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EC number: 275-276-0 | CAS number: 71216-01-8
Bioaccumulation: aquatic / sediment
Administrative data
Link to relevant study record(s)
Description of key information
In conclusion, all available estimations are extremely well in line and the BCF of the target compound is expected to be below 500.
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 71216-01-8 (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 bioaccumulation are not provided.
The bioaccumulative potential was assessed in a weight of evidence approach including several QSAR estimations and data on the molecular size and log Kow.The single QSAR models and their results are summarized in the table below.
Model |
|
BCF |
logBCF |
Remarks |
Catalogic v5.11.15 BCF Baseline model |
|
32.36 (corrected) |
1.51 |
all mitigating factors applied; substance is in mechanistic and parametric domain but 71.43% in the structural domain (28.57% unknown) Main mitigating factors: size and metabolism |
|
2722.7 (max) |
3.435 |
No mitigating factors applied;substance is in mechanistic and parametric domain but 71.43% in the structural domain (28.57% unknown) |
|
EPISuite v4.11 (measured logPow) |
Regression-based estimate |
281 |
2.45 |
Within the applicability domain |
Arnot-Gobas upper trophic level; incl. biotransformation estimates |
9.194 |
0.964 |
Within the applicability domain but biotransformation rate estimation may be less accurate |
|
Arnot-Gobas upper trophic level; incl. biotransformation rate of zero |
20420 |
4.31 |
Within the applicability domain |
|
VEGA CAESAR v2.1.13 |
|
2 |
0.39 |
According to the model’s global AD index, the predicted substance is out of the Applicability Domain of the model. |
VEGA Meylan v1.0.2 |
|
501 |
2.7 |
According to the model’s global AD index, the predicted substance is out of the applicability domain of the model. |
VEGA Read across v1.0.2 |
|
3 |
0.45 |
According to the model’s global AD index, the predicted substance is out of the applicability domain of the model. |
US EPA T.E.S.T v.4.1 |
|
2.44 |
0.39 |
The substance is within the applicability domain of the Consensus method. Based on the mean absolute error, the confidence in the predicted BCF values is low. |
Other evidence Toxicological studies
|
No indication for bioaccumulation could be found in the available studies
|
(see IUCLID section 7.1) |
Other evidence Size (Catalogic v5.11.15)
|
DiamMax average 2.4 nm (MW 584.85) |
DiamMax average > 1.7 nm is an indication for limited bioavailability (ECHA guidance R.11, PBT/vPvB assessment (Nov 2014), p.54) |
According to the results of the models the compound has a low bioaccumulative potential.
The BCF base-line model integrated in Catalogic 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 model, 71% of the fragments of the target chemical are present in correctly predicted training chemicals. Nevertheless, the result is regarded as reliable and suitable to be used in a weight of evidence approach. With all mitigating factors applied the BCF is determined as 32.36. Without considering any mitigating factors the BCFmax is 2723 L/kg.The biggest influence on the bioaccumulative potential has size followed by metabolism, both limiting the uptake. Therefore, the BCF corrected is assessed to be more realistic.
US EPA’s EPISuite includes the regression-based estimation and the Arnot-Gobas model which takes biotransformation processes into account. The substance is within the applicability domain of the BCFBAF submodel: Bioconcentration factor (BCF; Meylan et al., 1997/1999), Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).The substance fullfills not all criteria for the applicability domain of the BCFBAF submodel: Biotransformation rate in fish (kM; Arnot et al., 2008a/b). However, only one fragment has one more instance compared to any of the training sets.
The regression-based model predicted a BCF of 281 L/kg. The Arnot-Gobas model predicted BCF values of 9.2 and 20420 L/kg for the upper trophic level including biotransformation rate estimates and biotransformation rates of zero. The EPISuite results were regarded as suitable in the weight of evidence approach. Concerning the Arnot Gobas method the BCF considering biotransformation effects is considered to be more realistic.
The VEGA package includes three different estimations tools with each of them providing detailed information on the applicability domain.
The VEGA CAESAR model detected structural alerts which should be carefully taken into account and are known to be primarily present in non-bioaccumulative compound.
Descriptors for this compound have values outside the descriptor range of the compounds of the training set, logP is the main reason. However, the experimental logPow differs from the calculated logPow in the model.
In conclusion, the prediction of the VEGA CEASAR model seems to be adequate for the use in a weight-of-evience approach. According to the model the target compound is not expected to significantly accumulate in organisms.
VEGA Read-across: However, although the similar compounds do not result in a positive assessment in the first index (highest similarity found for similar compounds), they comprise important structures for bioaccumulation which are also present in the target compound. Neither of the five most similar structures have experimental values which indicate a significant potential to bioaccumulate (<500). Therefore, although the BCF prediction is only moderately reliable it seems to be acceptable in a weight-of-evidence approach.
VEGA Meylan: One of the biggest issues in the assessment of the applicability domain is the reliability of the logP which was predicted as 8.69. However, the experimentally derived logPow value is lower. Episuite calculations using the regression based estimate (which is based on the same methodology as VEGA Meylan) and the experimentally derived logPow resulted in a lower BCF (281). Moreover, the five most similar compounds have experimental values significantly lower than the predicted values. It is therefore expected, that the experimental value of the target compound is lower than the predicted value as well.
The BCF values of the CEASAR, Meylan and Read-across models were 2, 501, and 3, respectively, whereas the result of the Meylan model represents an overestimation of the BCF compared to EPIsuite regression based estimate using the experimentally derived logPow. Therefore, the BCF of 501 should not be considered. The other models were taken into account in the weight-of-evidence approach although the compound is out of the applicability domain of the Caesar and the Read-across model.
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 averaged in the consensus approach to provide a higher reliability. 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 low and the results are therefore questionable. 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 2.44. As this value fits well to other model predictions , the T.E.S.T result was taken into account in the weight of evidence approach although the reliability of every single submodel was low.
According to ECHA’s Guidance on Information Requirements and Chemical Safety Assessment chapter 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. The present compound has a DiamMax-average of 2.4nm. Although the molecular weight is only 584.85 it can be concluded that the compound has a limited potential to cross biological membranes. Furthermore, the toxicological studies show no evidence for bioaccumulation.
Only two QSAR calculations reveal BCF values > 500 (2723-20420). However, in these calculations no mitigating factor as size and metabolism were considered.
In conclusion, all available estimations are extremely well in line and the BCF of the target compound is expected to be below 500.
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