2-(2-heptadec-8-enyl-2-imidazolin-1-yl)ethanol

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:

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 ionises at a physiological relevant pH.

Justification for type of information:

- QMRF: see 'Overall remarks, attachments'.
- QPRF: see 'Executive summary'.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Calculation using BCFBAF (v3.01)

GLP compliance:

no

Specific details on test material used for the study:

- SMILES code: CCCCCCCCC=CCCCCCCCC1=NCCN1CCO

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation software: EPISuite-BCFBAF (version 3.01)
- Result based on measured/calculated log Pow of: 7.51

Type:

BCF

Value:

1 890 L/kg

Basis:

whole body w.w.

Calculation basis:

other: regression-based estimate

Remarks on result:

other: The substance is within the applicability domain of the BCFBAF submodel: Bioconcentration factor (BCF; Meylan et al., 1997/1999).

Type:

BCF

Value:

371.8 L/kg

Basis:

whole body w.w.

Calculation basis:

kinetic

Remarks on result:

other: The substance is not completely the applicability domain of the BCFBAF submodel as ionic: Biotransformation rate in fish (kM; Arnot et al., 2008a/b).

Remarks:

Arnot-Gobas upper trophic

Type:

BCF

Value:

6 332 L/kg

Basis:

whole body w.w.

Calculation basis:

steady state

Remarks on result:

other: The substance is not completely the applicability domain of the BCFBAF submodel as ionic: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).

Remarks:

Arnot-Gobas upper trophic

Type:

BAF

Value:

15 580 L/kg

Basis:

whole body w.w.

Calculation basis:

kinetic

Remarks on result:

other: The substance is not completely the applicability domain of the BCFBAF submodel as ionic: Biotransformation rate in fish (kM; Arnot et al., 2008a/b).

Remarks:

Arnot-Gobas upper trophic

Type:

BAF

Value:

14 460 000 L/kg

Basis:

whole body w.w.

Calculation basis:

steady state

Remarks on result:

other: The substance is not completely the applicability domain of the BCFBAF submodel as ionic: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).

Remarks:

Arnot-Gobas upper trophic

Summary Results:

Log BCF (regression-based estimate): 3.28 (BCF = L/kg wet-wt)

Biotransformation Half-Life (days): 7.38 (normalized to 10 g fish)

Log BAF (Arnot-Gobas upper trophic): 4.19 (BAF = 1.56e+004 L/kg wet-wt)

 

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 7.51

 

Equation Used to Make BCF estimate:

Log BCF = -0.49 log Kow + 7.554 + Correction

 

Correction(s): Value

Alkyl chains (8+ -CH2- groups) -0.596

 

Estimated Log BCF = 3.276 (BCF = 1887 L/kg wet-wt))

 

Whole Body Primary Biotransformation Rate Estimate for Fish:

TYPE	NUM	LOG BIODEGRADATION FRAGMENT DESCRIPTION	COEFF	VALUE
Frag	1	Linear C4 terminal chain [CCC-CH3]	0.0341	0.0341
Frag	1	Aliphatic alcohol [-OH]	-0.0616	-0.0616
Frag	1	Methyl [-CH3]	0.2451	0.2451
Frag	16	-CH2- [linear]	0.0242	0.3870
Frag	2	-CH2- [cyclic]	0.0963	0.1925
Frag	2	-C=CH [alkenyl hydrogen]	0.0988	0.1977
Frag	2	-C=CH [alkenyl hydrogen]	0.0000	0.0000
L Kow	*	Log Kow = 7.51 (KowWin estimate)	0.3073	2.3093
MolWt	*	Molecular Weight Parameter		-0.8990
Const	*	Equation Constant		-1.5371
Result	Log Bio Half-Life (days)			0.8680
Result	Bio Half-life (days)			7.38

 

Biotransformation Rate Constant:

kM (Rate Constant): 0.09393/day (10 gram fish)

kM (Rate Constant): 0.05282/day (100 gram fish)

kM (Rate Constant): 0.0297/day (1 kg fish)

kM (Rate Constant): 0.0167/day (10 kg fish)

