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Bioaccumulation: aquatic / sediment

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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:
other: The QSAR result is considered reliable according to OECD principles. The QSAR model is scientifically valid and benzyl salicylate falls within its applicability domain.
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
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.
Type:
BCF
Value:
202 L/kg
Remarks on result:
other: model result
Type:
BCF
Value:
311 L/kg
Remarks on result:
other: model result adjusted based on the predicted and experimental data for the analogue substance, cyclohexyl salicylate
Details on results:
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.

PREDICTED VALUE (MODEL RESULT):
- Benzyl salicylate was predicted to have a log BCF of 2.306 (BCF = 202 L/kg wet-wt).
- No correction factors were applicable for benzyl salicylate
- The BCFBAF v3.01 results file is attached

CONSIDERATION ON STRUCTURAL ANOLOGUES:
- A valid experimental BCF value of 600-900 L/Kg is available for cyclohexyl salicylate (see key study endpoint for full details)
- The predicted BCF for cyclohexyl salicylate using the BCFBAF v3.01 regression based QSAR is 586 (the BCFBAF v 3.01 results file is attached).
- The experimental and predicted values are in close agreement supporting the applicability of the QSAR regression to salicylate esters and the reliability of the BCF prediction for benzyl salicylate

ADEQUACY OF PREDICTION:
- Benzyl salicylate is a non-ionised chemical with a logKow of 4 and MW of 228.25 and falls within the applicability domain described above.
- Taking into consideration the experimental and predicted values for the structural analogue, a correction factor of 1.54 (900/586) may be applied to the benzyl salicylate predicted value of 202 L/kg to give a conservative BCF estimate for benzyl salicylate of 311 L/kg.

More detailed information is provided in the attached QPRF file.
Reported statistics:
Reported statistics
n = 396, r2 = 0.792, Q2 = 0.78, std dev = 0.511, avg dev = 0.395
Conclusions:
The BCFBAF v3.01 regression-based QSAR model gives a reliable estimated BCF value for benzyl salicylate of 202 L/Kg. The model result is adjusted to 311 L/kg after taking into consideration predicted and experimental values of the analogue substance, cyclohexyl salicylate.
Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
A valid BCF is available for the analogue substance, cyclohexyl salicylate (GLP study in accordance with EU Method C.13). As the study is being used in a read-across approach, it is rated reliability 2 (the maximum for read-across). The read-across is an analogue approach based on the hypothesis that benzyl salicylate (the registration substance) and cyclohexyl salicylate (source substance) have similar aquatic bioaccumulation potential as a result of structural similarity, expected similar metabolic potential in fish and limited differences in lipophilicity (as modelled by log Kow).
Qualifier:
according to
Guideline:
EU Method C.13 (Bioconcentration: Flow-through fish test)
Version / remarks:
EEC-Directive 79/831, Annex V, Part C
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 305 E (Bioaccumulation: Flow-through Fish Test)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Details on properties of test surrogate or analogue material (migrated information):
PHYSICO-CHEMICAL PROPERTIES
- Vapour pressure: 0.055Pa at 20'C (Gas Saturation method, data submitter is data owner)
- Water solubility: 5.3mg/l at 20'C (OECD 105, data submitter is data owner)
- log Pow: 4.7 (OECD 117, data submitter is data owner)

OTHER PROPERTIES (relevant for this endpoint)
- Ready biodegradability: Readily biodegradable - 87% biodegradation after 28 days with the 10-day window fulfilled (OECD 301F, data submitter is data owner)
Radiolabelling:
yes
Details on sampling:
Fish were sampled from the two basins at regular intervals to measure the concentration of 14C-labelled test substance in the tissues.
Vehicle:
yes
Details on preparation of test solutions, spiked fish food or sediment:
PREPARATION AND APPLICATION OF TEST SOLUTION
- Method: automatic dosing system adding proportionate volumes of test substance solution and dilution water to the mixing vessel; the mixing ratio of test substance concentrate and dilution water is 1:100
- Controls: not required since 14C-labelled test material was used
- Chemical name of vehicle (organic solvent, emulsifier or dispersant): ethanol
- Concentration of vehicle in test medium (stock solution and final test solution(s) at different concentrations and in control(s)): 100-times concentrates contained 0.1 mL ethanol per one concentrate
- Evidence of undissolved material (e.g. precipitate, surface film, etc): no
Test organisms (species):
Danio rerio (previous name: Brachydanio rerio)
Details on test organisms:
TEST ORGANISM
- Common name: zebra fish
- Source: West Aquarium GmbH
- Age at study initiation (mean and range, SD): not given
- Length at study initiation (lenght definition, mean, range and SD): about 3 cm
- Weight at study initiation (mean and range, SD): 0.219 ± 0.05 g for fish used for lipid content determination
- Weight at termination (mean and range, SD): 0.295 ± 0.07 g for fish used for lipid content determination
- Health status: low mortality of < 1% during the last two weeks before study start
- Description of housing/holding area: test basins with 6 L volume (minimal volume 3 L), about 10 water changes per day, automatic cleaning and removal of food residues and faeces, constant temperature of 23 °C ± 1 °C

