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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

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 DL-alpha-Tocopherol (CAS 10191 -41 -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 of bioaccumulation potential:

In accordance with REACH Annex XI, the bioaccumulation test in aquatic species does not need to be conducted. As the substance is highly insoluble in water, it will not be significantly bioavailable and no significant exposure of aquatic organisms is expected. DL-alpha-Tocopherol (CAS 10191 -41 -0) is commonly used as food additive (Vitamin E supply) and is therefore considered being not bioaccumulative in organisms.

In support of this conclusion, a bioaccumulation assessment of DL-alpha-Tocopherol (CAS 10191-41-0) was performed based on several QSAR models. Based on the chemical properties of the substance (mainly the high log Kow), the substance was outside of the applicability domain of most of the available models. Therefore, the estimated BCF values may be less accurate. A weight-of-evidence approach was selected to evaluate the estimated BCF values.

Summary of relevant information on aquatic bioaccumulation: Predicted BCF values for applied QSAR models sorted by BCF:

(AD = Applicability domain)

Model

BCF [L/kg]

In AD

Restraints

BCFBAF v3.01 (EPI Suite v4.11): Arnot-Gobas BCF, upper trophic, incl. biotransformation

0.925

no

- Log Kow is outside the range of the training set

- The occurrences of one fragment exceeded those of the test data set

BCFBAF v3.01 (EPI Suite v4.11): Arnot-Gobas BCF, upper trophic, incl. biotransformation of zero

1.457

no

- Log Kow is outside the range of the training set

- The occurrences of one fragment exceeded those of the test data set

CAESAR v2.1.14 (VEGA v1.1.3)

5

no

- no similar compounds have been found

- similar molecules have experimental values that disagree with the predicted value

- the maximum error in prediction of similar molecules has a moderate value, considering the experimental variability

BCF baseline model v.02.09 (OASIS Catalogic v5.11.19): incl. mitigating factors

6.6

no

- With regard to the structural domain, the test substance is not within the applicability domain of the model.

BCF baseline model v.02.09 (OASIS Catalogic v5.11.19): not considering mitigating factors

16.0

no

- With regard to the structural domain, the test substance is not within the applicability domain of the model.

BCFBAF v3.01 (EPI Suite v4.11): Meylan et al. (1997/1999)

38.59

no

- Log Kow is outside the range of the training set

Meylan v1.0.3 (VEGA v1.1.3)

39

no

- only moderately similar compounds with known experimental value have been found

- accuracy of prediction for similar molecules is not adequate

- some similar molecules have experimental values that disagree with the predicted value

- the maximum error in prediction of similar molecules has a high value, considering the experimental variability

- reliability of logP value used by the model is not adequate

- LogP of this compound is outside the defined range [-1.37,11.26]

 

BCF KNN/Read-Across v1.1.0 (VEGA v1.1.3)

151.4

unclear

- only moderately similar compounds with known experimental value have been found

- some similar molecules have experimental values that disagree with the predicted value

US EPA T.E.S.T. v4.2.1: Bioaccumulation: Consensus method

272

yes

- The confidence in the predicted result is low

UBA (2011) collection of 13 log Kow regressions

7.17E-04 – 7.24E+10

no

- the log Kow was not within the recommended range of the models

 

In conclusion, the applied QSAR models calculated a BCF in a range between 0.925 L/kg and 272 L/kg. The results of the log Kow regressions (UBA, 2011) were not considered, as the log Kow was not in the recommended range of the models. Therefore, these estimated results indicate DL-alpha-Tocopherol (CAS 10191-41-0) is not to be expected to significantly accumulate in organisms (estimated BCF <500 L/kg).

Several publications provide supplementary information, indicating that bioaccumulation of Vitamin E (DL-alpha-Tocopherol) is not to be expected in organisms, due to its well-known, essential function as a lipid soluble, chain-breaking antioxidant:

- Feeding studies with e.g. commercial broilers (Cobb 500; Bottje et al., 1997) and Korean rockfish (Sebastes schlegeli,; Bai & Lee, 1998) showed a dose response concerning the concentration of alpha-Tocopherol in liver tissue.

- In addition, Hsu & Shiau (1999) outline several feeding studies with DL-alpha-Tocopheryl acetate, demonstrating DL-alpha-Tocopherol to be the major form of Vitamin E “stored” in the liver of Hybrid Tilapia (Oreochrimis niloticus x O. aureus) and of Rainbow Trouts (from Hung et al. 1998). Metabolized to alpha-Tocopheryl-acetate, Vitamin E is furthermore the major form found in blood or muscle tissue of Hybrid Tilapia and also shrimp (Penaeus monodon).

- Such findings are supplemented by the fact that the antioxidant activities of tocopherols are imparted by their ability to donate their phenolic hydrogen atoms to lipid free radicals by converting to tocopheryl-acetate (Burton & Ingold 1989). In addition, Vitamin E directly effects positive growth performance of e.g. muscle tissue and enhances the stability of erythrocytic membranes (Paul et al. 2004).

Taken together, these results indicate Vitamin E to be stored after ingestion in the liver, which is known to be the central metabolic organ of higher vertebrates. Over time Vitamin E is successively metabolized and deposited by the respective organism.

Therefore, the studies strongly suggest that bioaccumulation of Vitamin E in organisms is not to be expected. 

References:

- S.-C. Bai & K.-J. Lee (1998) "Different levels of dietary DL-alpha-tocopheryl acetate affect the vitamin E status of juvenile Korean rockfish, Sebastes schlegeli"; Aquaculture 161: 405 - 414

- W. G. Bottje, G. F. Erf, T. K. Bersi, S. Wang, D. Barnes & K. W. Beers (1997) "Effect of Dietary dl-alpha-Tocopherol on Tissue alpha- and gamma-Tocopherol and Pulmonary Hypertension Syndrome (Ascites) in Broilers."; Poultry Science 76: 1506 -1512

- G. W. Burton & K. U. Ingold (1989) "Mechanisms of antioxidant action: preventive and chain-breaking antioxidants" (in) J. Miquel, A. T. Quintanilha, & H. Weber (es.), Handbook offree radicals and antioxidants in biomedicine (Vol. 2, pp. 29). Boca Raton, FL, CRC Press.

- T. S. Hsu & S. Y. Shiau (1999) "DL-alpha-Tocopheryl Acetate is Not the Only Tissue Storage Form of Vitamin E in Tilapia Fed Dietary

DL-alpha-Tocopheryl Acetate."; Fisheries Science 65: 959 - 960

- S. S. O. Hung, T. W. Moon, J. W. Hilton & S. Slinger (1982) "Uptake, Transport and Distribution of DL-alpha-Tocopheryl Acetate compared to

DL-alpha-Tocopherol in Rainbow Trout, Salmo gairdneri."; J. Nutr. 112: 1590 -1599

- B. N. Paul, S. Sarkar, S. N. Mohanty (2004) "Dietary Vitamin E requirement of mrigal, Cirrhinus mrigala, fry."; Aquaculture 242: 529 -536