Introduction and objective:
Pyrethroids are widely used pesticides in agriculture. Growing evidence suggests that they may be harmful for human health. Experimental studies show that pyrethroids can induce seizures and impairments of cognitive and motor functions in animals. Caffeine, a widely used psychoactive substance, may influence these disorders. The aim of the current study was to assess whether co-exposure to pyrethroid (zeta-cypermethrin) and caffeine could affect their neurotoxic potential.

Material and methods:
The study was conducted in adult male Swiss mice. The effects of combined exposure to zeta-cypermethrin and caffeine on pyrethroid-induced convulsions, as well as learning in the passive avoidance test and motor coordination in the rota-rod test, were assessed in animals. In the current study, Fury 100 EW, an insecticide with zeta-cypermethrin as an active ingredient, was used. Substances were administered as single intraperitoneal injections. Caffeine was used at doses affecting the neurobehavioural effects of other pesticides, as previously described.

Zeta-cypermethrin-induced seizures were not influenced by caffeine (40 mg/kg) administration. Pyrethroid, at its 1/5 CD50, did not impair learning or motor coordination in mice. Caffeine did not interact with zeta-cypermethrin in the behavioural tests.

Based on the results obtained, it can be concluded that combined exposure to zeta-cypermethrin and caffeine has no effect on their neurotoxic potential in mice.

Richardson JR, Fitsanakis V, Westerink RHS, et al. Neurotoxicity of pesticides. Acta Neuropathol. 2019;138(3):343–362.
Tang W, Wang D, Wang J, et al. Pyrethroid pesticide residues in the global environment: An overview. Chemosphere. 2018;191:990–1007.
Klimowska A, Amenda K, Rodzaj W, et al. Evaluation of 1-year urinary excretion of eight metabolites of synthetic pyrethroids, chlorpyrifos, and neonicotinoids. Environ Int. 2020;145:106119.
Pitzer EM, Williams MT, Vorhees CV. Effects of pyrethroids on brain development and behavior: Deltamethrin. Neurotoxicol Teratol. 2021;87:106983.
Weiner ML, Nemec M, Sheets L, et al. Comparative functional observational battery study of twelve commercial pyrethroid insecticides in male rats following acute oral exposure. Neurotoxicology. 2009;30(Suppl 1):S1-16.
Rajawat NK, Soni I, Syed F, et al. Effect of ß-cyfluthrin (synthetic pyrethroid) on learning, muscular coordination and oxidative stress in Swiss albino mice. Toxicol Ind Health. 2019;35(5):358-367.
Liu Z, Chandrasekaran A, Becker JM. Determination of offspring NOAEL for zeta-cypermethrin using internal exposure data from rat developmental neurotoxicity studies. Regul Toxicol Pharmacol. 2019;108:104425.
Calderón-Segura ME, Gómez-Arroyo S, Cortés-Eslava J, et al. In vitro cytotoxicity and genotoxicity of Furia®180 SC (zeta-cypermethrin) and Bulldock 125®SC (ß-cyfluthrin) pyrethroid insecticides in human peripheral blood lymphocytes. Toxicol Mech Methods. 2018;28(4):268–278.
Łukawski K, Raszewski G, Czuczwar SJ. Neurotoxic effects of combined exposure to caffeine and pyrethroids in mice. Ann Agric Environ Med. 2022;29(3):370–374.
Temple JL, Bernard C, Lipshultz SE, et al. The safety of ingested caffeine: a comprehensive review. Front Psychiatry. 2017;8:80.
Cappelletti S, Piacentino D, Sani G, et al. Caffeine: cognitive and physical performance enhancer or psychoactive drug? Curr Neuropharmacol. 2015;13(1):71–88.
van Dam RM, Hu FB, Willett WC. Coffee, Caffeine, and Health. N Engl J Med. 2020;383(4):369-378.
Bulczak EM, Chmurzyńska AU. Caffeine Consumption in Polish Adults: Development and Validation of a Polish Questionnaire for Assessing Caffeine Intake. J Am Nutr Assoc. 2023;1–7. doi:10.1080/27697061.2023.2172749.
Glade MJ. Caffeine-Not just a stimulant. Nutrition. 2010;26(10):932-938.
van Koert RR, Bauer PR, Schuitema I, et al. Caffeine and seizures: A systematic review and quantitative analysis. Epilepsy Behav. 2018;80:37-47.
Azevedo JEC, da Silva ALM, Vieira LR, et al. Caffeine intoxication: Behavioral and electrocorticographic patterns in Wistar rats. Food Chem Toxicol. 2022;170:113452.
Dubroqua S, Low SR, Yee BK, et al. Caffeine impairs the acquisition and retention, but not the consolidation of Pavlovian conditioned freezing in mice. Psychopharmacology (Berl). 2015;232(4):721‒731.
Almosawi S, Baksh H, Qareeballa A, et al. Acute Administration of Caffeine: The Effect on Motor Coordination, Higher Brain Cognitive Functions, and the Social Behavior of BLC57 Mice. Behav Sci (Basel). 2018;8(8):65.
Łukawski K, Raszewski G, Kruszyński K, et al. Neurological effects of acute exposure to caffeine and organophosphates in mice. Pol J Vet Sci. 2021;24(2):211‒216.
Litchfield JT, Wilcoxon F. A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther. 1949;96(2):99‒113.
Ullah MS, Ahmad M, Ahmad N, et al. Toxic effects of cypermethrin in female rabbits. Pakistan Vet J. 2006;26(4):193–196.
Chugh Y, Sankaranarayanan A, Sharma PL. MK-801 antagonizes the lethal action of centrally and peripherally administered cypermethrin in mice and rats. J Pharm Pharmacol. 1992;44(6):521–523.
Condés-Lara M, Graff-Guerrero A, Vega-Riveroll L. Effects of cypermethrin on the electroencephalographic activity of the rat: a model of chemically induced seizures. Neurotoxicol Teratol. 1999;21(3):293–298.
Ravula AR, Yenugu S. Pyrethroid based pesticides – chemical and biological aspects. Crit Rev Toxicol. 2021;51(2):117–140.
Chwedorowicz R, Łukawski K, Raszewski G, et al. Effect of caffeine on the anticonvulsant action of pregabalin against electroconvulsions in mice. Pharmacol Rep. 2022;74(2):431–437.
Chwedorowicz R, Łukawski K, Raszewski G, et al. Caffeine impairs anticonvulsant effects of levetiracetam in the maximal electroshock seizure threshold test in mice. J Basic Clin Physiol Pharmacol. 2022. doi:10.1515/jbcpp-2022-0224.
Chrustek A, Hołyńska-Iwan I, Dziembowska I, et al. Current research on the safety of pyrethroids used as insecticides. Medicina (Kaunas). 2018;54(4):61.
Breckenridge CB, Holden L, Sturgess N, et al. Evidence for a separate mechanism of toxicity for the Type I and the Type II pyrethroid insecticides. Neurotoxicology. 2009;30(Suppl 1):S17‒31.