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Endpoint:
bioaccumulation: aquatic / sediment
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
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:
VALIDITY OF MODEL
The model is valid according to the following five OECD principles.

1. Defined Endpoint: Bioconcentration factor (BCF) and bioaccumulation factor (BAF) in fish
2. Unambiguous algorithm: Separate QSAR equations to predict log BAF, log BCF and log kM.
3. Applicability domain: The log BAF and BCF QSARs are applicable to non-ionized chemicals with a log Kow of <9. The log Kow and molecular weight (MW) applicability domain of the kM model are 0.31 to 8.7 and 68.08 to 959.17 respectively. The kM QSAR also includes 57 molecular substructures.
4. Statistical characteristics: For log Km model: a) internal performance; n = 421, r2 = 0.82, mean absolute error (MAE) = 0.38 log units, q2 = 0.75; b) External validation; n = 211, r2 = 0.73, MAE = 0.45 log units.
5. Mechanistic interpretation: The Arnot-Gobas BCF and BAF 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.

More detailed information is provided in the attached QMRF file.

ADEQUACY PREDICTION:
- Decanal is a non-ionised chemical with a logKow of 3.8 and MW of 156.27 and as such falls within the general applicability domain described above
- By manually checking the fragments used in the prediction (see attached BCFBAF v3.01 results file) with the structure of decanal, it is concluded that decanal also falls within the structural fragment domain of the kM model.
- The predicted BCF of 309 L/kg wet-wt (corrected to 5% lipid content, assuming a biotransformation rate of zero) is considered a conservative maximum estimate for decanal as this model was developed to fit upper bound BCF estimates. Moreover, decanal is readily biodegradable and it is generally accepted that readily biodegradable chemicals have a higher probability of being metabolised to a significant extent in exposed organisms than less biodegradable chemicals. In addition, an in vitro study for an analogue substance, dodecanal, shows that linear aldehydes are rapidly metabolised by trout liver S9 fractions. Thus decanal is likely to undergo metabolism in vivo leading to a reduced BCF value.
- The model results (including biotransformation rate estimates) are considered more relevant and reliable for the following two reasons: 1) decanal may be metabolised in fish based on its ready biodegradability status and an in vitro study for an analogue substance, dodecanal, 2) the predicted whole body primary biotransformation rate (kM), which is used as an input parameter, is considered reliable since decanal falls within both the descriptor and structural domain of the model.
- The BCF estimates (corrected to 5% lipid content, including biotransformation rate estimates) are 112L/kg wet-wt (upper trophic), 172 L/Kg wet-wt (mid trophic) and 190 L/Kg (lower trophic). The different estimates obtained from the three general trophic levels of fish probably reflect different assumptions regarding body size. To this end, it is considered most appropriate to use the highest value of 190 L/Kg wet-wt as a relevant and reliable conservative estimate of the BCF of decanal.

- More detailed information is provided in the attached QPRF file.
Principles of method if other than guideline:
BCFBAF v3.01 Arnot-Gobas BCF & BAF method for non-ionic chemicals in 3 general trophic levels of fish (lower, middle, upper). The model is available in the BCFBAF v3.01 programme, which is part of EpiSuite v4.10 available at http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm.
To estimate BAF and BCF (including biotransformation rate estimates), the whole body primary biotransformation rate constant kM (“normalized” for a 10 g fish at 15ºC) is estimated and converted to a Km value for the typical body size of an upper trophic, middle trophic and lower trophic fish.
For regulatory purposes, the predicted BCF values are corrected to a lipid content of 5%. This is the average lipid content of small fish used in the OECD 305 and the common lipid basis used for bioaccumulation assessment under REACH (ECHA Guidance R.7.10.4.1 and R.11.1.3.2).
Specific details on test material used for the study:
SMILES: O=CCCCCCCCCC
The SMILES and measured log Kow value of 3.8 were used as input for the BCFBAF v3.01 model prediction.
Type:
BCF
Value:
112 L/kg
Remarks on result:
other: upper trophic, including biotransformation rate estimates, corrected to 5% lipid content
Type:
BCF
Value:
172 L/kg
Remarks on result:
other: mid trophic, including biotransformation rate estimates, corrected to 5% lipid content
Key result
Type:
BCF
Value:
190 L/kg
Remarks on result:
other: lower trophic, including biotransformation rate estimates, corrected to 5% lipid content
Type:
BCF
Value:
309 L/kg
Remarks on result:
other: upper trophic, assuming a biotransformation rate of zero, corrected to 5% lipid content
Details on results:
PREDICTED VALUE (MODEL RESULT):
- Including biotransformation rate estimates:
Estimated Log BCF (upper trophic) = 2.380 (BCF = 239.8 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 2.380 (BAF = 239.8 L/kg wet-wt)
Estimated Log BCF (mid trophic) = 2.370 (BCF = 234.6 L/kg wet-wt)
Estimated Log BAF (mid trophic) = 2.372 (BAF = 235.5 L/kg wet-wt)
Estimated Log BCF (lower trophic) = 2.355 (BCF = 226.5 L/kg wet-wt)
Estimated Log BAF (lower trophic) = 2.363 (BAF = 230.5 L/kg wet-wt)

