isostearic acid monoisopropanolamide

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

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:

QSAR prediction from a well-known and acknowledged tool.

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSARs: Chapter R.6. QSARs and grouping of chemicals

Principles of method if other than guideline:

The Bioconcentration factor (BCF) value was calculated for the test subsatnce using BCFBAF v3.02 program of EPI Suite v 4.11. Since the test substance is an UVCB, the BCF values were estimated for individual constituents using SMILES codes as the input parameter.

Key result

Type:

BCF

Value:

400.3 L/kg

Basis:

whole body w.w.

Calculation basis:

other: BCF Regression based methodology

Remarks on result:

other: Low bioaccumulation potential (Log BCF= 2.60)

Key result

Type:

BCF

Value:

111.5 L/kg

Basis:

whole body w.w.

Calculation basis:

other: Arnot-Gobas BCF-BAF method

Remarks on result:

other: Low bioaccumulation potential (Log BCF= 2.05)

Predicted value:

The estimated BCF values for the different constituents using the regression-based equation and Arnot-Gobas methods were as follows:

Table 1: BCF predictions: Regression-based method

Constituents/Carbon chain length*	Mean/adjusted conc	Mole fraction Xi = (mi/Mi)/∑ (mi/Mi)	BCF	BCF * xi	Domain evaluation
Branched	95	1	400.3	400.3	MW(ID), Log KOW (ID), instances of correction factor (ID)
			BCF=	400.3000
			Log BCF	2.60

*Glycerol or MIPA residues have not been considered for the QSAR prediction

Table 2: BCF predictions: Arnot-Gobas BAF-BCF Method

Constituents/Carbon chain length*	Mean/adjusted conc	Mole fraction Xi = (mi/Mi)/∑ (mi/Mi)	BCF	BCF * xi	Domain evaluation
Branched	95	1	111.5	111.5	ID - Log Kow, ID - structural domain (non-ionic and not a pigment, dye, or perfluorinated substance).
			BCF=	111.5000
			Log BCF	2.05

*Glycerol or MIPA residues have not been considered for the QSAR prediction

BCF prediction results

SMILES : O=C(NCC(O)C)CCCCCCCCCCCCCCC(C)C

CHEM  : Barnched

MOL FOR: C21 H43 N1 O2

MOL WT : 341.58

--------------------------------- BCFBAF v3.01 --------------------------------

Summary Results:

 Log BCF (regression-based estimate): 2.60 (BCF = 400 L/kg wet-wt)

 Biotransformation Half-Life (days) : 0.45 (normalized to 10 g fish)

 Log BAF (Arnot-Gobas upper trophic): 2.06 (BAF = 115 L/kg wet-wt)

 

=============================

BCF (Bioconcentration Factor):

=============================

Log Kow (estimated) : 6.53

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 6.53

 

Equation Used to Make BCF estimate:

  Log BCF = 0.6598 log Kow - 0.333 + Correction

 

     Correction(s):                   Value

      Alkyl chains (8+ -CH2- groups) -1.374

 

  Estimated Log BCF = 2.602 (BCF = 400.3 L/kg wet-wt)

 

===========================================================

Whole Body Primary Biotransformation Rate Estimate for Fish:

===========================================================

------+-----+--------------------------------------------+---------+---------

 TYPE | NUM | LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION | COEFF | VALUE 

------+-----+--------------------------------------------+---------+---------

 Frag | 1 | Aliphatic alcohol [-OH]                 | -0.0616 | -0.0616

 Frag | 1 | Amide  [-C(=O)-N or -C(=S)-N]          | -0.5952 | -0.5952

 Frag | 3 | Methyl [-CH3]                           | 0.2451 | 0.7353

 Frag | 15 | -CH2- [linear]                          | 0.0242 | 0.3628

 Frag | 2 | -CH-  [linear]                          | -0.1912 | -0.3825

 L Kow| * | Log Kow =  6.53 (KowWin estimate)       | 0.3073 | 2.0075

 MolWt| * | Molecular Weight Parameter               |        | -0.8759

 Const| * | Equation Constant                        |        | -1.5371

============+============================================+=========+=========

  RESULT  |       LOG Bio Half-Life (days)           |        | -0.3466

  RESULT  |           Bio Half-Life (days)           |        | 0.4502

  NOTE    | Bio Half-Life Normalized to 10 g fish at 15 deg C  |

============+============================================+=========+=========

 

