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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Reference
Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
2017-09-12
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Remarks:
well-accepted (Q)SAR model
Justification for type of information:
1. SOFTWARE
BCFBAF Program, included in EPISuite v.4.00-4.10 © U.S. EPA, for estimation of the bioconcentration (BCF) in fish including biotransformation and bioaccumulation.

2. MODEL (incl. version number)
BCFBAF program v.3.01 (September 2010), ©2000 US EPA

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CAS Number: 101-37-1;
Measured LogKow: 3.51
- Further information: see attached document.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Further information: see attached document.

5. APPLICABILITY DOMAIN
- Further information: see attached document.

6. ADEQUACY OF THE RESULT
- Further information: see attached document.
Reason / purpose:
other: Experimental logKow
Guideline:
other: Reach Guidance on information requirements and chemical safety assessment, Chapter R.6: QSARs and grouping of chemicals
Version / remarks:
May 2008
Principles of method if other than guideline:
QSAR calculation: BCFBAF v3.01 (2010) by U.S. Environmental Protection Agency, included in EPI SUITE TM v4.00-v4.10 © 2000-2008 US-EPA
GLP compliance:
no
Remarks:
(Q)SAR nodel
Specific details on test material used for the study:
CAS Number: 101-37-1 (input data)
measured logKow: 3.51 (input data)
Smiles Code: O(c(nc(OCC=C)nc1OCC=C)n1)CC=C
Radiolabelling:
no
Test organisms (species):
not specified
Nominal and measured concentrations:
QSAR calculation
Details on estimation of bioconcentration:
QSAR calculation

BASIS INFORMATION
- Measured/calculated logPow: 3.51

BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF v.3.01
- Result based on measured log Pow of: 3.51
Key result
Type:
BCF
Value:
29.24 L/kg
Basis:
whole body w.w.
Calculation basis:
other: QSAR BCFBAF program, part of EPI suite
Details on results:
The logKow of the test substance of 3.51 (worst-case) has been used to estimate the potential of bioconcentration by the BCFBAF programm v3.01. The regression-based estimate resulted in a BCF value of 29.24 L/kg wet-wt, corresponding to a log BCF of 1.466. The biotransformation rate constant has been predicted to be 1.572/ day (10 gram fish), corresponding to a biotransformation half-life of 0.441 days (normalized to 10g fish) at 15 °C. Based on the method of Arnot-Gobas, including biotransformation rate estimates, the BCF is between 114.6 L/kg wet wt for the lower trophic and 120.1 L/kg wet wt for the upper trophic. The BAF value is in the same range of 115.3 l/kg wet wt to 120.1 L/kg wet wt. Assuming a biotransformation rate of zero, the BCF is estimated to be 343.1 L/kg wet wt for the upper trophic and the BAF is predicted to be 488.2 L/kg wet wt by the Arnot-Gobas method.

SMILES : O(c(nc(OCC=C)nc1OCC=C)n1)CC=C

CHEM : 1,3,5-Triazine, 2,4,6-tris(2-propenyloxy)-

MOL FOR: C12 H15 N3 O3

MOL WT : 249.27

--------------------------------- BCFBAF v3.01 --------------------------------

Summary Results:

Log BCF (regression-based estimate): 1.47 (BCF = 29.2 L/kg wet-wt)

Biotransformation Half-Life (days) : 0.441 (normalized to 10 g fish)

Log BAF (Arnot-Gobas upper trophic): 2.08 (BAF = 120 L/kg wet-wt)

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 3.51 (user entered)

Equation Used to Make BCF estimate:

Log BCF = 0.6598 log Kow - 0.333 + Correction

Correction(s):                            Value

Aromatic sym-triazine ring         -0.517

Estimated Log BCF = 1.466 (BCF = 29.24 L/kg wet-wt)

===========================================================

Whole Body Primary Biotransformation Rate Estimate for Fish:

===========================================================

------+-----+--------------------------------------------+---------+---------

TYPE | NUM | LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION | COEFF | VALUE