- Assuming a biotransformation rate of zero:
Estimated Log BCF (upper trophic) = 2.820 (BCF = 661.2 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 3.079 (BAF = 1199 L/kg wet-wt)

- Biotransformation Half-Life (HL): Estimated Log (HL) = -0.0507 (HL = 0.8898 days, normalised to 10 gram fish)

- Biotransformation Rate Constant (kM): 0.779 /day (10 gram fish)

- The BCFBAF v3.01 results file is attached

PREDICTED VALUE (COMMENTS):
The Arnot-Gobas model assumes default lipid contents of 10.7%, 6.85% and 5.98% for the upper, middle and lower trophic levels. For regulatory purposes, the predicted BCF values have been corrected to a lipid content of 5%. This is the average lipid content of small fish used in the OECD 305 and the common lipid basis used for bioaccumulation assessment under REACH (see sections R.7.10.4.1 and R.11.1.3.2 in the ECHA Guidance on information requirements and chemicals safety assessment, and section 5.4 of the attached QMRF).

- Estimated BCF, corrected to 5% lipid content (Including biotransformation rate estimates):
Estimated BCF (upper trophic) = (240 / 0.107 ) * 0.05 = 112 L/kg wet-wt
Estimated BCF (mid trophic) = (235 / 0.0685) * 0.05 = 172 L/kg wet-wt
Estimated BCF (lower trophic) = (227 / 0.0598) * 0.05 = 190 L/kg wet-wt

- Estimated BCF, corrected to 5% lipid content (Assuming a biotransformation rate of zero):
Estimated BCF (upper trophic) = (661/ 0.107) * 0.05 = 309 L/kg wet-wt)



Conclusions:
The substance decanal was predicted to have a BCF in the range of 112 to 309 L/kg wet-wt in fish (corrected to 5% lipid). The predicted values are being used as part of a consensus modelling approach to assess the bioaccumulation potential of decanal.
Endpoint:
bioaccumulation: aquatic / sediment
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
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:
VALIDITY OF MODEL
The model is valid according to the following five OECD principles.

1. Defined Endpoint: Bioconcentration factor (BCF) in fish
2. Unambiguous algorithm: Submodel linear regression QSAR for non-ionic substances with log Kow of 1.0 to 7.0; Log BCF = 0.6598 Log Kow - 0.333 + Σ correction factors
3. Applicability domain: applicable to non-ionized chemicals with a log Kow value in the range of 1 to 7. The molecular weight range of the training data set was 68.08 to 959.17.
4. Statistical characteristics: a) internal performance; n = 396, r2 = 0.792, Q2 = 0.78, std dev = 0.511, avg dev = 0.395. b) External validation; n = 158, r2 = 0.82, std dev = 0.59, avg dev = 0.46.
5. Mechanistic interpretation: The mechanistic basis is the assumption that bioconcentration is a thermodynamically driven partitioning process
between water and the lipid phase of the exposed organism and therefore can be modelled using n-octanol as a surrogate for biological lipids. The basis for identifying chemical classes for correction factors was empirical. However, certain correction factors can be rationalized on the basis of either known biotransformation reactions or likely reactivity.

More detailed information is provided in the attached QMRF file.

