Recent insights on indirect mechanisms in developmental toxicity of nanomaterials.

BACKGROUND: Epidemiological and animal studies provide compelling indications that environmental and engineered nanomaterials (NMs) pose a risk for pregnancy, fetal development and offspring health later in life. Understanding the origin and mechanisms underlying NM-induced developmental toxicity will be a cornerstone in the protection of sensitive populations and the design of safe and sustainable nanotechnology applications. MAIN BODY: Direct toxicity originating from NMs crossing the placental barrier is frequently assumed to be the key pathway in developmental toxicity. However, placental transfer of particles is often highly limited, and evidence is growing that NMs can also indirectly interfere with fetal development. Here, we outline current knowledge on potential indirect mechanisms in developmental toxicity of NMs. SHORT CONCLUSION: Until now, research on developmental toxicity has mainly focused on the biodistribution and placental translocation of NMs to the fetus to delineate underlying processes. Systematic research addressing NM impact on maternal and placental tissues as potential contributors to mechanistic pathways in developmental toxicity is only slowly gathering momentum. So far, maternal and placental oxidative stress and inflammation, activation of placental toll-like receptors (TLRs), impairment of placental growth and secretion of placental hormones, and vascular factors have been suggested to mediate indirect developmental toxicity of NMs. Therefore, NM effects on maternal and placental tissue function ought to be comprehensively evaluated in addition to placental transfer in the design of future studies of developmental toxicity and risk assessment of NM exposure during pregnancy.

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

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.

The Preliminary Assessment of New Biomaterials Necessitates a Comparison of Direct and Indirect Cytotoxicity Methodological Approaches.

BACKGROUND: Cytotoxicity testing is a primary method to establish the safety of biomaterials, e.g., biocomposites. Biomaterials involve a wide range of medical materials, which are usually solid materials and are used in bone regeneration, cardiology, or dermatology. Current advancements in science and technology provide several standard cytotoxicity testing methods that are sufficiently sensitive to detect various levels of cellular toxicity, i.e., from low to high. The aim was to compare the direct and indirect methodology described in the ISO guidelines UNE-EN ISO 10993-5:2009 Part 5. METHODS: Cell proliferation was measured using WST-1 assay, and cytotoxicity was measured using LDH test kit. RESULTS: The results indicate that the molecular surface of biomaterials have impact on the cytotoxicity and proliferation profile. Based on these results, we confirm that the indirect method does not provide a clear picture of the cell condition after the exposure to the surface, and moreover, cannot provide complete results about the effects of the material. CONCLUSIONS: Comparison of both methods shows that it is pivotal to investigate biomaterials at the very early stages using both indirect and direct methods to access the influence of the released toxins and surface of the material on the cell condition.

Effectiveness of long-lasting insecticide netting on Tribolium castaneum is modulated by multiple exposures, biotic, and abiotic factors.

BACKGROUND: Prevention is the first line of defense in mitigating losses of post-harvest crops. Long-lasting insecticide treated (LLIN) could be used in food facilities to expose insects to insecticide at different areas within a facility. Prior research has shown that single short exposures reduce movement and longer exposures increase mortality for stored-product insect pests, but we do not know how multiple short duration exposures and biotic and abiotic conditions affect insects exposed to LLIN. Here, we repeatedly exposed red flour beetles, Tribolium castaneum, to LLIN to assess the cumulative effects. We also examined the effects of beetle age and time of day during exposure, and temperature, humidity and food availability during recovery after a single exposure to LLIN. RESULTS: We found that four repeated 10-min exposures had similar knockdown effects as a single 30-min exposure. We also found that beetles were more affected when aged 1-6 days versus 14-20 days or were exposed at mid- or late in the day versus earlier in the day. Higher recovery levels were observed with food and at higher relative humidity. In addition, older beetles were more active than younger beetles during exposure, which could reduce time in contact with netting and partially explain why older beetles tended to be less affected. CONCLUSION: Some individuals can recover after exposure to LLIN, dependent on exposure duration and environmental factors, but our study shows that sublethal effects likely persist and future work should consider the physiology of T. castaneum before, during, and after exposure to LLIN. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.

