peer reviewed | Metconazole (MEZ), a chiral triazole fungicide, produces enantioselective adverse effects in non-target organisms. Among MEZ's isomers, cis-MEZ displays robust antimicrobial properties. Evaluating MEZ and cis-MEZ's toxicity may mitigate fungicide usage and safeguard non-target organisms. Our study evaluated the toxicity of MEZ and its cis-isomers at concentrations of 0.02, 0.2, 2, and 4 mg L−1. We report stereoselectivity and severe cardiovascular defects in zebrafish, including pericardial oedema, decreased heart rate, increased sinus venous and bulbous arteries distances, intersegmental vessel defects, and altered cardiovascular development genes (hand2, gata4, nkx2.5, tbx5, vmhc, amhc, dll4, vegfaa, and vegfc). Further, MEZ significantly increased oxidative stress and apoptosis in zebrafish, primarily in the cardiac region. Isoquercetin, an antioxidant found in plants, partially mitigates MEZ-induced cardiac defects. Furthermore, MEZ upregulated the Wnt/β-catenin pathway genes (wnt3, β-catenin, axin2, and gsk-3β) and β-catenin protein expression. Inhibitor of Wnt Response-1 (IWR-1) rescued MEZ-induced cardiotoxicity. Our findings highlight oxidative stress, altered cardiovascular development genes, and upregulated Wnt/β-catenin signaling as contributors to cardiovascular toxicity in response to MEZ and cis-MEZ treatments. Importantly, 1R,5S-MEZ exhibited greater cardiotoxicity than 1S,5R-MEZ. Thus, our study provides a comprehensive understanding of cis-MEZ's cardiovascular toxicity in aquatic life. © 2024 Elsevier Ltd

While the health impacts of larger particulate matter, such as PM₁₀ and PM₂.₅, have been studied extensively, research regarding ultrafine particles (UFPs or PM₀.₁) and particle surface area concentration (PSC) is lacking. This case-crossover study assessed the associations between exposure to PSC and UFP number concentration (UFPnc) and hospital admissions for cardiovascular diseases (CVDs) in New York State (NYS), 2013–2018. We used a time-stratified case-crossover design to compare the PSC and UFPnc levels between hospitalization days and control days (similar days without admissions) for each CVD case. We utilized NYS hospital discharge data to identify all CVD cases who resided in NYS. UFP simulation data from GEOS-Chem-APM, a state-of-the-art chemical transport model, was used to define PSC and UFPnc. Using a multi-pollutant model and conditional logistic regression, we assessed excess risk (ER)% per inter-quartile change of PSC and UFPnc after controlling for meteorological factors, co-pollutants, and time-varying variables. We found immediate and lasting associations between PSC and overall CVDs (lag0–lag0-6: ERs% (95% CI%) ranges: 0.4 (0.1,0.7) - 0.9 (0.7–1.2), and delayed and prolonged ERs%: 0.1–0.3 (95% CIs: 0.1–0.5) between UFPnc and CVDs (lag0-3–lag0-6). Exposure to larger PSC was associated with immediate ER increases in stroke, hypertension, and ischemic heart diseases (1.1%, 0.7%, 0.8%, respectively, all p < 0.05). The adverse effects of PSC on CVDs were highest among children (5–17 years old), in the fall and winter, and during cold temperatures. In conclusion, we found an immediate, lasting effects of PSC on overall CVDs and a delayed, prolonged impact of UFPnc. PSC was a more sensitive indicator than UFPnc. The PSC effects were higher among certain CVD subtypes, in children, in certain seasons, and during cold days. Further studies are needed to validate our findings and evaluate the long-term effects.

Plastic pollution has been a growing concern in recent decades due to the proliferation and ease of manufacturing of single use plastic products and inadequate waste and recycling management. Microplastic, and even smaller nanoplastic, particles are persistent pollutants in aquatic and terrestrial systems and are the subject of active and urgent research. This review will explore the current research on how exposure to plastic particles occurs and the risks associated from different exposure routes: ingestion, inhalation, and dermal exposure. The effects of microplastics on the cardiovascular system are of particular importance due to its sensitivity and ability to transport particles to other organ systems. The effects of microplastics and nanoplastics on the heart, platelet aggregation, and thrombus formation will all be explored with focus on how the particle characteristics modulate their effect. Plastic particle interactions are highly dependent on both their size and their surface chemistry and interesting research is being done with the interaction of particle characteristics and effect on thrombosis and the cardiovascular system. There is significant uncertainty surrounding some of the findings in this field as research in this area is still maturing. There are undoubtedly more physiological consequences than we are currently aware of resulting from environmental plastic exposure and more studies need to be conducted to reveal the full extent of pathologies caused by the various routes of microplastic exposure, with particular emphasis on longitudinal exposure effects. Further research will allow us to recognize the full extent of physiological impact and begin developing viable solutions to reduce plastic pollution and potentially design interventions to mitigate in-vivo plastic effects following significant or prolonged exposure.

