ENPRA was one of the earlier multidisciplinary European Commission FP7-funded projects aiming to evaluate the risks associated with nanomaterial (NM) exposure on human health across pulmonary, ...cardiovascular, hepatic, renal, and developmental systems. The outputs from this project have formed the basis of this review. A retrospective interpretation of the findings across a wide range of in vitro and in vivo studies was performed to identify the main highlights from the project. In particular, focus was placed on informing what advances were made in the hazard assessment of NM, as well as offering some suggestions on the future of "nanotoxicology research" based on these observations, shortcomings, and lessons learned from the project. A number of issues related to the hazard assessment of NM are discussed in detail and include use of appropriate NM for nanotoxicology investigations; characterization and dispersion of NM; use of appropriate doses for all related investigations; need for the correct choice of experimental models for risk assessment purposes; and full understanding of the test systems and correct interpretation of data generated from in vitro and in vivo systems. It is hoped that this review may assist in providing information in the implementation of guidelines, model systems, validation of assessment methodology, and integrated testing approaches for risk assessment of NM. It is vital to learn from ongoing and/or completed studies to avoid unnecessary duplication and offer suggestions that might improve different aspects of experimental design.
Intensive discussions are ongoing about the interpretation of pulmonary effects observed in rats exposed to poorly soluble particles. Alveolar clearance differs between rats and humans and becomes ...impaired in rats at higher exposure concentrations. Some have doubted the human relevance of toxic effects observed in rats under impaired clearance conditions and have suggested that experimental exposures should stay below concentrations inducing impaired clearance. However, for regulatory purposes, insight in potential health effects at relatively high concentrations is needed to fully understand the hazard. Many aspects of impaired particle clearance remain unclear, hampering human health hazard and risk assessment. For an adequate evaluation of the impact of impaired clearance on pulmonary toxicity, a clear definition of alveolar clearance is needed that enables to quantitatively relate the level of impairment to the induction of adverse pulmonary health effects. Also, information is needed on the mechanism of action and the appropriate dose metric for the pulmonary effects observed. In absence of these data, human hazard and risk assessment can only be performed in a pragmatic way. Unless available data clearly point out otherwise, rat pulmonary toxicity including lung inflammation and tumour formation, needs to be considered relevant for human hazard and risk assessment.
•Evaluation of PSP-induced pulmonary effects should be based on mechanism of action.•Extrapolation of PSP-induced toxicity on an appropriate dose metric is preferred.•Test concentrations need to include conditions of impaired clearance.•Human risk for PSP-induced lung lesions is to be assessed on a case-by-case basis.
Exposure to air pollution is an important risk factor for cardiovascular morbidity and mortality, and is associated with increased blood pressure, reduced heart rate variability, endothelial ...dysfunction and myocardial ischaemia. Our objectives were to assess the cardiovascular effects of reducing air pollution exposure by wearing a facemask.
In an open-label cross-over randomised controlled trial, 15 healthy volunteers (median age 28 years) walked on a predefined city centre route in Beijing in the presence and absence of a highly efficient facemask. Personal exposure to ambient air pollution and exercise was assessed continuously using portable real-time monitors and global positional system tracking respectively. Cardiovascular effects were assessed by continuous 12-lead electrocardiographic and ambulatory blood pressure monitoring.
Ambient exposure (PM2.5 86 +/- 61 vs 140 +/- 113 mug/m3; particle number 2.4 +/- 0.4 vs 2.3 +/- 0.4 x 104 particles/cm3), temperature (29 +/- 1 vs 28 +/- 3 degrees C) and relative humidity (63 +/- 10 vs 64 +/- 19%) were similar (P > 0.05 for all) on both study days. During the 2-hour city walk, systolic blood pressure was lower (114 +/- 10 vs 121 +/- 11 mmHg, P < 0.01) when subjects wore a facemask, although heart rate was similar (91 +/- 11 vs 88 +/- 11/min; P > 0.05). Over the 24-hour period heart rate variability increased (SDNN 65.6 +/- 11.5 vs 61.2 +/- 11.4 ms, P < 0.05; LF-power 919 +/- 352 vs 816 +/- 340 ms2, P < 0.05) when subjects wore the facemask.
