Uptake and depuration of gold nanoparticles in Daphnia magna

This study presents a series of short-term studies (total duration 48 h) of uptake and depuration of engineered nanoparticles (ENP) in neonate Daphnia magna. Gold nanoparticles (Au NP) were used to study the influence of size, stabilizing agent and feeding on uptake and depuration kinetics and animal body burdens. 10 and 30 nm Au NP with different stabilizing agents [citrate (CIT) and mercaptoundecanoic acid (MUDA)] were tested in concentrations around 0.5 mg Au/L. Fast initial uptake was observed for all studied Au NP, with CIT stabilized Au NP showing similar rates independent of size and MUDA showing increased uptake for the smaller Au NP (MUDA 10 nm > CIT 10 nm, 30 nm > MUDA 30 nm). However, upon transfer to clean media no clear trend on depuration rates was found in terms of stabilizing agent or size. Independent of stabilizing agent, 10 nm Au NP resulted in higher residual whole-animal body burdens after 24 h depuration than 30 nm Au NP with residual body burdens about one order of magnitude higher of animals exposed to 10 nm Au NP. The presence of food (P. subcapitata) did not significantly affect the body burden after 24 h of exposure, but depuration was increased. While food addition is not necessary to ensure D. magna survival in the presented short-term test design, the influence of food on uptake and depuration kinetics is essential to consider in long term studies of ENP where food addition is necessary. This study demonstrates the feasibility of a short-term test design to assess the uptake and depuration of ENP in D. magna. The findings underlines that the assumptions behind the traditional way of quantifying bioconcentration are not fulfilled when ENPs are studied.Peer reviewed: YesNRC publication: Ye

Impact of Engineered Nanomaterials on Health: Considerations for Benefit-Risk Assessment

Nanotechnology encompasses the design, characterisation, production and application of materials and systems by controlling shape and size at the nanoscale (nanometres). Nanomaterials may differ from other materials because of their relatively large specific surface area, such that surface properties become particularly important. There has been rapid growth in investment in nanotechnology by both the public and private sectors worldwide. In the EU, nanotechnology is expected to become an important strategic contributor to achieving economic gain and societal and individual benefits. At the same time there is continuing scientific uncertainty and controversy about the safety of nanomaterials. It is important to ensure that timely policy development takes this into consideration. Uncertainty about safety may lead to polarised public debate and to business unwillingness to invest further. A clear regulatory framework to address potential health and environmental impacts, within the wider context of evaluating and communicating the benefit-risk balance, must be a core part of Europe's integrated efforts for nanotechnology innovation. While a number of studies have been carried out on the effect of environmental nanoparticles, e.g. from combustion processes, on human health, there is yet no generally acceptable paradigm for safety assessment of nanomaterials in consumer and other products. Therefore, a working group was established to consider issues for the possible impact of nanomaterials on human health focussing specifically on engineered nanomaterials. This represents the first joint initiative between EASAC and the Joint Research Centre of the European Commission. The working group was given the remit to describe the state of the art of benefits and potential risks, current methods for safety assessment, and to evaluate their relevance, identify knowledge gaps in studying the safety of current nanomaterials, and recommend on priorities for nanomaterial research and the regulatory framework. This report focuses on key principles and issues, cross-referencing other sources for detailed information, rather than attempting a comprehensive account of the science. The focus is on human health although environmental effects are also discussed when directly relevant to healt

A microphysiological system model of therapy for liver micrometastases

Metastasis accounts for almost 90% of cancer-associated mortality. The effectiveness of cancer therapeutics is limited by the protective microenvironment of the metastatic niche and consequently these disseminated tumors remain incurable. Metastatic disease progression continues to be poorly understood due to the lack of appropriate model systems. To address this gap in understanding, we propose an all-human microphysiological system that facilitates the investigation of cancer behavior in the liver metastatic niche. This existing LiverChip is a 3D-system modeling the hepatic niche; it incorporates a full complement of human parenchymal and non-parenchymal cells and effectively recapitulates micrometastases. Moreover, this system allows real-time monitoring of micrometastasis and assessment of human-specific signaling. It is being utilized to further our understanding of the efficacy of chemotherapeutics by examining the activity of established and novel agents on micrometastases under conditions replicating diurnal variations in hormones, nutrients and mild inflammatory states using programmable microdispensers. These inputs affect the cues that govern tumor cell responses. Three critical signaling groups are targeted: the glucose/insulin responses, the stress hormone cortisol and the gut microbiome in relation to inflammatory cues. Currently, the system sustains functioning hepatocytes for a minimum of 15 days; confirmed by monitoring hepatic function (urea, α-1-antitrypsin, fibrinogen, and cytochrome P450) and injury (AST and ALT). Breast cancer cell lines effectively integrate into the hepatic niche without detectable disruption to tissue, and preliminary evidence suggests growth attenuation amongst a subpopulation of breast cancer cells. xMAP technology combined with systems biology modeling are also employed to evaluate cellular crosstalk and illustrate communication networks in the early microenvironment of micrometastases. This model is anticipated to identify new therapeutic strategies for metastasis by elucidating the paracrine effects between the hepatic and metastatic cells, while concurrently evaluating agent efficacy for metastasis, metabolism and tolerability.National Institutes of Health (U.S.) (Grant 1UH2TR000496-01)United States. Defense Advanced Research Projects Agency. Microphysiological Systems Program (W911NF-12-2-0039