Although short-term exposure to air pollution can trigger sudden heart attacks, evidence is scarce regarding the relationship between sub-daily changes in air pollution level and the risk of acute myocardial infarction (AMI). Here we assessed the intraday effect of air pollution on AMI risk and potential effect modification by pre-existing cardiac risk factors. Hourly data on emergency department visits (EDVs) for AMI and air pollutants in Brisbane, Australia during 2013–2015 were acquired from pertinent government departments. A time-stratified case-crossover analysis was adopted to examine relationships of AMI risk with hourly changes in particulate matters (aerodynamic diameter ≤ 2.5 μm (PM₂.₅) and ≤10 μm (PM₁₀)) and gaseous pollutants (ozone and nitrogen dioxide) after adjusting for potential confounders. We also conducted stratified analyses according to age, gender, disease history, season, and day/night time exposure. Excess risk of AMI per 10 μg/m³ increase in air pollutant concentration was reported at four time windows: within 1, 2–6, 7–12, and 13–24 h. Both single- and multi-pollutant models found an elevated risk of AMI within 2–6 h after exposure to PM₂.₅ (excessive risk: 12.34%, 95% confidence interval (CI): 1.44%–24.42% in single-pollutant model) and PM₁₀ within 1 h (excessive risk: 5.21%, 95% CI: 0.26%–10.40% in single-pollutant model). We did not find modification effect by age, gender, season or day/night time, except that PM₂.₅ had a greater effect on EDVs for AMI during night-time than daytime. Our findings suggest that AMI risk could increase within hours after exposure to particulate matters.

Hexafluoropropylene oxide dimer acid (HFPO-DA) is a perfluorooctanoic acid (PFOA) substitute. In the current study, potential developmental cardiotoxicity and hepatotoxicity following HFPO-DA exposure in chicken embryo has been investigated, focusing on the roles of peroxisome proliferator activated receptor alpha (PPARα), the major molecular target in PFOA-induced toxicities. HFPO-DA was exposed to fertile chicken eggs via air cell injection, morphology and function of the target organs (heart and liver) in hatchlings were investigated with histopathology and electrocardiography, and the serum levels of HFPO-DA had been measured with quadrupole-time of flight liquid chromatograph-mass spectrometer (Q-TOF LC/MS). Additionally, lentivirus-mediated in ovo PPARα silencing was used to assess the roles of PPARα in HFPO-DA induced developmental toxicities. The results indicated that developmental exposure to HFPO-DA induced developmental cardiotoxicity, including thinned right ventricular wall and elevated heart rates, similar to those observed with PFOA exposure, as well as developmental hepatotoxicity in the form of steatosis. Silencing of PPARα alleviated such effects, suggesting participation of PPARα in HFPO-DA induced developmental toxicities in chicken embryo. Moreover, enhanced expression of PPARα downstream genes, cluster of differentiation 36 (CD36) and enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH), were observed in HFPO-DA exposed animal heart tissues, which can be abolished by PPARα silencing. On the other hand, liver-type fatty acid binding protein (L-FABP) and CD36 expression were effectively enhanced in exposed liver tissues, but not EHHADH, suggesting differential mechanism of toxicity in heart and liver tissues. In summary, developmental exposure to HFPO-DA induced developmental cardiotoxicity and hepatotoxicity in hatchling chickens similar to PFOA, and PPARα still participates in such toxicities, with some differential downstream gene regulations in different organs. Further investigation on HFPO-DA-induced developmental toxicities is guaranteed.

Bifenazate is a novel acaricide for selective foliar spraying and is widely used to control mites in agricultural production. However, its toxicity to aquatic organisms is unknown. Here, a zebrafish model was used to study bifenazate toxicity to aquatic organisms. Exposure to bifenazate was found to cause severe cardiotoxicity in zebrafish embryos, along with disorders in the gene expression related to heart development. Bifenazate also caused oxidative stress. Cardiotoxicity caused by bifenazate was partially rescued by astaxanthin (an antioxidant), accompanied by cardiac genes and oxidative stress-related indicators becoming normalized. Our results showed that exposure to bifenazate can significantly change the ATPase activity and gene expression levels of the calcium signaling pathway. These led to heart failure, in which the blood accumulated outside the heart without entering it, eventually leading to death. The results indicated that bifenazate exposure caused cardiotoxicity in zebrafish embryos through the induction of oxidative stress and inhibition of the calcium signaling pathway.

