Adverse and hormetic effects in rats exposed for 12 months to low dose mixture of 13 chemicals: RLRS part III. (August 2019)

• Record Type: Journal Article
• Authors: Docea, Anca Oana; Goumenou, Marina; Calina, Daniela; Arsene, Andreea Letitia; Dragoi, Cristina Manuela; Gofita, Eliza; Pisoschi, Catalina Gabriela; Zlatian, Ovidiu; Stivaktakis, Polychronis D.; Nikolouzakis, Taxiarchis Konstantinos; Kalogeraki, Alexandra; Izotov, Boris N.; Galateanu, Bianca; Hudita, Ariana; Calabrese, Edward J.; Tsatsakis, Aristidis
• Is Part Of: Toxicology letters. Volume 310(2019)
• Page Start: 70
• Page End: 91
• Publication Date: 2019-08
• Subjects: Mixtures -- Pesticides -- Non-monotonic responses -- Hormesis -- Low dose exposure -- Real life risk simulation (RLRS); ADI acceptable daily intake -- ALP alkaline phosphatase -- ALT alanine aminotransferase -- ALT alanine aminotransferase -- ASC ascorbic acid -- AST aspartat aminotransferase -- AST aspartat aminotransferase -- BAS basophils -- BIL bilirubin -- BUN blood urea nitrogen -- BWG body weight gain -- CAT catalase -- CHOL cholesterol -- Cl− chloride level -- CPK creatine phosphokinase -- CRE creatinine -- EDTA calcium disodium ethylene diamine tetra-acetate -- EOS eosinophils -- FER Feed efficacy ratio -- GLU glucose -- GLU glucose -- GPO glycerol-3-phosphate oxidase -- GPO-PAP glycerol-3-phosphate oxidase -- HCT haematocrit -- HD high dose -- HGB haemoglobin -- IFN-γ Interferon-γ -- IL-10 Interleukin-10 -- IL-12p70 Interleukin-12p70 -- IL-13 Interleukin-13 -- IL-22 Interleukin-22 -- IL-6 Interleukin-6 -- K+ Potassium -- KET ketones -- LD low dose -- LDH lactate dehydrogenase -- LYM lymphocytes -- MCH medium cell haemoglobin -- MCHC medium cell haemoglobin concentration -- MCP-1 Monocyte Chemoattractant Protein-1 -- MCV medium cell volume -- MD medium dose -- MON monocytes -- MPV medium platelet volume -- Na+ sodium -- NAD+ nicotinamide adenine dinucleotide -- NADH the reduced form of NAD+ -- NEU neutrophils -- NIT nitrates -- OPs organophosphates -- PChE pseudocholinesterase -- PChE pseudocholinesterase -- PCT plateletcrit -- PDW platelet distribution width -- PLT platelets -- POD peroxidase -- PROT proteins -- TP total protein -- RBC red blood cells -- RC red cells -- RDW red cell distribution width -- RLRS real life risk simulation -- SG specific gravity -- TBIL total bilirubin -- TCA trichloroacetic acid -- TDI tolerable daily intake -- TG triglycerides -- TNF Tumour Necrosis Factor -- Tris–HCl trishydroxymethylaminomethane hydrochloride -- TRV toxicological relevance values -- UBG urobilinogen -- WBC white blood cells -- WHO World Health Organization; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2019.04.005
• Languages: English
• ISSNs: 0378-4274

Abstract

Graphical abstract: Highlights: Exposure to very low dose of chemicals mixture can lead in various adverse effects. Monotonic increase of appetite in both sexes and of body weight gain in females. Non-monotonic effects on anabolism, AST, ALT and PChE in males. Monocytes significantly increased in both sexes only in low dose group. TNF-α and IFN-γ increased in male rats from medium dose groups. 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.