ADEQUACY PREDICTION:
- Decanal is a non-ionised chemical with a logKow of 3.8 and Mw of 156.27 and falls within the applicability domain described above.
- Decanal is readily biodegradable. It is generally accepted that readily biodegradable chemicals have a higher probability of being metabolised to a significant extent in exposed organisms than less biodegradable chemicals. In addition, an in vitro study for an analogue substance, dodecanal, shows that linear aldehydes are rapidly metabolised by trout liver S9 fractions. Therefore, decanal may have a lower BCF than that predicted using the BCFBAF v3.01 regression QSAR which is based only on logKow (i.e. no correction factors were applicable for decanal).

- More detailed information is provided in the attached QPRF file.
Principles of method if other than guideline:
BCFBAF v3.01 regression-based BCF estimate for non-ionic chemicals with a log Kow of 1.0 to 7.0.
Specific details on test material used for the study:
The following were used as input for the BCFBAF model:
- SMILES: O=CCCCCCCCCC
- Measured log Kow value of 3.8 (OECD 117 study, GLP, reliability 1).
Type:
BCF
Value:
149 L/kg
Details on results:
PREDICTED VALUE (MODEL RESULT):
- Decanal was predicted to have a log BCF of 2.174 (BCF = 149.4 L / kg wet-wt).
- No correction factors were applicable for Decanal.
- The BCFBAF v3.01 results file is attached


Reported statistics:
n = 396, r2 = 0.792, Q2 = 0.78, std dev = 0.511, avg dev = 0.395
Conclusions:
The substance decanal was predicted to have a log BCF of 2.174 (BCF = 149 L / kg wet-wt) in fish. The prediction is being used as part of a consensus modelling approach to assess the bioaccumulation potential of decanal.
Endpoint:
bioaccumulation: aquatic / sediment
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:
QSAR is for slowly metabolized chemical, whereas decanal is expected to be rapidly metabolised in fish.
Justification for type of information:
VALIDITY OF MODEL
The linear model developed by Veith et al (1979) is based on a training set of organic chemicals with a log Kow range of 1 to 6.91. It is presented in the EU TGD as an example of a QSAR model that can be used to predict the BCF for fish for chemicals with a log Kow of 2 to 6. It is directly implemented in EUSES for assessing secondary poisoning. The model is also presented in the ECHA guidance, Chapter R.7C as a commonly used QSAR for predicting fish BCFs for neutral, non ionized chemicals with a log Kow of 1 to 5.5. The model is valid according to the following five OECD principles.

1. Defined Endpoint: Bioconcentration factor (BCF) in fish
2. Unambiguous algorithm: linear regression QSAR, Log BCF = 0.85 Log Kow - 0.70
3. Applicability domain: applicable to neutral, non-ionized slowly metabolized chemicals with a log Kow value of < 6.
4. Statistical characteristics: number in data set (n) = 59, correlation coefficient (r2) = 0.897
5. Mechanistic interpretation: The mechanistic basis is the assumption that bioconcentration is a thermodynamically driven partitioning process
between water and the lipid phase of the exposed organism and therefore can be modelled using n-octanol as a surrogate for biological lipids.

More detailed information is provided in the attached QMRF file.

ADEQUACY PREDICTION:
- Decanal is a neutral, non-ionised chemical with a measured logKow of 3.8 and as such falls within the applicability domain described above.
- Decanal is readily biodegradable. It is generally accepted that readily biodegradable chemicals have a higher probability of being metabolised to a significant extent in exposed organisms than less biodegradable chemicals. In addition, an in vitro study for an analogue substance, dodecanal, shows that linear aldehydes are rapidly metabolised by trout liver S9 fractions. Therefore, decanal is expected to have a lower BCF than that predicted using the QSAR developed by Veith et al (1979), which is based only on log Kow and slowly or non-metabolised substances.

More detailed information is provided in the attached QPRF file.
Principles of method if other than guideline:
Linear model to estimate BCF for neutral, non-ionized chemicals with a log Kow of 1.0 to 6.0.
Specific details on test material used for the study:
The measured log Kow value of 3.8 (OECD 117 study, GLP, reliability 1) was used as the input descriptor for the linear BCF model.
Type:
BCF
Value:
339 L/kg
Details on results:
PREDICTED VALUE (MODEL RESULT):
- Decanal was predicted to have a log BCF of 2.35 (BCF = 339 L / kg wet-wt) using the equation Log BCF = 0.85 Log Kow - 0.70. The measured log Kow of 3.8 was used as input.


