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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
Guideline:
other: 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 calculated log Pow of: 12.65 (KOWWIN v.1.68)
Type:
BCF
Value:
0.91 L/kg
Basis:
whole body w.w.
Remarks on result:
other: including biotransformation, upper trophic
Remarks:
Constituent 1 (smallest component)
Type:
other: log BCF
Value:
-0.04 dimensionless
Basis:
whole body w.w.
Remarks on result:
other: including biotransformation, upper trophic
Remarks:
Constituent 1 (smallest component)

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.
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: 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 calculated log Kow of: 12.65 (estimated, KOWWIN v.1.68)
Type:
BCF
Value:
22.7 L/kg
Basis:
whole body w.w.
Remarks on result:
other:
Remarks:
constituent 1 (smallest component)
Type:
other: log BCF
Value:
1.36 dimensionless
Basis:
whole body w.w.
Remarks on result:
other:
Remarks:
constituent 1 (smallest component)

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, 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
Guideline:
other: 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 calculated log Pow of: 14.89 (KOWWIN v.1.68)
Type:
BCF
Value:
0.89 L/kg
Basis:
whole body w.w.
Remarks on result:
other: including biotransformation, upper trophic
Remarks:
Constituent 2 (biggest component)
Type:
other: log BCF
Value:
-0.05 dimensionless
Basis:
whole body w.w.
Remarks on result:
other: including biotransformation, upper trophic
Remarks:
Constituent 2 (biggest component)

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.
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: 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 calculated log Kow of: 14.89 (estimated, KOWWIN v.1.68)
Type:
BCF
Value:
3.16 L/kg
Basis:
whole body w.w.
Remarks on result:
other:
Remarks:
Constituent 2 (biggest component)
Type:
other: log BCF
Value:
0.5 dimensionless
Basis:
whole body w.w.
Remarks on result:
other:
Remarks:
Constituent 2 (biggest component)

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

Description of key information

Based on the available data, the potential of bioaccumulation forFatty acids, C16, C18 and C18-unsaturated, C12-15 alcohol (linear and branched), esters is expected to be low.

Key value for chemical safety assessment

Additional information

The substance has a high, estimated log Kow of > 10.0 (QSAR models), suggesting a high potential for bioaccumulation. Experimental data for bioaccumulation are not available. However, all the available information on the environmental behaviour and metabolism discussed below, provide evidence that the effective potential for bioaccumulation is likely negligible.

Environmental behaviour

The very low water solubility (< 6.57 µg/L at 20 °C, pH 6.3, OECD 105) and high estimated log Kow (> 10.0, QSAR models) indicate that the substance is highly lipophilic. However, only low concentrations of the substance are expected to reach the environment in the first place, if at all. Due to the ready biodegradability and high potential for adsorption, the substance is effectively removed from conventional sewage treatment plants (STPs) by biodegradation and sorption to biomass. Whatever fraction reaches the aquatic environment is expected to undergo extensive biodegradation and sorption to organic matter, leading to an effective reduction of bioavailability in the water column. Thus, the overall bioavailability of the substance in surface water is presumably low and the most relevant route of uptake by aquatic organisms is expected to occur via ingestion of particle bound substance. However, based on the high sorption potential of the substance, the bioavailability in the sediment is presumably also very low, which reduces the probability of chronic exposure of sediment organisms in general.

Metabolization of aliphatic esters

The substance is an aliphatic ester. In the case where aliphatic esters should be ingested by fish, they are expected to be initially metabolized via enzymatic hydrolysis during the process of digestion and absorption in the intestinal tissue, resulting in the corresponding free fatty acids and the free fatty alcohols. Hydrolysis is catalyzed by classes of enzymes known as carboxylesterases or esterases (Heymann, 1980). The catalytic activity of this enzyme family leads to a rapid biotransformation/metabolization of xenobiotics, which reduces the bioaccumulation or bioconcentration potential (Lech & Bend, 1980). Carboxylesterase activity has been noted in a wide variety of tissues in fish as well as in invertebrates (Leinweber, 1987; Soldano et al, 1992; Barron et al., 1999, Wheelock et al., 2008). In mammals, the most important are the B-esterases in the hepatocytes (Heymann, 1980; Anders, 1989).

