Abstract: Penconazole is a widely used fungicide in the UK; however, to date, there have been no peer-reviewed publications reporting human metabolism, excretion or biological monitoring data. The objectives of this study were to i) develop a robust analytical method, ii) determine biomarker levels in volunteers exposed to penconazole, and, finally, to iii) measure the metabolites in samples collected as part of a large investigation of rural residents’ exposure. An LC-MS/MS method was developed for penconazole and two oxidative metabolites. Three volunteers received a single oral dose of 0.03 mg/kg body weight and timed urine samples were collected and analysed. The volunteer study demonstrated that both penconazole-OH and penconazole-COOH are excreted in humans following an oral dose and are viable biomarkers. Excretion is rapid with a half-life of less than four hours. Mean recovery of the administered dose was 47% (range 33%–54%) in urine treated with glucuronidase to hydrolyse any conjugates. The results from the residents’ study showed that levels of penconazole-COOH in this population were low with >80% below the limit of detection. Future sampling strategies that include both end of exposure and next day urine samples, as well as contextual data about the route and time of exposure, are recommended.
Abstract: Psychotropic pharmaceuticals present in the environment may impact organisms both directly and via interaction strengths with other organisms, including predators; therefore, this study examined the potential effects of pharmaceuticals on behavioral responses of fish to avian predators. Wild-caught juvenile perch (Perca fluviatilis) were assayed using a striking bird model after a seven-day exposure to psychotropic pharmaceuticals (the antidepressants fluoxetine or sertraline, or the β-blocker propranolol) under the hypotheses that exposure would increase vulnerability to avian predation via increasing the probability of predator encounter as well as degrading evasive behaviors upon encounter. None of the substances significantly affected swimming activity of the fish, nor did they increase vulnerability by affecting encounter probability or evasive endpoints compared to control treatments. Counter to our expectations, fish exposed to 100 μg/L fluoxetine (but no other concentrations or pharmaceuticals) were less likely to enter the open area of the arena, i.e., less likely to engage in risky behavior that could lead to predator encounters. Additionally, all fish exposed to environmentally relevant, low concentrations of sertraline (0.12 μg/L) and propranolol (0.1 μg/L) sought refuge after the simulated attack. Our unexpected results warrant further research as they have interesting implications on how these psychotropic pharmaceuticals may affect predator-prey interactions spanning the terrestrial-aquatic interface.
Abstract: Since the 1970s, hazardous air pollutants (HAPs), so-called air toxics, have been of great concern because they can cause serious human health effects and have adverse effects on the environment. More noticeably, some of them are known to be human carcinogens. The objective of this paper is to investigate the regulatory systems and human health effects of air toxics which have been designated by the Taiwan government under the Air Pollution Control Act. These toxic air pollutants include acutely toxic gas (i.e., ammonia, chlorine, fluorides, hydrochloric acid, hydrogen cyanide, hydrogen sulfide, nitric acid, phosphoric acid and sulfuric acid), gas containing heavy metals, and carcinogenic chemicals (including formaldehyde, vinyl chloride, asbestos and matter containing asbestos, dioxins and furans, volatile organic compounds, polycyclic aromatic hydrocarbons, and polychlorinated biphenyls). In line with international concern about the carcinogenic risk and environmental persistence of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/PCDFs) and heavy metals in recent years, the current status in monitoring and reducing the emissions of PCDDs/PCDFs from stationary sources was analyzed as a case study in the present study. Furthermore, the control strategies for reducing emissions of air toxics from stationary sources in Taiwan were also addressed.
Abstract: People are exposed to phthalates through their wide use as plasticizers and in personal care products. Many phthalates are endocrine disruptors and have been associated with adverse health outcomes. However, knowledge gaps exist in understanding the molecular mechanisms associated with the effects of exposure in early and late pregnancy. In this study, we examined the relationship of eleven urinary phthalate metabolites with isoprostane, an established marker of oxidative stress, among pregnant Mexican-American women from an agricultural cohort. Isoprostane levels were on average 20% higher at 26 weeks than at 13 weeks of pregnancy. Urinary phthalate metabolite concentrations suggested relatively consistent phthalate exposures over pregnancy. The relationship between phthalate metabolite concentrations and isoprostane levels was significant for the sum of di-2-ethylhexyl phthalate and the sum of high molecular weight metabolites with the exception of monobenzyl phthalate, which was not associated with oxidative stress at either time point. In contrast, low molecular weight metabolite concentrations were not associated with isoprostane at 13 weeks, but this relationship became stronger later in pregnancy (p-value = 0.009 for the sum of low molecular weight metabolites). Our findings suggest that prenatal exposure to phthalates may influence oxidative stress, which is consistent with their relationship with obesity and other adverse health outcomes.
Abstract: Hemoglobin-based oxygen carriers (HBOCs) are being developed as oxygen and plasma volume-expanding therapeutics though their potential to promote oxidative tissue injury has raised safety concerns. Using a guinea pig exchange transfusion model, we examined the effects of polymerized bovine hemoglobin (HbG) on the transcriptional regulation, activity, and expression of the renal antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). HbG infusion downregulated the mRNA levels for genes encoding SOD isoforms 1-3, GPx1, GPx3, GPx4, and CAT. This transcriptional suppression correlated with decreased enzymatic activities for SOD, CAT, and GPx. Immunostaining revealed decreased protein expression of SOD1, CAT, and GPx1 primarily in renal cortical tubules. DNA methylation analyses identified CpG hypermethylation in the gene promoters for SOD1-3, GPx1, GPx3, and GPx4, suggesting an epigenetic-based mechanism underlying the observed gene repression. HbG also induced oxidative stress as evidenced by increased renal lipid peroxidation end-products and 4-HNE immunostaining, which could be the result of the depleted antioxidant defenses and/or serve as a trigger for increased DNA methylation. Together, these findings provide evidence that the renal exposure to HbG suppresses the function of major antioxidant defense systems which may have relevant implications for understanding the safety of hemoglobin-based products.
Abstract: Single cell imaging mass spectrometry opens up a complete new perspective for strategies in toxicological risk assessment and drug discovery. In particular, time-of-flight secondary ion mass spectrometry (ToF-SIMS) with its high spatial and depth resolution is becoming part of the imaging mass spectrometry toolbox used for single cell analysis. Recent instrumentation advancements in combination with newly developed cluster ion guns allow 3-dimensional reconstruction of single cells together with a spatially resolved compound location and quantification on nanoscale depth level. The exact location and quantification of a single compound or even of a set of compounds is no longer restricted to the two dimensional space within single cells, but is available for voxels, a cube-sized 3-dimensional space, rather than pixels. The information gathered from one voxel is further analysed using multivariate statistical methodology like maximum autocorrelation factors to co-locate the compounds of interest within intracellular organelles like nucleus, mitochondria or golgi apparatus. Furthermore, the cell membrane may be resolved, including adhering compounds and potential changes of the lipid patterns. The generated information can be used further for a first evaluation of intracellular target specifity of new drug candidates or for the toxicological risk assessment of environmental chemicals and their intracellular metabolites. Additionally, single cell lipidomics and metabolomics enable for the first time an in-depth understanding of the activation or inhibition of cellular biosynthesis and signalling pathways.