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

Estimated Log BCF (upper trophic) = 2.570 (BCF = 371.8L/kg wet-wt)

Estimated Log BAF (upper trophic) = 4.193 (BAF = 1.558e+004L/kg wet-wt)

Estimated Log BCF (mid trophic) = 2.712 (BCF = 515L/kg wet-wt)

Estimated Log BAF (mid trophic) = 4.616 (BAF = 4.13e+004L/kg wet-wt)

Estimated Log BCF (lower trophic) = 2.755 (BCF = 568.9L/kg wet-wt)

Estimated Log BAF (lower trophic) = 4.868 (BAF = 7.383e+004 L/kg wet-wt)

 

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

Estimated LogBCF (upper trophic) = 3.802 (BCF = 6332L/kg wet-wt)

Estimated Log BAF (upper trophic) = 7.160 (BAF = 1.446e+007 L/kg wet-wt)

Executive summary:

QPRF: BCFBAF v3.01 

1.	Substance	See “Test material identity”
2.	General information
2.1	Date of QPRF	See “Data Source (Reference)”
2.2	QPRF author and contact details	See “Data Source (Reference)”
3.	Prediction
3.1	Endpoint (OECD Principle 1)	Endpoint	Bioaccumulation (aquatic)
		Dependent variable	- Bioconcentration factor (BCF) - Bioaccumulation factor (BAF; 15 °C) - Biotransformation rate (kM) and half-life
3.2	Algorithm (OECD Principle 2)	Model or submodel name	BCFBAF Submodels: 1) Bioconcentration factor (BCF; Meylan et al., 1997/1999) 2) Biotransformation rate in fish (kM; Arnot et al., 2008a/b) 3) Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003)
		Model version	v. 3.01
		Reference to QMRF	Estimation of Bioconcentration, bioaccumulation and biotransformation in fish using BCFBAF v3.01 (EPI Suite v4.11)
		Predicted value (model result)	See “Results and discussion”
		Input for prediction	Chemical structure via CAS number or SMILES; log Kow (optional)
		Descriptor values	- SMILES: structure of the compound as SMILES notation - log Kow - Molecular weight
3.3	Applicability domain (OECD principle 3)	Domains:
		1) Bioconcentration factor (BCF; Meylan et al., 1997/1999)
		a) Ionic/non-Ionic	The substance is ionic.
		b) Molecular weight (range of test data set): - Ionic: 68.08 to 991.80 - Non-ionic: 68.08 to 959.17 (On-Line BCFBAF Help File, Ch. 7.1.3 Estimation Domain and Appendix G)	The substance is within range (350.59 g/mol).
		c) log Kow (range of test data set): - Ionic: -6.50 to 11.26 - Non-ionic: -1.37 to 11.26 (On-Line BCFBAF Help File, Ch. 7.1.3 Estimation Domain and Appendix G)	The substance is within range (7.51).
		d) Maximum number of instances of correction factor in any of the training set compounds (On-Line BCFBAF Help File, Appendix E)	Not exceeded.
		2) Biotransformation rate in fish (kM; Arnot et al., 2008a/b)
		a) The substance does not appreciably ionize at physiological pH. (On-Line BCFBAF Help File, Ch. 7.2.3)	Not fulfilled
		b) Molecular weight (range of test data set): 68.08 to 959.17 (On-Line BCFBAF Help File, Ch. 7.2.3)	The substance is within range (350.59 g/mol).
		c) The molecular weight is ≤ 600 g/mol. (On-Line BCFBAF Help File, Ch. 7.2.3)	Fulfilled
		d) Log Kow: 0.31 to 8.70 (On-Line BCFBAF Help File, Ch. 7.2.3)	The substance is within range (7.51).
		e) The substance is no metal or organometal, pigment or dye, or a perfluorinated substance. (On-Line BCFBAF Help File, Ch. 7.2.3)	Fulfilled
		f) Maximum number of instances of biotransformation fragments in any of the training set compounds (On-Line BCFBAF Help File, Appendix F)	Not exceeded.
		3) Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003)
		a) Log Kow ≤ 9 (On-Line BCFBAF Help File, Ch. 7.3.1)	Fulfilled
		b) The substance does not appreciably ionize. (On-Line BCFBAF Help File, Ch. 7.3.1)	Not fulfilled
		c) The substance is no pigment, dye, or perfluorinated substance. (On-Line BCFBAF Help File, Ch. 7.3.1)	Fulfilled
3.4	The uncertainty of the prediction (OECD principle 4)	1. Bioconcentration factor (BCF; Meylan et al., 1997/1999) Statistical accuracy of the training data set (non-ionic plus ionic data): - Correlation coefficient (r^2) = 0.833 - Standard deviation = 0.502 log units - Absolute mean error = 0.382 log units   2. Biotransformation Rate in Fish (kM) Statistical accuracy (training set): - Correlation coefficient (r^2) = 0.821 - Correlation coefficient (Q^2) = 0.753 - Standard deviation = 0.494 log units - Absolute mean error = 0.383 log units   3. Arnot-Gobas BAF/BCF model No information on the statistical accuracy given in the documentation.
3.5	The chemical mechanisms according to the model underpinning the predicted result (OECD principle 5)	1. The BCF model is mainly based on the relationship between bioconcentration and hydrophobicity. The model also takes into account the chemical structure and the ionic/non-ionic character of the substance.   2. Bioaccumulation is the net result of relative rates of chemical inputs to an organism from multimedia exposures (e.g., air, food, and water) and chemical outputs (or elimination) from the organism.   3. The model includes mechanistic processes for bioconcentration and bioaccumulation such as chemical uptake from the water at the gill surface (BCFs and BAFs) and the diet (BAFs only), and chemical elimination at the gill surface, fecal egestion, growth dilution and metabolic biotransformation (Arnot and Gobas 2003). Other processes included in the calculations are bioavailability in the water column (only the freely dissolved fraction can bioconcentrate) and absorption efficiencies at the gill and in the gastrointestinal tract.

