Allyl 3-cyclohexylpropionate

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

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:

QSAR prediction

Guideline:

other: REACH guidance on QSARs R.6, May/July 2008

Principles of method if other than guideline:

The bioconcentration factor of allyl 3-cyclohexylpropionate was estimated using the BCFBAF modelling program version 3.01 (as of September 2010) and with QSAR models based on the correlation between BCF and KOW (Veith et al. 1979)

GLP compliance:

no

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), QSAR model proposed by Veith et al. (1979) based on guidance R.7c.
- Result based on measured log Pow of: 4.276

Key result

Type:

BCF

Value:

307.8 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Calculated with QSAR (Meylan et al. 1999)

Key result

Type:

BCF

Value:

861 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Calculated with QSAR (Veith et al. 1979)

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 allyl 3-cyclohexylpropionate. The relevant physico-chemical properties should be gathered, which was done for allyl 3-cyclohexylpropionate. The substance has a vapour pressure of 3.8 Pa at 25 °C, a water solubility of 16.5 mg/L at 20 °C, a log KOW of 4.276, a Henry’s Law constant of 42.2 Pa · m3/mol and an estimated adsorption coefficient of log KOC = 3.27. If the log KOW is greater 3, a preliminary BCF estimate should be done with linear models (e.g. Veith et al. 1979 and Meylan et al. 1999) for substances with log KOW < 6, which is the case for allyl 3-cyclohexylpropionate.

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. The substance allyl 3-cyclohexylpropionate belongs to a group of allyl esters used as flavour ingredients (WHO 1991). However, experimental data on bioconcentration of the different substances in this group are not available. All esters included in the group are expected to be hydrolysed enzymatically to carboxylic acids and alcohols via carboxylesterases found in most tissues throughout the body, the most important of which are the beta-esterases (WHO 1991). The degradation products of allyl 3-cyclohexylpropionate, allyl alcohol and 3-cyclohexylpropionic acid, are non-bioaccumulative.

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 not available for allyl 3-cyclohexylpropionate.

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 of allyl 3-cyclohexylpropionate 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 2.488. Second, the BCF was calculated with the equation proposed by Veith et al. 1979 giving a log BCF value of 2.935. Both QSAR models give BCFs indicating that allyl 3-cyclohexylpropionate may have a certain potential for bioaccumulation in aquatic organ-isms. 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 allyl 3-cyclohexylpropionate.

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 for allyl 3-cyclohexylpropionate.

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 allyl 3-cyclohexylpropionate 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 2.488 and the model of Veith et al. (1979) gives a log BCF of 2.935. 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, allyl 3-cyclohexylpropionate should not be considered as bio-accumulative. Taking further into account that allyl 3-cyclohexylpropionate was grouped with other allyl ester substances into a group of flavour materials that are likely to undergo rapid enzyme-mediated hydrolysis in organisms (WHO 1991), it is concluded that BCFs obtained with QSAR models are appropriately covering this endpoint and that the B criterion is not met for allyl 3-cyclohexylpropionate. Further testing on the BCF of the substance in aquatic organisms is deemed not necessary.

STEP 4B: not applicable

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 a QSAR built on the relationship between log Kow and BCF (Veith et al. 1979). The predicted values were 308 L/kg and 861 L/kg, respectively. The B criterion is not fulfilled for the substance allyl 3-cyclohexylpropionate and the substance is considered as not bioaccumulative.

Executive summary:

The bioconcentration factor of the substance allyl 3-cyclohexylpropionate 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 4.276 was used in the calculation. The estimated BCF was 308 L/kg. Additionally, the BCF of the substance was calculated using a QSAR model built on the relationship between the log Kow and BCF (Veith et al. 1979). The estimated BCF with the second model was 861 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 for the substance allyl 3-cyclohexylpropionate 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 861 L/kg in the chemical safety assessment as this was the maximum predicted BCF.

Key value for chemical safety assessment

BCF (aquatic species):

861 L/kg ww

Additional information

As the substance has an log Pow of 4.276, its bioaccumulative potential was assessed. The bioconcentration factor of the substance allyl heptanoate was calculated with the BCFBAF program (as of September 2010, described in Meylan et al. 1999) using a fragment based QSAR model and with a QSAR model built on the relationship between the log Kow and BCF (Veith et al. 1979). The BCFs calculated with the models were 307.8 L/kg and 861 L/kg. 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 for allyl 3-cyclohexylpropionate and the substance is considered as not bioaccumulative.

 

In Article 13 of Regulation (EC) No 1907/2006, it is laid down that information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI (of the same Regulation) are met. Furthermore according to Article 25 of the same Regulation testing on vertebrate animals shall be undertaken only as a last resort.

According to Annex XI of Regulation (EC) No 1907/2006 (Q)SAR results can be used if (1) the scientific validity of the (Q)SAR model has been established, (2) the substance falls within the applicability domain of the (Q)SAR model, (3) the results are adequate for the purpose of classification and labeling and/or risk assessment and (4) adequate and reliable documentation of the applied method is provided.

For the assessment of allyl 3-cyclohexylpropionate (Q)SAR results were used to estimate the bioconcentration factor (BCF) for fish. The criteria listed in Annex XI of Regulation (EC) No 1907/2006 are considered to be adequately fulfilled and therefore the endpoint(s) sufficiently covered and suitable for risk assessment.

 

Therefore, and for reasons of animal welfare, further experimental studies on bioaccumulation are not provided.