Approaches to hazard assessment and classification of chemicals with sensitizing effects

Introduction. The World Health Organization considers sensitizing effects to be effects that require close attention, especially in terms of research and regulation, due to the high allergenic background among the population, including the Russian Federation. The allergic effect of chemicals is taken into account when organizing the workflow, conducting a special assessment of working conditions, preliminary and periodic medical examinations of employees, etc. Many hygienic standards for substances in the air of the work area were justified in the 50s and 80s. of the last century and may not fully reflect the real picture of the danger. Currently, the international community has developed new approaches to testing, assessing and classifying the hazards of chemicals by sensitizing effects, and therefore the regulatory and methodological framework of the Russian Federation also requires updating.

The study aims to harmonize domestic and foreign approaches to the study and assessment of exposure and to develop a national list of chemicals that cause sensitization of the skin and/or respiratory tract, classified in accordance with the Globally Harmonized System of Hazard Classification and Labelling of Chemical Products (GHS).

Materials and methods. The experts have analyzed national and international approaches to the assessment, classification of hazards and regulation of chemicals with sensitizing effects; documents from United Nations agencies, scientific articles, monographs, information from official national and foreign databases on sensitizing effects.

Results. The article presents a phasing scheme for conducting a study on the study of sensitizing effects, in which in vivo methods are a priority. The harmonization of international approaches to the assessment of the GHS effect with domestic experimental practice has been carried out. A national list of chemicals with sensitizing effects has been formed, which includes 1186 names, of which 928 are skin sensitizers, 23 are respiratory, and 235 are substances with both skin and respiratory sensitization. The necessity of developing and (or) updating hygienic standards in the air of the working area, taking into account this type of exposure, is indicated.

Limitations. The national list of chemicals with sensitizing effects, developed on the basis of the results of experimental studies presented in open sources of information, is not exhaustive.

Conclusion. The authors have carried out the harmonization of domestic and foreign approaches to the study and assessment of the sensitizing effects of chemicals in order to update the regulatory and methodological bases of the Russian Federation. Scientists have proposed a classification of the dangers of skin sensitizers in accordance with the GHS using in vivo research methods introduced into the practice of domestic toxicology. They have compiled a national list of chemicals that cause sensitization of the skin and/or respiratory organs, which can be used to identify substances that are a priority for regulating the content in the air of the work area, and update existing regulations taking into account this type of exposure.

Ethics. The study does not require an opinion from the Bioethics Commission.

Contributions:
Khamidulina H.H. — concept and design of research, collection and processing of material, writing and editing of text;
Tarasova E.V. — concept and design of research, collection and processing of material, writing and editing of text;
Dorofeeva E.V. — writing and editing text;
Zamkova I.V. — writing and editing text;
Proskurina A.S. — writing and editing text;
Rabikova D.N. — writing and editing text;
Nazarenko A.K. — writing and editing text;
Lastovetsky M.L. — writing and editing text;
Araslanov I.N. — writing and editing text;
Aniskova Yu.Y. — writing and editing text;
Balashov P.E. — writing and editing text.

Funding. The study was carried out as part of the research project "Validation of alternative research methods in assessing the hazards and risks of exposure to chemicals on human health as a tool for regulating the safety of a chemical factor".

Conflict of interest. The authors declare no conflict of interest.

Received: 02.12.2025 / Accepted: 10.12.2025 / Published: 20.12.2025

1. Bormann J.L., Maibach H.I. Draize human repeat insult patch test (HRIPT): Seven decades of pitfalls and progress. Regul. Toxicol. Pharmacol. 2021; 121: 104867. https://doi.org/10.1016/j.yrtph.2021.104867

2. Basketter DA. The human repeated insult patch test in the 21st century: a commentary. Cutan. Ocul. Toxicol. 2009; 28(2): 49–53. https://doi.org/10.1080/15569520902938032

3. Khamidulina Kh.Kh., Rabikova D.N. Development of the national list of carcinogens, mutagens and reprotoxicants and its implementation in the regulation of the circulation of chemicals over the territory of the Russian Federation and member states of the Eurasian economic union. Gigiena i sanitariya. 2021; 100(9): 897–902. https://doi.org/10.47470/0016-9900-2021-100-9-897-902 (in Russian).

4. Khamidulina Kh.Kh., Tarasova E.V., Nazarenko A.K., Rabikova D.N., Proskurina A.S. Proposals for improving the methodic and regulatory framework of the Russian Federation in the field of chemical safety. Toksikologicheskij vestnik. 2023; 31(4): 214–225. https://doi.org/10.47470/0869-7922-2023-31-4-214-225 (in Russian).