References

- 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.

- Arnot JA, Mackay D, Parkerton TF, Bonnell M. 2008a. A database of fish biotransformation rates for organic chemicals. Environmental Toxicology and Chemistry 27(11), 2263-2270.

- Arnot JA, Mackay D, Bonnell M. 2008b. Estimating metabolic biotransformation rates in fish from laboratory data. Environmental Toxicology and Chemistry 27: 341-351.

- 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.

- 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). 

- US EPA (2012). On-Line BCFBAF Help File. .

Identified Correction Factors (Appendix E)

Correction Factors: Not used for Log Kow < 1. No fragments identified.

 

Biotransformation Fragments and Coefficient values (Appendix F)  

Fragment Description	Coefficient value	No. compounds containing fragment in total training set	Maximum number of each fragment in any individual compound	No. of instances of each fragment for the current substance
Linear C4 terminal chain  [CCC-CH3]	0.03412373	43	3	1
Aliphatic alcohol  [-OH]	-0.06155701	7	3	1
Methyl  [-CH3]	0.24510529	170	12	1
-CH2-  [linear]	0.02418707	109	28	16
-CH2-  [cyclic]	0.09625069	36	12	2
-C=CH  [alkenyl hydrogen]	0.09884729	34	6	2

 

Assessment of Applicability Domain Based on Molecular Weight and log Kow

 

1. Bioconcentration Factor (BCF; Meylan et al., 1997/1999)                             

Training set: Molecular weights	Ionic	Non-ionic
Minimum	68,08	68,08
Maximum	991,80	959,17
Average	244,00	244,00
Assessment of molecular weight	Molecular weight within range of training set
Training set: Log Kow	Ionic	Non-ionic
Minimum	-6,50	-1,37
Maximum	11,26	11,26
Assessment of log Kow	Log Kow within range of training set.

 

2. Biotransformation Rate in Fish (kM; Arnot et al., 2008a/b)                            

Training set: Molecular weights
Minimum	68,08
Maximum	959,17
Average	259,75
Assessment of molecular weight	Molecular weight within range of training set
Training set: Log Kow
Minimum	0,31
Maximum	8,70
Assessment of log Kow	Log Kow within range of training set.

