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Research on engineered nanomaterials (ENM) has progressed rapidly from the very early stages of studying their unique, size-dependent physicochemical properties and commercial exploration to the development of products that influence our everyday lives. We have previously reviewed various methods for synthesis, surface functionalization, and analytical characterization of ENM in a publication titled ‘Engineered Nanomaterials: Preparation, Functionalization and Characterization’. In this second, inter-linked document, we first provide an overview of important applications of ENM in products relevant to human healthcare and consumer goods, such as food, textiles, and cosmetics. We then highlight the challenges for the design and development of new ENM for bio-applications, particularly in the rapidly developing nanomedicine sector. The second part of this document is dedicated to nanotoxicology studies of ENM in consumer products. We describe the various biological targets where toxicity may occur, summarize the four nanotoxicology principles, and discuss the need for careful consideration of the biodistribution, degradation, and elimination routes of nanosized materials before they can be safely used. Finally, we review expert opinions on the risk, regulation, and ethical aspects of using engineered nanomaterials in applications that may have direct or indirect impact on human health or our environment.

The primary objective of this glossary is to give clear definitions for those who contribute to studies relevant to these disciplines, or who must interpret them, but are not themselves reproductive physiologists or physicians. This applies especially to chemists who need to understand the literature of reproductive and teratogenic effects of substances without recourse to a multiplicity of other glossaries or dictionaries. The glossary includes terms related to basic and clinical reproductive biology and teratogenesis, insofar as they are necessary for a self-contained document, particularly terms related to diagnosing, measuring, and understanding the effects of substances on the embryo, the fetus, and on the male and female reproductive systems. The glossary consists of about 1200 primary alphabetical entries and includes Annexes of common abbreviations and examples of chemicals with known effects on human reproduction and development. The authors hope that toxicologists, pharmacologists, medical practitioners, risk assessors, and regulatory authorities are among the groups who will find this glossary helpful, in addition to chemists. In particular, the glossary should facilitate the worldwide use of chemical terminology in relation to occupational and environmental risk assessment.

The primary objective of this Glossary of Terms Used in Neurotoxicology is to give clear definitions for those who contribute to studies relevant to neurotoxicology, or must interpret them, but are not themselves neurotoxicologists, neuroscientists or physicians. This applies especially to chemists who need to understand the literature of neurotoxic effects of substances without recourse to a multiplicity of other glossaries or dictionaries. The Glossary includes terms related to basic and clinical neurology insofar as they are necessary for a self-contained document, and particularly terms related to diagnosing, measuring, and understanding effects of substances on the central and peripheral nervous systems. The glossary consists of about 800 terms as primary alphabetical entries, and includes Annexes of common abbreviations, and examples of chemicals with known effects on the nervous system. The authors hope that among the groups who will find this glossary helpful, in addition to chemists, are toxicologists, pharmacologists, medical practitioners, risk assessors, and regulatory authorities. In particular, it should facilitate the worldwide use of chemistry in relation to occupational and environmental risk assessment.

This report discusses the history and mechanisms of vaccination of humans as well as the engineering of therapeutic antibodies. Deeper understanding of the molecular interactions involved in both acquired and innate immunity is allowing sophistication in design of modified and even synthetic vaccines. Recombinant DNA technologies are facilitating development of DNA-based vaccines, for example, with the recognition that unmethylated CpG sequences in plasmid DNA will target Toll-like receptors on antigen-presenting cells. Formulations of DNA vaccines with increased immunogenicity include engineering into plasmids with “genetic adjuvant” capability, incorporation into polymeric or magnetic nanoparticles, and formulation with cationic polymers and other polymeric and non-polymeric coatings. Newer methods of delivery, such as particle bombardment, DNA tattooing, electroporation, and magnetic delivery, are also improving the effectiveness of DNA vaccines. RNA-based vaccines and reverse vaccinology based on gene sequencing and bioinformatic approaches are also considered. Structural vaccinology is an approach in which the detailed molecular structure of viral epitopes is used to design synthetic antigenic peptides. Virus-like particles are being designed for vaccine deliveries that are based on structures of viral capsid proteins and other synthetic lipopeptide building blocks. A new generation of adjuvants is being developed to further enhance immunogenicity, based on squalene and other oil–water emulsions, saponins, muramyl dipeptide, immunostimulatory oligonucleotides, Toll-like receptor ligands, and lymphotoxins. Finally, current trends in engineering of therapeutic antibodies including improvements of antigen-binding properties, pharmacokinetic and pharmaceutical properties, and reduction of immunogenicity are discussed. Taken together, understanding the chemistry of vaccine design, delivery and immunostimulation, and knowledge of the techniques of antibody design are allowing targeted development for the treatment of chronic disorders characterized by continuing activation of the immune system, such as autoimmune disorders, cancer, or allergies that have long been refractory to conventional approaches.

This work compiles information on the principles of diagnostic immunochemical methods and the recent advances in this field. It presents an overview of modern techniques for the production of diagnostic antibodies, their modification with the aim of improving their diagnostic potency, the different types of immunochemical detection systems, and the increasing diagnostic applications for human health that include specific disease markers, individualized diagnosis of cancer subtypes, therapeutic and addictive drugs, food residues, and environmental contaminants. A special focus lies in novel developments of immunosensor techniques, promising approaches to miniaturized detection units and the associated microfluidic systems. The trends towards high-throughput systems, multiplexed analysis, and miniaturization of the diagnostic tools are discussed. It is also made evident that progress in the last few years has largely relied on novel chemical approaches.

