Characterization of a chloroacetanilide derivative in a chronic oral toxicology study in rats

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Abstract

Introduction. For the treatment of agricultural crops, an original herbicide of selective action was created — propisochlor, a derivative of chloroacetanilide. Its characteristics in an acute toxicological experiment didn’t reveal the features of the pathogenesis of intoxication. The identification of regularities in the manifestation of the toxic properties of propisochlor in various regimens with the oral route of exposure is necessary at the stage of production design. Moreover, it is necessary to substantiate a number of hygienic regulations for safe production and its further application in agriculture, which lies in the plane of solving the leading state tasks aimed at protecting human health and its environment, and meets the requirements of international legislation. A special role in the development of such methods and methods belongs to the sanitary-toxicological study of new xenobiotics and generic molecules, as a result of which threshold and subthreshold doses of pesticide preparations and their active substances are determined.

The aim of this study was to characterize propisochlor in a chronic oral toxicology study in rats. To achieve the goal, it was necessary to solve the following tasks: to study the chronic oral effect of the chloroacetanilide derivative on the rat organism; establish a dose that does not have a visible undesirable effect (NOELch); set the lowest dose at which no adverse effects are observed (LOAELch); calculate the allowable daily intake, or allowable daily exposure (ADD, or ADI, or PDE) for a person.

Material and methods. The object of testing in this work was a herbicide from the class of chloroacetanilide, propisochlor. The test system in the chronic experiment was white male rats, on which the influence of the test compound was evaluated in dynamics after 1, 3, 6 and 12 months according to the state of integral indicators.

Results. The parameters of the oral toxicity of the test compound were determined and the changes in the studied integral indicators were evaluated at various stages of the experiment in a chronic experiment.

Conclusion. Based on the comparative characterization of a new herbicide propisochlor in a chronic oral toxicology study in rats, a non-acting dose (NOEL), the lowest effective dose (LOAEL), and an acceptable daily dose for humans (ADI, or PDE) are justified.

Compliance with ethical standards. the study was approved by the Commission on Bioethics of F.F. Erisman Federal Scientific Center of Hygiene of Rospotrebnadzor, carried out in accordance with the European Convention for the Protection of Vertebrate Animals used for Experimental or other Scientific Purposes (ETS No. 123), Directive of the European Parliament and the Council of the European Union 2010/63/EU of September 22, 2010 on the protection of animals used for scientific purposes.

Author contribution. All co-authors made an equal contribution to the research and preparation of the article for publication.

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

Funding. The study was not sponsored.

Received: June 08, 2022 / Accepted: January 2023 / Published: February 28, 2023

About the authors

Natal’ya Sergeevna Beloedova

Federal Budgetary Establishment of Science «F.F. Erisman Federal Scientific Center of Hygiene» of the Federal Service for Surveillance on Consumer Rights Protection and Human Well-being

Author for correspondence.
Email: beloedovans@fferisman.ru
ORCID iD: 0000-0002-8090-1962

Кандидат биол. наук, старший научный сотрудник ФБУН «ФНЦГ им. Ф.Ф. Эрисмана» Роспотребнадзора, 141014, Мытищи, Российская Федерация.

e-mail: beloedovans@fferisman.ru

Russian Federation

Tatiana Alekseevna Sinitskaya

Federal Budgetary Establishment of Science «F.F. Erisman Federal Scientific Center of Hygiene» of the Federal Service for Surveillance on Consumer Rights Protection and Human Well-being

Email: sinitskaiata@fferisman.ru
ORCID iD: 0000-0003-1344-3866

Член-корреспондент РАН, доктор медицинских наук, профессор, зам. директора Института гигиены, токсикологии пестицидов и химической безопасности пестицидов ФНЦГ им. Ф.Ф. Эрисмана Роспотребнадзора 141014, Мытищи, Российская Федерация.

e-mail: sinitskaiata@fferisman.ru

Russian Federation

Mikhail Andreevich Poroshin

Federal Budgetary Establishment of Science «F.F. Erisman Federal Scientific Center of Hygiene» of the Federal Service for Surveillance on Consumer Rights Protection and Human Well-being

Email: poroshinma@fferisman.ru
ORCID iD: 0000-0001-9668-8361

Врач-ординатор, младший научный сотрудник ФБУН «ФНЦГ им. Ф.Ф. Эрисмана» Роспотребнадзора, 141014, Мытищи, Российская Федерация.

e-mail: poroshinma@fferisman.ru

Russian Federation

Khalidya Khizbulayevna Khamidulina

Federal Budgetary Establishment of Science «F.F. Erisman Federal Scientific Center of Hygiene» of the Federal Service for Surveillance on Consumer Rights Protection and Human Well-being; State Budgetary Educational Institution of Additional Professional Educations «Russian Medical Academy of Post-Graduate Education»

Email: noemail@neicon.ru
ORCID iD: 0000-0001-7319-5337

Доктор медицинских наук, профессор, директор филиала «Российский регистр потенциально опасных химических и биологических веществ» ФБУН «Федеральный научный центр гигиены им. Ф.Ф. Эрисмана» Роспотребнадзора, 121087, Москва; заведующая кафедрой общей гигиены и медицины труда ФБУН «Федеральный научный центр гигиены им. Ф.Ф. Эрисмана» Роспотребнадзора, 141014, Мытищи, Российская Федерация.

e-mail: director@rpohv.ru

Russian Federation

Vitaly Vasilyevich Safandeev

Federal Budgetary Establishment of Science «F.F. Erisman Federal Scientific Center of Hygiene» of the Federal Service for Surveillance on Consumer Rights Protection and Human Well-being

Email: visa.doc@mail.ru
ORCID iD: 0000-0002-0073-1677

Head of the Department of Inhalation Toxicology of the F.F. Erisman Federal Scientific Center of Hygiene of Rospotrebnadzor, 140014, Mytishchi, Russian Federation.

e-mail: visa.doc@mail.ru

Russian Federation

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Copyright (c) 2023 Beloedova N.S., Sinitskaya T.A., Poroshin M.A., Khamidulina K.K., Safandeev V.V.



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