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EC number: 252-346-9 | CAS number: 35074-77-2
Bioaccumulation: aquatic / sediment
Administrative data
Link to relevant study record(s)
Description of key information
The compound is not expected to accumulate in aquatic organisms.
Key value for chemical safety assessment
Additional information
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 CAS 35074-77-2 (Q)SAR results were used for 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 bioaccumulation are not provided.
The bioaccumulative potential of CAS 35074-77-2 was assessed in a weight-of-evidence approach including several QSAR tools and information on the logKow and molecular size and weight. The following QSAR tools were used.
Model |
|
BCF |
logBCF |
Remarks |
Catalogic v5.11.15 |
|
7.4 |
0.87 |
All mitigating factors applied; in parametric and mechanistic domain and 95% in structural domain |
T.E.S.T. v4.1 |
|
29.02 |
1.46 |
Consensus method |
EPISuite v4.11 |
Regression-based estimate |
9.56 |
0.98 |
The molecular weight is within the range of the training set. The logKow is above the range of the training set. One correction factor exceeded the maximum number of instances. |
Arnot-Gobas upper trophic level; incl. biotransformation estimates |
0.8953 |
-0.048 |
The substance is not within the applicability domain of the BCFBAF submodel. |
|
Arnot-Gobas upper trophic level; incl. biotransformation rate of zero |
2.425 |
0.385 |
The substance is not within the applicability domain of the BCFBAF submodel |
|
VEGA CAESAR v2.1.14 |
|
3 |
0.51 |
According to the model’s global AD index, the predicted substance is out of the applicability domain of the model. |
VEGA Meylan v1.0.3 |
|
6 |
0.74 |
According to the model’s global AD index, the predicted substance is outside the applicability domain of the model. |
VEGA Read across v1.1.0 |
|
6.3 |
0.8 |
According to the model’s AD index, the read-across seems to be unreliable due to low similarity in found molecules. |
According to the QSAR estimations the compound is not expected to significantly accumulate in organisms.
The BCF base-line model integrated in Catalogic is a sophisticated model that takes into account different mitigating factors, i.e. acids, metabolism, phenols, size and water solubility. The compound was inside the parametric and the mechanistic domains of the compound and > 95% of the fragments of the compound are present in correctly predicted training chemicals. The mitigating factors with the highest influence on the bioaccumulative potential are metabolism and the size of the compound. The model estimated a BCF of 7.4 with all mitigating factors applied. The BCF max (without any mitigating factor) was estimated to be 23.6. The result is regarded as highly reliable due to the good fit of the compound into the applicability domain.
US EPA’s Toxicity Estimation Software Tool (T.E.S.T.) uses five submodels to estimate the BCF of the target chemical. These results are then averaged in the consensus approach to provide a higher reliability. With the exception of the Group Contribution Method, the target compound is inside of the applicability domain of the single submodels. However the confidence in the estimated BCF values of the single submodels is not optimal. The consensus model predicts the BCF by calculating the average of the predicted BCF values from the other QSAR methodologies while taking the applicability domain of the models into account. This method typically provides the highest prediction accuracy since errant predictions are dampened by the predictions from the other methods. In addition this method provides the highest prediction coverage because several methods with slightly different applicability domains are used to make a prediction. The averaged result of the consensus method was a BCF of 29.02.
US EPA’s EPISuite includes the regression-based estimation and the Arnot-Gobas model which takes biotransformation processes into account. The present chemical is within the molecular weight range of the regression-based estimation. The logKow is slightly above the range of the training set compounds of the regression-based estimation. Furthermore, the maximum number of instances of correction factors in any of the training set compound is exceeded in one case. The regression-based model predicted a BCF of 9.56. Despite the logKow and the exceedance of the correction factors in one instance the result seems to be reliable in a weight-of-evidence approach. Especially since the logKow is clearly above the critical value of 10 (cf. below).
The Arnot-Gobas delivers further information on possible transformation processes. The model estimates the biotransformation rate kM in fish and subsequently the BCF and BAF of the compound. When deriving the biotransformation rate kM the compound exceeded the molecular weight and logKow ranges of the training chemicals. In the subsequent determination of the BCF and the BAF the logKow range was exceeded as well. Although the model delivers useful information on possible biotransformation processes the estimate is less accurate and needs to be treated carefully in a weight-of-evidence approach. Including biotransformation estimates the BCF is predicted to be 0.8953. Without considering the biotransformation rate the BCF is 2.425. Since the result well reflects the other QSAR results it is regarded as suitable in a weight-of-evidence approach.
The VEGA package includes three different estimation tools with each of them providing detailed information on the applicability domain. Neither of the models delivered a reliable result. The domain score of the models delivered a bad assessment and consequently the models were not taken into account.
The models clearly indicate that the compound does not significantly accumulate in organisms. This assumption is further supported by the molecular size of the compound. According to ECHA’s Guidance on Information Requirements and Chemical Safety Assessment R.11 – PBT Assessment, compounds with an average maximum diameter of >1.7 nm together with molecular weight of greater than 1100 are unlikely to have a BCF of >2000. Although the compound has a molecular weight of only 639 the DiamMax-average is 2.2 nm and even the DiamMax-Min is 1.78 nm. Therefore it can be assumed that the compound does not easily cross biological membranes.Furthermore, according to the R.11 the aquatic BCF of a substance is probably lower than 2000 L/kg if the calculated logKow is higher than 10. The present compound has a calculated logKow of 11.74 and it can be assumed that the BCF is clearly below 2000.
In conclusion, the compound is not expected to significantly accumulate in organisms. The BCF is assumed to be below 500.
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