The primary objective of this “Glossary of Terms Used in Immunotoxicology” is to give clear definitions for those who contribute to studies relevant to immunotoxicology but are not themselves immunologists. This applies especially to chemists who need to understand the literature of immunology without recourse to a multiplicity of other glossaries or dictionaries. The glossary includes terms related to basic and clinical immunology insofar as they are necessary for a self-contained document, and particularly terms related to diagnosing, measuring, and understanding effects of substances on the immune system. The glossary consists of about 1200 terms as primary alphabetical entries, and Annexes of common abbreviations, examples of chemicals with known effects on the immune system, autoantibodies in autoimmune disease, and therapeutic agents used in autoimmune disease and cancer. The authors hope that among the groups who will find this glossary helpful, in addition to chemists, are toxicologists, pharmacologists, medical practitioners, risk assessors, and regulatory authorities. In particular, it should facilitate the worldwide use of chemistry in relation to occupational and environmental risk assessment.

Numerous species of metal ions cause immunosensitization in humans. Possible approaches to determine those occupational and environmental exposures to metals that result in immunological changes include lymphocyte transformation assay, cytokine profiling, and measurement of lymphocyte subpopulations. In two previous papers, we considered lymphocyte transformation assay [1] and cytokine profiling [2]. Here we review the effects of exposures to metals on lymphocyte subpopulations. Specific consideration is given to beryllium, chromium, cobalt, nickel, palladium and platinum, cadmium, gold, mercury, and lead. Analysis of the scientific literature shows that immunosensitizing metals may have influences on the lymphocyte subset composition, but only in a few instances does exposure to metals cause reproducible shifts of lymphocyte subpopulations. If lymphocyte subpopulations are analyzed, each diagnostic step, including indication, sample handling, analytic procedure, and data interpretation, should adhere to good quality assurance and quality control.

Immunosensitization to metal ions through occupational and environmental exposure has been described in earlier papers from this project. Here we discuss the possible role of cytokine profiling in demonstrating and understanding this phenomenon. The cytokines are a large family of polypeptides exerting autocrine, paracrine, and/or endocrine effects. They include interleukins (ILs), interferons (IFNs), and growth factors. They may be grouped as pro-inflammatory (e.g., IL-1, IL-6, IL-12, IL-18, TNF-α), anti-inflammatory (e.g., IL-10), or those regulating T-helper (TH) cell function. The latter are subdivided into those associated with TH1 (e.g., IL-2, IL-12, IFN-γ, TNF-β) or TH2 (e.g., IL-4, IL-5, IL-13) cell function. Because different types of immune reactions (e.g., immediate reaction vs. delayed-type hypersensitivity) differentially involve TH1 and TH2 cells, measurement of cytokine production in response to metal ions can potentially give insight into underlying immune mechanisms and responses. Examples are given for species of Ni, Cr, Co, Hg, Cd, and Be; and in less detail for species of Fe, Pt, Pd, and Rh. Antibodies are available commercially that allow for the determination of many cytokines, and such measurements are most usefully performed with body fluids, supernatants from stimulated lymphocyte cultures, or lysates of lymphocytes or other biopsied cells. The predominant methods include enzyme-linked immunosorbent assay (ELISA) and flow cytometric measurement of the cytokine, bioassay of its activity in cell culture, and polymerase chain reaction (PCR) assessment of its mRNA level. In practice, levels of individual cytokines are highly variable between individuals, and reliable reference values are generally lacking. Ratios of cytokines are more informative than absolute concentrations, and biological variability in cytokine production dictates that repeated testing is necessary to confirm trends. Determining cytokine profiles is presently of questionable diagnostic utility in individual cases of metal sensitization, but is providing mechanistic insights in a research context.

The lymphocyte transformation test (LTT) has been proven useful especially in the diagnosis of drug-induced allergic disorders. It is an in vitro test which is based on the fact that lymphocytes, which have been sensitized by a certain antigen, transform into blasts and proliferate when they are again exposed to this antigen. This proliferation is determined by measurement of the incorporation of [3H ]-thymidine or bromodeoxyuridine into replicating DNA. The test has the advantage over skin tests of avoiding re-exposure of individuals, and it was, therefore, hoped that it may also help to diagnose metal allergies and especially sensitization toward beryllium. However, the LTT measures only the sensitization of lymphocytes, but not the effector reaction, i.e., there may be positive results in exposed individuals even in the absence of clinical symptoms. There are several reports evaluating the LTT toward gold salts (Au), amalgam (Hg), nickel (Ni), beryllium (Be), and several other metals. With metals other than Be, the LTT appears to be of little use. In contrast, the LTT with Be may, indeed, define patients at risk of developing chronic beryllium disease (CBD), which affects mainly the respiratory tract and may even cause death. Beryllium sensitization progresses to CBD at a rate of 7-11 % per year. Since the Be-LTT can detect sensitization in workers who have not yet developed a disease it is an important diagnostic tool to detect individuals at risk. In conclusion, the LTT can detect a cell-mediated immunological response of an individual to metals. However, for most metals its usefulness is questionable, with the exception of Be; a positive Be-LTT can identify not only patients with CBD, but also persons at risk of developing CBD in later years.