Occurrence, spatial distribution, and fate of polycyclic musks in sediments from the catchment of Chaohu Lake, China.

Twenty-nine surface sediments from Chaohu Lake in China and from its six main tributaries were sampled to investigate the concentrations of two important polycyclic musks (PCMs), 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta(g)-2-benzopyran (galaxolide, HHCB) and 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (tonalide, AHTN), as well as the concentration of 4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta(g)-2-benzopyran-1-one (galaxolidon, HHCB-lactone), which is the main degradation product of HHCB. Except for the high concentrations of AHTN and HHCB measured in the Nanfei River (879 ng/g dw and 5,513 ng/g dw, respectively), the levels of AHTN and HHCB in the river sediments were 7.08-44.9 ng/g dw and 20.6-268 ng/g dw, respectively, which are slightly lower than those documented in various areas worldwide. The concentrations of AHTN and HHCB in the sediments of Chaohu Lake were one or two orders of magnitude lower than those in the tributary rivers and showed a clear regional distribution. The concentrations of HHCB-lactone were comparable to those of HHCB and presented a significant positive correlation with the concentrations of HHCB, suggesting that the HHCB-lactone originated directly from the degradation of HHCB in wastewater treatment plants (WWTPs) or in the natural environment. The diagnostic ratios of HHCB/AHTN and HHCB-lactone/HHCB and the enantiomeric fractions (EFs) of these PCMs showed that the direct origins of the target PCMs in the study area were municipal and industrial wastewaters discharged from adjacent cities or point sources and that the HHCB-lactone in sediment originated from the natural degradation of HHCB in the rivers and the lake. The results of the risk assessment showed that the PCMs in the watershed sediments were unlikely to pose a threat to aquatic species. However, the effluents of industrial and municipal wastewaters that are discharged into the Nanfei River should be investigated in future research.

Development of aquatic life criteria for tonalide (AHTN) and the ecological risk assessment.

AHTN (tonalide) is a polycyclic musk that is widely used as fragrance additive in numerous consumer products. AHTN is of great worldwide concern owing to its adverse effects on aquatic organisms and frequent detection in both domestic and foreign aquatic environments. Therefore, derivation of the aquatic life criteria for AHTN exposure is urgently needed. In this work, AHTN toxicity data for eight Chinese native freshwater organisms were used to derive a criterion maximum concentration of 59.39 µg/L and a criterion continuous concentration of 22.43 µg/L using United States Environmental Protection Agency guidelines. Toxicity tests showed that the annelid L. hoffmeisteri and the amphibian R. nigromaculata were the least and most sensitive species to AHTN, respectively. The sensitivity of the planktonic crustacean D. magna to AHTN obviously differed from that of the benthic crustacean M. nipponense. The AHTN and HHCB correlation analysis exhibited a strong positive linear correlation (R2 = 0.8622) in water. The ecological risk assessment showed that AHTN and HHCB posed a higher risk in foreign surface waters than Chinese waters, but a lower risk in foreign wastewater treatment plant effluent than in China. The ecological risks of AHTN and HHCB in most surveyed water bodies of various countries were at acceptable levels, with a few exceptions.

Antioxidative enzyme activities in the Rhodeinae sinensis Gunther and Macrobrachium nipponense and multi-endpoint assessment under tonalide exposure.