------+-----+--------------------------------------------+---------+---------

Frag | 1 | Triazine ring (symmetric) | -0.0123 | -0.0123

Frag | 3 | Aromatic ether [-O-aromatic carbon] | -0.0694 | -0.2082

Frag | 3 | -CH2- [linear] | 0.0242 | 0.0726

Frag | 9 | -C=CH [alkenyl hydrogen] | 0.0988 | 0.8896

Frag | 9 | -C=CH [alkenyl hydrogen] | 0.0000 | 0.0000

L Kow| * | Log Kow = 3.51 (user-entered ) | 0.3073 | 1.0788

MolWt| * | Molecular Weight Parameter | | -0.6392

Const| * | Equation Constant | | -1.5058

============+============================================+=========+=========

RESULT | LOG Bio Half-Life (days) | | -0.3558

RESULT | Bio Half-Life (days) | | 0.4408

NOTE | Bio Half-Life Normalized to 10 g fish at 15 deg C |

============+============================================+=========+=========

Biotransformation Rate Constant:

kM (Rate Constant): 1.572 /day (10 gram fish)

kM (Rate Constant): 0.8843 /day (100 gram fish)

kM (Rate Constant): 0.4973 /day (1 kg fish)

kM (Rate Constant): 0.2796 /day (10 kg fish)

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

Estimated Log BCF (upper trophic) = 2.079 (BCF = 120.1 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 2.080 (BAF = 120.1 L/kg wet-wt)

Estimated Log BCF (mid trophic) = 2.073 (BCF = 118.4 L/kg wet-wt)

Estimated Log BAF (mid trophic) = 2.074 (BAF = 118.5 L/kg wet-wt)

Estimated Log BCF (lower trophic) = 2.059 (BCF = 114.6 L/kg wet-wt)

Estimated Log BAF (lower trophic) = 2.062 (BAF = 115.3 L/kg wet-wt)

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

Estimated Log BCF (upper trophic) = 2.535 (BCF = 343.1 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 2.689 (BAF = 488.2 L/kg wet-wt)

Validity criteria fulfilled:
not applicable
Remarks:
QSAR estimation
Conclusions:
The BCF was estimated to be 29.24 L/kg wet wt according to the regression-based QSAR model BCFBAF. The results indicates a low potential for bioaccumulation and is far below the bioaccumulation criterion of 2000 in the PBT assessment.

Description of key information

Due to its physico-chemical properties, triallyl cyanurate is expected to have a low potential for bioaccumulation. The BCF for fish has been estimated using a QSAR approach. Based on the log Pow of 3.51, the BCF has been calculated to be 29.24 L/kg wet weight.

Key value for chemical safety assessment

BCF (aquatic species):
29.24 L/kg ww

Additional information

To derive a conclusion on the endpoint of bioaccumulation, all relevant data should be considered in a weight-of-evidence approach according to the REACh guidance document R.7c (v.3.0, 2017). Measured fish BCF data, predicted BCF values and the physico-chemial properties should be assessed together in this approach and measured data on bioconcentration would preferred if available to assess the potential of bioaccumulation. However, AnnexXI of the REACh regulation also applies and encourages the use of alternative information before a new vertebrate test is conducted (Guidance document R.7c v3.0, 2017). For the test substance Triallyl cyanurate measured BCF data in fish are not available. However, another line of the weight-of-evidence approach is the estimation of the BCF by QSAR analysis. Several methods and models to predict bioaccumulation based on measured data have been developed and are still under development. These models are applicable for several classes of organic substances. Therefore, the estimation of the BCF based on the logKow value can be used to evaluate the potential of bioaccumulation.

In the weight of evidence approach, the substance should be characterized first of all to consider the applicability of QSAR models. The test substance is an organic, non-ionised mono-constituent and has a defined molecular structure, which enables the use of the structure for predictions by QSAR models. The physico-chemical properties of the test substance are described in the specific endpoint in detail. In summary, Triallyl cyanurate has a molecular weight of 249 and shows a moderate water solubility. The logKow has been determined to be 3.51 in a worst-case approach (the actual logKow might be lower; see endpoint partition coefficient). The logKow value has been determined by separate determination of water solubility and octanol-solubility, to take any unexpected effect of surface tension into account.