Furthermore, it is known that esters are readily metabolized in fish (Barron et al., 1999) and literature clearly shows that esters do not readily bioaccumulate in fish (Rodger & Stalling, 1972; Murphy & Lutenske, 1990; Barron et al., 1990). In fish species this might be explained by the wide distribution of carboxylesterase, high tissue content, rapid substrate turnover and limited substrate specificity (Lech & Melancon, 1980; Heymann, 1980). The metabolization of the enzymatic hydrolysis products is presented in the next section below.

Metabolization of enzymatic hydrolysis products

Fatty alcohols

The metabolism of alcohols is well known. Free alcohols can either be esterified to form wax esters which are similar to triglycerides or they can be metabolized to fatty acids in a two-step enzymatic process by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) using NAD+ as coenzyme as shown in the fish gourami (Trichogaster cosby) (Sand et al., 1973). The responsible enzymes ADH and ALDH are present in a large number of animals, plants and microorganisms (Sund & Theorell, 1963; Yoshida et al., 1997). They were found, among others, in the zebrafish (Reimers et al., 2004; Lassen et al., 2005), carp and rainbow trout (Nilsson, 1988; Nilsson, 1990). The metabolism of alcohols was also investigated in the zebrafish Danio rerio, which is a standard organism in aquatic ecotoxicology. Two cDNAs encoding zebrafish ADHs were isolated and characterized. A specific metabolic activity was shown in in-vitro assays with various alcohol components ranging from C4 to C8. The corresponding aldehyde can be further oxidized to the fatty acid catalyzed by an ALDH. Among ALDHs, the ALDH2 located in the mitochondria is the most efficient. The ALDH2 cDNA of the zebrafish was cloned and a similarity of 75% to mammalian ALDH2 enzymes was found. Moreover, ALDH2 from zebra fish exhibits a similar catalytic activity for the oxidation of acetaldehyde to acetic acid compared to the human ALDH2 protein (Reimers at al., 2004). The same metabolic pathway was shown for longer chain alcohols like stearyl- and oleyl alcohol which were enzymatically converted to its corresponding acid in the intestines (Calbert et al., 1951; Sand et al., 1973; Sieber et al., 1974). Branched alcohols show a high degree of similarity in biotransformation compared to linear alcohols. They will be oxidized to the corresponding carboxylic acid followed by the ß-oxidation as well. The presence of a side chain does not terminate the ß-oxidation process (OECD, 2006).

The influence of biotransformation on bioaccumulation of alcohols was confirmed in GLP studies with the rainbow trout (according to OECD 305) with commercial branched alcohols with chain lengths of C10, C12 and C13 (de Wolf & Parkerton, 1999). This study resulted in an experimental BCF of 16, 29 and 30, respectively for the three alcohols tested. The 2-fold increase of BCF for C12 and C13 alcohol was explained by a possible saturation of the enzyme system leading to a decreased elimination.

Fatty acids

The metabolization of fatty acids in mammals is well known and has been investigated intensively (Stryer, 1994). Free fatty acids can either be stored as triglycerides or oxidized via mitochondrial ß-oxidation removing C2-units to provide energy in the form of ATP (Masoro, 1977). Acetyl-CoA, the product of the ß-oxidation, can further be oxidized in the tricarboxylic acid cycle to produce energy in the form of ATP. As fatty acids are naturally stored as triglycerides in fat tissue and re-mobilized for energy production, it can be concluded that even if they bioaccumulate, bioaccumulation will not pose a risk to living organisms. Fatty acids (typically C14 to C24 chain lengths) are also a major component of biological membranes as part of the phospholipid bilayer and therefore constitute an essential biological component for the integrity of cells in every living organism (Stryer, 1994). Saturated fatty acids (SFA; C12 - C24) as well as mono-unsaturated (MUFA; C14 - C24) and poly-unsaturated fatty acids (PUFA; C18 - C22) were naturally found in muscle tissue of the rainbow trout (Danabas, 2011) and in the liver (SFA: C14 - C20; MUFA: C16 - C20; PUFA: C18 - C22) of the rainbow trout (Dernekbasi, 2012).

