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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
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
Remarks:
The (Q)SAR is an accepted calculation method, therefore generally being considered as reliable study with restrictions. As this approach is taken from (1) ECHA's Guidance on information requirements and chemical safety assessment - Chapter R.7c: Endpoint specific guidance, and from (2) "European Chemical Bureau Technical Guidance Document on Risk Assessment Part III", the computation method is considered a valid.
Justification for type of information:
1. SOFTWARE
BCFBAF and CAESAR

2. MODEL (incl. version number)
BCFBAF (version 3.02), CAESAR QSAR model proposed by Zhao et al. (2008) based on guidance R.7c.

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Measured log Pow of: 4.78

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

5. APPLICABILITY DOMAIN
See attached QPRF

6. ADEQUACY OF THE RESULT
See attached QPRF
Reference:
Composition 1
Composition 2
Composition 3
Composition 4
Guideline:
other: REACH guidance on QSARs R.6, May/July 2008
Principles of method if other than guideline:
The bioconcentration factor of isopentyl p-methoxycinnamate was estimated using the BCFBAF modelling program version 3.01 (as of September 2010) and with CAESAR QSAR model for BCF (Zhao et al. 2008).
GLP compliance:
no
Test material information:
Composition 1
Details on sampling:
not applicable
Details on preparation of test solutions, spiked fish food or sediment:
not applicable
Test organisms (species):
other: fish
Details on test organisms:
not applicable
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF (version 3.02), CAESAR QSAR model proposed by Zhao et al. (2008) based on guidance R.7c.
- Result based on measured log Pow of: 4.78
Type:
BCF
Value:
662 L/kg
Basis:
whole body w.w.
Remarks on result:
other: Calculated with QSAR (Meylan et al. 1999)
Type:
BCF
Value:
28 L/kg
Basis:
whole body w.w.
Remarks on result:
other: Calculated with QSAR (Zhao et al. 2008)

The ECHA guidance R.7c proposes a scheme for the thought processes that must be considered with regard to the BCF for substances produced or imported at 100 t/y or above (building on the concepts discussed by de Wolf et al. 2007).

STEP 1: Characterisation of the substance

This includes the verification of the chemical structure, which is well known for isopentyl p-methoxycinnamate. The relevant physico-chemical properties should be gathered, which was done for isopentyl p-methoxycinnamate. The substance has a vapour pressure of 0.0066 Pa at 25 °C, a water solubility of 0.8 mg/L at 20 °C, a log KOW of 4.78 and an estimated adsorption coefficient of log KOC = 3.56. If the log KOW is greater 3, a preliminary BCF estimate should be done with linear models (e.g. Meylan et al. 1999) for substances with log KOW < 6, which is the case for isopentyl p-methoxycinnamate.

STEP 2: Identification of possible analogues

A search for experimental data on chemical analogues should be performed. This may lead to the conclusion that the substance belongs to a group of substances that are known to have potential to bioaccumulate. It may also help to clarify if log KOW is a good predictor for bioaccumulation.

A structural similar substance with experimental BCF data was found: 2-ethylhexyl 4-methoxycinnamate (BCF = 433 whole body w.w.)

STEP 3A: Evaluation of existing in vivo data

It should be evaluated if in vivo data on the substance, including data on invertebrates, are available that can be used for the characterisation of bioaccumulation potential. Such information is available for isopentyl p-methoxycinnamate (see step 2).

STEP 3B: Evaluation of non-testing data

The use of log KOW based QSARs normally is recommended if KOW is a good predictor of bioconcentration. A justification for use of a particular model should be provided. In general, a cautious conclusion on the predicted BCF values should be drawn and the upper range of predicted values of the most relevant and reliable QSAR models should be used. In this study, the BCF was predicted with two models being proposed in the ECHA guidance R.7c. First, the BCF was estimated with the BCFBAF program included in the EPI Suite program of the US EPA, which applies the fragment-based approach of Meylan et al. 1999. The model gave a log BCF of 2.82. Second, the BCF was calculated with the CAESAR BCF model proposed by Zhao et al. 2008 giving a log BCF value of 1.45. Both QSAR models give BCFs indicating that isopentyl p-methoxycinnamate may have a certain potential for bioaccumulation in aquatic organisms. Nevertheless, BCFs predicted with the models are below the cut-off criterion of 2000 L/kg used for classification of a substance as bioaccumulative. Thus, the B criterion is not fulfilled for isopentyl p-methoxycinnamate.

