Archives of Toxicology

, Volume 93, Issue 1, pp 211–212 | Cite as

Re: Gi et al. 2018, In vivo positive mutagenicity of 1,4-dioxane and quantitative analysis of its mutagenicity and carcinogenicity in rats, Archives of Toxicology 92:3207–3221

  • Paul A. WhiteEmail author
  • Andreas Zeller
  • Stefan Pfuhler
  • George E. Johnson
Letter to the Editor, News and Views

Gi et al. recently published an in vivo genotoxicity study of 1,4-dioxane, examining, amongst other endpoints, treatment-induced transgene mutations in the livers of gpt delta rats (Gi et al. 2018). The authors employed the BMDS and PROAST software packages to analyze the dose–response data and determine a point of departure (PoD) metric known as the BMD or Benchmark Dose. With respect to BMDS, the authors used one standard deviation of the concurrent control group as the benchmark response (BMR), and determined the lower confidence limit of the BMD1SD (i.e., the BMDL1SD). With respect to PROAST, they used 10% increase over the mean concurrent control group as the BMR, also known as the critical effect size (CES), and determined the lower confidence limit of the BMD10 (i.e., the BMDL10). The authors also examined the no observed effect level (NOEL), the highest tested dose that failed to elicit a significant increase in response relative to the concurrent control.

The authors’...


  1. Barlow S, Renwick AG, Kleiner J, Bridges JW, Busk L, Dybing E, Edler L, Eisenbrand G, Fink-Gremmels J, Knaap A, Kroes R, Liem D, Muller DJ, Page S, Rolland V, Schlatter J, Tritscher A, Tueting W, Wurtzen G (2006) Risk assessment of substances that are both genotoxic and carcinogenic report of an International Conference organized by EFSA and WHO with support of ILSI Europe. Food Chem Toxicol 44:1636–1650CrossRefGoogle Scholar
  2. Benford D, Bolger PM, Carthew P, Coulet M, DiNovi M, Leblanc JC, Renwick AG, Setzer W, Schlatter J, Smith B, Slob W, Williams G, Wildemann T (2010) Application of the Margin of Exposure (MOE) approach to substances in food that are genotoxic and carcinogenic. Food Chem Toxicol 48(Suppl 1):S2–S24. CrossRefGoogle Scholar
  3. Gi M, Fujioka M, Kakehashi A, Okuno T, Masumura K, Nohmi T, Matsumoto M, Omori M, Wanibuchi H, Fukushima S (2018) In vivo positive mutagenicity of 1,4-dioxane and quantitative analysis of its mutagenicity and carcinogenicity in rats. Arch Toxicol 92:3207–3221. CrossRefGoogle Scholar
  4. Johnson GE, Soeteman-Hernandez LG, Gollapudi BB, Bodger OG, Dearfield KL, Heflich RH, Hixon JG, Lovell DP, MacGregor JT, Pottenger LH, Thompson CM, Abraham L, Thybaud V, Tanir JY, Zeiger E, van Benthem J, White PA (2014) Derivation of point of departure (PoD) estimates in genetic toxicology studies and their potential applications in risk assessment. Environ Mol Mutagen 55:609–623. CrossRefGoogle Scholar
  5. Wills JW, Johnson GE, Battaion HL, Slob W, White PA (2017) Comparing BMD-derived genotoxic potency estimations across variants of the transgenic rodent gene mutation assay. Environ Mol Mutagen 58:632–643. CrossRefGoogle Scholar
  6. Zeller A, Duran-Pacheco G, Guerard M (2017) An appraisal of critical effect sizes for the benchmark dose approach to assess dose-response relationships in genetic toxicology. Arch Toxicol 91:3799–3807. CrossRefGoogle Scholar

Copyright information

© © Crown 2018

Authors and Affiliations

  • Paul A. White
    • 1
    Email author
  • Andreas Zeller
    • 2
  • Stefan Pfuhler
    • 3
  • George E. Johnson
    • 4
  1. 1.Environmental Health Science and Research Bureau, Health CanadaOttawaCanada
  2. 2.Pharmaceutical SciencespRED Innovation Center Basel, F. Hoffmann-La Roche LtdBaselSwitzerland
  3. 3.The Procter & Gamble CompanyMason Business CentreMasonUSA
  4. 4.Swansea University Medical SchoolSwansea UniversitySwanseaUK

Personalised recommendations