Conclusion

The biochemical processes involved in the metabolization of aliphatic esters, comprising enzymatic hydrolysis and the subsequent metabolization of the corresponding carboxylic acid and alcohol, are ubiquitous in the animal kingdom. Hence, it can be concluded that the high log Kow, which indicates a potential for bioaccumulation, overestimates the true bioaccumulation potential of the substance since it does not take into account the metabolization of substances in living organisms. Current knowledge suggests that log Kow values of 10 or above are indicators of reduced bioconcentration, as stated in the Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7c: Endpoint specific Guidance (ECHA, 2017) as well as in Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.11: PBT/vPvB assessment v2.0 (ECHA, 2017).

This conclusion is supported by (Q)SAR calculations for BCF values in fish. Though the components do not fully lie within the applicability domain of the model, the predictions are considered sufficiently reliable for the indication of probable trends. The BCF values obtained by the regression-based estimate ranged from 3.16 L/kg wet-wt to 22.7 L/kg wet-wt. The BCF values obtained by the Arnot-Gobas method (including biotransformation, upper trophic) were around 0.90 L/kg wet-wt for all constituents. Thus, the estimated BCF values are well below the threshold value of 2000 L/kg for bioaccumulative substances, as laid down by the REACH regulation (EC) No 1907/2006, section 1 of Annex XIII.

Thus, in consideration of all the available information discussed above, it can be concluded that the potential for bioaccumulation ofFatty acids, C16, C18 and C18-unsaturated, C12-15 alcohol (linear and branched), estersis low.

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within the CSR.

 

REFERENCES

Anders, M.W. (1989): Biotransformation and bioactivation of xenobiotics by the kidney. In: Hutson, D.H., Caldwell, J. & Paulson, G.D., eds, Intermediary Xenobiotic Metabolism in Animals, New York: Taylor & Francis, 81-97.

Barron, M.G., Charron, K.A., Stott, W.T., Duvall, S.E. (1999): Tissue carboxylesterase activity of rainbow trout. Environ Toxicol Chem 18(11): 2506-2511.

Barron, M.G., Mayes, M.A., Murphy, P.G., Nolan, R.J. (1990): Pharmacokinetics and metabolism of triclopyr butoxyethyl ester in coho salmon. Aquat Toxicol 16: 19-32.

Calbert, C.E., Greenberg, S.M., Kryder, G., Deuel, H.J. (1951): The digestibility of stearyl alcohol, isopropyl citrates, and stearyl citrates, and the effect of these materials on the rate and degree of absorption of margarine fat. Food Res 16(4): 294-305.

Danabas, D. (2011): Fatty acids profiles of rainbow trout (Oncorhynchus mykiss walbaum, 1792), fed with zeolite (Clinoptilolite). J Anim Plant Sci 21(3): 561-565.

De Wolf, W & Parkerton, T. (1999): Higher alcohols bioconcentration: Influence of biotransformation. American Chemical Society, Division of Environmental Chemistry. Preprints of extended abstracts presented at 217th ACS National Meeting Anaheim, CA, USA. 39(1), 101-103.

Dernekbasi, S. (2012): Digestibility and liver fatty acid composition of rainbow trout (Oncorhynchus mykiss) fed by graded levels of canola oil. Turk J Fish Aquat Sc 12;105-113.