Reported statistics:
R2 = 0.897 (correlation coefficient)
N = 59 (number of independent measurements)
Conclusions:
The substance decanal was predicted to have a BCF of 339 L/kg in fish. The predicted value is being used as part of a consensus modelling approach to assess the bioaccumulation potential of decanal. It is considered a conservative maximum worst-case fish BCF. Decanal is readily biodegradable and it is generally accepted that readily biodegradable chemicals have a higher probability of being metabolised to a significant extent in exposed organisms than less biodegradable chemicals. In addition, an in vitro study for an analogue substance, dodecanal, indicates that linear aldehydes are rapidly metabolised by trout liver S9 fractions. Therefore, decanal is expected to have a lower BCF than that predicted using the QSAR developed by Veith et al (1979), which is based only on log Kow and a training set of chemicals that are not expected to be metabolised.
Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
other: in vitro experimental data for the analogue substance dodecanal
Adequacy of study:
supporting study
Study period:
10 July to 24 July 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: In vitro data, generated from a pre-validated method, for the analogue substance dodecanal is considered reliable and provides evidence for a reduced BCF due to metabolism for linear aliphatic aldehydes.
Justification for type of information:
The analogue substance (dodecanal) and target substance (decanal) are expected to have similar metabolic potential as a result of their similar chemical structure, which is supported by the fact that both substances are profiled by the QSAR Toolbox 3.4.0.17 as having the same "Bioaccumulation - metabolism alerts": Aldehyde [-CHO], -CH2- [linear], Linear C4 terminal chain [CCC-CH3] and Methyl [-CH3]. The "Bioaccumulation - metabolism half-lives" profiler in the QSAR Toolbox assigns chemicals into categories of expected biotransformation rates. Dodecanal and decanal were classified respectively as moderate (half-life = 1-10 days) and fast (half-life = 0.1-1 day), indicating that decanal may be biotransformed more rapidly than dodecanal. The predicted half-life is obtained from the "Whole Body Primary Biotransformation Rate Estimate" model in the BCFBAF programme. Using the BCFBAF v3.01 model directly in EPI Suite 4.1 gives a predicted half-life of 0.8668 days for decanal and 1.645 days for dodecanal. The slight difference in the predicted rate is attributed to the number of -CH2- groups, the estimated log Kow and molecular weight. In vitro data, generated from a pre-validated method, is available for the analogue substance dodecanal (lauraldehyde). Input of this data into the IVIVE (in-vitro to in vivo extrapolation) model generates reduced BCF estimates of 159 to 194 L/kg for dodecanal compared to 3972 when no metabolism is assumed. This provides evidence for a reduced BCF due to metabolism for linear aliphatic aldehydes and supports the use of BCF QSAR models that take into account metabolism.
Principles of method if other than guideline:
The bioaccumulation potential is estimated from an in vitro fish liver S9 standardised assay, pre-validated by a consortium under the coordination of HESI/ILSI (Johanning et al, 2012). In vitro metabolic stability is determined by monitoring the disappearance of the test item as a function of time. The rate of substance depletion may be used as input into an "in vitro - in vivo" extrapolation (IVIVE) model to generate an estimated BCF value for a "standardised fish" (one that weighs 10g, has a 5% lipid content, and is living at 15'C) (Nichol et al, 2006).
GLP compliance:
no
Specific details on test material used for the study:
Details on properties of analogue material
SMILES: O=CCCCCCCCCCCC
Measured log Kow: 4.9
Test organisms (species):
Oncorhynchus mykiss (previous name: Salmo gairdneri)
Details on test organisms:
Rainbow Trout (Oncorhynchus mykiss) liver S9 fractions were purchased from Lifetechnologies (formerly CellzDirect/Invitrogen) (“Pooled Male Hatchery Rainbow Trout Liver S9”; product code CZDTRS9PL, Lot# TR015) and stored at -80°C. The average body weight of the fish used for the preparation of S9 fractions was 800 g.
Route of exposure:
other: in vitro assay
Details on test conditions:
Initially, a range finding experiment was performed to determine the optimal incubation times to be used in the main experiments.