Tonalide or acetyl hexamethyl tetralin (AHTN) is used as a fragrance additive in various household products. Recently, AHTN has drawn attention owing to its negative health effects on aquatic organisms. Data on AHTN toxicity toward aquatic species are limited. Therefore, this study tested the oxidative stress induced by AHTN exposure on the Rhodeinae sinensis Gunther and Macrobrachium nipponense. In this study, malonaldehyde (MDA) content and the activities of acetyl cholinesterase (AchE), superoxide dismutase (SOD), glutathione S-transferase (GST), and catalase (CAT) in R. sinensis Gunther were tested after 30 days of exposure to 30.093, 34.005, 38.426, 43.421, 49.067, 55.444, 62.652, 70.800, and 80.000 µg/L AHTN, respectively. The MDA, AchE, SOD, GST and CAT in M. nipponense were tested after 40 days of exposure to 60.000, 72.000, 86.400, 103.680, 124.416, 149.299, 179.159, 214.991, and 257.989 µg/L AHTN, respectively. In addition, an integrated biomarker response (IBR) index was utilised to evaluate the integrated toxic effects of AHTN on R. sinensis Gunther and M. nipponense. Finally, the predicted no-effect concentrations (PNECs) of AHTN, based on reproduction, biochemistry, survival, chronic toxicity, and acute toxicity endpoints were derived. The results indicated that low concentrations of AHTN can induce significant changes of oxidative stress biomarkers. The no observed effect concentrations (NOECs) of SOD, GST, AchE, CAT, and MDA were 103.680, 72.000, <60.000, 72.000, and <60.000 µg/L for R. sinensis Gunther and 38.426, 43.421, 30.093, 30.093, and 38.426 µg/L for M. nipponense, respectively. The IBR calculation results showed that 149.299 µg/L AHTN caused the highest toxic effect on R. sinensis Gunther after 30 days of exposure, whereas 70.797 µg/L AHTN caused the greatest damage to M. nipponense after 40 days of exposure. The PNECs of AHTN based on the non-traditional endpoints of biochemistry and reproduction were 0.00145 µg/L and 0.000395 µg/L, respectively, which were significantly lower than the PNEC of 2.636 µg/L for traditional endpoint survival. Therefore, the protection of aquatic organisms based on non-traditional toxicity endpoints should be considered in ecological risk assessment.

A carbon nanotube-enhanced real-time immuno-PCR for ultrasensitive detection of AHTN in water.

Polycyclic musks (PCMs) in the aquatic environment have become an emerging environmental issue because of their potential risk. The most commonly used method for analysis of PCMs is gas chromatography-mass spectrometer (GC-MS) with different sample extractions, which are somewhat expensive to operate, laborious and complex. In this paper, a carbon nanotube-enhanced real time immuno-PCR was developed for ultrasensitive detection of AHTN in water for the first time. The SWCNTs were used to immobilize numerous amino-DNA and polyclonal antibody to form polyclonal antibody-CNTs-DNA conjugates, which were used as a signal-amplifier in the proposed immunoassay system. This proposed carbon nanotube enhanced real time immuno-PCR assay was used to determine AHTN in water samples ranging from 5 pg/L-0.1 ng/L; using sample size as low as 10 µL. This proposed carbon nanotube enhanced real time immuno-PCR is the most ultrasensitive one for determination of AHTN in water without pre-concentration or extractions; and it provide a potential way for ultra-trace AHTN detection in the aquatic environment.

Synthetic musk compounds and benzotriazole ultraviolet stabilizers in breast milk: Occurrence, time-course variation and infant health risk.

Synthetic musk compounds (SMCs) and benzotriazole ultraviolet stabilizers (BUVSs) are used as additives in many consumer products. Limited data are available on the accumulation of SMCs in human fluids, and no data are available on BUVSs. In this study, 208 human breast milk samples were collected from 87 participants during the lactation period at <7, 15, 30, and 90 days after delivery in Korea. The total concentrations of SMCs and BUVSs ranged from

Synthetic musks in the natural environment: Sources, occurrence, concentration, and fate-A review of recent developments (2010-2023).

