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Toxicol Lett. 2019 Aug 3. pii: S0378-4274(19)30214-0. doi: 10.1016/j.toxlet.2019.07.026. [Epub ahead of print]

The effect of chronic vitamin deficiency and long term very low dose exposure to 6 pesticides mixture on neurological outcomes - a Real-Life Risk Simulation approach.

Author information

1
Center of Toxicology Science & Research, Medical School, University of Crete, Heraklion, Crete, Greece; Spin-Off Toxplus S.A., 71601 Heraklion, Greece. Electronic address: tsatsaka@uoc.gr.
2
Federal State Budgetary Scientific Institution "Federal Research Centre of Nutrition, Biotechnology and Food Safety", 109240, Moscow, Russia. Electronic address: tnv@ion.ru.
3
Department of Toxicology, University of Medicine and Pharmacy, Faculty of Pharmacy, Craiova 200349, Romania. Electronic address: ancadocea@gmail.com.
4
Federal State Budgetary Scientific Institution "Federal Research Centre of Nutrition, Biotechnology and Food Safety", 109240, Moscow, Russia. Electronic address: sish29@mail.ru.
5
Federal State Budgetary Scientific Institution "Federal Research Centre of Nutrition, Biotechnology and Food Safety", 109240, Moscow, Russia. Electronic address: sidorovaulia28@mail.ru.
6
Federal State Budgetary Scientific Institution "Federal Research Centre of Nutrition, Biotechnology and Food Safety", 109240, Moscow, Russia. Electronic address: petrov-nikita-y@mail.ru.
7
Department of Microbiology, University of Medicine and Pharmacy, Faculty of Pharmacy, Craiova 200349, Romania. Electronic address: ovidiu.zlatian@gmail.com.
8
Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine SAS, Dubravska Cesta 9, SK-84104 Bratislava, Slovakia. Electronic address: mojmir.mach@savba.sk.
9
Center for Alternatives to Animal Testing, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; Department of Pharmacology and Toxicology, University of Konstanz, 78464 Konstanz, Germany. Electronic address: thartun1@jhu.edu.
10
Federal State Budgetary Scientific Institution "Federal Research Centre of Nutrition, Biotechnology and Food Safety", 109240, Moscow, Russia. Electronic address: tutelyan@ion.ru.

Abstract

We investigate the long-term effect of very-low dose exposure to a mixture of six pesticides associated with hydrophilic vitamin deficiency on the neurobehavioral outcomes of rats. Two hundred Wistar rats were divided into four groups, two control groups, a vitamin sufficient control group and a vitamin deficiency control group and 2 test groups, a vitamin sufficient test group, and a vitamin deficiency group. The test groups were exposed for 9 months to a mixture of diquat, imazamox, imazethapyr, tepraloxydin, bentazone and acifluorfen in doses of 0.01xNOAEL (mg/kg bw/day). After 9 months of exposure, the behavior changes were evaluated by open field test and elevated plus maze test and the memory was assessed by passive avoidance test. Chronic vitamin deficiency decreased locomotor and special orientation activity and increased anxiety-like behavior in rats. Exposure to very low doses of a mixture of 6 pesticides caused central nervous effects, manifested as decreased locomotor activity, and increased anxiety levels. Vitamin deficiency and low dose chronic pesticides mixture exposure thus affected the central nervous system, especially long-term memory.

KEYWORDS:

elevated plus maze test; hormesis; mixture; open field test; passive avoidance test; pesticides; real-life risk simulation; vitamin deficiency

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