A stock solution of Aldehyde C12 Lauric (10 mM) was prepared freshly in methanol and diluted in water resulting in 10 μM solutions. Stock solutions of cofactors were prepared freshly in 0.1 M potassium phosphate buffer, pH 7.8. Alamethicin was dissolved in methanol (5 mg/ml; aliquots stored at -80°C) and diluted in buffer (250 μg/ml).

Rainbow trout liver S9 fractions were thawed on ice. All incubations were performed in potassium phosphate buffer at pH 7.8 (0.1 M) in Hirschmann glass tubes incubated at 12°C in a Thermomixer (Eppendorf) at 700 rpm. Active S9 fractions protein or heat inactivated protein as control (1 mg/ml) was preincubated on ice with alamethicin (final concentration: 25 µg/ml). Alamethicin is a pore-forming peptide antibiotic which permeabilises microsomal membranes and activates glucuronidation by allowing free transfer of UDPGA and glucuronide product across the membrane. After addition of cofactors for Phase I (NADPH, Nicotinamide adenine dinucleotide 2′-phosphate reduced) and Phase II enzymes (UDPGA, Uridine 5′-diphosphoglucuronic acid; PAPS, Adenosine 3′-phosphate 5′-phosphosulfate; GSH, reduced L-glutathione), the reaction was initiated by addition of the test substance. Final concentrations of cofactors, protein and test substance are listed in the table in the section entitled "any other information on materials and methods incl. tables".

In the range finding experiment, Aldehyde C12 Lauric (1 µM) was incubated in presence of 1 mg/ml active S9 protein and cofactors in duplicate for up to 120 minutes. As controls, the test substance was incubated in presence of heat inactivated S9 protein (1 mg/ml) and cofactors or with active S9 protein in absence of any cofactors. Reactions were stopped at 0, 30 and 120 minutes incubation by addition of acetonitrile (200 µl) containing methyl laurate (1 µM) as internal standard to the Hirschmann tubes. Samples were extracted with MTBE (200 µl) in the same tubes by vortexing for 30 seconds, centrifuged to allow a better phase separation and separation of protein (Eppendorf centrifuge, 12 000 rpm, 5 min, room temperature) and subjected to GC-MS analysis.

In the two independent main experiments, Aldehyde C12 Lauric (1 µM) was incubated in presence of 0.25 mg/ml active S9 protein and cofactors in triplicate for up to 10 minutes (1st main experiment) or 2 minutes (2nd main experiment) as described above. Reactions were stopped at time 0, 2.5, 5,7.5 and 10 minutes (1st main experiment) or at time 0, 0.5, 1, 1.5 and 2 minutes (2nd main experiment). As control, the test substance was incubated in presence of heat inactivated S9 protein (0.25 mg/ml) and cofactors for 0 minutes and 10 or 2 minute, and in presence of active S9 protein in absence of any cofactors for 10 or 2 minutes, respectively (1st and 2nd main experiment). Reactions were stopped and extracted as described above.
Type:
other: % decrease of parent
Value:
79.7 other: %
Remarks on result:
other: within 2 minutes using 0.25mg/ml fish liver S9 protein; analogue substance, dodecanal
Type:
other: rate of substance depletion
Value:
21.49 other: /h
Remarks on result:
other: input into an in vitro - in vivo extrapolation model results in a reduced BCF of 159-194 compared to 3972 when no metabolism is assumed for the analogue substance, dodecanal
Details on results:
An almost complete, very rapid decrease of Aldehyde C12 Lauric was observed within 30 minutes incubation (91.7% decrease; 92.0% decrease in 120 minutes) in the range finding experiment with active S9 protein (1 mg/ml). In the absence of any cofactors added, a decrease of Aldehyde C12 Lauric was also observed (89.5% decrease within 120 minutes). A slight decrease of Aldehyde C12 Lauric was observed in the control samples with heat inactivated protein (1 mg/ml) (6.3% decrease within 120 minutes) (Appendix 2).
Thus, incubations were carried in the presence of lower concentrations of S9 protein (0.25 mg/ml) and for shorter incubation periods (up to 10 minutes in the 1st main experiment). However, enzymatic turnover was still very rapid and a 64.6% decrease of Aldehyde C12 Lauric was observed already in 2.5 minutes (Fig. 1a). Thus, the experiment was repeated using an even shorter incubation period (2nd main experiment). Enzymatic turnover of Aldehyde C12 Lauric was very rapid in presence of cofactors: 79.7% decrease was observed in 2 minutes (Fig. 1b). A slower turnover of Aldehyde C12 Lauric was found with active S9 protein in the absence of cofactors (36.5% decrease in 2 minutes). A similar, slow decrease of the parent was observed with inactive S9 protein (27.7% decrease in 2 minutes).

