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Following its introduction as an alternative to perfluorooctanoic acid, hexafluoropropylene oxide dimer acid (HFPO-DA) has been extensively detected in various environmental matrices. Despite this prevalence, limited information is available regarding its hepatotoxicity biomarkers. In this study, toxicokinetic simulations indicated that under repeated treatment, HFPO-DA in mice serum reached a steady state by the 4th day. To assess its subacute hepatic effects and identify potential biomarkers, mice were administered HFPO-DA orally at doses of 0, 0.1, 0.5, 2.5, 12.5, or 62.5 mg/kg/d for 7 d. Results revealed that the lowest observed adverse effect levels were 0.5 mg/kg/d for hepatomegaly and 2.5 mg/kg/d for hepatic injury. Serum metabolomics analysis identified 34, 58, and 118 differential metabolites in the 0.1, 0.5, and 2.5 mg/kg/d groups, respectively, compared to the control group. Based on weighted gene coexpression network analysis, eight potential hepatotoxicity-related metabolites were identified; among them, kynurenic acid (KA) in mouse serum exhibited the highest correlation with liver injury. Furthermore, liver-targeted metabolomics analysis demonstrated that HFPO-DA exposure induced metabolic migration of the kynurenine pathway from KA to nicotinamide adenine dinucleotide, resulting in the activation of endoplasmic reticulum stress and the nuclear factor kappa-B signaling pathway. Notably, pretreatment with KA significantly attenuated liver injury induced by HFPO-DA exposure in mice, highlighting the pivotal roles of KA in the hepatotoxicity of HFPO-DA.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Fluorocarburos , Propionatos , Masculino , Ratones , Animales , Ácido Quinurénico , Fluorocarburos/toxicidad , BiomarcadoresRESUMEN
Current toxicity screening approaches to evaluate the vast number of environmental chemicals that require assessment are hampered due to their significant costs, time requirements, and reliance on live animal testing. The aim of the present study was to develop an adverse outcome pathway (AOP)-anchored transcriptome analysis (AATA) catalogue to expedite the discovery of environmental toxicants. 437 AOPs from the AOPwiki (https://aopwiki.org/) and 2280 transcriptomics data sets from NCBI Gene Expression Omnibus (GEO) and EMBL-EBI ArrayExpress (AE) repositories were comprehensively reviewed and analyzed. By using the differentially expressed molecular key event (mKE) genes as connection nodes, we created a large-scale environmental substanceâtarget gene (mKE)âpredicted adverse outcomes (SGAs) network that included 78 substances, 1099 genes, and 354 adverse outcomes (AOs). To validate the reliability of the network, comprehensive literature verification was conducted. We demonstrated that 164 of the 354 AOs identified have been previously characterized in the literature. The results for 136 of these AOs were consistent with the predictions of the AATA catalogue, representing an accuracy rate of 82.9%. Besides, distinct patterns in molecular KEs and AOs among categories of substances, such as biocides and metals, were demonstrated. Some representative substances, including atrazine and copper, pose significant risks to fish at various levels of biological organization. Moreover, experimental verification of the AATA predictions was conducted, including exposures of zebrafish to perfluorooctanesulfonate, cresyl diphenyl phosphate, and lanthanum. Results demonstrated consistency with predictions of the AATA catalogue, with an accuracy rate of 92.3%. Collectively, the present findings support the AATA catalogue as an efficient and promising platform for identifying environmental toxicants to fish and thereby provide novel insights into the understanding of potential risks of environmental contaminants.
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Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is inevitable among pregnant women. Nevertheless, there is a scarcity of research investigating the connections between prenatal PFAS exposure and the placental structure and efficiency. Based on 712 maternal-fetal dyads in the Ma'anshan Birth Cohort, we analyzed associations between individual and mixed PFAS exposure and placental measures. We repeatedly measured 12 PFAS in the maternal serum during pregnancy. Placental weight, scaling exponent, chorionic disc area, and disc eccentricity were used as the outcome variables. Upon adjusting for confounders and implementing corrections for multiple comparisons, we identified positive associations between branched perfluorohexane sulfonate (br-PFHxS) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) with placental weight. Additionally, a positive association was observed between br-PFHxS and the scaling exponent, where a higher scaling exponent signified reduced placental efficiency. Based on neonatal sex stratification, female infants were found to be more susceptible to the adverse effects of PFAS exposure. Mixed exposure modeling revealed that mixed PFAS exposure was positively associated with placental weight and scaling exponent, particularly during the second and third trimesters. Furthermore, br-PFHxS and 6:2 Cl-PFESA played major roles in the placental measures. This study provides the first epidemiological evidence of the relationship between prenatal PFAS exposure and placental measures.
