Considerable efforts have been devoted to achieving stable acene derivatives for electronic applications; however, the instability is still a major issue for such derivatives. To achieve higher stability with minimum structural change, CC units in the acenes were replaced with isoelectronic BN units to produce a novel BN‐embedded tetrabenzopentacene (BNTBP). BNTBP, with a planar structure, is highly stable to air, moisture, light, and heat. Compared with its carbon analogue tetrabenzopentacene (TBP), BN embedment lowered the highest occupied molecular orbital (HOMO) energy level of BNTBP, changed the orbital distribution, and decreased the HOMO orbital coefficients at the central carbon atoms, which stabilize BNTBP molecules upon exposure to oxygen and sunlight. The single‐crystal microribbons of BNTBP exhibited good performance in field‐effect transistors (FETs). The high stability and good mobility of BNTBP indicates that BN incorporation is an effective approach to afford stable large‐sized acenes with desired properties.

A highly efficient modular synthetic method for BN-fused polycyclic aromatic hydrocarbons (PAHs) composed of a borazaronaphthalene core along with multiple functionalized sites is reported. The halogenated 2,1-borazaronaphthalene cores are constructed through a ring-closing reaction between o-ethynylaniline derivatives and boron halides. The controllable halogen substituents make further derivatization of 2,1-borazaronaphthalene cores feasible by using metal-catalyzed cross-coupling reactions. On the basis of the carefully designed precursors, various functional aromatic rings can be fused to the azaborine core via a one-pot nucleophilic tandem reaction, affording previously inaccessible PAHs in moderate yields.

Toxicogenomics and physiologically based pharmacokinetic (PBPK) models are useful approaches in chemical risk assessment, but the methodology to incorporate toxicogenomic data into a PBPK model to inform risk assessment remains to be developed. This study aimed to develop a probabilistic human health risk assessment approach by integrating toxicogenomic dose–response data and PBPK modeling using perfluorooctane sulfonate (PFOS) as a case study. Based on the available human in vitro and mouse in vivo toxicogenomic data, we identified the differentially expressed genes (DEGs) at each exposure paradigm/duration. Kyoto Encyclopedia of Genes and Genomes and disease ontology enrichment analyses were conducted on the DEGs to identify significantly enriched pathways and diseases. The dose–response data of DEGs were analyzed using the Bayesian benchmark dose (BMD) method. Using a previously published PBPK model, the gene BMDs were converted to human equivalent doses (HEDs), which were summarized to pathway and disease HEDs and then extrapolated to reference doses (RfDs) by considering an uncertainty factor of 30 for mouse in vivo data and 10 for human in vitro data. The results suggested that the median RfDs at different exposure paradigms were similar to the 2016 U.S. Environmental Protection Agency’s recommended RfD, while the RfDs for the most sensitive pathways and diseases were closer to the recent European Food Safety Authority’s guidance values. In conclusion, genomic dose–response data and PBPK modeling can be integrated to become a useful alternative approach in risk assessment of environmental chemicals. This approach considers multiple endpoints, provides toxicity mechanistic insights, and does not rely on apical toxicity endpoints.

The rapid growth of nanomaterial applications has raised safety concerns for human health. A number of studies have been conducted to assess the toxicokinetics, toxicology, dose–response, and risk assessment of different nanomaterials using in vitro and in vivo animal and human models. However, current studies cannot meet the demand for efficient assessment of toxicokinetics, dose–response relationships, or the toxicological risk arising from the rapidly increasing number of newly synthesized nanomaterials. In this article, we review the methods for conducting toxicokinetics, hazard identification, dose–response, exposure, and risk assessment studies of nanomaterials, identify the knowledge gaps, and discuss the challenges remaining. We provide the rationale behind the appropriate design of nanomaterial plasma toxicokinetic and tissue distribution studies, including caveats on the interpretation and correlation of in vitro and in vivo toxicology studies. The potential of using physiologically based pharmacokinetic (PBPK) models to extrapolate toxicokinetic and toxicity findings from in vitro to in vivo and from animals to humans is discussed, and the knowledge gaps of PBPK modeling for nanomaterials are identified. While challenges still exist, there has been progress in the toxicokinetics, hazard identification, and risk assessment of nanomaterials in the past two decades. Recent advancements in the field are highlighted with relevant examples. We also share latest guidelines as well as our perspectives on future studies needed to characterize the toxicokinetics, toxicity, and dose–response relationship in support of nanomaterial risk assessment.This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine