Abstract

Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) is used as a flame retardant in electronics, building and construction materials, and automotive materials. Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) was nominated for toxicology and in vivo genotoxicity study by the National Institute of Environmental Health Sciences because, although human exposure potential may be low, there was concern that this chemical has carcinogenic potential and has not been adequately studied. The compound was also selected for study because dibromo-1-propanol (the core structure of the 2,3-dibromopropyl ether side chain) has been studied by NTP and found to be carcinogenic. Male and female F344/NTac rats and B6C3F1/N mice were administered tetrabromobisphenol A-bis(2,3-dibromopropyl ether) (approximately 94% pure) in corn oil by gavage for 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes.

Groups of 10 male and 10 female F344/NTac rats were administered 0, 62.5, 125, 250, 500, or 1,000 mg tetrabromobisphenol A-bis(2,3-dibromopropyl ether)/kg body weight in corn oil by gavage, 5 days per week for 14 weeks, and additional groups of 10 male and 10 female rats were administered the same doses for 23 days. Groups of 10 male and 10 female mice were administered 0, 125, 250, 500, 1,000, or 2,000 mg/kg for 14 weeks. Two 62.5 mg/kg male rats died during week 6 (one dosing accident), and one vehicle control female rat died during week 8. All mice survived to the end of the study. Final mean body weights and body weight gains of male and female rats and mice were similar to those of the vehicle controls except the final mean body weight of 250 mg/kg female mice was 11% more than that of the vehicle controls. There were no treatment-related clinical findings. Microsomal protein levels were increased in treated rats and mice. There were no chemical-related changes in absolute or relative organ weights in male or female rats or mice. There were no gross or histologic lesions in rats or mice that were considered treatment related. There were no chemical-related hematology or clinical chemistry findings in rats or mice.

Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) was not mutagenic in Salmonella typhimurium strains TA98, TA100, or TA102, with or without rat liver S9 metabolic activation enzymes. In vivo, no significant increases in the frequencies of micronucleated erythrocytes were observed in peripheral blood samples from male or female B6C3F1/N mice in the 3-month study. In addition, no significant changes in the percentage of polychromatic erythrocytes were seen in these mice, suggesting that tetrabromobisphenol A-bis(2,3-dibromopropyl ether) did not cause bone marrow toxicity.

Under the conditions of these 3-month gavage studies, there were no clinical findings or treatment-related lesions in male or female F344/NTac rats or B6C3F1/N mice administered tetrabromobisphenol A-bis(2,3-dibromopropyl ether) at 0, 62.5, 125, 250, 500, or 1,000 mg/kg in rats or 0, 125, 250, 500, 1,000, or 2,000 mg/kg in mice. Final mean body weights of treated rats and mice were generally within 10% of vehicle controls, and there were no treatment-related effects on organ weights.

Synonyms: 2,2-Bis[3,5-dibromo-4-(2,3-dibromopropoxy)phenyl]propane; 2,2-bis[3,5-dibromo-4-(2,3-dibromopropyloxy)phenyl]propane; 2,2-bis[4-(2,3-dibromopropoxy)-3,5-dibromophenyl]propane; 2,2-bis[4-(2,3-dibromopropyloxy)-3,5-dibromophenyl]propane; bis(2,3-dibromopropoxy)tetrabromobisphenol A; bis(2,3-dibromopropyl)tetrabromobisphenol A; 1,1′-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromopropoxy)benzene]; 1,1′-(1-methylethylidene)bis[3,5-dibromo-4-(2,3-dibromopropoxy)]benzene; TBBPA-DBPE; 3,3′,5,5′-tetrabromobisphenol A bis(2,3-dibromopropyl) ether; tetrabromobisphenol A dibromopropyl ether

Trade names: 403AF, Bromcal 66.8, Bromkal 66-8, CHEMPACIFIC 34721, D 5532, EcoFlame B-943, FG 3100, Fire Guard 3100, Flame Cut 121K, Flame Cut 121R, FR 720, GX 5532, HP-800 AG, HP-800 AGC, PE-68, Pyroguard SR 720, SAYTEX^® HP-800 A, SR 720

Contents

• Foreword
• Collaborators
• Contributors
• Peer Review
• Publication Details
• Introduction
  • Chemical and Physical Properties
  • Production, Use, and Human Exposure
  • Regulatory Status
  • Absorption, Distribution, Metabolism, and Excretion
  • Toxicity
  • Reproductive and Developmental Toxicity
  • Carcinogenicity
  • Genetic Toxicity
  • Study Rationale
• Materials and Methods
  • Procurement and Characterization
  • Preparation and Analyses of Dose Formulations
  • Animal Source
  • Animal Welfare
  • Three-month Studies
  • Statistical Methods
  • Quality Assurance Methods
  • Genetic Toxicology
• Results
  • Three-month Study in Rats
  • Special Respiratory System Microscopic Review
  • Genetic Toxicology
• Discussion
• References
• Appendix A. Summary of Nonneoplastic Lesions in Rats and Mice
• Appendix B. Clinical Pathology Results
• Appendix C. Organ Weights and Organ-Weight-To-Body-Weight Ratios
• Appendix D. Reproductive Tissue Evaluations and Estrous Cycle Characterization
• Appendix E. Genetic Toxicology
• Appendix F. Microsomal Protein Concentration and Liver Enzyme Activity Data
• Appendix G. Chemical Characterization and Dose Formulation Studies
• Appendix H. Ingredients, Nutrient Composition, and Contaminant Levels In NTP-2000 Rat and Mouse Ration
• Appendix I. Sentinel Animal Program