumulation of Reaction mass of N-(1-oxooctadecyl)sarcosine and N-hexadecanoyl-N-methylglycine (EC 947-850-7) is unlikely to occur.

 

Table 1. Summary of BCF/BAF predictions.

(Q)SAR model

BCF [L/kg]

BAF [L/kg]

constituent 1

constituent 2

constituent 1

constituent 2

BCFBAF v.3.01

regression-based estimate

10

10

--

--

BCFBAF v.3.01

Arnot-Gobas incl. biotransformation for fish (upper trophic)

399.9

421.7

411.7

435.5

VEGA v.1.2.3

CAESAR 2.1.14

11

17

--

--