Frontiers in toxicology最新文献

Gadolinium-based contrast agents are increasingly used in clinical practice. While these pharmaceuticals are verified causal agents in nephrogenic systemic fibrosis, there is a growing body of literature supporting their role as causal agents in symptoms associated with gadolinium exposure after intravenous use and encephalopathy following intrathecal administration. Gadolinium-based contrast agents are multidentate organic ligands that strongly bind the metal ion to reduce the toxicity of the metal. The notion that cationic gadolinium dissociates from these chelates and causes the disease is prevalent among patients and providers. We hypothesize that non-ligand-bound (soluble) gadolinium will be exceedingly low in patients. Soluble, ionic gadolinium is not likely to be the initial step in mediating any disease. The Kidney Institute of New Mexico was the first to identify gadolinium-rich nanoparticles in skin and kidney tissues from magnetic resonance imaging contrast agents in rodents. In 2023, they found similar nanoparticles in the kidney cells of humans with normal renal function, likely from contrast agents. We suspect these nanoparticles are the mediators of chronic toxicity from magnetic resonance imaging contrast agents. This article explores associations between gadolinium contrast and adverse health outcomes supported by clinical reports and rodent models.

Glyphosate-based herbicides (GBH) are a widely used group of pesticides that have glyphosate (GLY) as main active compound and are used to control a wide range of weeds. Experimental and epidemiological studies point to neurotoxicity and endocrine disruption as main toxic effects. The aim of this study was to investigate the effects of developmental exposure to GLY and GBH on locomotor behavior, and the possible contribution of GR-mediated signaling. We used zebrafish (Danio rerio) larvae in a continuous exposure regimen to GLY or GBH in the rearing medium. Alongside TL wildtype, we used a mutant line carrying a mutation in the GR which prevents the GR from binding to DNA (gr^s357), as well as a transgenic strain expressing a variant of enhanced green fluorescent protein (d4eGFP) controlled by a promoter carrying multiple GR response elements (SR4G). We found that acute exposure to GBH, but not GLY, activates GR-mediated signaling. Using a continuous developmental exposure regime, we show that wildtype larvae exposed to GBH display decreased spontaneous activity and attenuated response to environmental stimuli, a pattern of alteration similar to the one observed in gr^s357 mutant larvae. In addition, developmental exposure to GBH has virtually no effects on the behavior of gr^s357 mutant larvae. Taken together, our data indicate that developmental exposure to GBH has more pronounced effects than GLY on behavior at 5 dpf, and that interference with GR-mediated signaling may have a relevant contribution.

The herbicide atrazine (ATR) has been one of the most widely used herbicides worldwide. However, due to its indiscriminate use, it has been considered an environmental contaminant. Several studies have classified ATR as an endocrine disruptor, and it has been found to have neurotoxic effects on behavior, along with alterations in the dopaminergic, GABAergic, and glutamatergic systems in the basal ganglia of male rodents. These findings suggest that these neurotransmitter systems are targets of this herbicide. However, there are no studies evaluating the neurotoxicity of ATR in female rodents. Our study aimed to assess the effects of repeated IP injections of 100 mg ATR/kg or a vehicle every other day for 2 weeks (six injections) on the locomotor activity, content of monoamines, GABA, glutamate, and glutamine in the striatum, nucleus accumbens, ventral midbrain, and prefrontal cortex, and tyrosine hydroxylase (TH) protein levels in striatum and nucleus accumbens of female rats. Repeated 100 mg ATR/kg injections immediately decreased all the locomotor activity parameters evaluated, and such hypoactivity persisted for at least 48 h after the last ATR administration. The ATR administration increased dopamine and DOPAC content in the nucleus accumbens and the dopamine and DOPAC and serotonin and 5-HIAA content in the ventral midbrain. In contrast, the TH protein levels in the striatum and nucleus accumbens were similar between groups. Meanwhile, GABA, glutamine, and glutamate levels remained unaltered in all brain regions evaluated. The observed behavioral alterations could be associated with the monoamine changes presented by the rats. These data reveal that the nucleus accumbens and ventral midbrain are susceptible to repeated ATR exposure in female rats.

Respiratory sensitization is a complex immunological process eventually leading to hypersensitivity following re-exposure to the chemical. A frequent consequence is occupational asthma, which may occur after long latency periods. Although chemical-induced respiratory hypersensitivity has been known for decades, there are currently no comprehensive and validated approaches available for the prospective identification of chemicals that induce respiratory sensitization, while the expectations of new approach methodologies (NAMs) are high. A great hope is that due to a better understanding of the molecular key events, new methods can be developed now. However, this is a big challenge due to the different chemical classes to which respiratory sensitizers belong, as well as because of the complexity of the response and the late manifestation of symptoms. In this review article, the current information on respiratory sensitization related processes is summarized by introducing it in the available adverse outcome pathway (AOP) concept. Potentially useful models for prediction are discussed. Knowledge gaps and gaps of regulatory concern are identified.