Biotransformation Rate Constant:

 kM (Rate Constant): 1.54 /day (10 gram fish)

 kM (Rate Constant): 0.8658 /day (100 gram fish)

 kM (Rate Constant): 0.4869 /day (1 kg fish)

 kM (Rate Constant): 0.2738 /day (10 kg fish)

 

Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):

  Estimated Log BCF (upper trophic) = 2.047 (BCF = 111.5 L/kg wet-wt)

  Estimated Log BAF (upper trophic) = 2.062 (BAF = 115.4 L/kg wet-wt)

  Estimated Log BCF (mid trophic)  = 2.185 (BCF = 153 L/kg wet-wt)

  Estimated Log BAF (mid trophic)  = 2.474 (BAF = 298.1 L/kg wet-wt)

  Estimated Log BCF (lower trophic) = 2.227 (BCF = 168.5 L/kg wet-wt)

  Estimated Log BAF (lower trophic) = 3.079 (BAF = 1198 L/kg wet-wt)

 

Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):

  Estimated Log BCF (upper trophic) = 4.262 (BCF = 1.83e+004 L/kg wet-wt)

  Estimated Log BAF (upper trophic) = 6.864 (BAF = 7.31e+006 L/kg wet-wt)

 

Validity criteria fulfilled:

not applicable

Conclusions:

The BCF values for test substance were predicted using regression based method and Arnot-gobas based method of the BCFBAF v.3.02 program (EPI SuiteTM v4.11), to be 400.30 L/Kg w/w (Log BCF = 2.60) and 111.5 L/Kg w/w (Log BCF= 2.05), respectively.

Executive summary:

The bioaccumulation factor of the test substance, C18 iso-MIPA, was estimated using both regression based and Arnot-Gobas BCF-BAF sub models of BCFBAF v.3.02 program (EPI SuiteTM v4.11). Using the regression-based equation for non-ionic compounds, the predicted BCF values for the constituents were estimated to be400.30 L/Kg w/w (Log BCF = 2.60).Similarly, using the Arnot-Gobas BAF-BCF sub-model, which uses mitigating factors (e.g., growth dilution and metabolic biotransformation’s), the predicted upper trophic BCF value for the constituents was predicted to be111.5 L/Kg w/w (Log BCF= 2.05)(US EPA, 2019). The test substance contains single constituent substance and was within the specified descriptor and structural domain criteria. Therefore, the BCF prediction for the test substance using BCFBAF model of EPI Suite TM can be considered to be reliable with high to moderate confidence. Overall considering either the individual BCF predictions for the constituents or the weighted average values, the test substance is expected to have a low bioaccumulation potential.

Reference 2

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From January 16, 2003 to August 27, 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 305 (Bioconcentration: Flow-through Fish Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

yes

Remarks:

14C-labelled test substance (Batch no.: 01BLY098)

Details on sampling:

Fish and water sampling:
5 sampling points were spaced during both uptake phase and depuration phase. The whole period counted 97 days.
- Water samples (10 or 500 mL) were taken from treated and control tanks and the radioactivity was determined directly by liquid scintillation counting (LSC).
- Fish samples. Treated tanks: On each sampling occasion, 6 fish were collected and 4 of them were analysed. After 47 and 55 days of accumulation, 8 fish were sampled and stored at -20°C. At day 11 and day 55, 6 fish were additionaly sampled for lipid determination. Control tanks: at the beginning (day 11) and end (day 55) of the accumulation period and at the end of the depuration period, 6 fish were taken and four of them were analysed for radioactivity.
Sample preparation:
- Water. Duplicate samples of 10 mL water in the presence of 10 mL DMF and water samples of 500 mL at all 5 sampling time points were analysed for total radioactivity by LSC.
- Fish. Fish were weighed and solubilized and subsamples were measured by LSC. The fish lipid/wet weight ratio was also determined in homogenates.

