Bis(2-propylheptyl) phthalate

Bioaccumulation: aquatic / sediment

Description of key information

DPHP is not expected to significantly accumulate in organisms.

Key value for chemical safety assessment

BCF (aquatic species):

55 L/kg ww

Additional information

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 DPHP (CAS 53306-54-0) (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.

 

Assessment

No experimental data are available for DPHP (CAS 53306-54-0) on bioaccumulation. Therefore, the bioaccumulation potential is assessed via the log Kow and several QSAR models relevant for this endpoint. In the following the results of all available models are discussed with regard to their applicability domain.

 

The log Kow was experimentally determined via HPLC to be greater than 6 (log Kow >> 6; BASF AG, 1995; rep. no. 94L00318; see IUCLID Ch. 4.7). The estimation with MedChem v3.54 (BASF AG, 1995) resulted for both isomers in log Kow values of 10.8 and 10.6. Information on the applicability domain of this model is not available. Therefore, the log Kow was also calculated using KOWWIN v1.68 (EPI Suite v4.11, see IUCLID Ch. 4.7) which resulted in a similar log Kow of 10.36. The substance is within the applicability domain of the model. As pointed out in the REACH guidance document R.11, a decreasing relationship between the log Kow and bioaccumulation is observed at very high log Kow values of > 6.

 

In addition the bioconcentration factor was calculated using different models for which information on the applicability domain of the respective models were available. The results are discussed as part of a weight-of-evidence approach for the assessment of the bioaccumulation potential of DPHP. The majority of the reliable models predict BCF values of clearly below 500, indicating that the substance does neither fulfil the "B"-criterion nor leads to a classification based on BCF limits according to CLP.

 

BCF base-line model v.02.07 of OASIS Catalogic v5.11.13 (BASF SE, 2014):

The model considers different mitigating factors regarding bioaccumulation, e.g. water solubility, metabolism, molecular size. The model predicts a maximum BCF of 166 (without mitigating factors), which is reduced to a BCF of 7.7 L/kg by molecular size, metabolism and to a lesser extent by water solubility. The substance is completely within the applicability domain of the model (structural, mechanistic, parametric = 100%).

Molecular size and water solubility are discussed within the literature whether certain threshold values are suitable as cut-off criteria for indication of limited bioaccumulation. Regarding molecular size, the PBT working group on hazardous substances discussed a maximum diameter of > 17.4 Å (Comber et al., 2006). The average maximum diameter of the test item is determined to be 18.6 Å (range: 15.7 to 22.8 Å); thus meeting this criterion.

Based on the predicted BCF of 7.7, significant bioaccumulation is not to be expected in organisms.

 

BCFBAF v3.01 (EPI Suite v4.11; BASF SE, 2014):

BCFBAF provides three submodels for the estimation of the bioaccumulation potential of which two calculate BCF and/or BAF values. The submodel based on Meylan et al. (1997/1999) predicts the BCF based on the log Kow and (if applicable) correction factors for structural features of the substance. The BCF was estimated to be 76 L/kg. DPHP was within the applicability domain of the submodel.

Using the Arnot & Gobas (2003) submodel, the BCF for the upper trophic level was calculated to be 38 L/kg not considering biotransformation, while it was reduced to a BCF of 1.3 L/kg after taking biotransformation into account. The BAF including biotransformation according to Arnot & Gobas (2003) are slightly higher than the respective BCF, but do not lead to a different assessment (BAF = 13 L/kg). However, it must be noted that the substance was not within the applicability domain of the submodel as the log Kow was greater than the max. value (max log Kow = 8.70). Based on the predicted BCF of 76, significant bioaccumulation is not to be expected in organisms.

 

CAESAR v2.1.13 (VEGA v1.0.8; BASF SE, 2014)

This model prediction is reliable as the substance meets the constraints of the model (Global Applicability Domain Index = 0.96). Relevant fragments have been identified by the model but were assessed by the model not to be in conflict with its applicability domain. The BCF was predicted to be 9 L/kg. It should be pointed out that the log Kow used by the model was clearly lower than that of previous calculation (log Kow = 6.24). Based on the predicted BCF of 9, significant bioaccumulation is not to be expected in organisms.

 

BCF Read-Across v1.0.2 (VEGA v1.0.8; BASF SE, 2014)

This model prediction is reliable as well as the substance meets the constraints of the model (Global Applicability Domain Index = 0.97). The BCF was predicted to be 17 L/kg. It should be pointed out that the two models for the prediction of the log Kow resulted in deviating values, but which both were greater than 6 (ALogP: log Kow = 9.4; MLogP: log Kow = 6.24). Nevertheless as the model uses molecules of similar structure to derive the BCF, the result can be regarded as reliable. Based on the predicted BCF of 17, significant bioaccumulation is not to be expected in organisms.

 

BCF Model - Meylan v1.0.2 (VEGA v1.0.8; BASF SE, 2014)

The model output notes that accuracy of prediction for similar molecules found in the training set is not optimal as experimental values for similar compounds disagree with the estimated BCF value. In addition the log Kow value of 10.36 is marked as not adequate. The Global Applicability Domain Index was stated as 0.75, meaning that the substance is out of the applicability domain of the model. Although the estimated log Kow can be regarded as reliable, the calculated BCF of 302 L/kg is clearly higher than the reliable estimates of other models. Thus the result of this model will not be used in the assessment of the bioaccumulation potential of DPHP.

 

Bioaccumulation model (T.E.S.T. v4.1, US EPA; BASF SE, 2014)

The consensus method calculated a BCF of 15 L/kg (range: 3.8 to 65 L/kg) based on the results of the five submodels. The reliability of the program’s five submodels (hierarchical clustering, single model, group contribution, FDA, nearest neighbor) is assessed via the mean average error between the entire training and validation datasets and substance with a similarity coefficient <= 0.5. According to this measure, the estimated BCF values of all submodels and hence the resulting consensus method are not reliable, although the substance is within the applicability domain of the models. Thus the result of this model will not be used in the assessment of the bioaccumulation potential of DPHP.

 

QSAR method based on log Kow (published by UBA, Müller & Nendza, 2011; BASF SE, 2014)

Müller and Nendza (2011) published a comparative analysis of 13 models for the calculation of the BCF based on log Kow. The log Kow estimated with KOWWIN v1.68 was used in the calculation of the BCF with the available models. As expected based on the high log Kow, only one model by Nendza (1991) accepted the log Kow, while the value was out of the range of the models' log Kow limits. The log BCF values ranged from 0.36 (BCF = 2) to 9.04. The model by Nendza resulted in a BCF of approx. 600000 (log BCF = 5.78). This value is valid based on its log Kow range, but detailed information on the applicability of the model regarding the molecule’s structure are not available. Therefore, the estimated BCF value is in strong disagreement with the other available and reliable results and should therefore not be used in the assessment of the bioaccumulation potential.

 

The available reliable results are used in a weight-of-evidence approach to assess the bioaccumulation potential of DPHP (CAS 53306-54-0). The BCF estimates range from 8 to 166. The mean BCF is 55. The maximum value is a worst-case estimate not taking into account mitigating factors like molecular size and metabolism. After considering these factors, this BCF is reduced to 8. It can be concluded that DPHP is not expected to accumulate significantly in organisms.