The in vitro intrinsic clearance was calculated from the log-transformed measured concentrations of parent compound as a function of time for Aldehyde C12 Lauric: 135.68 ml/h/mg protein (Appendix 3). Since there was a significant, but slower decrease of the parent in presence of inactive S9 protein a corrected in vitro intrinsic clearance was calculated by subtraction of the putative abiotic decrease: 85.98 ml/h/mg protein. This putative abiotic decrease followed first order kinetic and was slower in the range finding experiment with a higher concentration of inactive protein. We do not know the reason for this difference. Causes for the putative abiotic decrease could be due to solubility issues, abiotic reaction with proteins, or most likely due to abiotic oxidation to lauric acid. This effect was not further studied, since the difference in the two enzymatic turnover rates did have only a minor impact on the refined BCF estimate.

The average reaction rates were used for the calculation of the refined BCF estimates: 33.92/h and 21.49/h (corrected rate). For details see Table 1 in the section "Any other information on results incl. tables").

Table 1. Selected parameters and refined BCF estimates calculated with the "in vitro–in vivo" extrapolation model.1 

 

 

Aldehyde C12 Lauric (initial rate)

Aldehyde C12 Lauric (corrected rate)2

Parameter

fu calc3

fu=1.04

fu calc3

fu=1.04

Input parameter: in vitro data

 

 

 

 

S9 concentration (CS9) (mg/mL)

0.25

0.25

0.25

0.25

Reaction rate (Rate) (1/h)

33.92

33.92

21.49

21.49

Input Parameter

 

 

 

 

LogKow

4.9

4.9

4.9

4.9

 

 

 

 

 

Calculated Parameters

 

 

 

 

Partitioning based BCF, assuming no metabolism (BCFp)

3972

3972

3972

3972

In vitrointrinsic clearance (CLIN VITRO,INT) (ml/h/mg protein)

167.0

167.0

105.8

105.8

In vivointrinsic clearance (CLIN VIVO,INT) (l/d/kg fish)

3007

3007

1905

1905

Scaled clearance for 10 g fish (CLIN VIVO,INT,10) (l/d/kg fish)

 

8992

8992

5697

5697

Corrected clearance for 10 g fish (CLIN VIVO,INT,10,CORR) (l/d/kg fish)

22481

22481

14243

14243

Hepatic clearance (CLH) (L/d/kg fish)

21.4

24.5

19.9

24.5

Whole-body metabolism rate (kMETAB) (1/d)

3.3

3.7

3.0

3.7

BCF,on a total conc. basis, w/out lipid norm.(BCFTOT) (l/kg)

181

159

194

159

1J. Nichols, personal communication, based on a previous publication from Nichol [2006] (version: “S9spreadsheet_4202012_standardfish_consensusver-1.xlsx”)2corrected rate: Enzymatic turnover rate of Aldehyde C 12 was corrected by subtracting the putative abiotic decrease of the parent in presence of inactive S9 protein

3fu, plasma binding correction term; “fu calc”, hepatic clearance is calculated taking into account a theoretically calculated difference betweenin vitroandin vivobinding

4fu, plasma binding correction term; “fu = 1.0”, hepatic clearance is calculated assuming equal in vitro and in vivo binding by setting fu = 1.0

The model version used was “S9spreadsheet_4202012_standardfish_consensusver-1.xlsx”. The S9 in vitro substrate depletion rate is converted to a whole-fish metabolism rate constant (Kmetab) using a number of extrapolation and scaling factors. The estimated Kmetab value is then used to refine the partitioning based BCF model prediction. A binding term, fu, is used to correct for the difference in free chemical concentration between in vivo and the in vitro system. Two assumptions are possible: 1) fu can be calculated as the ratio of predicted free fractions in plasma and in the in vitro system using logKow-based algorithms, or 2) binding in vitro and in vivo can be assumed to be equal ( fu = 1.0). The refined BCF has been estimated using both approaches. The partition based BCF (assuming no metabolism) and the refined BCF (incorporating biotransformation rate estimates) for Aldehyde C12 Lauric have been estimated.