FEEDING DURING STUDY
- Food type: Altromin fish food N-1324
- Amount: about 2% of actual fish wet weight
- Frequency: automatically

ACCLIMATION
- Acclimation period: fish were delivered about one month before study start, 2 days before start the fish were placed in the test basins
Route of exposure:
aqueous
Test type:
flow-through
Water / sediment media type:
natural water: freshwater
Total exposure / uptake duration:
28 d
Total depuration duration:
14 d
Hardness:
not reported
Test temperature:
Basin 1: 23 °C ± 0.13 °C
Basin 2: 23.1 °C ± 0.12 °C
pH:
Basin 1: 7.51 ± 0.07
Basin 2: 7.50 ± 0.08
Dissolved oxygen:
Basin 1: 79.9% of saturation ± 8.3%
Basin 2: 79.1% of saturation ± 9.3%
TOC:
not reported
Salinity:
not applicable
Details on test conditions:
TEST SYSTEM
- Type: open
- Material, size, headspace, fill volume: glass vessels, 6 L fill volume
- Aeration: continuous aeration
- Type of flow-through (e.g. peristaltic or proportional diluter): proportional diluter
- Renewal rate of test solution (frequency/flow rate): 10 renewals per day
- No. of organisms per vessel: Basin 1 contained 55 and Basin 2 40 fish
- No. of vessels per concentration (replicates): 1
- Biomass loading rate: 3 g fish wet weight/L

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: tap water filtered through active carbon
- Composition of test medium: not reported

OTHER TEST CONDITIONS
- Adjustment of pH: no
- Photoperiod: not reported
- Light intensity: not reported
Nominal and measured concentrations:
Nominal concentrations: 1 and 10 µg/L (Basin 1 and Basin 2, respectively)
Mean measured concentrations (measured with 14C activity determination) were 1.05 µg/L and 8.5 µg/L.
Reference substance (positive control):
no
Lipid content:
13.92 %
Time point:
start of exposure
Lipid content:
9.35 %
Time point:
end of exposure
Type:
BCF
Value:
1 136
Basis:
whole body w.w.
Time of plateau:
5 d
Remarks on result:
other: total radioactivity, read-across substance
Remarks:
Conc.in environment / dose:1 µg/L
Type:
BCF
Value:
1 170
Basis:
whole body w.w.
Time of plateau:
5 d
Remarks on result:
other: total radioactivity, read-across substance
Remarks:
Conc.in environment / dose:10 µg/L
Type:
BCF
Value:
600 - 900
Basis:
other: TLC analysis of ethanol extracts of fish showed the greatest portion of the extracted radioactivity (ca. 50 to 75%) was the unchanged test substance. From the analytical determinations, a BCF of 600 to 900 can be calculated for the parent substance.
Remarks on result:
other: parent specific analysis, read-across substance
Type:
BCF
Value:
120 - 180
Remarks on result:
other: Estimated, benzyl salicylate. Adjustment factor of 5 applied to the read-across substance values to take into account differences in log Kow
Elimination:
yes
Parameter:
DT50
Depuration time (DT):
2.5 d
Details on kinetic parameters:
Not calculated, but the depuration half-life was clearly below 3 days in the study
Metabolites:
Not investigated
Results with reference substance (positive control):
Not applicable
Details on results:
ANALOGUE APPROACH JUSTIFICATION: - See attached "Aquatic Bioaccumulation Read-Across Justification for Benzyl Salicylate" document for full details. In summary, the read-across is an analogue approach based on the hypothesis that the target substance (benzyl salicylate) and source substance (cyclohexyl salicylate) have similar aquatic bioaccumulation potential as a result of structural similarity, expected similar metabolic potential in fish and limited differences in lipophilicity (as modelled by log Kow). Important considerations for the use of the read-across are:
- The target and source substance are structurally closely related as both are alkyl 2-hydroxybenzoate esters. The only structural difference is the nature of the alkyl group (benzyl versus cyclohexyl), which is not expected to have a significant effect on the aquatic bioaccumulation potential of the two substances.
- The source and target substance are both mono-constituent substances with typical purities => 99.7%. They do not contain any impurities that are expected to affect their bioaccumulation properties.
- In applying the read-across two important aspects have been considered, i.e. the metabolic activity and the lipophilicity of both substances.
METABOLIC ACTIVITY: Both substances are expected to have similar metabolic potential in fish which is supported by the following indicators (see also table 1)
- Both substances are readily biodegradable and thus are likely to be rapidly metabolised in organisms.
- They share common “bioaccumulation metabolism alert substructures” as profiled in the BCFBAF v3.1 whole body primary biotransformation rate constant model for fish. Both substances contain an “ester”, “aromatic alcohol” and "benzene" structural fragment, which are considered potential sites of metabolic attack as indicated by the negative coefficient values. Benzyl salicylate also contains an “unsubstituted phenyl group” which, according to the model, may further increase the capacity of benzyl salicylate for biotransformation. As such benzyl salicylate may have a higher potential for metabolism than cyclohexyl saliclyate, making the read-across a conservative one.
LIPOPHILICTY: There is a limited difference in the log Kow values of the two substances. Since benzyl salicylate has a lower measured logKow value than the source substance (4.0 compared to 4.7 ) direct read-across represents a worst-case scenario (i.e. benzyl salicylate is likely to have a lower in vivo BCF value).

