Issues in the inhalation toxicity testing and hazard assessment for low density particulate materials such as synthetic amorphous silica (SAS)

Wolfgang Dekant; Evangelia E. Antoniou; Axel Bosch; Gustav Gerd Bruer; Thomas Colnot; Otto Creutzenberg; Claus Peter Drexel; Rodger Duffin; Nils Krueger; Jürgen Nolde; Craig Poland; Dirk Schaudien; Tobias B. Schuster; Michael Stintz; Klaus Weber; Benno Wessely; Maurice P. Zeegers

doi:10.1016/j.toxlet.2023.02.002

Issues in the inhalation toxicity testing and hazard assessment for low density particulate materials such as synthetic amorphous silica (SAS)

Wolfgang Dekant^*
, Evangelia E. Antoniou
, Axel Bosch
, Gustav Gerd Bruer
, Thomas Colnot
, Otto Creutzenberg
, Claus Peter Drexel
, Rodger Duffin
, Nils Krueger
, Jürgen Nolde
, Craig Poland
, Dirk Schaudien
, Tobias B. Schuster
, Michael Stintz
, Klaus Weber
, Benno Wessely
, Maurice P. Zeegers

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Inhalation toxicity testing of particulate materials is mandated for classification. According to CLP, particulate materials should be tested as marketed and many particulate materials are marketed as non-respirable particles. However, OECD TG 413 requires exposure to particle sizes that are respirable and reach the alveoli. The requirement for exposure of rats to respirable particles is thus in contrast to CLP and requires the application of high shear forces. The exposure to artificially small particles causes a number of issues that hamper the interpretation of the results of the testing. These issues are aerosol altering in the exposure system, assessment of the adversity of the inflammatory lung responses, inclusion of recovery groups, and extrapolation of the results to humans exposed under occupational condition. In addition, effects of many particulate materials after testing according to OECD 413 are not intrinsic properties, but a general reaction of the lung to the deposited material, show very similar NOAECs for chemical diverse materials, and often are completely reversible.

Original language	English
Pages (from-to)	2-11
Number of pages	10
Journal	Toxicology Letters
Volume	399
Early online date	1 Jan 2023
DOIs	https://doi.org/10.1016/j.toxlet.2023.02.002
Publication status	Published - Aug 2024

Keywords

Classification and labelling
Inhalation toxicity
Lung responses
OECD TG 413
Particulate materials

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10.1016/j.toxlet.2023.02.002Licence: CC BY-NC-ND

Correction: Belimumab for Treating Active Autoantibody-Positive Systemic Lupus Erythematosus: An Evidence Review Group Perspective of a NICE Single Technology Appraisal
Otten, T., Riemsma, R., Wijnen, B., Armstrong, N., Stirk, L., Gordon, C., Ramaekers, B., Kleijnen, J., Joore, M. & Grimm, S., Nov 2023, In: Pharmacoeconomics. 41, 11, p. 1551-1551 1 p.
Research output: Contribution to journal › Erratum / corrigendum › Academic

Open Access
Corrigendum to “Issues in the inhalation toxicity testing and hazard assessment for low density particulate materials such as synthetic amorphous silica (SAS)” [Toxicol. Lett. (in press)] (Toxicology Letters, (S0378427423000905), (10.1016/j.toxlet.2023.02.002))
Dekant, W., Antoniou, E. E., Bosch, A., Bruer, G. G., Colnot, T., Creutzenberg, O., Drexel, C.-P., Duffin, R., Krueger, N., Nolde, J., Poland, C., Schaudien, D., Schuster, T. B., Stintz, M., Weber, K., Wessely, B. & Zeegers, M. P., 15 Aug 2023, In: Toxicology Letters. 385, p. 29-30 2 p.
Research output: Contribution to journal › Erratum / corrigendum › Academic

Open Access

Cite this

Dekant, W., Antoniou, E. E., Bosch, A., Bruer, G. G., Colnot, T., Creutzenberg, O., Drexel, C. P., Duffin, R., Krueger, N., Nolde, J., Poland, C., Schaudien, D., Schuster, T. B., Stintz, M., Weber, K., Wessely, B., & Zeegers, M. P. (2024). Issues in the inhalation toxicity testing and hazard assessment for low density particulate materials such as synthetic amorphous silica (SAS). Toxicology Letters, 399, 2-11. https://doi.org/10.1016/j.toxlet.2023.02.002

@article{361c9a20830a4fa0ac6255b8b5c6e214,

title = "Issues in the inhalation toxicity testing and hazard assessment for low density particulate materials such as synthetic amorphous silica (SAS)",

abstract = "Inhalation toxicity testing of particulate materials is mandated for classification. According to CLP, particulate materials should be tested as marketed and many particulate materials are marketed as non-respirable particles. However, OECD TG 413 requires exposure to particle sizes that are respirable and reach the alveoli. The requirement for exposure of rats to respirable particles is thus in contrast to CLP and requires the application of high shear forces. The exposure to artificially small particles causes a number of issues that hamper the interpretation of the results of the testing. These issues are aerosol altering in the exposure system, assessment of the adversity of the inflammatory lung responses, inclusion of recovery groups, and extrapolation of the results to humans exposed under occupational condition. In addition, effects of many particulate materials after testing according to OECD 413 are not intrinsic properties, but a general reaction of the lung to the deposited material, show very similar NOAECs for chemical diverse materials, and often are completely reversible.",

