A1 Refereed original research article in a scientific journal

Simulating real-life exposures to uncover possible risks to human health: A proposed consensus for a novel methodological approach




AuthorsTsatsakis AM, Kouretas D, Tzatzarakis MN, Stivaktakis P, Tsarouhas K, Golokhvast KS, Rakitskii VN, Tutelyan VA, Hernandez AF, Rezaee R, Chung G, Fenga C, Engin AB, Neagu M, Arsene AL, Docea AO, Gofita E, Calina D, Taitzoglou I, Liesivuori J, Hayes AW, Gutnikov S, Tsitsimpikou C, Tsitsimpikou C

PublisherSAGE PUBLICATIONS LTD

Publication year2017

JournalHuman and Experimental Toxicology

Journal name in sourceHUMAN & EXPERIMENTAL TOXICOLOGY

Journal acronymHUM EXP TOXICOL

Volume36

Issue6

First page 554

Last page564

Number of pages11

ISSN0960-3271

eISSN1477-0903

DOIhttps://doi.org/10.1177/0960327116681652

Web address http://journals.sagepub.com/doi/abs/10.1177/0960327116681652


Abstract
In real life, consumers are exposed to complex mixtures of chemicals via food, water and commercial products consumption. Since risk assessment usually focuses on individual compounds, the current regulatory approach doesn't assess the overall risk of chemicals present in a mixture. This study will evaluate the cumulative toxicity of mixtures of different classes of pesticides and mixtures of different classes of pesticides together with food additives (FAs) and common consumer product chemicals using realistic doses after long-term exposure. Groups of Sprague Dawley (CD-SD) rats (20 males and 20 females) will be treated with mixtures of pesticides or mixtures of pesticides together with FAs and common consumer product chemicals in 0.0, 0.25 x acceptable daily intake (ADI)/tolerable daily intake (TDI), ADI/TDI and 5 x ADI/TDI doses for 104 weeks. All animals will be examined every day for signs of morbidity and mortality. Clinical chemistry hematological parameters, serum hormone levels, biomarkers of oxidative stress, cardiotoxicity, genotoxicity, urinalysis and echocardiographic tests will be assessed periodically at 6 month intervals. At 3-month intervals, ophthalmological examination, test for sensory reactivity to different types of stimuli, together with assessment of learning abilities and memory performance of the adult and ageing animals will be conducted. After 24 months, animals will be necropsied, and internal organs will be histopathologically examined. If the hypothesis of an increased risk or a new hazard not currently identified from cumulative exposure to multiple chemicals was observed, this will provide further information to public authorities and research communities supporting the need of replacing current single-compound risk assessment by a more robust cumulative risk assessment paradigm.



Last updated on 2024-26-11 at 17:17