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Letter to the editor regarding recent publication titled “Developing an internal threshold of toxicological concern (iTTC)” by Arnot et al. (2022)

Journal of Exposure Science & Environmental Epidemiology volume 33, pages 840–841 (2023)Cite this article

We are writing in regard to a recent paper by Arnot et al. (J Expo Sci Environ Epidemiol. 2022 Nov;32(6):877-884.). The paper focused on the internal threshold of toxicological concern (iTTC), a risk assessment tool that scientists at Procter and Gamble (P&G) and Arnot and co-authors have independently put effort into developing. The approaches that Arnot et al. used resulted in calculated values that are considerably lower than previously derived interim iTTC values. In seeking to understand the reasons for such differences, the P&G group identified specific areas in the Arnot et al. paper that could raise questions or concerns that would benefit from clarification and further elaboration. The P&G group discussed these specific areas with Arnot and colleagues, and because of our mutual interest in advancing the science and utility of the iTTC approach, we decided to address these areas and provide clarifications by jointly submitting a letter to the editor.

Briefly, the threshold of toxicological concern (TTC) approach involves selecting conservative toxicity data (e.g., dividing the 5th percentile of a cumulative distribution of No Observed Adverse Effect Levels (NOAELs) from chronic oral systemic toxicity studies for a set of chemicals by appropriate uncertainty factors) to establish a low-level acceptable exposure value for which there is an extremely small probability of adverse effects occurring [1]. For substances with sparse toxicity data, the TTC can be used in lieu of chemical-specific experimentally derived health guidance values to help interpret predicted or measured exposure data in a human health risk context (exposures below the TTC are considered negligible risk).

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Authors and Affiliations

  1. The Procter & Gamble Company, 8700 Mason Montgomery Road, Cincinnati, OH, 45040, USA

    Corie A. Ellison, Susan P. Felter & George P. Daston

  2. ARC Arnot Research and Consulting Inc., Toronto, ON, Canada

    Jon A. Arnot, Liisa Toose, James M. Armitage, Alessandro Sangion, Alexandra Looky & Trevor N. Brown

  3. Department of Physical and Environmental Sciences, University of Toronto Scarborough, Toronto, ON, Canada

    Jon A. Arnot & Alessandro Sangion

  4. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada

    Jon A. Arnot

  5. American Chemistry Council, Washington, DC, USA

    Richard A. Becker

  6. School of Public Health, University of Nevada Reno, Reno, NV, USA

    Li Li

Authors
  1. Corie A. Ellison
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  2. Jon A. Arnot
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  3. Susan P. Felter
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  4. George P. Daston
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  5. Richard A. Becker
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  6. Liisa Toose
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  7. James M. Armitage
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  8. Alessandro Sangion
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  9. Alexandra Looky
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  10. Trevor N. Brown
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  11. Li Li
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Contributions

CAE, JAA, SPF, GPD and RAB drafted the first versions of the letter. CAE, JAA, SPF, GPD, RAB LT, JMA, AS, AL, TNB and LL contributed toward editing the letter to its final version.

Corresponding author

Correspondence to Corie A. Ellison.

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The authors declare no competing interests.

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Ellison, C.A., Arnot, J.A., Felter, S.P. et al. Letter to the editor regarding recent publication titled “Developing an internal threshold of toxicological concern (iTTC)” by Arnot et al. (2022). J Expo Sci Environ Epidemiol 33, 840–841 (2023). https://doi.org/10.1038/s41370-023-00571-9

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