The unrecognized occupational relevance of the interaction between engineered nanomaterials and the gastro-intestinal tract: a consensus paper from a multidisciplinary working group

Abstract

Background: There is a fundamental gap of knowledge on the health effects caused by the interaction of engineered nanomaterials (ENM) with the gastro-intestinal tract (GIT). This is partly due to the incomplete knowledge of the complex physical and chemical transformations that ENM undergo in the GIT, and partly to the widespread belief that GIT health effects of ENM are much less relevant than pulmonary effects. However, recent experimental findings, considering the role of new players in gut physiology (e.g. the microbiota), shed light on several outcomes of the interaction ENM/GIT. Along with this new information, there is growing direct and indirect evidence that not only ingested ENM, but also inhaled ENM may impact on the GIT. This fact, which may have relevant implications in occupational setting, has never been taken into consideration. This review paper summarizes the opinions and findings of a multidisciplinary team of experts, focusing on two main aspects of the issue: 1) ENM interactions within the GIT and their possible consequences, and 2) relevance of gastro-intestinal effects of inhaled ENMs. Under point 1, we analyzed how luminal gut-constituents, including mucus, may influence the adherence of ENM to cell surfaces in a size-dependent manner, and how intestinal permeability may be affected by different physico-chemical characteristics of ENM. Cytotoxic, oxidative, genotoxic and inflammatory effects on different GIT cells, as well as effects on microbiota, are also discussed. Concerning point 2, recent studies highlight the relevance of gastro-intestinal handling of inhaled ENM, showing significant excretion with feces of inhaled ENM and supporting the hypothesis that GIT should be considered an important target of extrapulmonary effects of inhaled ENM. Conclusions:In spite of recent insights on the relevance of the GIT as a target for toxic effects of nanoparticles, there is still a major gap in knowledge regarding the impact of the direct versus indirect oral exposure. This fact probably applies also to larger particles and dictates careful consideration in workers, who carry the highest risk of exposure to particulate matter.

Sub-chronic inhalation of lead oxide nanoparticles revealed their broad distribution and tissue-specific subcellular localization in target organs

“…These in vivo studies confirmed the presence of intratracheally instilled nanoparticles in liver and the other extrapulmonary organs similar as we observed by transmission electron microscope in all analyzed organs and confirmed also by EDX analysis in case of liver. Therefore, the translocation of nanoparticles through the circulation into secondary organs was confirmed but seems to be low [ 35 ], which likely corresponds to our experiments with the majority of nanoparticles observed to stay in the pulmonary tissues. On the other hand, it appears that the accumulation of nanoparticles in target organs might reach a critical threshold causing injury in the case of our sub-chronic exposure as was proposed previously [ 35 ].…”

Critical review of the safety assessment of titanium dioxide additives in food

“…Therefore, IARC classified TiO 2 as a Group 2B carcinogen [ 26 ]. Considering the widespread food-related uses, there is a pressing need to review the suitability of studies supporting the risk assessment of TiO 2 particles as food additive [ 27 ]. Comprehensive reviews on this topic have been provided inter alia by Shi et al [ 28 ], Heringa et al [ 29 ] and the Scientific Panel on Food Additives and Nutrient Sources added to Food (ANS Panel) [ 13 ].…”

Nitric oxide-dependent biodegradation of graphene oxide reduces inflammation in the gastrointestinal tract

“…15 Despite the potential implications on human health, the impact of nanomaterials on the GI tract has been largely overlooked. 16 We focused here on oral exposure to GO. It is well known that NO is produced in the GI tract through enzymatic and non-enzymatic reactions, 17 and we hypothesized that GO may undergo NO-dependent biodegradation ( Fig.…”