D-Glucitol, 1,5-anhydro-1-C-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-, 2,3,4,6-tetrakis(2,2-dimethylpropanoate), (1S)-

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2022

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
EPI Suite 4.1

2. MODEL (incl. version number):
BCFBAF v3.01.

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
The sub-models in BCFBAF v3.01 require chemical structure as SMILES as input. It also uses Log Kow as its main descriptor, which is generated with KOWWIN v1.68 if an experimental value is not available.
The SMILES code of the substance and Log Kow used by the model are available in the attached QPRF.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF.

5. APPLICABILITY DOMAIN
The structure of the modeled compound was well represented in the BCFBAF v3.01 sub-models. The modeled compound was within the sub-model's molecular weight and Log Kow ranges. See attached QPRF.

6. ADEQUACY OF THE RESULT
The main purpose of this QSAR analysis was to assess the bioaccumulation potential of the substance. The predicted BCF value using the KOWWIN estimated Log Kow value of 11.46, was equal to 87.1. Based on the estimated BCF value, the substance is not considered to meet the B assessment criterion and is considered not B/vB. Overall, the prediction can be considered appropriate for use within the bioaccumulation assessment. See attached QPRF.

Principles of method if other than guideline:

Estimation of the bioconcentration factor in fish using BCFBAF v3.01.

BCFBAF v3.01 contains a number of sub-models through which the following endpoints can be estimated:
Model 1 - Bioconcentration factor (BCF): calculates a generic BCF for fish based on a linear regression model
Model 2 - Biotransformation (kM): estimates the biotransformation rate of a substance in fish, represents the elimination of a compound in fish through biotransformation. This estimation is used for the calculation in Model 3.
Model 3 - Arnot-Gobas BAF-BCF: calculates BCF and BAF (bioaccumulation factor) in fish for three different trophic levels (low, mid and upper) using a food-web model that includes biotransformation in fish as an elimination pathway. Values without biotransformation are also provided for the upper trophic level.

GLP compliance:

no

Details on test organisms:

BCF calculations in BCFBAF v3.01 are made for fish. Depending on the model, fish of different trophic levels (low, mid and upper) are included.

Key result

Type:

BCF

Value:

87.1 L/kg

Basis:

whole body w.w.

Calculation basis:

other: QSAR estimation

Remarks on result:

other: using a log Kow of 11.46 (generated by KOWWIN)

Details on results:

For detailed description on the model and its applicability, see QPRF

Using the experimental Log Kow of >7.0, the modeled BCF value of 1.06 x 10⁴ was very high, yet considered unreliable due to the nature of the experimental Log Kow value (i.e., expressed as "greater than" due to the limitations of the used methodology). Using the Log Kow value of 11.46 as estimated using the KOWWIN model, the resulting BCF value was only 87.1 (i.e., greatly below the cutoff criterion to consider a substance as bioaccumulative). This value suggests that the test substance should not be considered bioaccumulative. Since the Log Kow value estimated using KOWWIN is more realistic than the experimental value (see above, as well as the QPRF documentation), and T003422 was also found to fall within the applicability domain of KOWWIN, the BCF value of 87.1 is considered more realistic as well. As such, T003422 is considered not bioaccumulative, based on its predicted BCF being much lower than the B assessment criterion of 2000.  

Validity criteria fulfilled:

yes

Conclusions:

The BCF for the test substance was estimated using the regression-based method implemented within the BCF/BAF v3.01 of EPI-Suite.
For the final estimation, the Log Kow value of 11.46 as estimated using the KOWWIN model was used, which resulted in a BCF value of 87.1 (i.e., greatly below the cutoff criterion to consider a substance as bioaccumulative). Hence, the modeled compound is considered as not B/vB.

Description of key information

The BCF for the test substance was estimated using the regression-based method implemented within the BCF/BAF v3.01 of EPI-Suite.
Using the experimental Log Kow of >7.0, the modeled BCF value of 1.06 x 10⁴ was very high, yet considered unreliable due to the nature of the experimental Log Kow value (i.e., expressed as "greater than" due to the limitations of the used methodology). Using the Log Kow value of 11.46 as estimated using the KOWWIN model, the resulting BCF value was only 87.1 (i.e., greatly below the cutoff criterion to consider a substance as bioaccumulative). This value suggests that the test substance should not be considered bioaccumulative. Since the Log Kow value estimated using KOWWIN is more realistic than the experimental value, and T003422 was also found to fall within the applicability domain of KOWWIN, the BCF value of 87.1 is considered more realistic as well. As such, T003422 is considered not bioaccumulative, based on its predicted BCF being much lower than the B assessment criterion of 2000.  

Key value for chemical safety assessment

BCF (aquatic species):

87.1 L/kg ww