Wearing a facemask appears to abrogate the adverse effects of air pollution on blood pressure and heart rate variability. This simple intervention has the potential to protect susceptible individuals and prevent cardiovascular events in cities with high concentrations of ambient air pollution.
Three light-duty vehicles in five different configurations a Honda Accord operating with diesel with a closed-coupled oxidation catalyst and an underfloor catalyst replaced in some tests with a ...diesel particle filter (DPF), a Toyota Corolla operating with gasoline, and a VW Golf alternatively operating with petrodiesel or biodiesel were tested in a dynamometer facility to develop an improved understanding of the factors affecting the toxicity of particulate exhaust emissions. The vehicles were tested using a variety of real-world driving cycles, more than the certification test (New European Driving Cycle). Particle samples were collected and analyzed for elemental and organic carbon (EC and OC, respectively), water soluble and water insoluble organic carbon (WSOC and WISOC, respectively), and inorganic ions, and the emission rates (mg/km) for each vehicle/configuration were determined. A dithiothreitol (DTT) assay was used to assess the oxidative potential of the particulate matter (PM) samples. The DPF-equipped diesel and gasoline vehicles were characterized by the lowest overall PM mass emissions, while the diesel and biodiesel cars produced the most potent exhaust in terms of oxidative activity. When the DPF was fitted on the Honda Accord diesel vehicle, the mass emission rates and distance-based oxidative potential were both decreased by 98%, compared to the original configuration. Correlation analysis showed that the DTT consumption rate was highly associated with WSOC, WISOC, and OC (R = 0.98, 0.93, and 0.94, respectively), consistent with previous findings.
•Particles emitted from diesel or biodiesel combustion reduced neuronal activity.•Diesel particles exhibit higher direct neurotoxic potency than biodiesel particles.•Effects are caused by adsorbed ...chemicals and not by the clean carbon core.•Simulated inhalation exposure only had limited effects on neuronal activity.•Toxic effects were absent in the lung model used to simulate inhalation exposure.
Combustion-derived particulate matter (PM) is a major source of air pollution. Efforts to reduce diesel engine emission include the application of biodiesel. However, while urban PM exposure has been linked to adverse brain effects, little is known about the direct effects of PM from regular fossil diesel (PMDEP) and biodiesel (PMBIO) on neuronal function. Furthermore, it is unknown to what extent the PM-induced effects in the lung (e.g., inflammation) affect the brain. This in vitro study investigates direct and indirect toxicity of PMDEP and PMBIO on the lung and brain and compared it with effects of clean carbon particles (CP).
PM were generated using a common rail diesel engine. CP was sampled from a spark generator. First, effects of 48 h exposure to PM and CP (1.2–3.9 µg/cm2) were assessed in an in vitro lung model (air–liquid interface co-culture of Calu-3 and THP1 cells) by measuring cell viability, cytotoxicity, barrier function, inflammation, and oxidative and cell stress. None of the exposures caused clear adverse effects and only minor changes in gene expression were observed.
Next, the basal medium was collected for subsequent simulated inhalation exposure of rat primary cortical cells. Neuronal activity, recorded using microelectrode arrays (MEA), was increased after acute (0.5 h) simulated inhalation exposure. In contrast, direct exposure to PMDEP and PMBIO (1–100 µg/mL; 1.2–119 µg/cm2) reduced neuronal activity after 24 h with lowest observed effect levels of respectively 10 µg/mL and 30 µg/mL, indicating higher neurotoxic potency of PMDEP, whereas neuronal activity remained unaffected following CP exposure.
These findings indicate that combustion-derived PM potently inhibit neuronal function following direct exposure, while the lung serves as a protective barrier. Furthermore, PMDEP exhibit a higher direct neurotoxic potency than PMBIO, and the data suggest that the neurotoxic effects is caused by adsorbed chemicals rather than the pure carbon core.
