Models of quantitative relationship “Structure – activity” in performing preliminary toxicological assessment of chemicals
- Authors: Guseva E.A.1, Nikolayeva N.I.1, Filin A.S.1, Rasskazova Y.V.1, Onishchenko G.G.1
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Affiliations:
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
- Issue: Vol 102, No 10 (2023)
- Pages: 1108-1111
- Section: PREVENTIVE TOXICOLOGY AND HYGIENIC STANDARTIZATION
- Published: 24.11.2023
- URL: https://rjpbr.com/0016-9900/article/view/638323
- DOI: https://doi.org/10.47470/0016-9900-2023-102-10-1108-1111
- EDN: https://elibrary.ru/npiccp
- ID: 638323
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Abstract
Introduction. In vivo testing of a huge number of chemical compounds is difficult from an ethical point of view, time-consuming, depends on a large number of objects of animal origin and requires large material costs for conducting experiments. Therefore, there is a need for new thinking to optimize the conduct of toxicological studies.
The purpose of this study is to substantiate the possibility of using structure-activity models in the framework of a preliminary assessment of chemicals toxicity.
Materials and methods. The study included three groups of chemicals including organothiophosphates, triazoles, and carbamates. The calculation of descriptors based on SMILES, the construction and validation of regression models was carried out using the tools of the Scikit-learn Version 1.2.2 library in an interactive cloud environment working with the Google Colaboratory program code.
Results. When comparing a number of models for predicting oral toxicity, it was revealed that a model based on decision trees has the best predictive ability for organothiophosphates and triazoles: 70.1% and 69.5% of cases of descriptor changes led to a change in the endpoint value, respectively; a model for predicting carbamate toxicity based on a random forest explains 53.1% of the observed variance common log (1/DL50).
Limitations. The study is limited to the area of distribution of the obtained mathematical models.
Conclusion. As the study showed, the constructed models can explain only some part of the studied effect, therefore, models based on the structure-activity relationship should be used exclusively for preliminary assessment of the toxicity of chemicals, as a screening tool.
Compliance with ethical standards. The study does not require the submission of the conclusion of the biomedical ethics committee or other documents.
Contribution:
Guseva E.A. — the concept and design of the study, collection and processing of material, writing a text;
Nikolayeva N.I. — writing a text, editing;
Filin A.S. — editing;
Rasskazova Yu.V. — collection and processing of material, editing;
Onishchenko G.G. — editing.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version
Conflict of interest. The authors declare no conflict of interest.
Acknowledgement. The study had no sponsorship.
Received: June 30, 2023 / Accepted: September 26, 2023 / Published: November 20, 2023
Keywords
About the authors
Ekaterina A. Guseva
I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
Author for correspondence.
Email: guseva_e_a@staff.sechenov.ru
ORCID iD: 0000-0001-8389-7981
Assistant of the Department of Human Ecology and Environmental Hygiene of the Institute of Public Health named after F.F. Erisman, Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University), Moscow, 199911, Russian Federation
e-mail: guseva_e_a@staff.sechenov.ru
Russian FederationNatalia I. Nikolayeva
I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
Email: fake@neicon.ru
ORCID iD: 0000-0003-1226-9990
Доктор медицинских наук, профессор кафедры экологии человека и гигиены окружающей среды Института общественного здоровья им. Ф.Ф. Эрисмана, ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет), 199911, Москва, Россия
Russian FederationAndrey S. Filin
I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
Email: fake@neicon.ru
ORCID iD: 0000-0002-9724-8410
Кандидат медицинских наук, доцент кафедры экологии человека и гигиены окружающей среды Института общественного здоровья им. Ф.Ф. Эрисмана, ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет), 199911, Москва, Россия
Russian FederationYulia V. Rasskazova
I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
Email: fake@neicon.ru
ORCID iD: 0009-0001-5772-2333
Студентка 6 курса Института общественного здоровья им.Ф.Ф. Эрисмана, ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет), 199911, Москва, Россия
Russian FederationGennadiy G. Onishchenko
I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
Email: fake@neicon.ru
ORCID iD: 0000-0003-0135-7258
Заведующий кафедры экологии человека и гигиены окружающей среды Института общественного здоровья им. Ф.Ф.Эрисмана, ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет), 199911, Москва, Россия
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