Vehicle:

yes

Remarks:

dimethylformamide (DMF) or DMF/purified water

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

Stock solutions: in DMF (aliquots stocked at -20°C)
Application solutions: in DMF/purified water (25/75)

Test organisms (species):

Oncorhynchus mykiss (previous name: Salmo gairdneri)

Details on test organisms:

Supplier: Forellenzucht Hohler, Zeiningen, Switzerland
Acclimatization: at least two weeks
Fish weight: 1-2g
Illumination: photoperiod of 16h light (300-400 Lux) and 8h darkness
Average target temperature: 13-17°C
Feed: once daily (H.U. Hofmann AG, HOKOVIT, "Forellenfutter", diet of known lipid and total protein content) and based on fish weight

Route of exposure:

aqueous

Justification for method:

other:

Test type:

flow-through

Water / sediment media type:

natural water: freshwater

Total exposure / uptake duration:

55 d

Total depuration duration:

49 d

Hardness:

210 mg CaCO3/L

Test temperature:

Exposure days: 14-17°C
Depuration days: 14-18°C

pH:

Exposure days: 6.9-8.0
Depuration days: 7.1-7.8

Dissolved oxygen:

Exposure days: 4.2-9.4 mg/L
Depuration days: 6.6-8.7 mg/L

TOC:

Exposure days (pre-equilibrium and accumulation period): 47.3 +/- 4.3, 45.9 +/- 1.8 and 47.7 +/- 7.4 mg/L for control, low dose and high dose tank, respectively.
NB: DMF was responsible for the higher TOC values. After correction, TOC values were below 2 mg/L.
Depuration days: 3.7 +/- 1.1, 3.2 +/- 1.4 and 3.2 +/- 2.3 mg/L for control, low dose and high dose tank, respectively.

Salinity:

-

Conductivity:

-

Details on test conditions:

Daily flow-through volume of 250L/day (with a final concentration of organic solvent in the water not exceeding 0.01%) to achieve final target of concentrations of 2 and 20 µg/L.

Nominal and measured concentrations:

Average low dose concentration of 2.0 µg/L for 55 days (31.5 mg 14C-labelled test substance in DMF (0.5 mg/25mL)
Average high dose concentration of 20.0 µg/L for 55 days (315 mg 14C-labelled test substance in DMF (5 mg/25mL)
(The pattern of radioactivity was determined by TLC analyses).

Reference substance (positive control):

no

Details on estimation of bioconcentration:

Bioconcentration kinetics:
The average plateau levels in fish were calculated from the three (high dose) or four (low dose) successive fish samples at the last time points, as well as by the non-linear parameter estimation program ORIGIN. The bioconcentration factor (BCF) was also determined.

Lipid content:

>= 27.1 - <= 29 other: mg/g fish

Time point:

other: day 11

Remarks on result:

other: for low and high dose, respectively

Lipid content:

>= 41.7 - <= 48.3 other: mg/g fish

Time point:

end of exposure

Remarks on result:

other: for low and high dose, respectively

Key result

Conc. / dose:

1.6 µg/L

Temp.:

>= 14 - <= 18 °C

pH:

7.4

Type:

BCF

Value:

>= 589 - <= 600 dimensionless

Basis:

other: exposure water and the plateau levels in fish

Time of plateau:

25 d

Calculation basis:

kinetic

Key result

Conc. / dose:

13.7 µg/L

Temp.:

>= 14 - <= 18 °C

pH:

7.4

Type:

BCF

Value:

>= 1 023 - <= 1 284 dimensionless

Basis:

other: exposure water and the plateau levels in fish

Time of plateau:

39 d

Calculation basis:

kinetic

Key result

Elimination:

yes

Parameter:

DT50

Remarks:

by first order kinetics

Depuration time (DT):

13.3 d

Remarks on result:

other: for the low dose

Key result

Elimination:

yes

Parameter:

DT50

Remarks:

by first order kinetics

Depuration time (DT):

9.1 d

Remarks on result:

other: for the high dose

Key result

Rate constant:

other: k2 (day-1): rate constant

Value:

0.094

Remarks on result:

other: for the low dose

Key result

Rate constant:

other: k2 (day-1): rate constant

Value:

0.034

Remarks on result:

other: for the high dose

Key result

Rate constant:

other: k1 day-1): accumulation rate constant

Value:

56

Remarks on result:

other: for the low dose

Key result

Rate constant:

other: k1 day-1): accumulation rate constant

Value:

44

Remarks on result:

other: for the high dose

Key result

Rate constant:

overall depuration rate constant (d-1)

Value:

0.052

Remarks on result:

other: for the low dose

Key result

Rate constant:

overall depuration rate constant (d-1)

Value:

0.056

Remarks on result:

other: for the high dose

Metabolites:

Metabolite patterns and characterization of radioactivity in exposure water:
Radioactivity present in the stock solution (100% DMF), the aqueous application solution (25% DMF), as well as in the exposure water (0.01% DMF) after partitioning were characterized by TLC. At both dose levels after TLC analyses of both organic and remaining aqueous phases, almost exclusively parent substance was found in the exposure water with a tendency to an increased polar/apolar ratio within the test substance during exposure period.

