Nejvíce citovaný článek - PubMed ID 36645448
A walk in the PARC: developing and implementing 21st century chemical risk assessment in Europe
With the introduction of "Safe and Sustainable by Design" (SSbD), momentum is created in Europe to shift from the reactive (mis)management of chemicals and materials toward a more proactive design and assessment approach to preventing pollution issues. SSbD is expected to steer the innovation process toward a green and sustainable industrial transition, substitute or minimize the production and use of substances of concern, and minimize the impact on health and the environment throughout the chemical/material life cycle. The European Commission has recommended a framework for operationalizing SSbD, but many open questions remain regarding its feasibility and implementation. Our analysis suggests that despite its potential, the EU SSbD framework in its current form cannot deliver on set ambitions. Suitable assessment methods are not available in many cases, and the complexity and data requirements of SSbD may hinder widespread adoption or result in paralysis by analysis. Moving forward, a more realistic, agile framework, accompanied by clear, simplified methods, and robust support for stakeholders, should be developed to ensure that SSbD principles are fully integrated into practice, leading to truly safer and more sustainable chemicals and materials. We further highlight opportunities to address identified gaps, establish such a framework, and enhance its operationalization.
BACKGROUND: Exposure to toxic trace elements, which include metals and metalloids, can induce adverse health effects, including life-threatening diseases. Conversely, essential trace elements are vital for bodily functions, yet their excessive (or inadequate) intake may pose health risks. Therefore, identifying levels and determinants of exposure to trace elements is crucial for safeguarding human health. METHODS: The present study analyzed urinary concentrations of 14 trace elements (arsenic, cadmium, cobalt, chromium, copper, mercury, manganese, molybdenum, nickel, lead, antimony, selenium, thallium, and zinc) and their exposure determinants in 711 individuals, spanning from children to young adults from a Central European population from the Czech Republic. Multivariate linear regression and non-parametric Kruskal-Wallis ANOVA were used to investigate exposure determinants. Estimates of 95th percentile concentrations and confidence intervals were carried out to establish reference values (RV95). The study also assessed the percentage of population exceeding health-based guidance values (GVs) to gauge health risks. RESULTS: Young adults showed elevated toxic element concentrations, whereas children exhibited higher concentrations of essential elements. Mercury concentrations were associated with both dental amalgam filling count and seafood intake; arsenic concentrations were associated with seafood, rice, and mushroom consumption. Mushroom consumption also influenced lead concentrations. Sex differences were found for cadmium, zinc, nickel, and cobalt. Between 17.9% and 25% of the participants exceeded recommended GV for arsenic, while 2.4% to 2.8% exceeded GV for cadmium. Only one participant exceeded the GV for mercury, and none exceeded GVs for chromium and thallium. Essential trace elements' GVs were surpassed by 38% to 68.5% participants for zinc, 1.3% to 1.8% for molybdenum, and 0.2% to 0.3% for selenium. IMPACT: The present study examines trace element exposure in a Central European population from the Czech Republic, unveiling elevated exposure levels of toxic elements in young adults and essential elements in children. It elucidates key determinants of trace element exposure, including dietary and lifestyle indicators as well as dental amalgam fillings. Additionally, the study establishes novel reference values and a comparison with established health-based human biomonitoring guidance values, which are crucial for public health decision-making. This comprehensive biomonitoring study provides essential data to inform public health policies and interventions.
- Klíčová slova
- Heavy metals, Human biomonitoring, Human exposure, Trace elements, Urine,
- Publikační typ
- časopisecké články MeSH
Through investigating the combined impact of the environmental exposures experienced by an individual throughout their lifetime, exposome research provides opportunities to understand and mitigate negative health outcomes. While current exposome research is driven by epidemiological studies that identify associations between exposures and effects, new frameworks integrating more substantial population-level metadata, including electronic health and administrative records, will shed further light on characterizing environmental exposure risks. Molecular biology offers methods and concepts to study the biological and health impacts of exposomes in experimental and computational systems. Of particular importance is the growing use of omics readouts in epidemiological and clinical studies. This paper calls for the adoption of mechanistic molecular biology approaches in exposome research as an essential step in understanding the genotype and exposure interactions underlying human phenotypes. A series of recommendations are presented to make the necessary and appropriate steps to move from exposure association to causation, with a huge potential to inform precision medicine and population health. This includes establishing hypothesis-driven laboratory testing within the exposome field, supported by appropriate methods to read across from model systems research to human.
- Klíčová slova
- Environment, Exposome, Exposure, GxE, Human Health, Molecular Biology, Toxicology,
- MeSH
- expozom * MeSH
- lidé MeSH
- molekulární biologie MeSH
- vystavení vlivu životního prostředí * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Carcinogenic chemicals, or their metabolites, can be classified as genotoxic or non-genotoxic carcinogens (NGTxCs). Genotoxic compounds induce DNA damage, which can be detected by an established in vitro and in vivo battery of genotoxicity assays. For NGTxCs, DNA is not the primary target, and the possible modes of action (MoA) of NGTxCs are much more diverse than those of genotoxic compounds, and there is no specific in vitro assay for detecting NGTxCs. Therefore, the evaluation of the carcinogenic potential is still dependent on long-term studies in rodents. This 2-year bioassay, mainly applied for testing agrochemicals and pharmaceuticals, is time-consuming, costly and requires very high numbers of animals. More importantly, its relevance for human risk assessment is questionable due to the limited predictivity for human cancer risk, especially with regard to NGTxCs. Thus, there is an urgent need for a transition to new approach methodologies (NAMs), integrating human-relevant in vitro assays and in silico tools that better exploit the current knowledge of the multiple processes involved in carcinogenesis into a modern safety assessment toolbox. Here, we describe an integrative project that aims to use a variety of novel approaches to detect the carcinogenic potential of NGTxCs based on different mechanisms and pathways involved in carcinogenesis. The aim of this project is to contribute suitable assays for the safety assessment toolbox for an efficient and improved, internationally recognized hazard assessment of NGTxCs, and ultimately to contribute to reliable mechanism-based next-generation risk assessment for chemical carcinogens.
- Klíčová slova
- NAM, NGTxC, PARC, new approach methodologies, non-genotoxic carcinogens,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
