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Testing Status of 3,3',4,4'-Tetrachloroazobenzene M882486

 

CASRN: 14047-09-7

Formula: C12-H6-Cl4-N2

Synonyms/Common Names

  • Diazene, bis(3,4-dichlorophenyl)- (9CI)
  • TCAB

Short-Term Toxicity

  • 18 days (Gavage)  (C29323)  Completed 
    • Pilot neurobehavioral study
    • Rats: Sprague Dawley
    • Dose: 0, 1.0, 3.0, or 10.0 mg/kg/day through PND 4-21/3 litters per group.
  • 2 weeks (Gavage)  (C88148)  Completed 
    • TOX-65 (NIH Number: 99-3945)
      Toxicity Studies of 3,3',4,4'-Tetrachloroazobenzene Administered by Gavage to F344/N Rats and B6C3F1 Mice
    • Rats: F344/N; Mice: B6C3F1
    • Dose: R: 12.5, 32, 80, 200 or 500 mg/kg body weight day. M: 1, 3.2, 10, 32 OR 100 mg/kg body weight day plus controls (M&F; 5/group).
  • 5 days (Gavage)  (C88486)  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
    • Dose: FR: 0, 0.1, 0.3, 1, 3, 10, 30, 100, 200, or 400 mg/kg; N=4. MR: 0, 0.1, 0.3, 1, 3, 10, 30, 100, 200, or 400 mg/kg; N=4.
  • 5 days (Gavage)  (C88486)  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
    • Dose: FR: 0, 0.1, 0.3, 1, 3, 10, 30, 100, 200, or 400 mg/kg; N=4. MR: 0, 0.1, 0.3, 1, 3, 10, 30, 100, 200, or 400 mg/kg; N=4.
  • 5 weeks (Gavage)  (C29323)  Completed 
    • Developmental toxicity
    • Rats: Sprague Dawley
    • Dose: FR: 0, 1.0, 3.0, or 10 mg/kg/day/30 per group (Prebreed); 25 per group (Timed-mated).
  • 13 weeks (Gavage)  (C88148)  Completed 
    • TOX-65 (NIH Number: 99-3945)  (Tox Peer Review 06/18/1998A )
      Toxicity Studies of 3,3',4,4'-Tetrachloroazobenzene Administered by Gavage to F344/N Rats and B6C3F1 Mice
    • Rats: F344/N; Mice: B6C3F1
    • Dose: R&M: 0, 0.1, 1.0, 3.0, 10, or 30 mg/kg body weight (M&F; 10/group).
  • 13 weeks (Gavage)  (C88148B)  Completed 
    • Rats: Harlan Sprague-Dawley
    • Dose: 0, .1, .3, 1, 10, 30, or 100 mg/kg; 10/sex/dose.

Long-Term Carcinogenicity

  • 2 years (Gavage)  (C88148C)  Completed 
    • TR-558 (NIH Number: 11-5899)  (Peer Review Approval 02/25/2009A )
      Toxicology and Carcinogenesis Studies of 3,3',4,4'-Tetrachloroazobenzene (CASRN 14047-09-7) in Harlan Sprague-Dawley Rats and B6C3F1 Mice (Gavage Studies)
    • Rats: Harlan Sprague-Dawley; Mice: B6C3F1/N
    • Carcinogenesis Results
      • Male Rats Clear Evidence 
      • Female Rats Clear Evidence 
      • Male Mice Clear Evidence 
      • Female Mice Clear Evidence 
    • Dose: R: 0, 10, 30, or 100 mg/kg. M: 0, 3, 10, or 30 mg/kg. 50/sex/species/dose.