Details on results:

- Levels of radioactivity in water during pre-equilibrium, exposure and depuration:
Pre-equilibrium phase (3 days): 0.3 - 1.5 µg/L and 6.1 - 11.4 µg/L for the low and the high dose level, respectively.

Exposure period: 1.6 +/- 0.35 µg/L and 13.7 +/- 3.0 µg/L for the low and the high dose level, respectively.
Due to partial non-specic binding to fish, glass and/or excreta, actual levels in the tanks remained about 20 -30% below the target values of 2 and 20 µg/L.

Depuration period: radioactivity levels decreased rapidly and were under the detection limit of 0.03 and 0.06 µg/L after 2 days and 3 weeks in the low dose and high dose condition, respectively.

Radioactivity levels in the water of the control tank were negligible during entire test period.
- Levels of radioactivity in fish during exposure (bioaccumulation):
Low dose - whole fish: the plateau level was reached after 25 days and amounted 943 +/- 120 µg-eq/kg (960 +/- 71 µg-eq/kg when ajusted by means of the best-fit)
High dose - whole fish: the plateau level was reached after 39 days and amounted 14,011 +/- 1,768 µg-eq/kg (17,597 +/- 4,579 µg-eq/kg when ajusted by means of the best-fit)
Untreated tank: negligible

Levels of radioactivity in fish during depuration:
Low dose: after 21 days, radioactivity was 256 µg-eq/kg (29.2%), and after 49 days 137 µg-eq/kg (15.6%). Elimination by first order kinetics with a 1/2 -life of 13.3 days.
High dose: after 21 days, radioactivity was 3,827 µg-eq/kg (24.6%), and after 49 days 1,950 µg-eq/kg (12.5%). Elimination by first order kinetics with a 1/2 -life of 9.1 days.

Bioconcentration factor:
Plateau levels: 943 - 960 µg-eq/kg with a SD of 7 -13% and 14,011 - 17,597 µg-ep/kg with a SD of 13 -26% for the low dose and the high dose, respectively.
BCF: 589 -600 and 1023 -1284 for the low dose and the high dose, respectively. Taking into account the high variablity in the high plateau levels, the difference between the BCF values of the two dose levels may not be significant. On average, the BCF value for the test substance was determined to be 874 +/- 340 in whole fish.
Almost exclusively parent substance was found.
Fat content in the fish at day 11 was 27.1 mg/g and 29.0 mg/g and at day 55 41.7 mg/g and 48.3 mg/g for low and high dose, respectively. Taking into account the concentrations of radioactivity, BCF values in fat were similar for both days anmounted at the low dose level to 12,361 (day 11) and 13,134 (day 55) and at the high dose level to 20,511 (day 11) and 23,500 (day 55), indicating that the concentration of radioactivity in fish strictly correlated to the lipid oncentration.
- Partitioning of exposure water:
After partitioning of the exposure water, the organic phase reflected the more apolar fractions and the aqueous phase, the more polar fractions. For both dose levels at exposure day 11, radioactivity partitioned to 56.3 - 61.5% in the organic phase. Accordingly, 38.5 - 3.8% of the radioactivity remained in the water phase. During exposure up to day 55 at both dose levels, the radioactivity partitioned in the organic water phase gradually decreased to 27.7 - 36.0%. Accordingly, partitioned in the water phase gradually increase to 64.0 - 72.3%. At both levels, a tendency to higher amounts of polar radioactive fractions were found over the exposure period.

Reported statistics:

Mean +/- SD

Validity criteria fulfilled:

yes

Conclusions:

Under the study conditions, the average BCF value of the test substance in whole fish (rainbow trout) is 874 after 55 d. Plateau levels were reached after 25 d (low dose) and 39 d (high dose). Depuration occurred with a half-life of about 9-13 d, indicating that the uptake of the test substance in fish was partially reversible.