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Ácidos Alcanesulfónicos , Contaminantes Ambientales , Fluorocarburos , Recién Nacido , Lactante , Humanos , Femenino , Embarazo , Placenta , Cohorte de Nacimiento , AlcanosulfonatosRESUMEN
Organic light-emitting materials (OLEMs) are emerging contaminants in the environment and have been detected in various environment samples. However, limited information is available regarding their contamination within the human body. Here, we developed a novel QuEChERS (quick, easy, cheap, effective, rugged, and safe) method coupled with triple quadrupole/high-resolution mass spectrometry to determine OLEMs in breast milk samples, employing both target and suspect screening strategies. Our analysis uncovered the presence of seven out of the 39 targeted OLEMs in breast milk samples, comprising five liquid crystal monomers and two OLEMs commonly used in organic light-emitting diode displays. The cumulative concentrations of the seven OLEMs in each breast milk sample ranged from ND to 1.67 × 103 ng/g lipid weight, with a mean and median concentration of 78.76 and 0.71 ng/g lipid weight, respectively, which were higher compared to that of typical organic pollutants such as polychlorinated biphenyls and polybrominated diphenyl ethers. We calculated the estimated daily intake (EDI) rates of OLEMs for infants aged 0-12 months, and the mean EDI rates during lactation were estimated to range from 30.37 to 54.89 ng/kg bw/day. Employing a suspect screening approach, we additionally identified 66 potential OLEMs, and two of them, cholesteryl hydrogen phthalate and cholesteryl benzoate, were further confirmed using pure reference standards. These two substances belong to cholesteric liquid crystal materials and raise concerns about potential endocrine-disrupting effects, as indicated by in silico predictive models. Overall, our present study established a robust method for the identification of OLEMs in breast milk samples, shedding light on their presence in the human body. These findings indicate human exposure to OLEMs that should be further investigated, including their health risks.
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Contaminantes Ambientales , Bifenilos Policlorados , Lactante , Femenino , Humanos , Leche Humana/química , Contaminantes Ambientales/análisis , Bifenilos Policlorados/análisis , Espectrometría de Masas , LípidosRESUMEN
There has been widespread concern about the health hazards of per- and polyfluoroalkyl substances (PFAS), which may be the risk factor for hyperuricemia with evidence still insufficient in the general population in China. Here, we conducted a nationwide study involving 9,580 adults aged 18 years or older from 2017 to 2018, measured serum concentrations of uric acid and PFAS (PFOA, PFOS, 6:2 Cl-PFESA, PFNA, PFHxS) in participants, to assess the associations of individual PFAS with hyperuricemia, and estimated a joint effect of PFAS mixtures. We found positive associations of higher serum PFAS with elevated odds of hyperuricemia in Chinese adults, with the greatest contribution from PFOA (69.37%). The nonmonotonic dose-response (NMDR) relationships were observed for 6:2 Cl-PFESA and PFHxS with hyperuricemia. Participants with less marine fish consumption, overweight, and obesity may be the sensitive groups to the effects of PFAS on hyperuricemia. We highlight the potential health hazards of legacy long-chain PFAS (PFOA) once again because of the higher weights of joint effects. This study also provides more evidence about the NMDR relationships in PFAS with hyperuricemia and emphasizes a theoretical basis for public health planning to reduce the health hazards of PFAS in sensitive groups.
