Amides, C16-C18 (even) , N,N'-ethylenebis

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

12 Nov - 24 Dec 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: Circular on the Japanese Test Methods of New Chemical Substances, bioaccumulation test

Deviations:

yes

Remarks:

no control of water and fish and no vehicle control

GLP compliance:

yes

Remarks:

according to the Japanese GLP Standard

Radiolabelling:

no

Details on sampling:

- Sampling intervals/frequency for test organisms: 2, 3, 4 and 6 weeks after exposure
- Sampling intervals/frequency for test medium samples: twice in a week
- Sample storage conditions before analysis: analysis was conducted immediately after sampling, no storage
- Details on sampling and analysis of test organisms and test media samples (e.g. sample preparation, analytical methods):1) test media: no pre-treatment; 2) Fish samples: measurement of weight and length, added with ethanol and potassium hydroxide, heated to reflux, cooled and filtered with glass wool.

Vehicle:

yes

Details on preparation of test solutions, spiked fish food or sediment:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: After test substance was mixed with crystal sugar and HCO-40, it was dissolved in ion-exchanged water
- Controls: dilution water
- Chemical name of vehicle (organic solvent, emulsifier or dispersant): crystal sugar and HCO-40
- Concentration of vehicle in test medium (stock solution and final test solution(s) at different concentrations and in control(s)): 3000 mg/L in stock solution

Test organisms (species):

Cyprinus carpio

Details on test organisms:

TEST ORGANISM
- Common name: Koi
- Source: Sugishimafish farms, Yashiro, Japan
- Age at study initiation (mean and range, SD): not stated
- Length at study initiation (mean): 9.6 cm
- Weight at study initiation (mean): 23.0 g
- Lipid content (mean): 3.9%
- Feeding during test: yes
- Food type: pellet mixed feed
- Amount: 2% of body weight
- Frequency: twice a day

ACCLIMATION
- Acclimation period: 52 days in an acclimation container and 7 days in a test container
- Acclimation conditions (same as test or not): 7 days: same as test
- Type and amount of food: pellet mixed feed, 2% of body weight
- Feeding frequency: twice a day
- Pretreatment: Treatment with Tetramycin (Pfeizer, Tokyo, Japan) and saline for 24 hours under a static condition

Route of exposure:

aqueous

Test type:

flow-through

Water / sediment media type:

natural water: freshwater

Total exposure / uptake duration:

6 wk

Test temperature:

25 ± 2 °C

Dissolved oxygen:

concentration 1 (0.830 mg/L, nominal): 5.7 - 6.6 mg/L
concentration 2 (0.083 mg/L, nominal): 6.2 - 7.0 mg/L

Details on test conditions:

TEST SYSTEM
- Test vessel: 100 L container
- Type (delete if not applicable): open
- Material, size, headspace, fill volume: glass,
- Aeration: not stated
- Type of flow-through (e.g. peristaltic or proportional diluter): proportional dilution
- Renewal rate of test solution (frequency/flow rate): 800 mL/min, 1158 L/day
- No. of organisms per vessel: 15
- No. of vessels per concentration (replicates): 1
- No. of vessels per control / vehicle control (replicates): not stated
- Biomass loading rate: no data

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: ground water
- Intervals of water quality measurement: once in 6 months

OTHER TEST CONDITIONS
- Adjustment of pH: not stated
- Photoperiod: not stated
- Light intensity: not stated

RANGE-FINDING / PRELIMINARY STUDY
- Results used to determine the conditions for the definitive study: Acute fish (Oryzias latipes) toxicity test was performed, and LC50 for 96 hours was determined as > 300 mg/L (based on a nominal concentration).

Nominal and measured concentrations:

Nominal concentrations:
concentration 1: 0.830 mg/L (substance A: 0,290 mg/L and substance B: 0.826 mg/L)
concentration 2: 0.083 mg/L, (substance A: 0,029 mg/L and substance B: 0.0826 mg/L)

Reference substance (positive control):

no

Lipid content:

3.9 %

Time point:

start of exposure

Type:

BCF

Value:

< 0.7 dimensionless

Basis:

whole body w.w.

Time of plateau:

6 wk

Calculation basis:

steady state

Remarks on result:

other: refers to test substance

Remarks:

Conc.in environment / dose:0.830 mg/L

Type:

BCF

Value:

< 6.2 dimensionless

Basis:

whole body w.w.

Time of plateau:

6 wk

Calculation basis:

steady state

Remarks on result:

other: refers to test substance

Remarks:

Conc.in environment / dose:0.083 mg/L

Details on results:

- Mortality of test organisms: no data
- Behavioural abnormalities: no data
- Observations on body length and weight: determined but no data
- Other biological observations: no data
- Organ specific bioaccumulation: not determined
- Mortality and/or behavioural abnormalities of control: no data
- Loss of test substance during test period: no data
- Results with vehicle control: not performed

Table 1. Measured concentration of test substance

		2 weeks	3 weeks	4 weeks	6 weeks
0.830 mg/L	A	0.245	0.243	0.245	0.247
	B	0.727	0.717	0.722	0.733
	C	0.739	0.733	0.736	0.750
0.0830 mg/L	A	0.0258	0.0258	0.0264	0.0259
	B	0.0785	0.0777	0.0791	0.0773
	C	0.0790	0.0794	0.0807	0.0800

A: stearamide (composition of test material), B: N-ethyl-stearamide (composition of test material), C: 1,2-bis(stearoylamino)ethane (active substance)

