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R Soc Open Sci
R Soc Open Sci
RSOS
royopensci
Royal Society Open Science
2054-5703
The Royal Society

rsos241011
10.1098/rsos.241011
1001199Chemistry
Comment
Comment regarding: ‘On the solubility of azodicarbonamide in water/DMSO mixtures: an experimental and computational study’ (2024), by Macetti et al.
Comment regarding: ‘On the solubility of azodicarbonamide in water/DMSO mixtures: an experimental and computational study’ (2024), by Macetti et al.
https://orcid.org/0009-0001-7629-2527
Arts Josje 1 Writing – review and editing josje.arts@nouryon.com

Kimber Ian 2 Writing – review and editing ian.kimber@manchester.ac.uk

1 Nouryon, Zutphenseweg 10 , 7418 AJ Deventer, The Netherlands
2 Faculty of Biology, Medicine and Health, University of Manchester , Manchester M13 9PL, UK
This article has been edited by the Royal Society of Chemistry, including the commissioning, peer review process and editorial aspects up to the point of acceptance.

9 2024
11 9 2024 September 11, 2024
11 9 2024 September 11, 2024
11 9 24101114 6 2024 June 14, 2024
13 8 2024 August 13, 2024
© 2024 The Author(s).
2024
https://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

respiratory allergy
; respiratory sensitization
; ADCA
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pmcAccording to Macetti et al. [1], in the Introduction section of their recent paper, reference is made to two published papers as follows: Even though ADCA is still employed in the production of foamed plastics [2], it was classified as a respiratory sensitizing agent (H334: May cause allergy or asthma symptoms or breathing difficulties if inhaled) as for CLP (Classification, Labelling and Packaging) Regulation (EC) No. 1272/2008, generating concerns especially at chemical industries where it is manufactured and used [3].

In our paper [2], we stated that although azodicarbonamide (ADCA, CAS no. 123-77-3) had been officially classified as a respiratory sensitizer, the purpose of our article was to consider whether this classification is appropriate based on clinical experience and relevant experimental data. We concluded that although there have been reports of an association between workplace exposure to ADCA and respiratory symptoms and occupational asthma, the evidence is considerably less than persuasive, with in many instances there being a lack of properly controlled and executed diagnostic procedures. In addition, ADCA fails to elicit positive responses in mouse and guinea pig predictive tests for skin sensitization—a lack of activity that is regarded as being inconsistent with respect to respiratory sensitizing potential. In addition, the German MAK Commission [4] indicated with respect to ADCA that the decisive factor for the assessment of a possible sensitizing potential is that none of the studies reported the origin, identity and purity of the substance that was causative at the workplace or used for diagnostics and that, in view of the numerous potential additives present during the production or use of ADCA, the substance is not clearly identifiable as the cause of the effects. Moreover, available results on metabolism and considerations on the reactivity and mode of action of the compound do not clearly point to protein binding in vivo, which would be a prerequisite for a sensitizing potential on the skin or airways, and thus the available data are not sufficient to demonstrate sensitizing effects for ADCA.

Collectively, the data reviewed in the paper by Arts & Kimber [2] and cited as reference number 4 by Macetti et al. in their recent paper [1] do not provide a sound basis for the classification of ADCA as a respiratory allergen.

Indeed, ADCA is widely used by industry in the manufacture of a variety of products, and it was noted [2] that, with only a single exception, associations between workplace exposure to ADCA and symptoms of respiratory allergy were reported before 2000, and in only three cases [5,6] were the symptoms and clinical investigations well documented. In addition, according to the MAK Commission [4], although ADCA has also been used as a blowing agent in Germany for a long time, no cases of sensitization have been observed.

It is, therefore, highly remarkable that Macetti et al. [1] are drawing inappropriate conclusions based upon a paper [3] published a quarter of a century ago.

Ethics

This work did not require ethical approval from a human subject or animal welfare committee.

Data accessibility

This article has no additional data.

Declaration of AI use

We have not used AI-assisted technologies in creating this article.

Authors’ contributions

J.A.: writing—review and editing; I.K.: writing—review and editing.

Both authors gave final approval for publication and agreed to be held accountable for the work performed herein.

Conflict of interest declaration

We declare we have no competing interests.

Funding

No funding has been received for this article.
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References

1. Macetti G, Sironi L, Rovida C, Geremia I, Soave R, Presti LL. 2024 On the solubility of azodicarbonamide in water/DMSO mixtures: an experimental and computational study. R. Soc. open sci. 11 , 231831. (10.1098/rsos.231831)39100163
2. Arts J, Kimber I. 2017 Azodicarbonamide (ADCA): a reconsideration of classification as a respiratory sensitiser. Regul. Toxicol. Pharmacol. 89 , 268–278. (10.1016/j.yrtph.2017.07.018)28734852
3. Cary R, Dobson S, Ball M. 1999 Azodicarbonamide. Concise International Chemical Assessment, document no. 16. Geneva, Switzerland: World Health Organization. See https://www.inchem.org/documents/cicads/cicads/cicad16.htm.
4. Hartwig A, MAK Commission. 2018 Azodicarbonamide/1,2-diazenedicarboxamide. In The MAK collection for occupational health and safety, vol. 3 , pp. 1034–1074. Weinheim, Germany: Wiley. (10.1002/3527600418)
5. Malo JL, Pineau L, Cartier A. 1985 Occupational asthma due to azobisformamide. Clin. Allergy 15 , 261–264. (10.1111/j.1365-2222.1985.tb02283.x)4006176
6. Kim CW, Cho JH, Leem JH, Ryu JS, Lee HL, Hong YC. 2004 Occupational asthma due to azodicarbonamide. Yonsei Med. J. 45 , 325–329. (10.3349/ymj.2004.45.2.325)15119006