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Hiperuricemia , Hiperuricemia/epidemiología , Hiperuricemia/sangre , Humanos , Estudios Transversales , Adulto , Masculino , Femenino , Fluorocarburos/sangre , Persona de Mediana Edad , China/epidemiología , Ácido Úrico/sangreRESUMEN
Milk and dairy products are excellent sources of mineral elements, including Ca, P, Mg, Na, K, and Zn. The purpose of this study was to determine the effect of nonthermal (homogenization) and thermal (heat treatment) treatments on the distribution of mineral elements in 4 milk fractions: fat, casein, whey protein, and aqueous phase. The study results revealed that the distribution of mineral elements (such as Mg and Fe) in fat fractions is extremely low, whereas significant mineral elements such as Ca, Zn, Fe, and Cu are mostly dispersed in casein fractions. For nontreated goat milk, Mo is the only element identified in the whey protein fraction, whereas K and Na are mostly found in the aqueous phase. Mineral element concentrations in fat (K, Zn, and so on) and casein fractions (Fe, Mo, and so on) increased dramatically after homogenization. Homogenization greatly decreased the concentration of mineral elements in the whey protein fraction (Ca, Na, and so on) and aqueous phase (Fe, Cu, and so on). After heat treatment, the element content in the fat fraction and casein fraction increased greatly when compared with raw milk, such as Cu and Mg in the fat fraction, Na and Cu in the whey protein fraction, the concentration of components such as Mg and Na in casein fraction increased considerably. In contrast, after homogenization, Zn in the aqueous phase decreased substantially, whereas Fe increased significantly. Therefore, both homogenization and heat treatment have an effect on the mineral element distribution in goat milk fractions.
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Cabras , Leche , Minerales , Animales , Leche/química , Minerales/análisis , Caseínas/análisis , Proteína de Suero de Leche/análisisRESUMEN
Cardiovascular diseases are the leading cause of premature death in humans and remain a global public health challenge. While age, sex, family history, and false nutrition make a contribution, our understanding of compounds acting as cardiovascular disruptors is far from complete. Here, we aim to identify cardiovascular disruptors via a reduced transcriptome atlas (RTA) approach, which integrates large-scale transcriptome data sets of zebrafish and compiles a specific gene panel related to cardiovascular diseases. Among 767 gene expression profiles covering 81 environmental compounds, 11 priority compounds are identified with the greatest effects on the cardiovascular system at the transcriptional level. Among them, metals (AgNO3, Ag nanoparticles, arsenic) and pesticides/biocides (linuron, methylparaben, triclosan, and trimethylchlorotin) are identified with the most significant effects. Distinct transcriptional signatures are further identified by the percentage values, indicating that different physiological endpoints exist among prioritized compounds. In addition, cardiovascular dysregulations are experimentally confirmed for the prioritized compounds via alterations of cardiovascular physiology and lipid profiles of zebrafish. The accuracy rate of experimental verification reaches up to 62.9%. The web-based RTA analysis tool, Cardionet, for rapid cardiovascular disruptor discovery was further provided at http://www.envh.sjtu.edu.cn/cardionet.jsp. Our integrative approach yields an efficient platform to discover novel cardiovascular-disrupting chemicals in the environment.
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Enfermedades Cardiovasculares , Sistema Cardiovascular , Nanopartículas del Metal , Animales , Humanos , Pez Cebra/genética , Enfermedades Cardiovasculares/metabolismo , Plata , Perfilación de la Expresión Génica , Transcriptoma , Embrión no Mamífero/metabolismoRESUMEN
With the replacement of perfluorooctanoic acid (PFOA) with perfluorinated ether carboxylic acids (PFECAs), residents living near fluorochemical industrial parks (FIPs) are exposed to various novel PFECAs. Despite expectations of low accumulation, short-chain PFECAs, such as perfluoro-2-methoxyacetic acid (PFMOAA), previously displayed a considerably high body burden, although the main exposure routes and health risks remain uncertain. Here, we explored the distribution of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in diverse environmental media surrounding a FIP in Shandong Province, China. PFECAs were found at elevated concentrations in all tested matrices, including vegetables, cereals, air, and dust. Among residents, 99.3% of the ∑36PFAS exposure, with a 43.9% contribution from PFECAs, was due to gastrointestinal uptake. Dermal and respiratory exposures were negligible at 0.1 and 0.6%, respectively. The estimated daily intake (EDI) of PFMOAA reached 114.0 ng/kg body weight (bw)/day, ranking first among all detected PFECAs. Cereals emerged as the dominant contributor to PFMOAA body burden, representing over 80% of the overall EDI. The median EDI of hexafluoropropylene oxide dimer acid (HFPO-DA) was 17.9 ng/kg bw/day, markedly higher than the USEPA reference doses (3.0 ng/kg bw/day). The absence of established threshold values for other PFECAs constrains a comprehensive risk assessment.