CORRECTED BCF VALUE:
- The BCF value of a substance is generally positively correlated with its lipophilicity (as modelled by log Kow). ECHA guidance R.7.10.3.2 advocates the application of a correction factor as long as the difference in log Kow is limited and gives the following example: “if the substance to be evaluated has one methyl group more than the compound for which a BCF value is available, the log Kow will be 0.5 higher and the estimated BCF from read-across is derived from the known BCF multiplied by a factor of 10 to the power of 0.5 “.
- Benzyl salicylate has a measured log Kow value of 4.0. Cyclohexyl salicylate has a log Kow value that is 0.7 log units higher. Therefore, an adjustment factor of 10 to the power of 0.7 (i.e. 5.0) has been applied to the cyclohexyl salicylate measured BCF value of 600-900 L/kg to give a reasonable worst-case estimate for benzyl salicylate of 120-180 L/kg.

Table 1: Summary of indicators of the bioaccumulation potential for benzyl salicylate (target substance) and cyclohexyl salicylate (source substance) that support the read-across approach.

 

Indicator of bioaccumulation potential

Benzyl Salicylate

Cyclohexyl Salicylate

Ready Biodegradability

readily

readily

Bioaccumulation – metabolism alerts

(BCFBAF v3.01). 

Number of each fragment in substance

Fragment description

Coefficient(1)

 

 

Ester [-C(=O)-O-C]

-0.7605

1

1

Unsubstituted phenyl group [C6H5]

-0.7605

1

0

Aromatic alcohol [OH]

-0.4727

1

1

Benzene

-0.4277

1

1

-CH- [cyclic]

0.0126

0

1

-CH2- [cyclic]

0.0963

0

5

Aromatic H

0.2664

4

4

Partition coefficient N-Octanol/water (Log Kow)(2)

4.0

4.7

BCFBAF v3.01 QSAR prediction

 

 

Regression-based BCF estimate, L/Kg

202

311(3)

586

Measured BCF, L/kg

 

600-900

1) Descriptors with positive signs reflect a general reduced capacity for biotransformation and negative values reflect a general increased capacity for biotransformation; 2) Determined according to OECD 107 guideline; 3) adjusted based on the predicted and experimental data for the analogue substance, cyclohexyl salicylate

Validity criteria fulfilled:
yes
Remarks:
The lipid content of fish at the end of the test was slightly lower than generally acceptable
Conclusions:
The bioconcentration factor for cyclohexyl salicylate (analogue substance) was determined by using 14C-labelled test material. The experimentally determined values at test concentrations of 1 and 10 µg/L were 1136 and 1170, respectively based on total radioactivity. Analytical determination of the test substance concentrations in ethanol extracts of fish tissue by thin layer chromatography gave BCF values ranging from 600 to 900.
Benzyl salicylate is less lipophilic than cyclohexyl salicylate. The difference in log Kow is 0.7 log units. Therefore, in line with ECHA guidance R.7.10.3.2 an adjustment factor of 10 to the power of 0.7 (i.e. 5.0) has been applied to the cyclohexyl salicylate measured BCF value of 600-900 L/kg to give a reasonable worst-case estimate for benzyl salicylate of 120-180 L/kg.
The read-across is being used in a weight-of-evidence approach along with a reliable QSAR (see separate endpoint record for details). Both methods estimate that the BCF of benzyl salicylate is < 500 L/kg. Thus the approach is considered adequate for the purpose of classification and labellng and/or risk assessment.
Executive summary:

The bioaccumulation potential of the radiolabelled test substance Cyclohexyl salicylate [Carboxyl 14-C] was determined under GLP in accordance with EU Method C.13 under flow-through conditions. Zebra fish (Danio rerio) of about 3 cm length and 0.2 to 0.3 g weight were used in the experiment. The lipid content of fish was about 14% at the begin of the study and decreased to 9.4% at the end of the study. This decrease was slightly above the generally acceptable decrease of 25%. Two test concentrations of nominal 1 and 10 µg/L were used in the accumulation phase over a period of 28 days. The measured time-weighted average concentrations were 1.05 and 8.5 µg/L, respectively. Fish were sampled at regular intervals, put into liquid nitrogen, weighed and measured. The animals were burned in an oxidiser and the concentration of radiolabelled substance was measured with a liquid scintillation counter. The plateau was reached quickly after a few days (less than 5). The experimentally determined BCF values obtained with the test concentrations of 1 and 10 µg/L were 1136 and 1170, respectively.

After 28 days, a 14-day depuration phase was started by placing the test fish in basins with dilution water not containing the test substance. A rapid depuration was seen and the corresponding depuration half-life was clearly less than 3 days. Analytical determination of the test substance concentrations in ethanol extracts of fish tissue by thin layer chromatography gave BCF values ranging from 600 to 900.

Overall, it can be concluded that the substance Cyclohexyl salicylate tends to rapidly bioconcentrate in the zebra fish and that a plateau is reached quickly within less than 5 days. However, also the depuration is very rapid and the depuration half-life is clearly less than 3 days. The experimentally determined bioconcentration factors are clearly below the threshold limit value of 2000 indicating bioaccumulation potential. The substance therefore should be considered as not bioaccumulative.

Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
April, 2020
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
To address BCF testing on fish as part of the REACH registration of benzyl salicylate (target substance) it is proposed to read‐across to cyclohexyl salicylate (source substance). This is an analogue approach for which the read‐across hypothesis is based on different compounds which have the same type of effect(s). It is covered by scenario 2 in the ECHA Read‐Across Assessment Framework [RAAF, ECHA2015].

This document provides scientific justification for the proposed read‐across and shows that the
source and target substance have similar aquatic bioaccumulation potential as a result of structural similarity, expected similar metabolic potential in fish and limited differences in lipophilicity (as modelled by log Kow).

Read‐across works within the spirit of REACH and the stated aim of the legislation to reduce animal testing where possible. Additionally, ECHA has put much effort and emphasis in to developing, validating and refining the process and procedures to be adopted for establishing successful read‐across.
Reason / purpose:
read-across source
Principles of method if other than guideline:
This read‐across is based on the hypothesis that the source and target substance have similar aquatic bioaccumulation potential as a result of structural similarity, expected similar metabolic potential in fish and limited differences in lipophilicity (as modelled by log Kow).

Potential source substances used within the fragrance industry were identified using the RIFM (Research Institute of Fragrance Materials) database and Givaudan internal experimental database. A total of 24 salicylate esters were identified. Cyclohexyl salicylate was chosen because it was the only analogue with an experimental BCF value and because the read‐across was considered suitable based on the limited differences in lipophilicity (as modelled by log Kow) between the source and target substance.