Special Studies

  • Absorption Disposition Metabolism Elimination (Gavage; Intravenous)  (S0295)  Completed 
    • Citation: Pillai UA, Ziegler TL, Wang DX, Kattnig MJ, McClure T, Liebler DC, Mayersohn M, Sipes IG. 3,3',4,4'-tetrachloroazobenzene absorption, disposition, and metabolism in male Fischer 344 rats. Drug Metab Dispos. 1996 Feb;24(2):238-44.Pubmed Abstract
    • Male Rats: Fischer 344
    • Dose: gavage 3.2 or 32 mg/kg. intravenous 3.2 mg/kg.
  • Metabolism (Gavage; Intravenous)  (S0596)  Completed 
    • Citation: Pillai UA, Ziegler TL, Wang DX, Kattnig MJ, McClure T, Liebler DC, Mayersohn M, Sipes IG. 3,3',4,4'-tetrachloroazobenzene absorption, disposition, and metabolism in male Fischer 344 rats. Drug Metab Dispos. 1996 Feb;24(2):238-44.Pubmed Abstract
    • Male Rats: Fischer 344
    • Dose: gavage 3.2 or 32 mg/kg. intravenous 3.2 mg/kg.
  • Metabolism (Gavage; Intravenous)  (S0809)  Completed 
    • Citation: Pillai UA, Ziegler TL, Wang DX, Kattnig MJ, McClure T, Liebler DC, Mayersohn M, Sipes IG. 3,3',4,4'-tetrachloroazobenzene absorption, disposition, and metabolism in male Fischer 344 rats. Drug Metab Dispos. 1996 Feb;24(2):238-44.Pubmed Abstract
    • Male Rats: Fischer 344
    • Dose: gavage 3.2 or 32 mg/kg. intravenous 3.2 mg/kg.
  • Toxicokinetic Study (Gavage)  (S0665)  Completed 
    • Citation: National Toxicology Program (NTP). 2010. NTP technical report on the toxicology and carcinogenesis studies of 3,3',4,4'-tetrachloroazobenzene (TCAB) in Harlan Sprague-Dawley rats and B6C3F1 mice (gavage studies). Research Triangle Park, NC: National Toxicology Program. Technical Report 558. https://ntp.niehs.nih.gov/go/tr558abs
    • Female Rats: Sprague Dawley
    • Dose: 0, 0.1, 3, or 100 mg/kg (repeat dose 13 weeks).

Genetic Toxicology

  • Micronucleus  (A43252)  Completed 
    • Citation: Witt, K.L., Zeiger, E., Tice, R.R., and van Birgelen, A.P.J.M. The genetic toxicity of 3,3',4,4'-tetrachloroazobenzene and 3,3',4,4'-tetrachloroazoxybenzene: discordance between acute mouse bone marrow and subchronic mouse peripheral blood micronucleus test results. Mutation Res. Vol. 472 (2000) 147-154
    • Mice: B6C3F1
    • Male Negative 
  • Micronucleus  (A95885)  Completed 
    • Citation: Witt, K.L., Zeiger, E., Tice, R.R., and van Birgelen, A.P.J.M. The genetic toxicity of 3,3',4,4'-tetrachloroazobenzene and 3,3',4,4'-tetrachloroazoxybenzene: discordance between acute mouse bone marrow and subchronic mouse peripheral blood micronucleus test results. Mutation Res. Vol. 472 (2000) 147-154
    • Mice: B6C3F1
    • Male Positive 
    • Female Positive 
  • Salmonella  (A17768)  Completed 
    •  Negative 
  • Salmonella  (A30420)  Completed 
    •  Negative 
  • Salmonella  (A71232)  Completed 
    •  Positive 

Organ Systems Toxicity

  • 1st generation Continuous Breeding (Legacy) (Gavage)  (RACB20101)  Completed 
    • Male and Female Rats: Sprague Dawley
    • Dose: 0, 0.1, 1, 3, or 10 mg/kg.
  • approximately 36 days Conventional Teratology (Gavage)  (R88486)  Completed 
    • Female Rats: Crl:CD (SD)
    • Dose: 0 or 10 mg/kg/day.
  • Neurobehavioral & immunologic function assessment; F0 (~54 days); F1 male (18 days); F1 female (39 days) Developmental Toxicity (Gavage)  (R88486B)  Completed 
    • Neurobehavioral & immunologic function
    • Male and Female Rats: Crl:CD (SD)
    • Dose: 0, 0.1, 1, or 10 mg/kg/day.
  • 28 days Immunotoxicity (Gavage)  (I88486)  Completed 
    • Female Rats: Sprague Dawley
    • Dose: 0, 0.1, 0.5, 1, 5, or 10 mg/kg/day.
  • 28 days Immunotoxicity (Gavage)  (I88486B)  Completed 
    • Female Rats: Crl:CD (SD)
    • Dose: 0, 0.1, 1 or 10 mg/kg/day.

Toxicogenomics

  • 5 days Transcriptome Sequencing (Gavage)  (T88486)  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)  (T88486)  Data in Review 
    • 5-Day Transcriptome Dose-Response Study
    • 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