Conclusions:
Rapid metabolic turnover by trout liver S9 fractions was observed for aldehyde C12 Lauric, indicating that linear aliphatic aldehydes are expected to be metabolised in vivo. The reaction rate (1/h) was calculated from the log-transform measured concentrations of the parent compound as a function of time: 33.92/h. In addition, a corrected rate was calculated by subtracting the first order putative abiotic decrease: 21.49/h. Both values were used as input into an in vitro - in vivo extrapolation model to generate reduced BCF estimates of 159 to 194 l/kg. In contrast, the estimated BCF for aldehyde C12 Lauric assuming no metabolism was 3972. The in vitro study provides evidence for a reduced BCF due to metabolism for linear aliphatic aldehydes.

Description of key information

Bioaccumulation tests are waived based on the fact that the available information is deemed sufficient for classification purposes, the PBT assessment and the chemical safety assessment.

Key value for chemical safety assessment

BCF (aquatic species):
190 L/kg ww

Additional information

According to REACH Annex IX, information on bioaccumulation in aquatic species, preferably fish, is required for substances manufactured or imported in quantities of 100 t/y or more unless the substance has a low potential for bioaccumulation (for instance a log Kow ≤ 3). However, REACH aims to reduce animal testing where possible and according to the Integrated Testing Strategy (ITS, Figure R.7.10-2) in ECHA Guidance R.7c (Endpoint specific guidance), all available information should be assessed before further testing for bioaccumulation is performed.

For classification purposes an experimentally derived high quality Log Kow value is suitable when a measured BCF on an aquatic organism is not available. Decanal has a measured log Kow of 3.8. This is below the CLP Regulation EC 1272/2008 cut-off value of 4. Thus Decanal is not considered to have the potential to bioconcentrate for EU CLP classification purposes.

For the PBT and vPvB assessment a screening criterion has been established, which is log Kow greater than 4.5. According to ECHA Guidance Chapter R.11, the assumption behind this is that the uptake of an organic substance is driven by its hydrophobicity. For organic substances with a log Kow value below 4.5 it is assumed that the affinity for the lipids of an organism is insufficient to exceed the B criterion, i.e. a BCF value of 2000 L/kg (based on wet weight of the organism, which refers to fish in most cases). Decanal has a measured log Kow of 3.8, which is below the B screening criterion.

For the chemical safety assessment, a reliable estimated BCF value may be used. A consensus modelling approach was employed to predict bioconcentration factors in fish.The experimentally determined high quality Log Kow value of 3.8 was used as an input term in three commonly used and scientifically valid QSARs. The estimated BCF values ranged from 112 to 339.

The BCF estimates of 309 L/kg and 339 L/kg obtained respectively from the Arnot-Gobas BCF QSAR (assuming a biotransformation rate of zero) and the linear model developed by Veith et al (1979) are considered conservative and worst-case.The Arnot-Gobas BCF QSAR (assuming a biotransformation rate of zero) was developed to fit upper bound BCF observations while the linear model developed by Veith et al (1979) is based on a limited data set of 56 chemicals, which are not expected to be metabolised.

Decanal is readily biodegradable and it is generally accepted that readily biodegradable chemicals have a higher probability of being metabolised to a significant extent in exposed organisms than less biodegradable chemicals. In addition, an in vitro study for an analogue substance, dodecanal, shows that linear aldehydes are rapidly metabolised by trout liver S9 fractions. As such the Arnot-Gobas BCF QSAR(including biotransformation rate estimates) model predictions of 112 L/kg (upper trophic), 172 L/kg (mid trophic) and 190 L/kg (lower trophic) are considered to be more relevant and reliable. The BCFBAF regression-based model predicts a similar BCF value of 149 L/kg. Although this regression model does not include biotransformation estimates (no correction factor was applied for decanal) it was developed from a large data set of 396 diverse chemical and as such has a tendency to arrive at an average BCF value. The highest value of 190 L/kg from the Arnot-Gobas BCF QSAR(including biotransformation rate estimates) has been chosen as a relevant and reliable conservative estimate for risk assessment purposes. Using this predicted BCF value, the chemical safety assessment does not show a need for further refinement.