The OECD QSAR Toolbox v3.3 was also used to check for potential source substances. A category was defined using the “ester and phenol” profile and Environmental Fate and Transport databases. The category consisted of 142 chemicals of which only 6 had measured BCF data. From the structures show in, it is clear that only cyclohexyl salicylate is a close analogue to the target substance.
Key result
Type:
BCF
Value:
>= 120 - <= 180 L/kg
Basis:
whole body w.w.
Calculation basis:
steady state
Remarks:
BCF value for BENZYL SALICYLATE from source substance (CYCLOHEXYL SALICYLATE) extrapolated for difference in hydrophobicity between the source- and target-substance.
Type:
BCF
Value:
>= 600 - <= 900 L/kg
Basis:
whole body w.w.
Calculation basis:
steady state
Remarks:
Based on Parent related radioactive fraction of SOURCE substance (CYCLOHEXYL SALICYLATE).
Conclusions:
A valid BCF value of 600‐900 L/kg is available for cyclohexyl salicylate. This analogue is considered a suitable read‐across substance based on its structural similarity to benzyl salicylate, expected similar metabolic potential in fish and limited differences in lipophilicity (as modelled by log Kow). The measured log Kow values for benzyl salicylate and cyclohexyl salicylate are 4.0 and 4.7 respectively. Since the BCF value of a substance is generally positively correlated with its lipophilicity (as modelled by log Kow), direct read‐across from cyclohexyl salicylate would represent a worst‐case and unrealistic estimate for benzyl salicylate. Thus in accordance with ECHA guidance R.7.10.3.2, the BCF value has been corrected by the same factor of difference as for Kow (i.e. 100.7 = 5.0) to give a reasonable realistic BCF estimate for benzyl salicylate of 120 ‐180 L/kg.

The read‐across is being used in a weight‐of evidence approach along with a reliable QSAR result
(BCFBAF v3.01 Regression‐based estimate – see Table 1 and separate endpoint record for details).

Both methods estimate that the BCF of benzyl salicylate is < 500 L/kg. Thus the weight‐of‐evidence approach is considered adequate for the purpose of classification and labelling and/or risk assessment.

Description of key information

The bioaccumulation potential of benzyl salicylate has been assessed using read-across and QSAR. In applying the read-across two important aspects have been considered: the similar potential for metabolism of the two substances and the slight difference in lipophilicity (as modelled by log Kow). In accordance with ECHA guidance R.7.10.3.2, the BCF value for the analogue has been corrected by the same factor of difference as for Kow to give a reliable realistic estimate for benzyl salicylate of 120 to 180 L/kg. The BCFBAF v3.01 regression-based QSAR model gives a reliable estimated BCF value for benzyl salicylate of 202 L/Kg, which was adjusted to 311 L/kg after taking into consideration predicted and experimental values of the analogue read-across substance.

Key value for chemical safety assessment

BCF (aquatic species):
311 L/kg ww

Additional information

Reliable measured aquatic bioaccumulation data is not available for benzyl salicylate. 

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 Annex XI encourages the use of alternative information before a new vertebrate test, including fish, is conducted.

Benzyl salicylate has a measured log Kow of > 3. Therefore a weight of evidence approach has been used to assess the bioaccumulation potential of benzyl salicylate using read-across from cyclohexyl salicylate, for which a valid BCF study is available and QSAR.

The read-across is based on the hypothesis that the target substance (benzyl salicylate) and source substance (cyclohexyl salicylate) have similar aquatic bioaccumulation potential as a result of structural similarity, expected similar metabolic potential in fish and limited differences in lipophilicity (as modelled by log Kow). The source and target substance are both mono-constituent substances with typical purities => 99.7%. They do not contain any impurities that are expected to affect their bioaccumulation properties.

The capability of fish to metabolise substances to more polar components, leads to lower BCF values. Therefore, when applying read-across it is important to examine the potential for metabolism for the substance to be evaluated and the analogue substance for which the BCF value is available. Indicators for similar potential for metabolism between the target (benzyl salicylate) and source substance (cyclohexyl salicylate) include:

1) The two substances are structurally closely related as both are alkyl 2-hydroxybenzoate esters. The only slight structural difference is the nature of the alkyl group (benzyl versus cyclohexyl).

2) The two substances share common “bioaccumulation metabolism alert substructures” as profiled in the BCFBAF v3.1 Whole Body Primary Biotransformation Rate constant model for fish (see table below). Both substances contain an “ester”, “aromatic alcohol” and "benzene" structural fragment, which are considered potential sites of metabolic attack as indicated by the negative coefficient values. Benzyl salicylate also contains an “unsubstituted phenyl group” which, according to the model, may further increase the capacity of benzyl salicylate for biotransformation. As such benzyl salicylate may have a higher potential for metabolism than cyclohexyl saliclyate, making the read-across a conservative one.