STEP 3C: Evaluation of in vitro data

If in vitro data are available these may be used to estimate a BCF value. Such data are not available.

STEP 4A: Weight of evidence assessment

The available and reliable information should be summarised and it should be examined if any single piece of information merits a conclusion on BCF or if further testing may be required. If no experimental fish BCF data are available, the BCF should be estimated from the KOW and it should be checked if the estimated BCF predicted from the KOW may be reduced by applying a set of strong and weak indicators given in ECHA guidance R.7c. Furthermore, data from invertebrate studies may be taken into account.

The screening criterion of log KOW > 3 is fulfilled showing that the substance may have the potential to bioaccumulate to a significant extent. Two different validated QSAR models were then applied to get further information on the substance’s BCF. The model from Meylan et al. (1999) gives a log BCF of 2.82 and the model of Zhao et al. (2008) gives a log BCF of 1.45. Both computed BCFs indicate that allyl 3-cyclohexylpropionate has a certain potential to bioaccumulate in aquatic organisms. Nevertheless, both QSAR models return BCFs of less than 2000 L/kg. A BCF above this cut-off value triggers classification of a substance as bioaccumulative. Consequently, the substance should not be considered as bio-accumulative. Further testing on the BCF of the substance in aquatic organisms is deemed not necessary.

Validity criteria fulfilled:
not applicable
Conclusions:
The BCF of the substance was calculated with the program BCFBAF using a fragment-based approach (Meylan et al. 1999) and with CAESAR QSAR (Zhao et al. 2008). The predicted values were 662 L/kg and 28 L/kg, respectively. The B criterion is not fulfilled and the substance is considered as not bioaccumulative.
Executive summary:

The bioconcentration factor of the substance was estimated with the BCFBAF model included in the Episuite tool (as of September 2010). This program uses a fragment-based approach that is based on a set of 610 non-ionic substances. The experimental log Kow value of 4.78 was used in the calculation. The estimated BCF was 662 L/kg. Additionally, the BCF of the substance was calculated using the CAESAR QSAR hybrid model (Zhao et al. 2008). The estimated BCF with the second model was 28 L/kg. Both modelled values are below the cut-off value of 2000 L/kg triggering classification of substances as bioaccumulative. The B criterion is not fulfilled and the substance is considered as not bioaccumulative.

Description of key information

The substance is considered as not bioaccumulative. It is proposed to use a BCF of 662 L/kg in the chemical safety assessment as this was the maximum predicted BCF.

Key value for chemical safety assessment

BCF (aquatic species):
662 L/kg ww

Additional information

The bioaccumulation factor (BCF) for fish was calculated using QSAR based software approaches. The QSAR model used by Episuite (Epiweb 4.0, BCFBAF program) is based on correlations between BCF and chemical hydrophobicity (as modelled by log KOW).

The Caesar BCF model is based on a dataset of 473 compounds with experimentally determined BCF values. The final model is a Neural Network based on 8 molecular descriptors.

For isopentyl p-methoxycinnamate

, a log KOW of 4.78 (see section 4.7 of the IUCLID dataset) was determined experimentally. Using this value, Episuite [BCFBAF (v3.00)] calculated a BCF value of 662 L/kg body weight (BCFBAF 2010). Using the Caesar QSAR model software a BCF value 28 L/kg body weight was obtained (Caesar 2010).

Both values are below the cut-off value of 2000 L/kg triggering classification of substances as bioaccumulative. It is concluded that the B criterion is not met and the substance is not considered as bioaccumulative.