                                  

3. Arnot-Gobas BAF/BCF (Arnot & Gobas, 2003)

Assessment of log Kow: Log Kow within acceptable range (log Kow ≤ 9).

Reference 2

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Qualifier:

no guideline followed

Principles of method if other than guideline:

Calculation using Catalogic v.5.12.1 BCF base-line model v.02.09

Specific details on test material used for the study:

- SMILES Code: CCCCCCCCC=CCCCCCCCC1=NCCN1CCO

Test organisms (species):

other: fish

Details on estimation of bioconcentration:

BASIS INFORMATION
- Measured/calculated logPow: calculated

BASIS FOR CALCULATION OF BCF
- Estimation software: BCF base-line model v02.09 of OASIS CATALOGIC v5.12.1

Type:

BCF

Value:

37.15 L/kg

Remarks on result:

other: Log BCF corrected = 1.57 ± 0.620; all mitigating factors applied.

Type:

BCF

Value:

17 100 L/kg

Remarks on result:

other: Log BCF max. = 4.233; no mitigating factors applied.

MODEL DOMAIN SIMILARITY:

- Parametric domain: The chemical fulfils the general properties requirements (Log Kow, molecular weight and water solubility).

- Structural domain: 72.00% correct fragments, 0% incorrect fragments (28.00% % unknown). The chemical is out of the interpolation structural space. 

- Mechanistic domain: The expected uptake mechanism of the target chemical is passive diffusion across biological membranes. The chemical is in the mechanistic domain of the model.

 

EFFECTS OF MITIGATING FACTORS ON BCF:

Acids	0.000
Metabolism	0.634
Phenols	0.000
Size	0.391
Water solubility	2.756E-005

 

Log BCF max: 4.233 L/kg wet

- Log BCF corrected: 1.57 ± 0.620 L/kg wet

 

MOLECULAR SIZE (Maximum diameter):

- Minimum: 14.415 Å

- Maximum: 28.814 Å

- Mean: 18.858 Å

Executive summary:

For QPRF see "Attached background material".

Description of key information

Bioaccumulation is not expected.

Additional information

The bioaccumulation potential of the substance is evaluated with two QSAR methods.

 

SRC BCFBAF

Based on the log Kow of 7.51, a BCF-value of 1890 L/kg wet-wt was calculated. The BCF-value taking biotransformation rate estimates into account, was calculated to be 371.8 L/kg, although the main constituent was not entirely within the applicability domain as it ionises at physiological pH.

 

CATALOGIC

The main constituent was in the parametric and mechanistic domain of the model, although out of the interpolation structural space (72% correct fragments). The BCF-value was estimated to be 37.15 L/kg. The main mitigating factors for bioaccumulation were metabolism and size. DiamMax Average is 18.858Å which indicates limited bioaccumulation potential according to Reach Guidance on Information Requirements and Chemical Safety Assessment Chapter R.11: PBT/vPvB Assessment.

 

Conclusion

The BCF is most likely overestimated in the presented calculations since the calculations were performed for the neutral molecule. The substance exists as a cation at environmentally relevant pH values (see 4.21) and thus the BCF is presumably lower. The estimated BCF-values are (well) below the relevant BCF cut-off value of 2000 L/kg. The substance is considered to be not bioaccumulative.

 

QSAR-disclaimer

In Article 13 of Regulation (EC) No 1907/2006, it is laid down that information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI (of the same Regulation) are met. Furthermore according to Article 25 of the same Regulation testing on vertebrate animals shall be undertaken only as a last resort.

 

According to Annex XI of Regulation (EC) No 1907/2006 (Q)SAR results can be used if (1) the scientific validity of the (Q)SAR model has been established, (2) the substance falls within the applicability domain of the (Q)SAR model, (3) the results are adequate for the purpose of classification and labeling and/or risk assessment and (4) adequate and reliable documentation of the applied method is provided.

 

For the assessment of CAS 95-38-5 (Q)SAR results of the main constituent were used for bioaccumulation: aquatic / sediment. The criteria listed in Annex XI of Regulation (EC) No 1907/2006 are considered to be adequately fulfilled for one out of three models. Therefore, the endpoint(s) is considered sufficiently covered and suitable for risk assessment.