3) Both substances are readily biodegradable and thus are likely to be rapidly metabolised in organisms.  

Indicator of bioaccumulation potential

Benzyl Salicylate

Cyclohexyl Salicylate

Ready Biodegradability

readily

readily

Bioaccumulation – metabolism alerts (BCFBAF v3.01). 

 

 

Fragment description

Coefficient(1)

 

 

Ester [-C(=O)-O-C]

-0.7605

1

1

Unsubstituted phenyl group [C6H5]

-0.7605

1

0

Aromatic alcohol [OH]

-0.4727

1

1

Benzene

-0.4277

1

1

-CH- [cyclic]

0.0126

0

1

-CH2- [cyclic]

0.0963

0

5

Aromatic H

0.2664

4

4

Partition coefficient N-Octanol/water (Log Kow)(2)

4.0

4.7

BCFBAF v3.01 QSAR prediction

 

 

Regression-based BCF estimate, L/Kg

202

311(3)

586

Measured BCF, L/kg

 

600-900

1) Descriptors with positive signs reflect a general reduced capacity for biotransformation and negative values reflect a general increased capacity for biotransformation; 2) Determined according to OECD 107 guideline; 3) adjusted based on the predicted and experimental data for the analogue substance, cyclohexyl salicylate

A valid BCF value of 600-900 L/kg is available for cyclohexyl salicylate. This analogue is considered a suitable read-across substance based on its structural similarity to benzyl salicylate, expected similar metabolic potential in fish and limited differences in lipophilicity (as modelled by log Kow). The measured log Kow values for benzyl salicylate and cyclohexyl salicylate are 4.0 and 4.7 respectively. Since the BCF value of a substance is generally positively correlated with its lipophilicity (as modelled by log Kow), direct read-across from cyclohexyl salicylate would represent a worst-case and unrealistic estimate for benzyl salicylate. Thus in accordance with ECHA guidance R.7.10.3.2, the BCF value has been corrected by the same factor of difference as for Kow (i.e. 100.7= 5.0) to give a BCF estimate for benzyl salicylate of 120 -180 L/kg.

The BCFBAF v3.01 regression-based QSAR model gives estimated BCF values for benzyl salicylate and cyclohexyl salicylate of 202 and 586 L/kg respectively. The latter is in close agreement with the experimental value of 600-900 L/kg supporting the applicability of the QSAR to this group of chemicals and the reliability of the BCF prediction for benzyl salicylate. However, since the predicted value for cyclohexyl salicylate is slightly lower than the maximum experimental value, a conservative approach has been taken and a correction factor of 1.54 (900/586) has been applied to the predicted value of 202 L/Kg to give a reliable conservative BCF estimate for benzyl salicylate of 311 L/Kg for risk assessment purposes.

Based on the above information, it is concluded that there is no need for further investigation of aquatic bioaccumulation with fish.

For classification purposes, an experimentally derived high quality log Kow value is suitable when a measured BCF on an aquatic organism is not available. Benzyl salicylate has a measured log Kow of 4.0, which just meets the CLP Regulation EC 1272/2008 cut-off value of log Kow ≥ 4 to identify substances with a potential to bioconcentrate. However, an experimentally determined BCF provides a better measure and is used in preference for classification purposes. Benzyl salicylate has an estimated BCF value of 120 - 180 L/kg, based on measured data for a read-across analogue substance and corrected for slight differences in log Kow. It has an estimated value of 311 L/Kg, based on a QSAR prediction and adjusted to take into account slight differences in predicted and experimental data for the analogue substance. Both estimates are significantly less than the CLP threshold value of BCF ≥ 500 L/kg. Thus benzyl salicylate is considered not to have the potential to bioconcentrate for classification purposes.

For PBT/vPvB assessment purposes, predicted BCF estimates and log Kow may be used to provisionally assess bioaccumulation potential. Benzyl salicylate has a measured log Kow of 4.0, which is less than the B screening criteria of ≤ 4.5. Estimated BCF values for benzyl salicylate are in the range of 120 to 311 L/kg. This is well below the B definitive criterion of BCF > 2000 L/kg.

The estimated BCF value for benzyl salicyate based on read-across and QSAR is in the range of 120 to 311 L/kg. The highest value of 311 L/kg has been chosen as a relevant and reliable conservative estimate for risk assessment purposes.