Executive summary:

A study was conducted to determine the bioaccumulation of the test substance, IsoC18 MIPA (96% active), in Rainbow trout (Oncorhynchus mykiss) according to OECD Guideline 305, in compliance with GLP. The fish were continuously exposed under flow-through conditions to 14C-labelled test substance at an average low dose of 1.60 µg/L and an average high dose of 13.70 µg/L for 55 d at a temperature of 14 -17°C, a pH ranging from 6.9 to 8.0 and an oxygen concentration ranging from 4.2-9.4 mg/L. Thereafter, the fish were transferred to flowing untreated water and the depuration of radioactivity was followed for 49 d. At the low dose level, the plateau level was reached after 25 d, amounting to 943 -960 µg parent equivalents/kg fish. Thereafter radioactivity was depurated from fish during 49 d with a half-life of about 13 d. At the end of the depuration period (49 d), concentrations decreased to 137 µg parent equivalents/kg (15.6%). At the high dose level, the plateau level was reached after 39 d, amounting to 14011-17597 µg parent equivalents/kg fish. Thereafter radioactivity was depurated from fish during 49 d with a half-life of about 9 d. At the end of the depuration period, concentrations decreased to 1950 µg parent equivalents/kg (12.5%). Based on the actual concentrations of parent test substance in exposure water and the plateau levels in fish, parent BCF amounted to 598-600 and 1023-1284 for the low dose and the high dose, respectively. Taking into account the variablity in the high plateau levels, the difference between the BCF values of the two dose levels may not be significant. On average, the BCF value for the test substance was determined to be 874 +/- 340 in whole fish. Analyses of radioactivity in the exposure water showed exclusively parent test substance at both doses throughout the entire exposure period. Additionally, a tendency to an increased polar/apolar ratio within the test substance during the exposure period was observed. The results also indicated the test substance uptake in fish was partially reversible (van Dijk, 2003).

Key value for chemical safety assessment

BCF (aquatic species):

874 dimensionless

Additional information

A study was conducted to determine the bioaccumulation of the test substance, isoC18 MIPA (96% active), in Rainbow trout (Oncorhynchus mykiss) according to OECD Guideline 305, in compliance with GLP. The fish were continuously exposed under flow-through conditions to 14C-labelled test substance at an average low dose of 1.60 µg/L and an average high dose of 13.70 µg/L for 55 d at a temperature of 14 -17°C, a pH ranging from 6.9 to 8.0 and an oxygen concentration ranging from 4.2-9.4 mg/L. Thereafter, the fish were transferred to flowing untreated water and the depuration of radioactivity was followed for 49 d. At the low dose level, the plateau level was reached after 25 d, amounting to 943 -960 µg parent equivalents/kg fish. Thereafter radioactivity was depurated from fish during 49 d with a half-life of about 13 d. At the end of the depuration period (49 d), concentrations decreased to 137 µg parent equivalents/kg (15.6%). At the high dose level, the plateau level was reached after 39 d, amounting to 14011-17597 µg parent equivalents/kg fish. Thereafter radioactivity was depurated from fish during 49 d with a half-life of about 9 d. At the end of the depuration period, concentrations decreased to 1950 µg parent equivalents/kg (12.5%). Based on the actual concentrations of parent test substance in exposure water and the plateau levels in fish, parent BCF amounted to 598-600 and 1023-1284 for the low dose and the high dose, respectively. Taking into account the variablity in the high plateau levels, the difference between the BCF values of the two dose levels may not be significant. On average, the BCF value for the test substance was determined to be 874 +/- 340 in whole fish. Analyses of radioactivity in the exposure water showed exclusively parent test substance at both doses throughout the entire exposure period. Additionally, a tendency to an increased polar/apolar ratio within the test substance during the exposure period was observed. The results also indicated the test substance uptake in fish was partially reversible (van Dijk, 2003).

The bioaccumulation factor of the test substance, C18 iso-MIPA, was also estimated using both regression based and Arnot-Gobas BCF-BAF sub models of BCFBAF v.3.02 program (EPI SuiteTM v4.11). Using the regression-based equation for non-ionic compounds, the predicted BCF values for the constituents were estimated to be400.30 L/Kg w/w (Log BCF = 2.60).Similarly, using the Arnot-Gobas BAF-BCF sub-model, which uses mitigating factors (e.g., growth dilution and metabolic biotransformation’s), the predicted upper trophic BCF value for the constituents was predicted to be111.5 L/Kg w/w (Log BCF= 2.05)(US EPA, 2019). The test substance contains single constituent substance and was within the specified descriptor and structural domain criteria. Therefore, the BCF prediction for the test substance using BCFBAF model of EPI Suite TM can be considered to be reliable with high to moderate confidence. Overall considering either the individual BCF predictions for the constituents or the weighted average values, the test substance is expected to have a low bioaccumulation potential.