Comparative assessment of the nature of the combined action of insecticides: different methodical approaches

Introduction. Pesticide mixtures containing insecticide methomyl are commonly used in agriculture. However, the interaction of their active ingredients in a mixture has been insufficiently studied.

The purpose of the study was to evaluate the nature of the combined action of a mixture of insecticides methomyl (carbamate) and bifenthrin (pyrethroid) using various methods: a classical model (orthogonal planning of the experiment using nonlinear variables); a generalized linear regression model for the binomial distribution (probit regression); and an isobologram. The study was conducted at the Federal Scientific Center of Hygiene named after F.F. Erisman of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing, according to the protocol approved by the local bioethical commission.

Materials and methods. Ninety male outbred rats were administered 9 combined doses of the insecticides (combinations of LD₁₆, LD₃₃ and LD₅₀ for the individual compounds, as devised from a preliminary study).

Results. Impaired coordination, tremor of the limbs and head, turning into convulsions, rapid (shallow) breathing were observed in all groups. The data on mortality as used to construct 2 mathematical models, as well as to construct an isobologram.

Limitations. The study was limited to studying the indicators of acute oral toxicity, without taking into account the possible repeated exposure.

Conclusion. The models showed that the additive effect for the combination of methomyl and bifenthrin was only observed for combinations when the individual dose of bifenthrin was equal to or greater than 45 mg/kg b.w. (LD₃₃) and the dose of methomyl was less than 30 mg/kg b.w., as all animals receiving a dose of 30 mg/kg b.w. of methomyl (LD₅₀) in the mixture died. Therefore, the dose of methomyl dictated the toxic effect of the mixture, which should be accounted for in hygienic regulation of methomyl-containing formulations.

Compliance with ethical standards. The study was approved by the Bioethical Commission of the of the Federal Scientific Center of Hygiene named after F.F. Erisman of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing, protocol № 01/22 dated 27.10.2022.

Contribution:
Veshchemova T.E. — research concept and design, material collection and data processing, statistical processing, text writing;
Masaltsev G.V. — research concept and design, material collection and data processing, statistical processing, text writing;
Rakitskii V.N. — concept and design of research, scientific guidance;
Chkhvirkiya E.G. — scientific guidance;
Kuzmin S.V. — scientific guidance;
Tsatsakis A.M. — scientific guidance.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version

Acknowledgment.  The study was carried out within the framework of the industry scientific program of the Federal Service For Surveillance on Consumer Rights Protection and Human Wellbeing of the Russian Federation (Rospotrebnadzor) “Hygienic scientific justification for minimizing risks to the health of the population of Russia” (2016–2020), “Scientific justification of the national system for ensuring sanitary and epidemiological well-being, health risk management and improving the quality of life of the population of Russia” (2021–2025).

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

Acknowledgement. The study had no sponsorship.

Received: May 16, 2024 / Revised: June 12, 2024 / Accepted: June 19, 2024 / Published: October 16, 2024