Heymann, E. (1980): Carboxylesterases and amidases. In: Jakoby, W.B., Bend, J.R. & Caldwell, J., eds., Enzymatic Basis of Detoxication, 2nd Ed., New York: Academic Press, pp. 291-323.

Lassen, N., Estey, T., Tanguay, L., Pappa, A., Reimers, M.J., Vasiliou, V. (2005): Molecular cloning, baculovirus expression, and tissue distribution of the zebrafish aldehyde dehydrogenase 2. Drug Metab Dispos 33(5): 649-656.

Lech, J., Melancon, M. (1980): Uptake, metabolism, and deposition of xenobiotic chemicals in fish. EPA-600 3-80-082. U.S. Environmental Protection Agency, Duluth, MN, USA.

Lech, J.J. & Bend, J.R. (1980): Relationship between biotransformation and the toxicity and fate of xenobiotic chemicals in fish. Environ. Health Perspec. 34, 115-131.

Leinweber, F.J. (1987): Possible physiological roles of carboxylic ester hydrolases. Drug Metab Rev 18: 379-439.

Masoro, E.J. (1977): Lipids and lipid metabolism. Annu Rev Physiol 39: 301-321.

Murphy, P.G., Lutenske, N.E. (1990): Bioconcentration of haloxyfop-methyl in bluegill (Lepomis macrochirus Rafinesque). Environ. Intern. 16, 219-230.

Nilsson, G.E. (1988): A comparative study of aldehyde dehydrogenase and alcohol dehydrogenase activities in crucian carp and three other vertebrates: apparent adaptations to ethanol production. J Comp Physiol B 158(4): 479-85.

Nilsson, G.E. (1990): Distribution of aldehyde dehydrogenase and alcohol dehydrogenase in summer-acclimatized crucian carp, Carassius carassius L. J Fish Biol 36(2): 175-179.

OECD (2006): SIDS Initial Assessment Report For SIAM 22, TOME 1: SIAR; Long Chain Alcohols.

Reimers, M.J., Hahn, M.E., Tanquay, R.L. (2004): Two zebrafish alcohol dehydrogenases share common ancestry with mammalian class I, II, IV, and V alcohol dehydrogenase genes but have distinct functional characteristics. J Biol Chem 279(37): 38303-38312.

Rodger, C.A., Stalling, D.L. (1972): Dynamics of an ester of 2,3-D in organs of three fish species. Weed Sci 20: 101-105.

Sand, D.M., Rahn, C.H., Schlenk, H. (1973): Wax esters in fish: Absorption and metabolism of oleyl alcohol in the gourami (Trichogaster cosby). J Nutr 103: 600-607.

Sieber, S.M., Cohn, V.H., Wynn, W.T. (1974): The entry of foreign compounds into the thoracic duct lympho of the rat. Xenobiotica 4(5): 265-284.

Soldano, S., Gramenzi, F., Cirianni, M., Vittozzi, L. (1992): Xenobiotic-metabolizing enzyme systems in test fish - IV. Comparative studies of liver microsomal and cytosolic hydrolases. Comp Biochem Phys C 101(1): 117-123.

Stryer, L. (1994): Biochemie. 2nd revised reprint, Heidelberg; Berlin; Oxford: Spektrum Akad. Verlag.

Sund, H. & Theorell, H. (1963): Alcohol dehydrogenase. In: The enzymes.Vol. 7. 2nd ed. Boyer, P.D., Lardy, H., Myrbäck, K., eds. Academic Press, New York, 25-83.

Wheelock, C.E., Phillips, B.M., Anderson, B.S., Miller, J.L., Hammock, B.D. (2008): Applications of carboxylesterase activity in environmental monitoring and toxicity identification evaluations (TIEs). Reviews in Environmental Contamination and Toxicology 195: 117-178.

Yoshida, A., Rzhetsky, A., Hsu, L.C., Chang, C. (1998): Human aldehyde dehydrogenase gene family. Eur J Biochem 251(3): 549-57.