CLH REPORT FOR TBBPA CLH report Proposal for Harmonised Classification and Labelling Based on Regulation (EC) No 1272/2008 (CLP Regulation), Annex VI, Part 2 International Chemical Identification: 2,2',6,6'-tetrabromo-4,4'-isopropylidenediphenol; tetrabromobisphenol-A (TBBPA) EC Number: 201-236-9 CAS Number: 79-94-7 Index Number: 604-074-00-0 Contact details for dossier submitter: Norwegian Environment Agency P.O. Box 5672 Torgarden, 7485 Trondheim, Norway [email protected] +47 73 58 05 00 Co-submitter: The Danish Environmental Protection Agency Version number: 2.0 Date: 18.09.2020 [04.01-MF-003.01] CLH REPORT FOR TBBPA CONTENTS 1 IDENTITY OF THE SUBSTANCE........................................................................................................................1 1.1 NAME AND OTHER IDENTIFIERS OF THE SUBSTANCE...............................................................................................1 1.2 COMPOSITION OF THE SUBSTANCE..........................................................................................................................2 2 PROPOSED HARMONISED CLASSIFICATION AND LABELLING............................................................3 2.1 PROPOSED HARMONISED CLASSIFICATION AND LABELLING ACCORDING TO THE CLP CRITERIA............................3 3 HISTORY OF THE PREVIOUS CLASSIFICATION AND LABELLING ......................................................5 4 JUSTIFICATION THAT ACTION IS NEEDED AT COMMUNITY LEVEL.................................................5 5 IDENTIFIED USES..................................................................................................................................................5 6 DATA SOURCES .....................................................................................................................................................5 7 PHYSICOCHEMICAL PROPERTIES .................................................................................................................5 8 EVALUATION OF PHYSICAL HAZARDS.........................................................................................................7 9 TOXICOKINETICS (ABSORPTION, METABOLISM, DISTRIBUTION AND ELIMINATION) ..............8 9.1 SHORT SUMMARY AND OVERALL RELEVANCE OF THE PROVIDED TOXICOKINETIC INFORMATION ON THE PROPOSED CLASSIFICATION(S).........................................................................................................................................................10 10 EVALUATION OF HEALTH HAZARDS ..........................................................................................................12 10.1 ACUTE TOXICITY - ORAL ROUTE.......................................................................................................................12 10.2 ACUTE TOXICITY - DERMAL ROUTE..................................................................................................................12 10.3 ACUTE TOXICITY - INHALATION ROUTE ...........................................................................................................12 10.4 SKIN CORROSION/IRRITATION ..........................................................................................................................12 10.5 SERIOUS EYE DAMAGE/EYE IRRITATION...........................................................................................................13 10.6 RESPIRATORY SENSITISATION ..........................................................................................................................13 10.7 SKIN SENSITISATION.........................................................................................................................................13 10.8 GERM CELL MUTAGENICITY.............................................................................................................................13 10.8.1 Short summary and overall relevance of the provided information on germ cell mutagenicity ...........16 10.8.2 Comparison with the CLP criteria ........................................................................................................17 10.8.3 Conclusion on classification and labelling for germ cell mutagenicity ................................................17 10.9 CARCINOGENICITY...........................................................................................................................................17 10.9.1 Short summary and overall relevance of the provided information on carcinogenicity .......................23 10.9.1.1 Mode of action (MoA) for uterine carcinogenesis in female rats and relevance to humans:.............................26 10.9.2 Comparison with the CLP criteria ........................................................................................................31 10.9.3 Conclusion on classification and labelling for carcinogenicity............................................................32 10.10 REPRODUCTIVE TOXICITY ................................................................................................................................33 10.10.1 Adverse effects on sexual function and fertility .....................................................................................33 10.10.2 Short summary and overall relevance of the provided information on adverse effects on sexual function and fertility36 10.10.3 Comparison with the CLP criteria ........................................................................................................40 10.10.4 Adverse effects on development.............................................................................................................41 10.10.5 Short summary and overall relevance of the provided information on adverse effects on development 42 10.10.6 Comparison with the CLP criteria ........................................................................................................43 10.10.7 Conclusion on classification and labelling for reproductive toxicity....................................................44 10.11 SPECIFIC TARGET ORGAN TOXICITY-SINGLE EXPOSURE ...................................................................................44 10.12 SPECIFIC TARGET ORGAN TOXICITY-REPEATED EXPOSURE ..............................................................................44 10.12.1 Short summary and overall relevance of the provided information on specific target organ toxicity – repeated exposure .....................................................................................................................................................51 10.12.2 Comparison with the CLP criteria ........................................................................................................53 10.12.3 Conclusion on classification and labelling for STOT RE......................................................................53 [04.01-MF-003.01] CLH REPORT FOR TBBPA 10.13 ASPIRATION HAZARD .......................................................................................................................................53 11 EVALUATION OF ENVIRONMENTAL HAZARDS.......................................................................................53 12 EVALUATION OF ADDITIONAL HAZARDS .................................................................................................53 13 ADDITIONAL LABELLING................................................................................................................................53 14 REFERENCES........................................................................................................................................................54 15 ANNEXES ...............................................................................................................................................................56 [04.01-MF-003.01] CLH REPORT FOR TBBPA 1 IDENTITY OF THE SUBSTANCE 1.1 Name and other identifiers of the substance Table 1: Substance identity and information related to molecular and structural formula of the substance Name(s) in the IUPAC nomenclature or other 2,2',6,6'-tetrabromo-4,4'-isopropylidenediphenol; international chemical name(s) tetrabromobisphenol-A Other names (usual name, trade name, 2,2',6,6'-tetrabromo-4,4'-isopropylidenediphenol abbreviation) 2,2-Bis(3,5-dibromo-4-hydroxyphenyl)propane; 2,2-bis(4-hydroxy-3,5-dibromophenyl)propane; 4,4′-isopropylidenebis(2,6-dibromophenol); 4,4′-(1-methylethylidene)bis(2,6-dibromophenol); 2,2′,6,6′-tetrabromobisphenol A; 3,3′,5,5′-tetrabromobisphenol A; 2,2′,6,6′-tetrabromo-4,4′-isopropylidenediphenol; Tetrabromodiphenylpropane; TBBPA ISO common name (if available and appropriate) - EC number (if available and appropriate) 201-236-9 EC name (if available and appropriate) 2,2',6,6'-tetrabromo-4,4'-isopropylidenediphenol CAS number (if available) 79-94-7 Other identity code (if available) - Molecular formula C15H12Br4O2 Structural formula SMILES notation (if available) CC(C)(C1=CC(Br)=C(O)C(Br)=C1)C1=CC(Br)=C(O)C(Br)=C1 Molecular weight or molecular weight range 543.88 Information on optical activity and typical ratio - of (stereo) isomers (if applicable and appropriate) Description of the manufacturing process and - identity of the source (for UVCB substances only) Degree of purity (%) (if relevant for the entry in - Annex VI) [04.01-MF-003.01] 1 CLH REPORT FOR TBBPA 1.2 Composition of the substance See confidential annex for information. Table 2: Constituents (non-confidential information) Constituent Concentration range (% Current CLH in Current self- (Name