Pyraclostrobin is a widely used and highly efficient fungicide that also has high toxicity to aquatic organisms, especially fish. Although some research has reported the toxic effects of pyraclostrobin on fish, the main toxic pathways of pyraclostrobin in fish remain unclear. The present study has integrated histopathological, biochemical and hematological techniques to reveal the main toxic pathways and mechanisms of pyraclostrobin under different exposure routes. Our results indicated that pyraclostrobin entered fish mainly through the gills. The highest accumulation of pyraclostrobin was observed in the gills and heart compared with accumulation in other tissues and gill tissue showed the most severe damage. Hypoxia symptoms (water jacking, tummy turning and cartwheel formation) in fish were observed throughout the experiment. Taken together, our results suggested that the gills are important target organs. The high pyraclostrobin toxicity to gills might be associated with oxidative damage to the gills, inducing alterations in ventilation frequency, oxygen-carrying substances in blood and disorders of energy metabolism. Our research facilitates a better understanding of the toxic mechanisms of pyraclostrobin in fish, which can promote the ecotoxicological research of agrochemicals on aquatic organisms.

Azoxystrobin (AZ) and pyraclostrobin (PY) are strobilurin fungicides that inhibit fungal mitochondrial respiration. In this study, a representative model, zebrafish (Danio rerio), was used as a test species for acute and developmental toxicity. Survival and malformation rates were observed only PY-treated embryos, with an LC₅₀ value of 77.75 ppb accompanied by a dramatic decrease in hatching rate, while AZ did not show great mortality. Morphological changes were observed in PY-treated embryos with the occurrence of pericadial edema at 25 ppb. A delay in growth was observed after treatment with pyraclostrobin at 50 ppb. Use of genetically engineered Tg(cmlc:EGFP) allowed fluorescence observation during heart development. PY interfered with normal heart development via upregulation of the nppa gene responsible for the expression of natriuretic peptides. Heart function was dramatically reduced as indicated by reduced heart rates. Increased expression of the nppa gene was also seen in AZ-treated embryos. The expression level of cyp24a1 was also up-regulated, while ugt1a1 and sult1st6 were down-regulated after treatment of zebrafish embryos with AZ or PY. Overall, strobilurin fungicides might inhibit normal heart formation and function within the range of concentrations tested.

Tetrabromobisphenol-A (TBBPA) is an emerging organic pollutant and a commonly used brominated flame retardant that has received much attention owing to its toxicity. Although TBBPA is ubiquitously detected in atmospheric particulate matter and dust, few studies have investigated the sub-chronic inhalation exposure to TBBPA. To further understand the excretion characteristics and tissue accumulation of TBBPA after inhalation exposure, we used the rat model to conduct a sub-chronic inhalation exposure study. Male rats were administered with different doses of aerosol TBBPA (12.9, 54.6, 121.6, and 455.0 mg/m³). TBBPA was found in the excretion (feces and urine) and all the target tissues (lung, liver, heart, thymus gland, spleen, testicles, muscles, kidneys, brain and serum). Feces were the main route of excretion, which contributed 19.18% to 72.54% (urine <0.10%). TBBPA excretion through feces following inhalation administration was much higher than that following oral and dermal exposure, thereby indicating lower bioavailability of TBBPA under inhalation exposure. Liver and serum showed higher levels of TBBPA compared with those of other tissues, thereby suggesting tissue-specific accumulation of TBBPA in rats. Owing to the relative non-invasiveness of serum sampling and greatest TBBPA concentration among the tissues, serum is a suitable matrix for estimation of TBBPA bioaccumulation after inhalation exposure.

β-blockers are a class of medications widely used to treat cardiovascular disorders, including abnormal heart rhythms, high blood pressure, and angina pectoris. The prevalence of β-blockers has generated a widespread concern on their potential chronic toxicity on aquatic organisms, highlighting the necessity of comprehensive studies on their environmental distribution, fate, and toxicity. This review summarizes the up-to-date knowledge on the source, global distribution, analytical methods, transformation, and toxicity of β-blockers. Twelve β-blockers have been detected in various environmental matrices, displaying significant temporal and spatial variations. β-blockers can be reduced by 0–99% at wastewater treatment plants, where secondary processes contribute to the majority of removal. Advanced oxidation processes, e.g., photocatalysis and combined UV/persulfate can transform β-blockers more rapidly and completely than conventional wastewater treatment processes, but the transformation products could be more toxic than the parent compounds. Propranolol, especially its (S)-enantiomer, exhibits the highest toxicity among all β-blockers. Future research towards improved detection methods, more efficient and cost-effective removal techniques, and more accurate toxicity assessment is needed to prioritize β-blockers for environmental monitoring and control worldwide.