Mobility of Stored Product Beetles after Exposure to a Combination Insecticide Containing Deltamethrin, Methoprene, and a Piperonyl Butoxide Synergist Depends on Species, Concentration, and Exposure Time.

: Adults of Rhyzopertha dominica (F.), the lesser grain borer, Cryptolestes ferrugineus (Stephens), the rusty grain beetle, and Sitophilus oryzae (L.), the rice weevil, were exposed for 1, 24, and 72 h on wheat treated with concentrations of 0% (untreated controls) to 100% of the proposed label rate of an experimental formulation of deltamethrin + Methoprene + piperonyl butoxide synergist. Movement and velocity of movement were assessed after each exposure time using a camera-based monitoring system (Ethovision®). Movement of R. dominica decreased with increasing concentration and exposure time, so that movement had virtually ceased at the 48 and 72 h exposures. Cryptolestes ferrugineus was less susceptible compared to R. dominica, but there was still a general pattern of decreased movement and velocity of movement with increasing concentration and exposure time. Sitophilus oryzae was the least susceptible species, with less differences at the 1 h exposure interval compared to the other two species, but after 24-72 h, the patterns of declining movement and velocity were apparent as the concentration increased. Data were analyzed using curve-fit equations to show the relationship between concentration and exposure time for each species. Results show that the Ethovison system can be used to assess the sub-lethal effects of exposure to grain protectant insecticides and elucidate behavioral variation between different stored product insects.

Aluminum and vaccines: Current state of knowledge.

French people have never been so wary about vaccines. The use of aluminum salts in vaccine adjuvants to enhance effectiveness is one of the major reasons for this lack of confidence. The direct toxicity of aluminum is often put forward. Direct toxicity of aluminum has long been known-especially with occupational exposure-to be associated with characteristic clinical manifestations and increased blood aluminum level. Intoxication related to the excessive amount of an element in the body, whether be it lead poisoning following exposure to lead or mercury poisoning for instance, is always associated with metal increase in biological media. To date no link has been established between the direct toxicity of aluminum and vaccines. Aluminum levels in biological media of vaccinated subjects are not different from those of unvaccinated subjects. This is consistent with the very small amount of aluminum contained in one dose of vaccine. Indirect toxicity of aluminum was suggested to explain macrophagic myofasciitis in humans in 2011, a disease that could be mediated by an autoimmune/autoinflammatory mechanism. This hypothesis has recently been refuted in a large pharmaco-epidemiological study proving that aluminum-containing adjuvants of vaccines are not responsible for this autoimmune/autoinflammatory syndrome.

Adverse Effects of Fine-Particle Exposure on Joints and Their Surrounding Cells and Microenvironment.

Current understanding of the health risks and adverse effects upon exposure to fine particles is premised on the direct association of particles with target organs, particularly the lung; however, fine-particle exposure has also been found to have detrimental effects on sealed cavities distant to the portal-of-entry, such as joints. Moreover, the fundamental toxicological issues have been ascribed to the direct toxic mechanisms, in particular, oxidative stress and proinflammatory responses, without exploring the indirect mechanisms, such as compensated, adaptive, and secondary effects. In this Review, we recapitulate the current findings regarding the detrimental effects of fine-particle exposure on joints, the surrounding cells, and microenvironment, as well as their deteriorating impact on the progression of arthritis. We also elaborate the likely molecular mechanisms underlying the particle-induced detrimental influence on joints, not limited to direct toxicity, but also considering the other indirect mechanisms. Because of the similarities between fine air particles and engineered nanomaterials, we compare the toxicities of engineered nanomaterials to those of fine air particles. Arthritis and joint injuries are prevalent, particularly in the elderly population. Considering the severity of global exposure to fine particles and limited studies assessing the detrimental effects of fine-particle exposure on joints and arthritis, this Review aims to appeal to a broad interest and to promote more research efforts in this field.