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Ácidos Alcanesulfónicos , Fluorocarburos , Contaminantes Químicos del Agua , Monitoreo del Ambiente , Grano Comestible/química , Éter , Ácidos Carboxílicos/análisis , Fluorocarburos/análisis , Éteres , Éteres de Etila , China , Contaminantes Químicos del Agua/análisisRESUMEN
Concerns about the endocrine-disrupting effects of per- and polyfluoroalkyl substances (PFASs) have raised questions about their potential influence on precocious puberty in girls, which is an emerging concern in some populations. However, epidemiological evidence is lacking. In this study, 882 serum samples were collected from girls with central precocious puberty (CPP, n = 226), peripheral precocious puberty (PPP, n = 316), and healthy controls (n = 340) in 2021 in Shanghai, China. The serum levels of 25 legacy and emerging PFASs and 17 steroids were measured. Results showed that PFAS exposure was positively associated with estradiol levels. Eleven PFASs were significantly or marginally associated with the higher odds of the overall precocious puberty. Across subtypes, PFASs were more clearly associated with PPP, while the associations with CPP were consistent in direction but did not reach statistical significance. These findings were consistent with the assessment of PFAS mixtures using quantile-based g-computation (qgcomp) and Bayesian kernel machine regression, with perfluorobutane sulfonate and 6:2 polyfluorinated ether sulfonate showing the highest contribution to joint effects. Although changes in serum estradiol could arise from various factors, our results suggest that the PFAS exposure may contribute to the increase in estradiol secretion, thereby increasing the risk of precocious puberty, especially PPP. The potential effects of PFASs on precocious puberty warrant further investigation, given the associated complications of public health concern, including psychological distress and increased risk of multiple diseases.
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Fluorocarburos , Pubertad Precoz , Femenino , Humanos , Pubertad Precoz/epidemiología , Teorema de Bayes , China/epidemiología , EstradiolRESUMEN
Synthetic glucocorticoids have been widely detected in aquatic ecosystems and may pose a toxicological risk to fish. In the present study, we described multiple end point responses of zebrafish to a commonly prescribed glucocorticoid, prednisolone (PREL), at concentrations between 0.001 and 9.26 µg/L. Of 23 end points monitored, 7 were affected significantly. Significant increases in the frequency of yolk extension formation, spontaneous contraction, heart rate, and ocular melanin density and significant decreases of ear-eye distance at PREL concentrations of 0.001 µg/L and above clearly pointed to the acceleration of embryonic development of zebrafish by PREL. Further confirmation came from the alterations in somite numbers, head-trunk angle, and yolk sac size, as well as outcomes obtained via RNA sequencing, in which signaling pathways involved in tissue/organ growth and development were highly enriched in embryos upon PREL exposure. In addition, the crucial role of glucocorticoid receptor (GR) for PREL-induced effects was confirmed by both, the coexposure to antagonist mifepristone (RU486) and GR-/- mutant zebrafish experiments. We further demonstrated similar accelerations of embryonic development of zebrafish upon exposure to 11 additional glucocorticoids, indicating generic adverse effect characteristics. Overall, our results revealed developmental alterations of PREL in fish embryos at low concentrations and thus provided novel insights into the understanding of the potential environmental risks of glucocorticoids.
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Glucocorticoides , Prednisolona , Animales , Glucocorticoides/metabolismo , Glucocorticoides/farmacología , Prednisolona/toxicidad , Prednisolona/metabolismo , Pez Cebra/genética , Receptores de Glucocorticoides/metabolismo , Ecosistema , Desarrollo Embrionario , Embrión no Mamífero/metabolismoRESUMEN
The placenta is pivotal for fetal development and maternal-fetal transfer of many substances, including per- and polyfluoroalkyl substances (PFASs). However, the intraplacental distribution of PFASs and their effects on placental vascular function remain unclear. In this study, 302 tetrads of matched subchorionic placenta (fetal-side), parabasal placenta (maternal-side), cord serum, and maternal serum samples were collected from Guangzhou, China. Eighteen emerging and legacy PFASs and five placental vascular biomarkers were measured. Results showed that higher levels of perfluorooctanoic (PFOA), perfluorooctane sulfonic acid (PFOS), and chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs) were detected in subchorionic placenta compared to parabasal placenta. There were significant associations of PFASs in the subchorionic placenta, but not in the serum, with placental vascular biomarkers (up to 32.5%) and lower birth size. Birth weight was negatively associated with PFOA (ß: -103.8, 95% CI: -186.3 and -21.32) and 6:2 Cl-PFESA (ß: -80.04, 95% CI: -139.5 and -20.61), primarily in subchorionic placenta. Mediation effects of altered placental angiopoietin-2 and vascular endothelial growth factor receptor-2 were evidenced on associations of adverse birth outcomes with intraplacental PFOS and 8:2 Cl-PFESA, explaining 9.5%-32.5% of the total effect. To the best of our knowledge, this study is the first to report on differential intraplacental distribution of PFASs and placental vascular effects mediating adverse birth outcomes and provides novel insights into the placental plate-specific measurement in PFAS-associated health risk assessment.
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Ácidos Alcanesulfónicos , Fluorocarburos , Humanos , Embarazo , Femenino , Placenta/química , Factor A de Crecimiento Endotelial Vascular , China , Fluorocarburos/análisis , BiomarcadoresRESUMEN
Mirtazapine is a commonly prescribed antidepressant and has been found widespread in aquatic environments. However, its toxicities to aquatic organisms has rarely been explored. Herein, we conducted a comprehensive study on the developmental effects of mirtazapine on early life stages of zebrafish at environmentally relevant concentrations (3.9 ng/L and 43.5 ng/L). Out of the endpoints measured, spontaneous contraction of embryos at 24 h post fertilization (hpf) and hatching rate and heart rate of embryos at 50 hpf and 56 hpf, respectively, were significantly affected. In light-dark transition behavior test, mirtazapine significantly reduced the swimming frequency and swimming speed of embryos at both concentrations of 3.9 ng/L and 43.5 ng/L. Furthermore, the total swimming distances in dark conditions were also significantly reduced. Transcriptomic analysis was further conducted. It demonstrated that the decreased neural activities in embryos may be associated with altered epinephrine and neuregulin signaling. The present results fill a data gap regarding the exposure of fish to mirtazapine at environmentally relevant concentrations and provide new insights into the neurotoxic mechanisms of mirtazapine exposure.
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Nafion by-product 2 (Nafion BP2), an emerging fluorinated sulfonic acid commonly used in polymer electrolyte membrane technologies, has been detected in various environmental and human matrices. To date, however, few studies have explored its toxicity. In this study, zebrafish embryos were exposed to Nafion BP2 at concentrations of 20, 40, 60, 80, 100, 120, 140, and 160 mg/L from fertilization to 120 post-fertilization (hpf), and multiple developmental parameters (survival rate, hatching rate, and malformation rate) were then determined. Results showed that Nafion BP2 exposure led to a significant decrease in survival and hatching rates and an increase in malformations. The half maximal effective concentration (EC50) of Nafion BP2 for malformation at 120 hpf was 55 mg/L, which is higher than the globally important contaminant perfluorooctane sulfonate (PFOS, 6 mg/L). Furthermore, exposure to Nafion BP2 resulted in additional types of malformations compared to PFOS exposure. Pathologically, Nafion BP2 caused abnormal early foregut development, with exfoliation of intestinal mucosa, damage to lamina propria, and aberrant proliferation of lamina propria cells. Nitric oxide content also decreased markedly. In addition, embryos showed an inflammatory response following Nafion BP2 exposure, with significantly increased levels of pro-inflammatory factors C4 and IL-6. Acidic mucin in the hindgut increased more than two-fold. 16 S rRNA sequencing revealed a marked increase in the pathogen Pseudomonas otitidis. Furthermore, pathways involved in intestinal protein digestion and absorption, inflammatory response, and immune response were significantly altered. Our findings suggest that the intestine is a crucial toxicity target of Nafion BP2 in zebrafish, thus highlighting the need to evaluate its health risks.
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Polímeros de Fluorocarbono , Homeostasis , Intestinos , Contaminantes Químicos del Agua , Animales , Humanos , Embrión no Mamífero , Polímeros de Fluorocarbono/toxicidad , Homeostasis/efectos de los fármacos , Intestinos/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Pez CebraRESUMEN
The popularity of vaping cannabis products has increased sharply in recent years. In 2019, a sudden onset of electronic cigarette/vaping-associated lung injury (EVALI) was reported, leading to thousands of cases of lung illness and dozens of deaths due to the vaping of tetrahydrocannabinol (THC)-containing e-liquids that were obtained on the black market. A potential cause of EVALI has been hypothesized due to the illicit use of vitamin E acetate (VEA) in cannabis vape cartridges. However, the chemistry that modifies VEA and THC oil, to potentially produce toxic byproducts, is not well understood under different scenarios of use. In this work, we quantified carbonyls, organic acids, cannabinoids, and terpenes in the vaping aerosol of pure VEA, purified THC oil, and an equal volume mixture of VEA and THC oil at various coil temperatures (100-300 °C). It was found under the conditions of our study that degradation of VEA and cannabinoids, including Δ9-THC and cannabigerol (CBG), occurred via radical oxidation and direct thermal decomposition pathways. Evidence of terpene degradation was also observed. The bond cleavage of aliphatic side chains in both VEA and cannabinoids formed a variety of smaller carbonyls. Oxidation at the ring positions of cannabinoids formed various functionalized products. We show that THC oil has a stronger tendency to aerosolize and degrade compared to VEA at a given temperature. The addition of VEA to the e-liquid nonlinearly suppressed the formation of vape aerosol compared to THC oil. At the same time, toxic carbonyls including formaldehyde, 4-methylpentanal, glyoxal, or diacetyl and its isomers were highly enhanced in VEA e-liquid when normalized to particle mass.
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Cannabinoides , Sistemas Electrónicos de Liberación de Nicotina , Lesión Pulmonar , Vapeo , Acetatos , Aerosoles , Dronabinol/química , Humanos , Vitamina E/químicaRESUMEN
Nafion byproduct 2 (H-PFMO2OSA) has been detected in the environment, but little is known about its toxicities. To compare the hepatotoxicity of H-PFMO2OSA with legacy perfluorooctane sulfonate (PFOS), male adult mice were exposed to 0.2, 1, or 5 mg/kg/d of each chemical for 28 days. Results showed that, although H-PFMO2OSA liver and serum concentrations were lower than those of PFOS, the relative liver weight in the H-PFMO2OSA groups was significantly higher than that in the corresponding PFOS groups. In addition, the increase in alanine transaminase and aspartate aminotransferase activity was greater in the H-PFMO2OSA groups than in the PFOS groups. Reduced glutathione (GSH) content and glutathione reductase activity in the liver increased in the 1 and 5 mg/kg/d H-PFMO2OSA groups and in the 5 mg/kg/d PFOS group. Liver quantitative proteome analysis demonstrated that, similar to PFOS, H-PFMO2OSA caused lipid metabolism disorder, and most lipid metabolism-related differentially expressed proteins (DEPs) were controlled by peroxisome proliferator-activated receptor alpha (PPARα). Additionally, KEGG enrichment analysis highlighted changes in the GSH metabolism pathway after PFOS and H-PFMO2OSA exposure. Then, there were eight DEPs involved in the GSH metabolism pathway that mostly were upregulated after exposure to H-PFMO2OSA but not after exposure to PFOS. In conclusion, H-PFMO2OSA induced higher levels of liver damage and more serious GSH metabolism dysregulation compared to PFOS.
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Ácidos Alcanesulfónicos , Enfermedad Hepática Inducida por Sustancias y Drogas , Fluorocarburos , Ácidos Alcanesulfónicos/toxicidad , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Éter/metabolismo , Éteres/metabolismo , Polímeros de Fluorocarbono , Fluorocarburos/toxicidad , Hígado/metabolismo , Masculino , Ratones , Ácidos SulfónicosRESUMEN
As novel alternatives to legacy poly- and perfluoroalkyl substances (PFAS), perfluoroalkyl ether carboxylic acids (PFECAs) have been widely detected in the environment; however, there is limited information and knowledge regarding their bioaccumulation and trophic transfer behavior along the food chain. This research presents the first known published data on the bioaccumulation and trophic transfer characteristics of PFECAs in a source-impacted estuary. Elevated PFECA concentrations were observed in organisms (for instance, conch, with perfluoro-2-methoxyacetic acid (PFMOAA) concentration reaches up to 16â¯700 ng/g dry weight (dw)), indicating exposure risks to the consumers. Conch can be acted as a potential environmental bioindicator of PFMOAA. PFMOAA, hexafluoropropylene oxide trimer acid (HFPO-TrA) and PFOA were predominant detected in biotas. On the basis of trophic magnification factors (TMFs), PFECAs with ≥6 perfluorinated carbons (HFPO-TrA, hexafluoropropylene oxide tetramer acid (HFPO-TeA) and perfluoro (3, 5, 7, 9, 11-pentaoxadodecanoic) acid (PFO5DoA)) could be biomagnified along the food chain (TMF > 1), while PFMOAA with the least perfluorinated carbons undergone biodilution (TMF < 1). As seafood is an important dietary source of protein to human, there is a potential health risk related to the consuming polluted aquatic products.
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Ácidos Alcanesulfónicos , Fluorocarburos , Contaminantes Químicos del Agua , Ácidos Alcanesulfónicos/análisis , Bioacumulación , Ácidos Carboxílicos , China , Monitoreo del Ambiente , Éter , Éteres , Fluorocarburos/análisis , Cadena Alimentaria , Humanos , Óxidos , Contaminantes Químicos del Agua/análisisRESUMEN
Understanding the mechanisms of individual susceptibility to exposure to environmental pollutants has been a challenge in health risk assessment. Here, an integrated approach combining a CRISPR screen in human cells and epidemiological analysis was developed to identify the individual susceptibility to the adverse health effects of air pollutants by taking formaldehyde (FA) and the associated chronic obstructive pulmonary disease (COPD) as a case study. Among the primary hits of CRISPR screening of FA in human A549 cells, HTR4 was the only gene genetically associated with COPD susceptibility in global populations. However, the association between HTR4 and FA-induced respiratory toxicity is unknown in the literature. Adverse outcome pathway (AOP) network analysis of CRISPR screen hits provided a potential mechanistic link between activation of HTR4 (molecular initiating event) and FA-induced lung injury (adverse outcome). Systematic toxicology tests (in vitro and animal experiments) were conducted to reveal the HTR4-involved biological mechanisms underlying the susceptibility to adverse health effects of FA. Functionality and enhanced expression of HTR4 were required for susceptibility to FA-induced lung injury, and FA-induced epigenetic changes could result in enhanced expression of HTR4. Specific epigenetic and genetic characteristics of HTR4 were associated with the progression and prevalence of COPD, respectively, and these genetic risk factors for COPD could be potential biomarkers of individual susceptibility to adverse respiratory effects of FA. These biomarkers could be of great significance for defining subpopulations susceptible to exposure to FA and reducing uncertainty in the next-generation health risk assessment of air pollutants. Our study delineated a novel toxicological pathway mediated by HTR4 in FA-induced lung injury, which could provide a mechanistic understanding of the potential biomarkers of individual susceptibility to adverse respiratory effects of FA.
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Contaminantes Atmosféricos , Lesión Pulmonar , Enfermedad Pulmonar Obstructiva Crónica , Contaminantes Atmosféricos/toxicidad , Animales , Biomarcadores , Formaldehído/efectos adversos , Formaldehído/toxicidad , Pulmón , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Hipersensibilidad RespiratoriaRESUMEN
Various per- and polyfluoroalkyl substances (PFASs) remain undiscovered and unexplored in the environment. The goals of this study were to discover new species of PFASs in effluent and surface waters from a fluorochemical industrial zone, and to assess their concentration, distribution, and temporal trends in the adjacent natural environment. In total, 83 emerging PFASs from 14 classes were identified, 22 of which were reported for the first time. Authentic standards were synthesized for 13 per- and polyfluoroalkyl ether carboxylic acids (PFECAs), thereby greatly expanding the scope of PFAS-targeted monitoring. The newly identified compounds accounted for 27%-95% of the total PFAS concentrations. Of note, a novel diether carboxylic acid, 2-[2-(trifluoromethoxy)hexafluoropropoxy]tetrafluoropropanoic acid (C7 HFPO-TA) was detected at an extremely high concentration in the fluorochemical zone effluent (447â¯000 ng/L) and at a median concentration in the fluorochemical zone surface water (670 ng/L), with detectable levels also found in the natural environment, that is, Wangyu River (23 ng/L) and Taihu Lake (5.6 ng/L). The distinct geographic distribution of C7 HFPO-TA suggests transport from the industrial point source to Taihu Lake via the Wangyu River. The concentration of C7 HFPO-TA in Taihu Lake, along with that of many other emerging PFASs, continued to grow in three sampling campaigns from 2016 to 2021. Considering the environmental persistence and toxicity of structurally similar PFECAs (e.g., HFPO-DA), studies on C7 HFPO-TA are urgently needed.
