Journal of Toxicology and Environmental Health-Part B-Critical Reviews最新文献

Male germ stem cells are responsible for transmission of genetic information to the next generation. Some chemicals exert a negative impact on male germ cells, either directly, or indirectly affecting them through their action on somatic cells. Ultimately, these effects might inhibit fertility, and may exhibit negative consequences on future offspring. Genotoxic anticancer agents may interact with DNA in germ cells potentially leading to a heritable germline mutation. Experimental information in support of this theory has not always been reproducible and suitable in vivo studies remain limited. Thus, alternative male germ cell tests, which are now able to detect phase specificity of such agents, might be used by regulatory agencies to help evaluate the potential risk of mutation. However, there is an urgent need for such approaches for identification of male reproductive genotoxins since this area has until recently been dependent on in vivo studies. Many factors drive alternative approaches, including the (1) commitment to the principles of the 3R's (Replacement, Reduction, and Refinement), (2) time-consuming nature and high cost of animal experiments, and (3) new opportunities presented by new molecular analytical assays. There is as yet currently no apparent appropriate model of full mammalian spermatogenesis in vitro, under the REACH initiative, where new tests introduced to assess genotoxicity and mutagenicity need to avoid unnecessary testing on animals. Accordingly, a battery of tests used in conjunction with the high throughput STAPUT gravity sedimentation was recently developed for purification of male germ cells to investigate genotoxicity for phase specificity in germ cells. This system might be valuable for the examination of phases previously only available in mammals with large-scale studies of germ cell genotoxicity in vivo. The aim of this review was to focus on this alternative approach and its applications as well as on chemicals of known in vivo phase specificities used during this test system development.

Ambient air pollution is a leading risk factor for the global burden of disease. One possible pathway of particulate matter (PM)-induced toxicity is through iron (Fe), the most abundant metal in the atmosphere. The aim of the review was to consider the complexity of Fe-mediated toxicity following inhalation exposure focusing on the chemical and surface reactivity of Fe as a transition metal and possible pathways of toxicity via reactive oxygen species (ROS) generation as well as considerations of size, morphology, and source of PM. A broad term search of 4 databases identified 2189 journal articles and reports examining exposure to Fe via inhalation in the past 10 years. These were sequentially analyzed by title, abstract and full-text to identify 87 articles publishing results on the toxicity of Fe-containing PM by inhalation or instillation to the respiratory system. The remaining 87 papers were examined to summarize research dealing with in vitro, in vivo and epidemiological studies involving PM containing Fe or iron oxide following inhalation or instillation. The major findings from these investigations are summarized and tabulated. Epidemiological studies showed that exposure to Fe oxide is correlated with an increased incidence of cancer, cardiovascular diseases, and several respiratory diseases. Iron PM was found to induce inflammatory effects in vitro and in vivo and to translocate to remote locations including the brain following inhalation. A potential pathway for the PM-containing Fe-mediated toxicity by inhalation is via the generation of ROS which leads to lipid peroxidation and DNA and protein oxidation. Our recommendations include an expansion of epidemiological, in vivo and in vitro studies, integrating research improvements outlined in this review, such as the method of particle preparation, cell line type, and animal model, to enhance our understanding of the complex biological interactions of these particles.

In recent years, increasing global attention has focused on "microplastics" (MPs) and "nanoplastics" (NPs) resulting in many studies on the effects of these compounds on ecological and environmental aspects. These tiny particles (<5000 µm), predominantly derived from the degradation of plastics, pollute the marine and terrestrial ecosystems with the ability to enter into the food chain. In this manner, human consumption of food contaminated with MPs or NPs is unavoidable, but the related consequences remain to be determined. The aim of this review is to complement previous reviews on this topic by providing new studies related to exposure, absorption, and toxicity in mammalian in vivo and in vitro systems. With respect to novel information, gaps and limitations hindering attainment of firm conclusions as well as preparation of a reliable risk assessment are identified. Subsequently, recommendations for in vivo and in vitro testing methods are presented in order to perform further relevant and targeted research studies.

Hundreds of consumer and commercial products containing silver nanoparticles (AgNPs) are currently used in food, personal-care products, pharmaceutical, and many other applications. Human exposure to AgNPs includes oral intake, inhalation, and dermal contact. The aim of this review was to focus on oral intake, intentional and incidental of AgNPs where well-known antimicrobial characteristics that might affect the microbiome and mucus in the gastrointestinal tract (GIT). This critical review summarizes what is known regarding the impacts of AgNPs on gut homeostasis. It is fundamental to understand the forms of AgNPs and their physicochemical characterization before and during digestion. For example, lab-synthesized AgNPs differ from "real" ingestable AgNPs used as food additives and dietary supplements. Similarly, the gut environment alters the chemical and physical state of Ag that is ingested as AgNPs. Emerging research on in vitro and in vivo rodent and human indicated complex multi-directional relationships among AgNPs, the intestinal microbiota, and the epithelial mucus. It may be necessary to go beyond today's descriptive approach to a modeling-based ecosystem approach that might quantitatively integrate spatio-temporal interactions among microbial groups, host factors (e.g., mucus), and environmental factors, including lifestyle-based stressors. It is suggested that future research (1) utilize more representative AgNPs, focus on microbe/mucus interactions, (2) assess the effects of environmental stressors for longer and longitudinal conditions, and (3) be integrated using quantitative modeling.