[This corrects the article DOI: 10.3389/ftox.2024.1376118.].

With the expansion of nanomaterials (NMs) usage, concerns about their toxicity are increasing, and the wide variety of NMs makes it difficult to assess their toxicity. Therefore, the development of a high-throughput, accurate, and certified method to evaluate the immunotoxicity of NMs is required. In this study, we assessed the immunotoxicity potential of various NMs, such as nanoparticles of silver, silica, and titanium dioxide, using the human Cell Line Activation Test (h-CLAT) at the cellular level. After exposure to silver nanoparticle dispersions, the expression levels of CD86 and CD54 increased, suggesting the activation of antigen-presenting cells (APCs) by silver nanoparticles. Quantification of silver ions eluted from silver nanoparticles and the activation of APCs by silver ions suggested that it was due to the release of silver ions. Silica nanoparticles also increased the expression of CD86 and/or CD54, and their activation ability correlated with the synthesis methods and hydrodynamic diameters. The ability of titanium dioxide to activate APCs differed depending on the crystal type and hydrodynamic diameter. These results suggest a potential method to evaluate the immunotoxicity potential of various NMs based on their ability to activate APCs using human monocytic THP-1 cells. This method will be valuable in assessing the immunotoxicity potential and elucidating the immunotoxic mechanisms of NMs.

Background: Pyrethroids are natural organic compounds extracted from flowers of pyrethrums and commonly used as domestic and commercial insecticides. Although it is effective in insect and parasitic control, its associated toxicity, including spermotoxicity, remains a challenge globally. Currently, the available reports on the effect of pyrethroids on semen quality are conflicting, hence an evaluation of its detrimental effect is pertinent. This study conducts a detailed systematic review and meta-analysis of the effects of pyrethroids on sperm quality. Materials and methods: The present study was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using a pre-defined strategic protocol, an internet search was done using combined text words. The criteria for eligibility were selected based on Population, Exposure, Comparator, Outcome, and Study Designs (PECO) framework, and relevant data were collected. Appraisal was done using The Office of Health Assessment and Translation (OHAT) tool for the evaluation of the Risk of Bias and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group guidelines for the certainty of evidence. A quantitative meta-analysis was conducted with the Review Manager (RevMan). Results: Only 12 out of the 4, 050 studies screened were eligible for inclusion in this study. The eligible studies were from China (4), Japan (3), Poland (3), and United States (2). All the eligible studies were cross-sectional. A total of 2, 050 male subjects were included in the meta-analysis. Pyrethroid exposure significantly reduced sperm motility. Region-stratified subgroup analyses revealed that pyrethroid significantly reduced sperm motility among men in Poland and United States, and decreased sperm count among men in Japan. Pyrethroid exposure also reduced sperm concentration among men in Poland but increased sperm concentration among men in the United States. Conclusion: Although the study revealed inconsistent evidence on the detrimental effect of pyrethroids on semen quality, the findings showed that pyrethroids have deleterious potentials on sperm motility, count, and concentration. Studies focusing on the assessment of semen quality in pyrethroid-exposed men, especially at specific varying levels of exposure, and employing prospective cohort studies or controlled cross-sectional designs are recommended.

The well-being of wildlife populations, ecosystem health, and human health are interlinked, and preserving wildlife is crucial for sustaining healthy ecosystems. Wildlife numbers, and in particular avian populations, have steeply declined over the past century, associated with anthropogenic factors originating from industry, urbanization, changing land use, habitat loss, pollution, emerging diseases, and climate change. All these factors combine to exert increasing stress and impair health for both humans and wildlife, with diminished metabolic, immune, and reproductive function, deteriorating overall health, and reduced longevity. The "toxic aging coin" suggests that these stressors may have dual impacts on aging-they can accelerate the aging process, and older individuals may struggle to cope with pollutants compared to younger ones. These responses are reflected in the health and productivity of individuals, and at a larger scale, the health and ability of populations to withstand disturbances. To understand the potential risk to health over the lifespan, it is important to articulate some of these global challenges and consider both their impacts on aging populations and on the aging process. In this review, we use the toxic aging coin and One Health conceptual frameworks to examine the interconnected health of humans, wildlife, and ecosystems. This exploration aims to develop proactive approaches for optimizing wildlife and human health.

In this perspective, the authors give their view on the developments and experiences on communicating on (nano)materials safety. We would like to share our experiences with the scientific community in order to make them useful for future communication activities. We present the long-term work of the science communication projects DaNa, DaNa2.0 and DaNa4.0, running from 2009 to 2023. Starting in the early 2000s with the beginnings of nanotechnology research, communication on the safety of nanomaterials with the public was still very new and faced the projects with many challenges. Today, science communication is indispensable for the dissemination of scientific findings and a fact-based approach like the DaNa "Knowledge Base Materials" creates a trustworthy dialogue with the public. This long-term project series has made a significant contribution to communication on the safety of nanomaterials, perhaps even the largest among publicly funded project series worldwide.