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Ácidos Alcanesulfónicos , Fluorocarburos , Contaminantes Químicos del Agua , Ácidos Alcanesulfónicos/análisis , Ácidos Carboxílicos , China , Monitoreo del Ambiente , Fluorocarburos/análisis , Lagos , Ríos , Contaminantes Químicos del Agua/análisisRESUMEN
The residues of pharmaceuticals in surface waters of megacities and ecotoxicological implications are of particular concern. In this study, we combined field investigations and model simulations to explore the contamination of cardiovascular and lipid-lowering drugs, one group of the most prescribed medications globally, in surface waters of a typical megacity, Shanghai, with a high wastewater treatment ratio (≈96%). Among 26 target substances, 19 drugs were detected with aqueous concentrations ranging from 0.2 (ketanserin) to 715 ng/L (telmisartan). Of them, angiotensin II receptor antagonists, telmisartan and irbesartan, were dominant besides ß-blockers. Spatial distribution analysis demonstrated their much higher levels in tributaries compared to the mainstream. The results of model simulations and field investigation revealed relatively low concentrations of cardiovascular and lipid-lowering drugs in surface waters of Shanghai compared to other cities in highly developed countries, which is associated with low per capita usage in China. Ecotoxicological studies in zebrafish embryos further revealed developmental effects, including altered hatching success and heart rate, by irbesartan, telmisartan, lidocaine, and their mixtures at ng/L concentrations, which are typical levels in surface waters. Overall, the present results suggest that the high wastewater treatment ratio was not sufficient to protect fish species in the aquatic ecosystem of Shanghai. Exposure to cardiovascular and lipid-lowering drugs and associated risks will further increase in the future due to healthcare improvements and population aging.
Asunto(s)
Contaminantes Químicos del Agua , Purificación del Agua , Animales , China , Ecosistema , Monitoreo del Ambiente , Irbesartán/análisis , Lípidos , Preparaciones Farmacéuticas , Telmisartán , Contaminantes Químicos del Agua/química , Pez CebraRESUMEN
Due to its wide usage and recent detection in environmental matrices, hexafluoropropylene oxide dimer acid (HFPO-DA, commercial name GenX) has attracted considerable attention. Here, we explored and compared the toxicity of GenX and its novel analogs with that of perfluorooctanoic acid (PFOA) to provide guidance on the structural design and optimization of novel alternatives to poly- and perfluoroalkyl substances (PFASs). Adult male BALB/c mice were continuously exposed to PFOA, GenX, perfluoro-2-methyl-3,6-dioxo-heptanoic acid (PFMO2HpA), and perfluoro-2-methyl-3,6,8-trioxo-nonanoic acid (PFMO3NA; 0, 0.4, 2, or 10 mg/kg/d) via oral gavage for 28 days. The PFOA, GenX, and PFMO3NA treatment groups showed an increase in relative liver weight, and bile acid metabolism was the most significantly affected pathway in all treatment groups, as shown via weighted gene coexpression network analysis. The highest total bile acid levels were observed in the 2 and 10 mg/kg/d PFMO3NA groups. The ratios of primary bile acids to all bile acids increased in the high-dose groups, while the ratios of secondary bile acids showed a downward trend. Thus, bile acid metabolism disorder may be a prominent adverse effect induced by exposure to GenX, its analogs, and PFOA. Results also showed that the hepatotoxicity of PFMO2HpA was lower than that of GenX, whereas the hepatotoxicity of PFMO3NA was stronger, suggesting that PFMO2HpA may be a potential alternative to GenX.