Current Opinion in Toxicology最新文献

The use of regulations to protect future generations is a form of risk management that continues to evolve. This article looks at three aspects of regulatory toxicology utilized in this pursuit: prenatal testing assessments, occupational exposure limits, and mandatory food fortification. Approaches to the identification of prenatal toxicants are founded in nonclinical, in vivo testing paradigms that offer the advantages of standardized study designs. New approach methods continue to be evaluated as replacements for animal studies. Greater inclusion of pregnant women in research should ultimately benefit therapeutic decisions for both mothers and infants. Development of occupational exposure limits that incorporate the physiology of pregnant workers across more varied occupations and for more chemical agents should improve workplace safety guidance. Utilizing regulatory approaches to allay nutritional deficiencies could protect future generations through birth defects prevention.

It is established in the scientific literature that environmental air pollution has acute and chronic harmful consequences on human health. In recent decades, studies showed that the harmful effects of bad air quality can impair future generations. Early exposure to bad air quality (in uterus, infant, and early childhood) can increase the susceptibility to noncommunicable diseases (NCDs) across the lifespan. Brazil and other countries do not meet health safety standards recommended by the World Health Organization, exposing large population to air pollution and its risks. Controlling air quality is crucial in order to face the increase in NCDs and protect the health of the population. Reducing air pollution should be considered a public health policy to prevent and manage NCDs, alongside with well-established recommendations for changes in lifestyle (eating healthy food, exercising, stopping tobacco smoking, etc.).

Human health risk assessments for complex mixtures can address real-world exposures and protect public health. While risk assessors typically prefer whole mixture approaches over component-based approaches, data from the precise exposure of interest are often unavailable and surrogate data from a sufficiently similar mixture(s) are required. This review describes recent advances in determining sufficient similarity of whole, complex mixtures spanning the comparison of chemical features, bioactivity profiles, and statistical evaluation to determine “thresholds of similarity.” Case studies, including water disinfection byproducts, botanical ingredients, and wildfire emissions, are used to highlight tools and methods. Limitations to application of sufficient similarity in risk-based decision making are reviewed and recommendations presented for developing best practice guidelines.

More than 200 million people around the world are exposed to unsafe levels of the environmental toxicant, arsenic. Both acute and chronic exposures, primarily through contaminated drinking water, are significant public health concerns. Human genetics does not fully explain observed arsenic-related diseases (arsenicosis), suggesting that other factors such as the microbiome play important roles in determining risk following exposure. Microorganisms have evolved diverse pathways for mitigating the toxic effects of arsenic, which may theoretically increase or decrease human arsenicosis by altering toxicity. Here, we review the current state-of-the-art regarding the genetic potential of microorganisms to influence arsenic toxicity, drawing particular attention to microbial arsenic biotransformation.

This article discusses the Swedish Chemicals Agency's proposal for estimating the size of a Mixture Assessment Factor (the KEMI MAF) for aquatic mixtures of chemicals. The KEMI MAF is an improvement over earlier approaches but is dependent on factors that are uncertain, such as: the number of chemicals that reach an aquatic receptor, the allocation of chemicals into assessment groups, and the impacts of future regulations on chemical concentrations in water. This article demonstrates that these uncertainties have significant impacts on the size of MAFs required for aquatic receptors. As part of this assessment a simplified method of calculating the KEMI MAF was developed.

Two-dimensional (2D) materials, including graphene-based materials, transition metal dichalcogenides, transition metal carbides and nitrides, and others, are increasingly developed for a wide range of applications owing to their exceptional and versatile properties. Understanding the biological interactions of 2D materials is critical for the safe and sustainable implementation of this emerging class of materials. Here, we discuss recent studies on the intricate interactions between 2D materials and the microbiome that dwells in and on all vertebrates, and the consequent impact on the host. We also address the underlying mechanisms of the antibacterial effects of 2D materials. Overall, investigations of 2D material interactions with the microbiome offer a new perspective on the biological impact of these materials.

The effect of chemical pollution on the microbiomes of wildlife has been given little attention. A new concept is emerging where microbiomes are vital to host animal or plant health, and for ecosystems. Data are mainly on mammals, birds, and fish. Changing environmental conditions (e.g., salinity, pH, season) and exposure to chemicals alter the composition of gill, gut and skin microbiomes. Gut microbiomes are also modulated by diet, and exposure to chemicals including metals, nanomaterials, fungicides or microplastics. However, a change in the microbiome does not necessarily infer adverse effects on the host, with some evidence of co-adaptation. Environmental risk assessment for biocides and new nanomaterials should be revisited in context with microbiome-host interactions to better protect wildlife and ecosystems.

Chemical pollution is characterised by sequential and simultaneous exposure to unintentional complex mixtures. The almost infinite number of real-life mixtures poses major challenges for investigations of all possible exposure scenarios through whole mixture or component-based approaches. As a pragmatic approach in data-poor situations, the application of a Mixture Assessment Factor to single substances assessments under REACH was announced in the European Chemicals Strategy for Sustainability. Current proposals for this factor are based on the assumption that mixtures behave additively, assuming that synergistic interactions are rare. This assumption is based on eight reviews published in the last 30 years. Synergistic deviations from additivity greater than two-fold were reported in roughly 5% of investigated mixtures. This was more, rather than less, frequent in the handful of suitable studies of low-dose mammalian mixture toxicity. This frequency is representative of mixtures toxicology studies in the literature and should not be interpreted as the frequency of synergisms in real-world exposures. Understanding the frequency and likelihood of synergisms would entail detailed understanding of the co-occurrence of groups of substances giving rise to such interactions in relevant environmental media. Assumptions that synergistic interactions in real-life mixtures are rare appear to be premature. While further research is required, potential synergisms should not be omitted from debates on the conservatism or otherwise of mixture allocation factor or other regulatory approaches to protect people and environment from mixture effects.

Cancer is one of the most prevalent and deadly diseases worldwide. Despite medical advances, the survival rate of patients with cancer remains poor, and v many standard chemotherapeutic choices are associated with toxic side effects that substantially impair their quality of life. 5-Fluorouracil (5-Fu) is a widely used chemotherapeutic drug. Administration of 5-Fu is known to cause diarrhoea and intestinal mucositis. Butyrate is a short-chain fatty acid produced during the fermentation of dietary fibre by the gut microbiota. Butyrate may mitigate 5-Fu's toxic effect of mucositis. In addition, butyrate enhanced the efficiency of 5-Fu. However, the pungent odour of butyrate renders it unpalatable to patients. The administration of butyrate-producing bacteria is a preferable alternative for patients seeking the positive effects of butyrate without an unpleasant taste. Furthermore, butyrate-producing bacteria could provide beneficial effects beyond butyrate production, including the restoration of microbial dysbiosis and anti-inflammatory effects. In this review, we provide an overview of the current research on butyrate-producing bacteria, concentrating on their possible effects and defence mechanism against 5-Fu toxicity, which indicates their potential applicability as an adjuvant treatment for patients with cancer.

Bioassays are the most common method of evaluating toxic effects of chemicals on living organisms. However, since simple bioassays cannot provide information on mechanisms of toxic effects, it is also important to establish test methods that yield clear molecular evidence derived from the adverse outcome pathway. It is possible that chemicals bearing juvenile hormone activity (juvenoids) used as insect growth regulators may seriously impact population viability by disturbing sex determination mechanisms in freshwater microcrustaceans, like Daphnia, a keystone species in lake ecosystems. This review describes the molecular mechanism by which juvenoid disrupts the sex determination of daphnids and also introduces a simple testing method we recently developed for substances with juvenile hormone activity using juvenile hormone receptors.