Experimental evaluation of the chronic oral effects of unsymmetrical dimethylhydrazine on male sexual function

Introduction. In preventive toxicology, the problem of the possible development of long-term effects in humans upon contact with various chemicals is one of the most significant. Since male personnel is predominantly involved in the production, storage and use of chemicals of varying degrees of toxicity, special attention should be paid to studying the effect of these compounds on male sexual function when developing measures to prevent long-term consequences. However, the gonadotoxic properties of unsymmetrical dimethylhydrazine (a component of rocket fuel) have not been studied in detail in the context of its long-term oral exposure.

The aim of the study was to experimentally evaluate the effects of chronic intragastric exposure of unsymmetrical dimethylhydrazine on male reproductive function with the establishment of threshold and maximum inactive doses.

Material and methods. The object of the study was unsymmetrical dimethylhydrazine (heptyl, 1,1-dimethylhydrazine (CH₃)₂N₂H₂, CAS No. 57-14-7) with a mass fraction of 99% and a specific density of d₄²⁰ = 0.7914 g/cm³. Heptyl in the form of aqueous solutions was orally administered daily for six months to male rats of three experimental groups (10 rats per group) in the following doses: 4·10^–⁴ mg/kg – 1^st experimental group; 8·10^–⁵ mg/kg – 2^nd experimental group and 1.5·10^–⁵ mg/kg – 3^rd experimental group. After the specified period, the spermogram, spermatogenesis and reproductive capacity of the males in each group were evaluated and fetal material was analyzed for the presence of developmental abnormalities.

Results. It was found that chronic intragastric administration of heptyl to white non-linear rats at the specified doses did not reduce the male rats’ ability to mate and fertilize, did not affect the spermogram parameters, and did not cause any teratogenic effects in the offspring. However, long-term exposure to the compound at the maximum dose significantly reduced the number of spermatogonia and the number of layers of spermatogenic epithelium in the testes of the experimental rats. Additionally, the offspring of the male rats in this group showed signs of embryotoxicity, which manifested as a decrease in cranio-caudal size.

Limitations. The experimental study of chronic oral exposure of heptyl on male reproductive function does not provide an assessment of other long-term effects.

Conclusion. Based on the complex of changes detected, the threshold dose of chronic intragastric exposure to unsymmetrical dimethylhydrazine on the reproductive function of male rats was recognized as 4.0·10^-⁴ mg/kg, and the maximum inactive dose – 8.0·10^-⁵ mg/kg. The identified features of the negative impact of unsymmetrical dimethylhydrazine were taken into account when justifying its MPC in water bodies.

Compliance with ethical standards. The experimental study was approved by the Research Institute of Hygiene, Toxicology and Occupational Pathology» of the FMBA of Russia (Protocol No. 5 of December 10, 2024) and conducted in accordance with the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (ETS No. 123), Directive of the European Parliament and of the Council of the European Union 2010/63/ EU of 22.09.2010 On the Protection of Animals Used for Scientific Purposes.

Authors’ contribution.
Maslennikov A.A. – study concept and design, analysis of the results, text writing;
Shateeva A.V. – research planning and execution;
Novikova O.N. – editing.
All co-authors – approval of the final version of the article, responsibility for the integrity of all parts of the article.

Conflict of interest. The authors declare that there are no obvious and potential conflicts of interest in connection with the publication of this article.

Funding. The study was conducted within the framework of the state program of the Russian Federation «Scientific and Technological Development of the Russian Federation».

Received: March 3, 2026 / Revised: May 4, 2026 /Accepted: June 1, 2026 / Published: June 30, 2026

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