Current opinion in toxicology最新文献

Interest in the use of animal models of human disease has been increasing both within pharmaceutical companies and regulatory authorities, as evidenced by several recent publications and inclusion of recommendations for the use of these models in regulatory guidances. While the use of conventional or healthy animal models will continue to be a central component of safety evaluation, there are certain instances in which the use of animal models is critical for the understanding of potential risk for a diseased population. This review article provides highlights of the use of animal models of disease and provides examples of recent uses of animal models in the elucidation of safety considerations for humans, focusing on instances in which the models have been utilized in regulatory filings.

The accuracy with which preclinical studies performed on infrahuman mammals predict the efficacy and safety of potential new therapeutics intended for human use is a topic of interest and concern to preclinical scientists, physicians, veterinarians, regulators, and patients everywhere. Factors that impact the potential accuracy of preclinical assessments of safety and efficacy in surrogate species for humans include substantial differences in the mechanisms of cardiac repolarization and excitation–contraction coupling, as well as in the isoforms of the heart's contractile proteins. Some species are so similar to humans that they suffer the same spontaneous heart diseases — and yet so different that toxic doses of drugs or interventions that would be instantly fatal to a human have literally no effect on them. These differences are in part explained by the sometimes enormous differences in size and scale among species and in part by genetic and biochemical differences that we have only recently begun to understand. In reviewing some of the more striking species differences and similarities in cardiovascular physiology, this article hopes to stimulate interest in and inform the choices of scientists involved in surrogate model selection as they work to improve both the positive and negative predictive value of preclinical drug studies.

This review summarizes the recent advances in the field of investigative toxicology with a particular focus on the toxicological endpoint drug-induced liver injury. Despite the recent progress in the field of microphysiological systems with human cells, tissues, or organoids, corresponding systems with animal tissues or organoids are often lacking. These animal in vitro systems are, however, important to (1) assess the concordance with the pivotal animal toxicity studies which are mandatory before the progression to First-in-Man studies and (2) evaluate if results from the in vitro approaches are specific for an animal species or actually relevant for humans.

Plant foods have been a major source of human sustenance from the primeval ages, and have continued to do so in recent times. Unfortunately, this food subgroup represents a significant source of food-borne contaminants, especially heavy metals. Some heavy metals are nonessential and toxic, even at the minutest concentration, with accumulative tendencies in human tissues. Excessive accumulation of heavy metals in plant foods grown in contaminated areas can, therefore, seriously affect food quality and safety. The consumption of such foods presents a potential risk to global food security and healthy living. However, understanding the risk posed by these metals through the food chain is complicated by the fact that multiple sources are implicated in heavy metal exposure in food. Food safety is a global priority for better human health, and precaution must, therefore, be taken to contain the menace of heavy metal contamination of plant foods.

Wood is a type of biomass commonly burnt as a means of energy. When burnt, it releases harmful components linked to adverse health outcomes. In the scientific community toxicologists and epidemiologists continue to consider the individual components of woodsmoke — such as particulate matter and polycyclic aromatic hydrocarbons — as a way to better understand the relationship between inhaled woodsmoke and acute and chronic disease. In recent years, research focus has shifted toward the underlying mechanisms that could be associated with long-term health consequences. Alongside this research, novel studies in molecular toxicology that examine the impacts of woodsmoke could provide a link between woodsmoke and telomere length. Such studies could provide scientists with a better understanding on how woodsmoke leads to chronic diseases. As researchers from various disciplines come together to work on this complex and widespread issue, hope emerges to reduce the morbidity and mortality associated with this global air pollutant.

Brazil is one of the world's top-four agricultural pesticide–consuming countries. The extensive use of pesticides raises concerns about the consequences for the human health. This review appraised the evidence provided by epidemiological studies on the adverse health effects of pesticides conducted in Brazil within the past 2–4 years. Available data come from ecological, cross-sectional, and case–control studies which are relatively easy, quick, and inexpensive to conduct but of limited usefulness for inferring causation and to identify hazards in pesticide risk assessment. Inaccurate exposure assessment is another weakness common to these studies. No longitudinal cohort investigation of pesticide adverse health effects and no analytical data–based biomonitoring study were found in the literature. In conclusion, studies conducted in Brazil failed to generate data relevant for risk assessment and management of pesticides. Large prospective cohorts studies and good analytical data on exposures are needed to bridge this public health research gap.

Flame retardants are widely used in electronic equipment, construction materials, and furniture to prevent fires from starting and to slow progression. Environmental monitoring studies show their presence in house dust, biomonitoring studies occasionally detect the chemicals in biological samples, and animal toxicology studies show high-dose effects. Yet laboratory studies and real-world fire statistics confirm that flame retardants have benefits that need to be weighed against possible risks to human health. Tetrabromobisphenol A (TBBPA), is used to make brominated epoxy printed wiring boards, and to a lesser extent, flame retarded acrylonitrile butadiene styrene (ABS) plastic is often used to make electronic casings. Evaluating available toxicology data and using conservative exposure assumptions, the risks of using TBBPA in these applications is exceedingly low. Given the benefits of TBBPA and flame retardants, it is essential that carefully conducted, chemical- and use-specific risk assessment be used to inform regulatory action which could possibly undermine public fire protection.

Numerous papers have highlighted the need for cumulative risk assessments that evaluate the impacts of multiple chemical and nonchemical stressors on human health [1,2]. Nonchemical stressors represent a diverse suite of factors (e.g., social and economic adversity) that are only beginning to be explored in risk assessment [3]. Approaches incorporating both chemical and nonchemical stressors are critical for better understanding relative contributions of real-world stressors and developing effective intervention strategies. However, moving from traditional single chemical evaluations to cumulative risk assessments presents multiple challenges.

The importance of oxidative stress has been increasingly recognized in diabetes and related cardiovascular complications as well as in chemical-induced toxicity, which makes it a potential therapeutic target for tackling such health issues. On the other hand, numerous herbal supplements have been reported effective to prevent diabetes and chemical-induced organ injury. Recently, emerging studies indicate that antioxidation is a possible mechanism responsible for the therapeutic effect of herbal extracts. Hereby, we reviewed the most recent studies regarding the antioxidant effect of herbal supplements. Also, we summarized the herbal extracts causing hepatotoxicity and nephrotoxicity via oxidative stress. We aim to highlight the importance of oxidative stress in the therapeutic effectiveness of herbal supplements, as well as in mediating their adverse effects.