keywords = "Classification and labelling, Inhalation toxicity, Lung responses, OECD TG 413, Particulate materials",

author = "Wolfgang Dekant and Antoniou, \{Evangelia E.\} and Axel Bosch and Bruer, \{Gustav Gerd\} and Thomas Colnot and Otto Creutzenberg and Drexel, \{Claus Peter\} and Rodger Duffin and Nils Krueger and J{\"u}rgen Nolde and Craig Poland and Dirk Schaudien and Schuster, \{Tobias B.\} and Michael Stintz and Klaus Weber and Benno Wessely and Zeegers, \{Maurice P.\}",

note = "Funding Information: This work was supported by SASforREACH , a consortium of the producers of synthetic amorphous silica. Authors were compensated for their time spent on manuscript preparation based on their usual consulting fees. Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2024",

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doi = "10.1016/j.toxlet.2023.02.002",

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Dekant, W, Antoniou, EE, Bosch, A, Bruer, GG, Colnot, T, Creutzenberg, O, Drexel, CP, Duffin, R, Krueger, N, Nolde, J, Poland, C, Schaudien, D, Schuster, TB, Stintz, M, Weber, K, Wessely, B & Zeegers, MP 2024, 'Issues in the inhalation toxicity testing and hazard assessment for low density particulate materials such as synthetic amorphous silica (SAS)', Toxicology Letters, vol. 399, pp. 2-11. https://doi.org/10.1016/j.toxlet.2023.02.002

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T1 - Issues in the inhalation toxicity testing and hazard assessment for low density particulate materials such as synthetic amorphous silica (SAS)

AU - Dekant, Wolfgang

AU - Antoniou, Evangelia E.

AU - Bosch, Axel

AU - Bruer, Gustav Gerd

AU - Colnot, Thomas

AU - Creutzenberg, Otto

AU - Drexel, Claus Peter

AU - Duffin, Rodger

AU - Krueger, Nils

AU - Nolde, Jürgen

AU - Poland, Craig

AU - Schaudien, Dirk

AU - Schuster, Tobias B.

AU - Stintz, Michael

AU - Weber, Klaus

AU - Wessely, Benno

AU - Zeegers, Maurice P.

N1 - Funding Information: This work was supported by SASforREACH , a consortium of the producers of synthetic amorphous silica. Authors were compensated for their time spent on manuscript preparation based on their usual consulting fees. Publisher Copyright: © 2023 The Authors

PY - 2024/8

Y1 - 2024/8

N2 - Inhalation toxicity testing of particulate materials is mandated for classification. According to CLP, particulate materials should be tested as marketed and many particulate materials are marketed as non-respirable particles. However, OECD TG 413 requires exposure to particle sizes that are respirable and reach the alveoli. The requirement for exposure of rats to respirable particles is thus in contrast to CLP and requires the application of high shear forces. The exposure to artificially small particles causes a number of issues that hamper the interpretation of the results of the testing. These issues are aerosol altering in the exposure system, assessment of the adversity of the inflammatory lung responses, inclusion of recovery groups, and extrapolation of the results to humans exposed under occupational condition. In addition, effects of many particulate materials after testing according to OECD 413 are not intrinsic properties, but a general reaction of the lung to the deposited material, show very similar NOAECs for chemical diverse materials, and often are completely reversible.

AB - Inhalation toxicity testing of particulate materials is mandated for classification. According to CLP, particulate materials should be tested as marketed and many particulate materials are marketed as non-respirable particles. However, OECD TG 413 requires exposure to particle sizes that are respirable and reach the alveoli. The requirement for exposure of rats to respirable particles is thus in contrast to CLP and requires the application of high shear forces. The exposure to artificially small particles causes a number of issues that hamper the interpretation of the results of the testing. These issues are aerosol altering in the exposure system, assessment of the adversity of the inflammatory lung responses, inclusion of recovery groups, and extrapolation of the results to humans exposed under occupational condition. In addition, effects of many particulate materials after testing according to OECD 413 are not intrinsic properties, but a general reaction of the lung to the deposited material, show very similar NOAECs for chemical diverse materials, and often are completely reversible.

KW - Classification and labelling

KW - Inhalation toxicity

KW - Lung responses

KW - OECD TG 413

KW - Particulate materials

U2 - 10.1016/j.toxlet.2023.02.002

DO - 10.1016/j.toxlet.2023.02.002

M3 - Article

C2 - 36806657

SN - 0378-4274

VL - 399

SP - 2

EP - 11

JO - Toxicology Letters

JF - Toxicology Letters

ER -

Issues in the inhalation toxicity testing and hazard assessment for low density particulate materials such as synthetic amorphous silica (SAS)

Abstract

Keywords

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Research output

Correction: Belimumab for Treating Active Autoantibody-Positive Systemic Lupus Erythematosus: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

Corrigendum to “Issues in the inhalation toxicity testing and hazard assessment for low density particulate materials such as synthetic amorphous silica (SAS)” [Toxicol. Lett. (in press)] (Toxicology Letters, (S0378427423000905), (10.1016/j.toxlet.2023.02.002))

Cite this