5. Khamidulina Kh.Kh., Rabikova D.N., Tarasova E.V., Sinitskaya T.A., Zamkova I.V., Nazarenko A.K. Modern approaches to the assessment and classification of the hazard posed by substances with mutagenic effects. Health Risk Analysis. 2024; 4: 4–13. https://doi.org/10.21668/health.risk/2024.4.01.eng (in Russian).

6. Bloemen K., Verstraelen S., Van Den Heuvel R., Witters H., Nelissen I., Schoeters G. The allergic cascade: review of the most important molecules in the asthmatic lung. Immunol. Lett. 2007; 113(1): 6–18. https://doi.org/10.1016/j.imlet.2007.07.010

7. Makarova M.N., Makarov V.G. Alternative methods for studying toxicity. Bioethical principles. Laboratory Animals for Science. 2022; 01: 52–76. https://doi.org/10.29296/2618723X-2022-01-07 (in Russian).

8. Pemberton M.A., Kimber I. Classification of chemicals as respiratory allergens based on human data: Requirements and practical considerations. Regul. Toxicol. Pharmacol. 2021; 123: 104925. https://doi.org/10.1016/j.yrtph.2021.104925

9. Palmer B., Gao Y., Ryan C., Kern P. Skin sensitisation elicitation: Evaluation of the general threshold and considerations for use. Contact Dermatitis. 2025; 92(3): 197–208. https://doi.org/10.1111/cod.14718

10. Hargitai R., Parráková L., Szatmári T., Monfort-Lanzas P., Galbiati V., Audouze K. et al. Chemical respiratory sensitization-Current status of mechanistic understanding, knowledge gaps and possible identification methods of sensitizers. Front. Toxicol. 2024; 6: 1331803. https://doi.org/10.3389/ftox.2024.1331803

11. Tiotiu A.I., Novakova S., Labor M., Emelyanov A., Mihaicuta S., Novakova P. et al. Progress in Occupational Asthma. Int. J. Environ. Res. Public Health. 2020; 17(12): 4553. https://doi.org/10.3390/ijerph17124553

12. Stuart M. Brooks, Understanding RADS. J. Clin. Cases Rep. 2019; 3(4): 126–138. https://doi.org/10.46619/joccr.2020.3-1071

13. Roio L.C.D., Mizutani R.F., Pinto R.C., Terra-Filho M., Santos U.P. Work-related asthma. J. Bras. Pneumol. 2021; 47(4): e20200577. https://doi.org/10.36416/1806-3756/e20200577

14. Cochrane S.A., Arts J.H.E., Ehnes C., Hindle S., Hollnagel H.M., Poole A., Suto H., Kimber I. Thresholds in chemical respiratory sensitisation. Toxicology. 2015; 333: 179–194. https://doi.org/10.1016/j.tox.2015.04.010

15. Vincent M.J., Bernstein J.A., Basketter D., LaKind J.S., Dotson G.S., Maier A. Chemical-induced asthma and the role of clinical, toxicological, exposure and epidemiological research in regulatory and hazard characterization approaches. Regul. Toxicol. Pharmacol. 2017; 90: 126–132. https://doi.org/10.1016/j.yrtph.2017.08.018

16. Gad S.C., Dunn B.J., Dobbs D.W., Reilly C., Walsh R.D. Development and validation of an alternative dermal sensitization test: the mouse ear swelling test (MEST). Toxicol. Appl. Pharmacol. 1986; 84(1): 93–114. https://doi.org/10.1016/0041-008x(86)90419-9

17. Khamidulina Kh.Kh., Tarasova E.V., Lastovetskiy M.L. Prognostic systems in preventive toxicology (literature review). Toxicological Review. 2025; 33(2): 134–143. https://doi.org/10.47470/0869-7922-2025-33-2-134-143 https://elibrary.ru/fxrxwa (in Russian).

18. Aleksic M., Rajagopal R., de-Ávila R., Spriggs S., Gilmour N. The skin sensitization adverse outcome pathway: exploring the role of mechanistic understanding for higher tier risk assessment. Crit. Rev. Toxicol. 2024; 54(2): 69–91. https://doi.org/10.1080/10408444.2024.2308816

19. Nishijo T., Api A.M., Gerberick G.F., Miyazawa M., Na M., Sakaguchi H. Implementation of a dermal sensitization threshold (DST) concept for risk assessment: structure-based DST and in vitro data-based DST. Crit. Rev. Toxicol. 2022; 52(1): 51–65. https://doi.org/10.1080/10408444.2022.2033162

20. Chilton M.L., Api A.M. et al. Updating the Dermal Sensitisation Thresholds using an expanded dataset and an in silico expert system. Regul. Toxicol. Pharmacol. 2022; 133: 105200. https://doi.org/10.1016/j.yrtph.2022.105200