Table 2. Result of BCF

		2 weeks	3 weeks	4 weeks	6 weeks
0.830 mg/L	A	> 0.7 > 0.7	> 0.7 > 0.7	> 0.7 > 0.7	> 0.7 > 0.7
	B	> 0.4 > 0.4	> 0.4 > 0.4	> 0.4 > 0.4	> 0.4 > 0.4
	C	> 0.7 > 0.7	> 0.7 > 0.7	> 0.7 > 0.7	> 0.7 > 0.7
0.0830 mg/L	A	> 6.6 > 6.6	> 6.6 > 6.6	> 6.6 > 6.6	> 6.6 > 6.6
	B	> 3.8 > 3.8	> 3.8 > 3.8	> 3.8 > 3.8	> 3.8 > 3.8
	C	> 6.2 > 6.2	> 6.2 > 6.2	> 6.2 > 6.2	> 6.2 > 6.2

Validity criteria fulfilled:

not specified

Reference 2

Endpoint:

bioaccumulation in aquatic species, other

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 1.1.4

2. MODEL (incl. version number)
BCF Read-Across v1.1.0

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

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

- Software tool(s) used including version: Vega v1.1.4
- Model(s) used: BCF Read-Across version 1.1.0
Full reference and details of the used formulas can be found in:
Manganaro, A., Pizzo, F., Lombardo, A., Pogliaghi, A., Benfenati, E., 2016. Predicting persistence in the sediment compartment with a new automatic software based on the k-Nearest Neighbor (k-NN) algorithm. Chemosphere 144, 1624–1630.
- 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

Test type:

other: calculation

Water / sediment media type:

natural water: freshwater

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation software: VegaNIC version 1.1.3, BCF Read-Across version 1.1.0
- Result based on calculated log Pow of: 7.21 - 7.92

Type:

other: log BCF

Value:

1.727 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Constituent C18 - C18

Type:

other: log BCF

Value:

1.07 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Constituent C18 - C16

Type:

other: log BCF

Value:

1.08 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Constituent C16 - C16

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

Reference 3

Endpoint:

bioaccumulation in aquatic species, other

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 1.1.4

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

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

- Software tool(s) used including version: Vega v1.1.4
- 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).
R. Todeschini and V. Consonni (2009) Molecular Descriptors for Chemoinformatics, Wiley-VCH U.S.

- 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 of: 7.21 - 7.92

Type:

BCF

Value:

2 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Constituent C18 - C18

Type:

other: log BCF

Value:

0.2 dimensionless

Basis:

whole body w.w.

Remarks on result:

other: Constituent C18 - C18

Type:

BCF

Value:

2 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Constituent C18 - C16

Type:

other: log BCF

Value:

0.29 dimensionless

Basis:

whole body w.w.

Remarks on result:

other: Constituent C18 - C16

Type:

BCF

Value:

3 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Constituent C16 - C16

Type:

other: Log BCF

Value:

0.41 dimensionless

Basis:

whole body w.w.

Remarks on result:

other: Constituent C16 - C16

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

Reference 4

Endpoint:

bioaccumulation in aquatic species, other

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 1.1.4

2. MODEL (incl. version number)
BCF Meylan Model v1.0.3

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

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

- Software tool(s) used including version: Vega v1.1.4
- Model(s) used: BCF Meylan Model version 1.0.3
Full reference and details of the used formulas can be found in:
Meylan W.M., Howard P.H., Boethling R.S. et al. Improved Method for Estimating Bioconcentration / Bioaccumulation Factor from Octanol/Water Partition Coefficient. 1999, Environ. Toxicol. Chem. 18(4): 664-672
- 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, Meylan Model version 1.0.3
- Result based on calculated log Pow of: 7.21 - 7.92

Type:

BCF

Value:

5 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Constituent C18-C18

Type:

other: log BCF

Value:

0.7 dimensionless

Basis:

whole body w.w.

Remarks on result:

other: Constituent C18-C18

Type:

BCF

Value:

15 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Constituent C18-C16

Type:

other: log BCF

Value:

1.18 dimensionless

Basis:

whole body w.w.

Remarks on result:

other: Constituent C18-C16

Type:

BCF

Value:

46 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Constituent C16-C16

Type:

other: log BCF

Value:

1.67 dimensionless

Basis:

whole body w.w.

Remarks on result:

other: Constituent C16-C16

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

Description of key information

The substance has a low potential for bioaccumulation.

Additional information

The low Pow calculated for the main substance components is > 10 indicating a limited potential for bioaccumulation. The bioavailability of the substance is assumed to be low since the substance is insoluble in water and has a high adsorption potential. This assumption is supported by experimental results and QSAR calculations available for the main substance components. The bioaccumulation potential of the substance was investigated in a flow-through test conducted with Cyprinus carpio as test organism (similar to OECD Guideline 305). The fish were exposed to test substance concentrations of 0.830 mg/L and 0.083 mg/L, respectively. Crystal sugar and HCO-40 were used as vehicles. The exposure period was 6 weeks. At the end of the test, estimated BCF values were <0.7 and <6.2 respectively. Further information was derived from QSAR calculations performed using the VEGA software models CAESAR v2.1.13, Meylan v1.0.2 and: Read-Across v1.0.2 (Vega version 1.1.4). The models were used to predict the BCF of the main substance components. All three models predict a low bioaccumulation potential for the main substance components. The CAESAR v2.1.13, estimated BCF values of 2 - 3 L/kg for the main substance components. The predicted BCF values by Meylan v1.0.2 ranged from 5-46 L/kg and the calculation with the Read-Across v1.0.2 model resulted in BCF values of 11.75 - 53.33 L/kg. Though the components are outside the applicability domain of the model and the results may not be fully reliable, the results support the experimentally derived low BCF of the substance.