Particles and fibres affect human health as a function of their properties such as chemical composition, size and shape but also depending on complex interactions in an organism that occur at various levels between particle uptake and target organ responses. While particulate pollution is one of the leading contributors to the global burden of disease, particles are also increasingly used for medical purposes. Over the past decades we have gained considerable experience in how particle properties and particle-bio interactions are linked to human health. This insight is useful for improved risk management in the case of unwanted health effects but also for developing novel medical therapies. The concepts that help us better understand particles’ and fibres’ risks include the fate of particles in the body; exposure, dosimetry and dose-metrics and the 5 Bs: bioavailability, biopersistence, bioprocessing, biomodification and bioclearance of (nano)particles. This includes the role of the biomolecule corona, immunity and systemic responses, non-specific effects in the lungs and other body parts, particle effects and the developing body, and the link from the natural environment to human health. The importance of these different concepts for the human health risk depends not only on the properties of the particles and fibres, but is also strongly influenced by production, use and disposal scenarios. Lessons learned from the past can prove helpful for the future of the field, notably for understanding novel particles and fibres and for defining appropriate risk management and governance approaches.

Development of cardiovascular disease (CVD), including coronary artery disease, arrhythmia, and ischemic stroke, depends on environmental and genetic factors. To investigate the epigenetic basis of myocardial infarction (MI), we performed an epigenome-wide association study for this condition in elderly Japanese subjects. A total of 192 case subjects with MI and 192 control subjects were recruited from hospital attendees and the general population, respectively. Genome-wide DNA methylation (DNAm) profiles for DNA isolated from whole blood were obtained by analysis with an Infinium HumanMethylation450 BeadChip. The relation of DNAm sites found to be significantly associated with MI to nearby single nucleotide polymorphisms (SNPs) previously shown to be associated with CVD was assessed in the control group. Three DNAm sites (cg06642177, cg07786668, cg17218495) showed genome-wide significant associations with MI (p = 4.33 × 10−8, 3.96 × 10−10, and 3.77 × 10−8, respectively). Two of these sites (cg07786668, cg17218495) still showed such associations after adjustment for classical risk factors of MI (p = 1.04 × 10−7 and 6.60 × 10−8, respectively). The DNAm sites cg07786668 and cg17218495 are located in ZFHX3 (zinc finger homeobox 3) and SMARCA4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4) genes, respectively. SNPs in ZFHX3 or SMARCA4 that were previously found to be associated with CVD were not significantly associated with these DNAm sites in our control subjects. We identified two DNAm sites—cg07786668 in ZFHX3 and cg17218495 in SMARCA4— that are independently and significantly associated with MI. Our results suggest that the development of MI might be influenced by changes in DNAm at these sites via a pathway that differs from that affected by CVD-associated SNPs in these genes. The Kita-Nagoya Genomic Epidemiology (KING) study, which was the source of control samples in the present study, was registered in ClinicalTrials.gov (NCT00262691) on 6 December 2005.

As the use of nanoparticles (NPs) is increasing, the potential toxicity and behavior of NPs in living systems need to be better understood. Our goal was to evaluate the developmental toxicity and bio-distribution of two different sizes of fluorescently-labeled SiO₂ NPs, 25 and 115 nm, with neutral surface charge or with different surface functionalization, rendering them positively or negatively charged, in order to predict the effect of NPs in humans. We performed a zebrafish embryo toxicity test (ZFET) by exposing the embryos to SiO₂ NPs starting from six hours post fertilization (hpf). Survival rate, hatching time, and gross morphological changes were assessed at 12, 24, 36, 48, 60, and 72 hpf. We evaluated the effect of NPs on angiogenesis by counting the number of sub-intestinal vessels between the second and seventh intersegmental vessels and gene expression analysis of vascular endothelial growth factor (VEGF) and VEGF receptors at 72 hpf. SiO₂ NPs did not show any adverse effects on survival rate, hatching time, gross morphology, or physiological angiogenesis. We found that SiO₂ NPs were trapped by the chorion up until to the hatching stage. After chemical removal of the chorion (dechorionation), positively surface-charged SiO₂ NPs (25 nm) significantly reduced the survival rate of the fish compared to the control group. These results indicate that zebrafish chorion acts as a physical barrier against SiO₂ NPs, and removing the chorions in ZFET might be necessary for evaluation of toxicity of NPs.