Due to the molecular structure, Triallyl cyanurate is not expected to fulfil the definition of a surfactant according to the EU Directive 648/2004, which is also cited in the REACh guidance document (see endpoint surface tension). The REACh guidance documents R.7a and R.7c indicate that surfactants consists of an apolar and a polar moiety (hydrophobic tail and the hydrophilic headgroup, respectively). The formation of the apolar and a polar part in the molecule, as it is observed in surfactants, does not seem to be likely for the completely symmetrical molecule structure of Triallyl cyanurate. Asymetrical side chains would promote the emergence of an apolar and polar moiety in the molecule, but this case is not given for the test substance. Physico-chemical effects like formation of emulsion or micelles in a relevant extent are not expected. Hence, the measurement of the logKow is considered reliable and the determination of the critical micelle concentration would not be appropriate to refine the results. In a worst-case approach, the theoretically highest achievable octanol/water partitioning coefficient has been used to estimate the BCF and is considered to take any unexpected effects into account.

Furthermore, the Koc value of the test substance is below 3, indicating that Triallyl cyanurate has a moderate adsorptive capacity. The test substance has a low vapour pressure of <0.001 hPa at 25°C. Ready biodegradation of the test substance has not been observed and hydrolysis of the substance is not expected. Based on the available studies, no relevant metabolites or degradation products are known. The molecule does not contain any halogens or metals, that could indicate partitioning to lipids.

In the next step, available data of in vivo experiments and non-animal testing data should be evaluated. As in vivo data for fish or toxicokinetic data from mammals are not available, QSARs are recommended as a good predictor of bioconcentration. QSARs models listed in the REACh guidance document R.7c (2017) have been used to predict the bioconcentration of Triallyl cyanurate under consideration of the applicability domain. These models show a good linear regression for logKow values of 1 to 6. The logKow of the test substance of 3.51 has been used in a worst-case approach (see endpoint partition coefficient) to estimate the BCF with QSAR models. A preliminary analysis of the bioaccumulation potential based on the logKow with a linear model, recommended for substance with a logKow <6, results in a logBCF of 1.68 (Meylan et al. 1999) and 2.28 (Veith et al.1979). In the key study, the BCFBAF program, which represents a commonly used model, has been used to estimate the BCF and revealed a BCF of 29.24 L/kg. The application domain of the model, as far as it is defined, is considered to be fulfilled.

To support the key result, the BCF has been calculated with further established QSAR models (listed in the guidance document). Overall, the models estimated bioconcentration values in the range of 48 to 271 L/kg (logBCF 1.68 to 2.41). Although the applicability domain is not well described for all models, the estimated values can be considered by weight-of-evidence approach. Additionally, a model based on the water solubility (Neely et al. 1974) revealed a bioconcentration factor also in this range. The BCFBAF model has been chosen as key study, as the model is well-accepted and training set represents substances with structural similarity. Overall, the QSAR models show consistent data, indicating a low potential of Triallyl cyanurate for bioconcentration.

Furthermore, referring to the acute fish toxicity test (see endpoint Short term toxicity in fish, key study), the effect levels have shown a minor progression in toxicity during the test, when comparing the EC50 values at 24 h, 48h, 72 h and 96 h. Therefore, a distinct bioaccumulation of the test substance is considered to be unlikely.

According to the integrated testing strategy (ITS) for aquatic bioaccumulation (Guidance document R.7c, v.30, 2017), the weight of evidence approach is used to estimate the BCF based on all available data and further conclusion can be drawn. The logKow is below the trigger value of 4 for classification and labeling. Based on the available studies with aquatic organisms, the test substance has been classified to be toxic to aquatic life with long lasting effects according to CLP. Regarding the B-criterion of the PBT assessment, the logKow is below the trigger value of 4.5. The estimated BCF value is also far below the criteria of 2000 L/kg for bioaccumulation. Considering that the actual logKow might be lower than the used logKow to estimate the BCF by QSAR, the estimation of the BCFs might represent overestimated values. In summary, it has been concluded, that the available data indicate a low potential for bioaccumulation and a test on bioaccumulation in fish is not necessary for further refinement.