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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Description of key information

Significant accumulation in organisms is not to be expected.

Key value for chemical safety assessment

Additional information

According to chapter 2, article 18 of REACH regulation (EC) no. 1907-2006, a study is not required for transported isolated intermediates of this tonnage band. 

However, in order to assess the bioaccumulation potential of the test substance, the BCF was calculated with several estimation models. The table below lists the applied (Q)SAR models, the estimated BCF values and basic information on the applicability domain (AD). Detailed information on the model’s results and the AD are given in the endpoint study records of IUCLID Chapter 5.3.1. The selected models comply with the OECD principles for (Q)SAR models.

 

Summary of relevant information on aquatic bioaccumulation:

(The predicted BCF values for applied QSAR models are sorted in ascending order)

Model

BCF

In AD*

Restraints

BCF baseline model 

v.02.07

(OASIS Catalogic

v5.11.13): 

mitigating factors considered

5.1

no

Substance is out of the model’s structural domain due to7.14% unknown fragments.

CAESAR v2.1.13

(VEGA v1.0.8)

6

no

Only moderately similar compounds have been

found; accuracy of prediction for similar molecules not optimal; values for similar molecules disagree with

target’s value.

US EPA T.E.S.T. v4.1: Bioaccumulation: Consensus method

21.7

yes

-

Meylan v1.0.2 

(VEGA v1.0.8)

31

no

Only moderately similar compounds have been

found; accuracy of prediction for similar molecules not adequate; reliability of logP value is not optimal.

BCFBAF v3.01

(EPI Suite v4.11):Arnot-Gobas BCF, upper trophic, incl. biotransformation

34

no

As the substance ionizes at physiologically relevant pH, the estimation may be less accurate.

BCFBAF v3.01

(EPI Suite v4.11): 

Meylan et al. (1997/1999)

110

yes

-

BCF Read-Across

v1.0.2(VEGA v1.0.8)

324

no

The highest similarity value found for similar compounds is not adequate for a reliable read-across.

BCFBAF v3.01

(EPI Suite v4.11):

Arnot-Gobas BCF, upper trophic, incl. biotransformation of zero

421

no

As the substance ionizes at physiologically relevant pH, the estimation may be less accurate.

BCF baseline model v02.07 (OASIS Catalogic v5.11.13): not considering mitigating factors

493.2

no

Substance is out of the model’s structural domain due to7.14% unknown fragments.

 * AD: Applicability domain

 

Amongst all (Q)SAR models applied, the substance is only within the applicability domain of two of the estimation models. The Meylan-model (1997/1999) of BCFBAF v3.0 (EPISuite v4.11) calculated the BCF to be 110 L/kg. In addition, the model (US EPA) T.E.S.T. v4.1 calculated a BCF of 21.7 L/kg. On average, the reliable estimation models calculated a mean BCF of 65.9 L/kg, thus indicating a low bioaccumulation potential for 2-ethylhexyl cyanoacetate.

A low bioaccumulation potential is additionally indicated by the estimation models CAESAR v2.1 (VEGA v1.0.8) and the BCF baseline model v02.08 of OASIS Catalogic v5.11.16. As the substance is not within the applicability domain of both of these (Q)SAR models, the calculated values were not considered for the assessment; however, these models call attention to molecular properties of the target item, related to decreasing effects on the bioaccumulation potential:

 

CAESAR v2.1 (VEGA v1.0.8) detected two relevant fragments. The model found a carbonyl residue. This specific residue has been found to be present in a very large number of non-bioaccumulative compounds, even if the log Kow was >3. In addition, the model found a >C=O polar group. In general, the presence of polar groups increases hydrophilicity, related to lower values of BCF.

The BCF baseline model v02.08 of OASIS Catalogic v5.11.16 considers mitigating factors such as metabolism, molecular size and the water solubility of substances, calculating for 2-ethylhexyl cyanoacetate a low BCF value of 5.1 L/kg; metabolism has the highest mitigating effect on the bioaccumulation potential.

 

Based on weight-of-evidence approach from calculated data and considering molecular properties as well as mitigating factors decreasing the bioaccumulation potential of the target item, it can be concluded that significant accumulation in organisms is not to be expected.

 

 

QSAR-disclaimer

 

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 2-ethylhexyl cyanoacetate (Q)SAR results were used for aquatic bioaccumulation.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 aquatic bioaccumulation are not provided.