期刊
HUMAN & EXPERIMENTAL TOXICOLOGY
卷 36, 期 6, 页码 554-564出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/0960327116681652
关键词
Pesticides; food additives; long-term toxicity; acceptable daily intake; tolerable daily intake; combined exposure
类别
资金
- University of Crete ELKE KA [3392]
- ERA.NET RUS PLUS NABUCO
- Russian Federation for young doctors of science [MD-7737.2016.5]
- Mashhad University of Medical Science, Iran
- Erisman Institute, Moscow
- University of Granada
- Research Group [BIO-253]
- Scientific and Technological Research Council of Turkey [214S112]
- Romanian Ministry of Education and Research - Research Grant [PN-II-PT-PCCA-2013-4-1386, PN-II-176/01.07.2014]
- Internal Research Grant of the University of Medicine and Pharmacy Craiova, Romania [15/8.01.2015]
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.
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