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

Docea, Anca Oana; Γούμενου, Μαρίνα; Calina, Daniela; Arsene, Andreea Letiția; Drăgoi, Cristina Manuela; Gofita, Eliza; Pisoschi, Cătălina Gabriela; Zlatian, Ovidiu; Stivaktakis, Polychronis; Νikolouzakis, Τaxiarchis Κonstantinos; Kalogeraki, Alexandra; Izotov, Boris N.; Gălățeanu, Bianca; Hudiţă, Ariana; Calabrese, Edward J.; Tsatsakis, Aristidis

doi:10.1016/j.toxlet.2019.04.005

Cited by 74 publications

(35 citation statements)

References 37 publications

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“…Some examples of such factors, based on existing studies, include titanium dioxide, air pollution, chlorpyrifos, aluminum sulfate, prenatal alcohol exposure, ZnO, oil fly ash, and many others (3)(4)(5)(6)(7)(8)(9). Also the real life exposure scenario in which we are exposed continuously to combination of stressors influences in the long term the immune system and the response of the organism to the viral stressors (10)(11)(12)(13)(14).…”

Section: Towards Effective Covid-19 Vaccines: Updates Perspectives Amentioning

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Towards effective COVID‑19 vaccines: Updates, perspectives and challenges (Review)

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In the current context of the pandemic triggered by SARS-cOV-2, the immunization of the population through vaccination is recognized as a public health priority. In the case of SARS-cOV-2, the genetic sequencing was done quickly, in one month. Since then, worldwide research has focused on obtaining a vaccine. This has a major economic impact because new technological platforms and advanced genetic engineering procedures are required to obtain a cOVId-19 vaccine. The most difficult scientific challenge for this future vaccine obtained in the laboratory is the proof of clinical safety and efficacy. The biggest challenge of manufacturing is the construction and validation of production platforms capable of making the vaccine on a large scale.

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Section: Towards Effective Covid-19 Vaccines: Updates Perspectives Amentioning

confidence: 99%

Towards effective COVID‑19 vaccines: Updates, perspectives and challenges (Review)

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“…In turn, advanced age, acute respiratory distress syndrome (ARdS) and mechanical ventilation are known to be associated with higher cOVId-19 mortality (26). The risk is also increased by modern life in which individuals are exposed to a multitude of chemicals, even in low doses that in the long-term predispose to chronic diseases and metabolic disturbances (27)(28)(29)(30)(31). Preexisting chronic metabolic diseases including diabetes, cardiovascular diseases (32), and obesity (33) are considered as risk factors for increased cOVId-19 susceptibility and mortality.…”

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Zinc and respiratory tract infections: Perspectives for COVID‑19 (Review)

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“…Pioneer studies trying to shift the current approaches for risk assessment toward the aforementioned real-life risk assessment simulation (RLRS) approach are emerging. These studies are utilizing true exposure scenarios (multiple chemicals, multiple adverse outcomes and doses around or well below regulatory limits) to derive respective exposure limits (Tsatsakis et al 2016(Tsatsakis et al , 2017Docea et al 2018Docea et al , 2019.…”

Section: The Role and Critical Assessment Of The Reliability And Relementioning

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“…There is a pressing need to develop methods, in particular with regard to their regulatory application, that are able to assess the health effects that may be produced by exposure to chemical mixtures with the aim of minimizing or preventing the risk of developing diseases (Kostoff et al 2018;Webster 2018). In general, the hazard of chemical mixtures can be assessed as a whole, using whole-mixture approaches (Wade et al 2002;Docea et al 2018Docea et al , 2019Taghizadeh et al 2019), or predicted based on individual components of the mixture (component-based approach), depending on the available data. The wholemixture approach is frequently applied for environmental samples, as it has the advantage of assessing the toxicity of mixtures of unknown composition and unknown potential for interactions, and measures directly the combined effect of the complete mixture.…”

Section: Introduction To Chemical Mixturesmentioning

confidence: 99%

“…To this end, experiments should have sufficient statistical power to detect effects at these lower doses . For this reason, novel methodological approaches simulating real-life exposures should be developed to assess the potential adverse health effects of long-term low-dose exposure to chemical mixtures simulating complex real-life human exposures (Tsatsakis et al 2016(Tsatsakis et al , 2017(Tsatsakis et al , 2019bDocea et al 2018Docea et al , 2019. Furthermore, special attention should be given to statistical methodologies used in these studies (Sun et al 2013;Lazarevic et al 2019).…”

Section: Introduction To Chemical Mixturesmentioning

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Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures

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Humans are exposed to multiple chemicals on a daily basis instead of to just a single chemical, yet the majority of existing toxicity data comes from single-chemical exposure. Multiple factors must be considered such as the route, concentration, duration, and the timing of exposure when determining toxicity to the organism. The need for adequate model systems (in vivo, in vitro, in silico and mathematical) is paramount for better understanding of chemical mixture toxicity. Currently, shortcomings plague each model system as investigators struggle to find the appropriate balance of rigor, reproducibility and appropriateness in mixture toxicity studies. Significant questions exist when comparing single-to mixture-chemical toxicity concerning additivity, synergism, potentiation, or antagonism. Dose/concentration relevance is a major consideration and should be subthreshold for better accuracy in toxicity assessment. Previous work was limited by the technology and methodology of the time, but recent advances have resulted in significant progress in the study of mixture toxicology. Novel technologies have added insight to data obtained from in vivo studies for predictive toxicity testing. These include new in vitro models: omics-related tools, organs-on-a-chip and 3D cell culture, and in silico methods. Taken together, all these modern methodologies improve the understanding of the multiple toxicity pathways associated with adverse outcomes (e.g., adverse outcome pathways), thus allowing investigators to better predict risks linked to exposure to chemical mixtures. As technology and knowledge advance, our ability to harness and integrate separate streams of evidence regarding outcomes associated with chemical mixture exposure improves. As many national and international organizations are currently stressing, studies on chemical mixture toxicity are of primary importance.

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

Cited by 74 publications

References 37 publications

Towards effective COVID‑19 vaccines: Updates, perspectives and challenges (Review)

Towards effective COVID‑19 vaccines: Updates, perspectives and challenges (Review)

Zinc and respiratory tract infections: Perspectives for COVID‑19 (Review)

Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures

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