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Testing Status of Tetrabromobisphenol A M200033

 

CASRN: 79-94-7

Formula: C15-H12-Br4-O2

Synonyms/Common Names

  • Phenol, 4,4'-(1-methylethylidene)bis(2,6-dibromo (9CI)
  • TBBPA

Short-Term Toxicity

  • 5 days (Gavage)  (C20033B)  Completed 
    • 5-Day Transcriptomic Dose-Response Studies
    • Rats: Harlan Sprague-Dawley
    • Dose: Female rats: 0, 4, 8, 16, 31.25, 62.5, 125, 250, 500, 1000, or 2000 mg/kg. Male rats: 0, 4, 8, 16, 31.25, 62.5, 125, 250, 500, 1000, or 2000 mg/kg.
  • 5 days (Gavage)  (C20033B)  Data in Review 
    • Rats: Harlan Sprague-Dawley
    • Dose: Female rats: 0, 4, 8, 16, 31.25, 62.5, 125, 250, 500, 1000, or 2000 mg/kg. Male rats: 0, 4, 8, 16, 31.25, 62.5, 125, 250, 500, 1000, or 2000 mg/kg.
  • 13 weeks (Gavage)  (C20033)  Completed 
    • Toxicogenomics
    • Citation: Sanders JM, Coulter SJ, Knudsen GA, Dunnick JK, Kissling GE, Birnbaum LS. Disruption of estrogen homeostasis as a mechanism for uterine toxicity in Wistar Han rats treated with tetrabromobisphenol A. Toxicol Appl Pharmacol. 2016;298:31-39
    • Rats: Wistar Han
    • Dose: 0, 25, 250, or 1000 mg/kg.
  • 13 weeks (Gavage)  (C20320)  Completed 
    • Rats: F344/NTac; Mice: B6C3F1/N
    • Dose: R&M: 0, 10, 50, 100, 500, or 1000 mg/kg; R: 20/sex/dose; M: 10/sex/dose.

Long-Term Carcinogenicity

  • 2 years (Gavage)  (C20320)  Completed 
    • TR-587 (NIH Number: 14-5929)  (Peer Review Approval 10/29/2013A )
      Toxicology Studies of Tetrabromobisphenol A in F344/NTac Rats and B6C3F1/N Mice and Toxicology and Carcinogenesis Studies of Tetrabromobisphenol A in Wistar Han [Crl:WI(Han)] Rats and B6C3F1/N Mice (Gavage Studies)
    • Rats: Wistar Han; Mice: B6C3F1/N
    • Carcinogenesis Results
      • Male Rats Equivocal Evidence 
      • Female Rats Clear Evidence 
      • Male Mice Some Evidence 
      • Female Mice No Evidence 
    • Dose: R&M: 0, 250, 500, or 1000 mg/kg; 50/sex/species/dose.

Special Studies

  • Absorption Distribution Metabolism Excretion (Gavage; Intravenous)  (S0897)  Completed 
    • Male Rats: F344/N
    • Dose: 2, 20, or 200 mg/kg; 20 mg/kg, 50 uCi/kg, 1 ml/kg.
  • C. elegans  (W20033)  Completed 
    • Citation: Behl M, Rice JR, Smith MV, Co CA, Bridge M, Hsieh JH, Freedman JH, Boyd WA. Comparative toxicity of organophosphate flame retardants and polybrominated diphenyl ethers to c. Elegans. Toxicol Sci. 2016 Aug;154(2):241-252Pubmed Abstract
    • C. elegans: N2
    • Dose: Feeding: 0, 2, 3.2, 5, 7.9, 13, 20, 32, 50, 79, 130, 200uMRepro: 0, 2, 3.2, 5, 7.9, 13, 20, 32, 50, 79, 130, 200uMGrowth: 0, 0.2, 0.4, 0.8, 1.6, 3.2, 6.3, 13, 25, 50, 100, 200uM.

Genetic Toxicology

  • Micronucleus  (A13260)  Completed 
    • Mice: B6C3F1
    • Male Negative 
    • Female Negative 
  • Salmonella  (968573)  Completed 
    • Citation: Mortelmans, K., Haworth, S., Lawlor, T., Speck, W., Tainer, B., and Zeiger, E. Salmonella mutagenicity tests. II. Results from the testing of 270 chemicals Environ. Mutagen. Vol. 8 (Suppl 7) (1986) 1-119
    •  Negative 
  • Salmonella  (G20033)  Completed 
    •  Negative 

Toxicogenomics

  • 13 weeks Microarray Analysis (Gavage)  (T20033)  Completed 
    • Microarray and RT-PCR
    • Rats: Wistar Han
    • Dose: 0, 25, 250, or 1000 mg/kg; 25 rats/group.
  • 5 days Transcriptome Sequencing (Gavage)  (T20033B)  Completed 
    • 5-Day Transcriptomic Dose-Response Studies
    • Citation: Gwinn WM, Auerbach SS, Parham F, Stout MD, Waidyanatha S, Mutlu E, Collins B, Paules RS, Merrick BA, Ferguson S, Ramaiahgari S, Bucher JR, Sparrow B, Toy H, Gorospe J, Machesky N, Shah RR, Balik-Meisner MR, Mav D, Phadke DP, Roberts G, DeVito MJ. Evaluation of 5-day In Vivo Rat Liver and Kidney With High-throughput Transcriptomics for Estimating Benchmark Doses of Apical Outcomes. Toxicol Sci. 2020 Aug 1;176(2):343-354. doi: https://doi.org/10.1093/toxsci/kfaa081.Pubmed Abstract
    • Rats: Harlan Sprague-Dawley
  • 5 days Transcriptome Sequencing (Gavage)  (T20033B)  Data in Review 
    • Citation: Gwinn WM, Auerbach SS, Parham F, Stout MD, Waidyanatha S, Mutlu E, Collins B, Paules RS, Merrick BA, Ferguson S, Ramaiahgari S, Bucher JR, Sparrow B, Toy H, Gorospe J, Machesky N, Shah RR, Balik-Meisner MR, Mav D, Phadke DP, Roberts G, DeVito MJ. Evaluation of 5-day In Vivo Rat Liver and Kidney With High-throughput Transcriptomics for Estimating Benchmark Doses of Apical Outcomes. Toxicol Sci. 2020 Aug 1;176(2):343-354. doi: https://doi.org/10.1093/toxsci/kfaa081.Pubmed Abstract
    • Rats: Harlan Sprague-Dawley