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Toxicol Lett. 2019 Aug;310:70-91. doi: 10.1016/j.toxlet.2019.04.005. Epub 2019 Apr 16.

Adverse and hormetic effects in rats exposed for 12 months to low dose mixture of 13 chemicals: RLRS part III.

Author information

1
Department of Toxicology, University of Medicine and Pharmacy, Faculty of Pharmacy, Craiova 200349, Romania. Electronic address: ancadocea@gmail.com.
2
Center of Toxicology Science & Research, Medical School, University of Crete, Heraklion, Crete, Greece. Electronic address: marina.goumenou@gmail.com.
3
Department of Clinical Pharmacy, University of Medicine and Pharmacy, Faculty of Pharmacy, Craiova 200349, Romania. Electronic address: calinadaniela@gmail.com.
4
Department of General and Pharmaceutical Microbiology, Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania. Electronic address: andreeanitulescu@hotmail.com.
5
Department of Biochemistry, Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania. Electronic address: manuela.dragoi@gmail.com.
6
Department of Toxicology, University of Medicine and Pharmacy, Faculty of Pharmacy, Craiova 200349, Romania.
7
Department of Biochemistry, University of Medicine and Pharmacy, Faculty of Pharmacy, Craiova 200349, Romania. Electronic address: c_pisoschi@yahoo.com.
8
Department of Microbiology, University of Medicine and Pharmacy, Faculty of Pharmacy, Craiova 200349, Romania. Electronic address: ovidiu.zlatian@gmail.com.
9
Center of Toxicology Science & Research, Medical School, University of Crete, Heraklion, Crete, Greece.
10
Laboratory of Anatomy-Histology-Embryology, Medical School, University of Crete, 71110 Heraklion, Crete, Greece. Electronic address: konstan10@hotmail.gr.
11
Department of Pathology-Cytopathology, Medical School, University of Crete, Heraklion, Crete, Greece. Electronic address: kalogerakimed@yahoo.gr.
12
Department of Analytical and Forensic Medical Toxicology, Sechenov University, Moscow 119991, Russian Federation.
13
Department of Biochemistry and Molecular Biology, University of Bucharest, 91-95 Splaiul Independentei Street, 050095 Bucharest, Romania. Electronic address: bianca.galateanu@bio.unibuc.ro.
14
Department of Biochemistry and Molecular Biology, University of Bucharest, 91-95 Splaiul Independentei Street, 050095 Bucharest, Romania. Electronic address: arianahudita@yahoo.com.
15
Department of Environmental Health Sciences, University of Massachusetts, Morrill I, N344, Amherst, MA, USA. Electronic address: edwardc@schoolph.umass.edu.
16
Center of Toxicology Science & Research, Medical School, University of Crete, Heraklion, Crete, Greece; Department of Analytical and Forensic Medical Toxicology, Sechenov University, Moscow 119991, Russian Federation. Electronic address: tsatsaka@uoc.gr.

Abstract

The aim of the current study was to evaluate the effects of a mixture of thirteen common chemicals on rats, after a one-year exposure to doses around the acceptable daily intake (ADIs), using blood and urinary tests. The influence of low doses of the mixture on weight gain, water consumption, feed consumption and feed efficiency, biochemistry parameters, haematological parameters, blood lymphocytes subsets, serum inflammation profile and urine parameters was evaluated. Our mixture caused a moderate monotonic increase of the males' appetite and a non-monotonic increase of anabolism and a monotonic increase of appetite for the females. Regarding biochemical parameters, the exposure to the test mixture caused non-monotonic increases of AST and ALT, a decrease of PChE in males and plausibly a monotonic biliary obstruction in both sexes. Monocytes significantly increased in low dose groups of both sexes. A significant decrease of all the lymphocytes subclasses and an increased expression of TNF-α protein associated with an increased expression of IFN-γ protein observed in various groups. It became apparent that after twelve months of exposure very low doses of the tested mixture had both non-monotonic and monotonic harmful effects on different levels on rats.

KEYWORDS:

Hormesis; Low dose exposure; Mixtures; Non-monotonic responses; Pesticides; Real life risk simulation (RLRS)

PMID:
30999039
DOI:
10.1016/j.toxlet.2019.04.005
[Indexed for MEDLINE]

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