Nanoparticles (NP) have a tendency to agglomerate after dispersion in physiological media, which can be prevented by the addition of serum. This may however result in modification of the toxic ...potential of particles due to the formation of protein corona. Our study aimed to analyze the role of serum that is added to improve the dispersion of 10 nm TiO
2
NPs on in vitro and in vivo effects following the exposure via the respiratory route. We characterized NP size, surface charge, sedimentation rate, the presence of protein corona and the oxidant-generating capacity after NP dispersion in the presence/absence of serum. The effect of serum on NP internalization, cytotoxicity and pro-inflammatory responses was assessed in a human pulmonary cell line, NCI-H292. Serum in the dispersion medium led to a slower sedimentation, but an enhanced cellular uptake of TiO
2
NPs. Despite this greater uptake, the pro-inflammatory response in NCI-H292 cells was lower after serum supplementation (used either as a dispersant or as a cell culture additive), which may be due to a reduced intrinsic oxidative potential of TiO
2
NPs. Interestingly, serum could be added 2 h after the NP treatment without affecting the pro-inflammatory response. We also determined the acute pulmonary and hepatic toxicity in vivo 24 h after intratracheal instillation of TiO
2
NPs in C57BL/6N mice. The use of serum resulted in an underestimation of the local acute inflammatory response in the lung, while a systemic response on glutathione reduction remained unaffected. In conclusion, serum as a dispersion agent for TiO
2
NPs can lead to an underestimation of the acute pro-inflammatory response in vitro and in vivo. To avoid potential unwanted effects of dispersants and medium components, we recommend that the protocol of NM preparation should be thoroughly tested, and reflect as close as possible realistic exposure conditions.
The terms “Safe innovation” and “Safe(r)-by-design” are currently popular in the field of nanotechnology. These terms are used to describe approaches that advocate the consideration of safety ...aspects already at an early stage of the innovation process of (nano)materials and nanoenabled products. Here, we investigate the possibilities of considering safety aspects during various stages of the innovation process of graphene, outlining what information is already available for assessing potential hazard, exposure, and risks. In addition, we recommend further steps to be taken by various stakeholders to promote the safe production and safe use of graphene.
Nowadays the development and applications of nanotechnology are of major importance in both industrial and consumer areas. However, the knowledge on human exposure and possible toxicity of ...nanotechnology products is limited. To understand the mechanism of toxicity, thorough knowledge of the toxicokinetic properties of nanoparticles is warranted. There is a need for information on the absorption, distribution, metabolism and excretion (ADME) of nanoparticles and validated detection methods of these man-made nanoparticles. Determination of the ADME properties of nanoparticles requires specialised detection methods in different biological matrices (e.g. blood and organs). In this paper, the current knowledge on the kinetic properties of nanoparticles is reviewed. Moreover, knowledge gaps from a kinetic point of view (detection, dose, ADME processes) are identified.
Airborne pollution particles have been shown to translocate from the mother's lung to the fetal circulation, but their distribution and internal placental-fetal tissue load remain poorly explored. ...Here, we investigated the placental-fetal load and distribution of diesel engine exhaust particles during gestation under controlled exposure conditions using a pregnant rabbit model. Pregnant dams were exposed by nose-only inhalation to either clean air (controls) or diluted and filtered diesel engine exhaust (1 mg/m
) for 2 h/day, 5 days/week, from gestational day (GD) 3 to GD27. At GD28, placental and fetal tissues (i.e., heart, kidney, liver, lung and gonads) were collected for biometry and to study the presence of carbon particles (CPs) using white light generation by carbonaceous particles under femtosecond pulsed laser illumination.
CPs were detected in the placenta, fetal heart, kidney, liver, lung and gonads in significantly higher amounts in exposed rabbits compared with controls. Through multiple factor analysis, we were able to discriminate the diesel engine exposed pregnant rabbits from the control group taking all variables related to fetoplacental biometry and CP load into consideration. Our findings did not reveal a sex effect, yet a potential interaction effect might be present between exposure and fetal sex.
The results confirmed the translocation of maternally inhaled CPs from diesel engine exhaust to the placenta which could be detected in fetal organs during late-stage pregnancy. The exposed can be clearly discriminated from the control group with respect to fetoplacental biometry and CP load. The differential particle load in the fetal organs may contribute to the effects on fetoplacental biometry and to the malprogramming of the fetal phenotype with long-term effects later in life.
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