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Category approach for selected brominated flame retardants ... Category approach for selected brominated flame retardants 7 a) The experimental data show comparable toxicological effects

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  • Category approach for selected brominated flame retardants Preliminary structural grouping of brominated flame retardants Environmental project No. 1872, 2016

  • 2 Category approach for selected brominated flame retardants

    Title:

    Category approach for selected brominated flame retardants

    Authors:

    Eva Bay Wedebye Nikolai Georgiev Nikolov Elsa Nielsen Julie Boberg Marta Axelstad Trine Klein Reffstrup Marianne Dybdahl Acknowledgements for contributions to the work: Lea Bredsdorff

    Published by:

    The Danish Environmental Protection Agency Strandgade 29 1401 Copenhagen K Denmark www.mst.dk/english

    Year:

    2016

    ISBN no.

    978-87-93435-90-2

    Disclaimer:

    When the occasion arises, the Danish Environmental Protection Agency will publish reports and papers concerning research and development projects within the environmental sector, financed by study grants provided by the Danish Environmental Protection Agency. It should be noted that such publications do not necessarily reflect the position or opinion of the Danish Environmental Protection Agency. However, publication does indicate that, in the opinion of the Danish Environmental Protection Agency, the content represents an important contribution to the debate surrounding Danish environmental policy. Sources must be acknowledged.

    http://www.mst.dk/english

  • Category approach for selected brominated flame retardants 3

    Contents

    1. Introduction ..................................................................................................... 10 1.1 Non-testing data ................................................................................................................... 10 1.2 (Q)SAR .................................................................................................................................. 11 1.3 Grouping and read-across .................................................................................................... 11 1.4 Preliminary structural grouping of BFRs ............................................................................ 12 1.5 Category hypothesis and (Q)SAR predictions for a selected BFR group ............................ 12 1.6 Evaluation of experimental data and identification of critical effect ................................. 12 1.7 Preliminary category justification and perspectives ........................................................... 12

    2. Preliminary structural grouping of BFRs .......................................................... 13 2.1 Data preparation ................................................................................................................... 13 2.2 (Q)SAR predictions ............................................................................................................... 16 2.3 Retrieval of ToxCast information ......................................................................................... 16 2.4 Grouping ............................................................................................................................... 17 2.5 Identified groups from the preliminary structural grouping .............................................. 18

    2.5.1 Group 1 (Aromatic substances) ............................................................................ 20 2.5.2 Group 2 (dibromo-(2,3- dibromopropoxy)benzene derivatives) ........................ 22 2.5.3 Group 3 (Cycloalkanes) ......................................................................................... 23 2.5.4 Group 4 (Phthalate acid and its anhydride) ......................................................... 25 2.5.5 Group 5 (Phenols and bisphenols) ....................................................................... 26 2.5.6 Group 6 (benzyl ethyl oxygen bridge derivatives) ............................................... 27 2.5.7 Group 7 (Methoxy dibromobenzene derivatives) ................................................ 28 2.5.8 Group 8 (Phthalates/Benzoate)............................................................................ 30 2.5.9 Group 9 (TBBPA ethers) ........................................................................................ 31 2.5.10 Group 10 (small alkyl alkohols) ............................................................................ 33 2.5.11 Group 11 (TBBPA esters/acrylate) ........................................................................ 34 2.5.12 Group 12 (Phosphates) ......................................................................................... 35 2.5.13 Group 13 (Triazines) ..............................................................................................37 2.5.14 Group 14 (Biphenyles) .......................................................................................... 38 2.5.15 Group 15 (Diphenyl ethers) .................................................................................. 39 2.5.16 Singletons .............................................................................................................. 40

    3. (Q)SAR predictions .......................................................................................... 42 3.1 Definition of the category .................................................................................................... 42 3.2 Identification of category members .................................................................................... 42 3.3 ToxCast/Tox21 ..................................................................................................................... 43 3.4 (Q)SAR models applied ....................................................................................................... 43 3.5 Results from the (Q)SAR predictions ................................................................................. 43

    3.5.1 Membership of existing OECD HPV Chemical Categories or US-EPA New Chemical Categories ..................................................................................... 43

    3.5.2 Bioavailability ........................................................................................................ 43 3.5.3 Metabolism / transformation ............................................................................... 43 3.5.4 Endocrine endpoints ............................................................................................. 44 3.5.5 Repro-developmental toxicity .............................................................................. 44 3.5.6 Organ toxicity ........................................................................................................ 44 3.5.7 Repeated dose toxicity .......................................................................................... 44

  • 4 Category approach for selected brominated flame retardants

    3.5.8 Genotoxicity and carcinogenicity ......................................................................... 44

    4. Experimental data ............................................................................................ 57 4.1 Data collection and evaluation of data ................................................................................. 57 4.2 Experimental studies on repeated dose toxicity and carcinogenicity ................................ 60

    4.2.1 Liver ....................................................................................................................... 67 4.2.2 Kidney and urinary bladder .................................................................................. 67 4.2.3 Oral cavity, esophagus, forestomach, and small and large intestines ................ 69 4.2.4 Hematopoietic system .......................................................................................... 69 4.2.5 Spleen .................................................................................................................... 70 4.2.6 Thyroid gland ........................................................................................................ 70 4.2.7 Pancreas ................................................................................................................ 70 4.2.8 Mammary gland .................................................................................................... 70 4.2.9 Clitoral gland .......................................................................................................... 71 4.2.10 Seminal vesicle ....................................................................................................... 71 4.2.11 Nose ........................................................................................................................ 71 4.2.12 Lung ........................................................................................................................ 71 4.2.13 Skin and Zymbal gland ......................................................................................... 72 4.2.14 Harderian gland .....................................................................................................73 4.2.15 Eye ..........................................................................................................................73 4.2.16 Mesothelioma .........................................................................................................73 4.2.17 Other tumors ..........................................................................................................73

    4.3 Experimental studies on reproductive toxicity ................................................................... 74 4.4 Experimental studies on toxicokinetics .........................................