Synthetic musks (SMs) have served as cost-effective substitutes for natural musk compounds in personal care and daily chemical products for decades. Their widespread use has led to their detection in various environmental matrices, raising concerns about potential risks. Despite numerous studies on SM levels in different natural environments, a systematic review of their contemporary presence is lacking. This review aims to address this gap by summarising recent research developments on SMs in diverse natural environments, including river water, lake water, seawater, estuarine water, groundwater, snow, meltwater, sediments, aquatic suspended matter, soils, sands, outdoor air, and atmospheric particulate matter. Covering the period from 2010 to 2023, the review focuses on four SM categories: nitro, polycyclic, macrocyclic, and alicyclic. It systematically examines their sources, occurrences, concentrations, spatial and temporal variations, and fate. The literature reveals widespread detection of SMs in the natural environment (freshwater and sediments in particular), with polycyclic musks being the most studied group. Both direct (e.g., wastewater discharges) and indirect (e.g., human recreational activities) sources contribute to SM presence. Levels of SMs vary greatly among studies with higher levels observed in certain regions, such as sediments in Southeast Asia. Spatial and temporal variations are also evident. The fate of SMs in the environment depends on their physicochemical properties and environmental processes, including bioaccumulation, biodegradation, photodegradation, adsorption, phase exchange, hydro-dilution effects. Biodegradation and photodegradation can decrease SM levels, but may produce more persistent and eco-toxic products. Modelling approaches have been employed to analyse SM fate, especially for indirect processes like photodegradation or long-distance atmospheric transport. Future studies should further investigate the complex fate if SMs and their environmental influence. This review enhances understanding of SM status in the natural environment and supports efforts to control environmental contamination.

Ecological risks of polycyclic musk in soils irrigated with reclaimed municipal wastewater.

HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8-hexamethylcyclopenta-c-2-benzopyrane) and AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene) are found in reclaimed municipal wastewater. They may accumulate in soils receiving long-term application of reclaimed water thus adversely impact the soil biota. We evaluated the extent of their accumulation in receiving soils using HYDRUS-1D based on reclaimed municipal wastewater irrigation data at a public park in Beijing. The potential for ecological harms were assessed according to tested and reported outcomes of acute toxicity tests using wheat (Triticum aetivum L), earthworm (Eisenia fetida) and springtail (Bourletiella hortensis) as target organisms. Results of comparison among EC50 values from wheat, earthworm and springtail showed the EC50 value for root elongation inhibition of wheat germination was the least. Based on the least EC50, predicted no effect concentration in soils were 290 and 320ng /g for HHCB and ATHN, respectively. Comparable results from simulation to experimental and field investigating date validated the using of HYDRUS-1D in the work. Results of risk prediction showed it would take 243 and 666 years for HHCB and AHTN accumulated in soils at current irrigation practice to reach the levels for the resulting risk characterization ratios (RCRs) to cause potential ecosystem harms.

Disposition and excretion of 14C-AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene) and 14c-hhcb (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta-gamma-2-benzopyran) after intravenous administration to Sprague-Dawley rats and domestic pigs.

7-Acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN ) and 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2-benzopyran (HHCB) are polycyclic musks widely used as fragrance ingredients in consumer products. Because their metabolic fate following systemic exposure is not fully characterized, disposition and excretion of (14)C-AHTN- and (14)C-HHCB-derived radioactivity were studied in Sprague-Dawley rats and domestic pigs following a single intravenous dose. Rats administered with AHTN or HHCB excreted 21% or 28% of the radioactivity in urine and 67% or 61% in feces, respectively, within 7 days. In pigs administered AHTN or HHCB, 86% or 74% of the dose was excreted in the urine, and 12% or 15% in feces, respectively, during the 14-day collection period. Radioactivity in the whole blood and plasma of both species and tissues of rats declined steadily until the end of the study (28 days) for both the materials. Radioactivity in rat adipose tissue reached peak at 2 hours after dosing, decreasing steadily thereafter. Radioactivity in pig blood declined rapidly from 70 ng equivalents/g at 10 minutes to 1 ng equivalent/g or less by 28 days after administration of either AHTN or HHCB. Radioactivity in pig skin and adipose tissue decreased to below the limit of detection by 28 days for both the materials. Thin-layer chromatography showed multiple radioactive components in both species' urine after administration of either material. Components found in the urine of the 2 species were qualitatively similar but quantitatively different. Both AHTN and HHCB were completely metabolized and excreted. No unchanged parent compound was detected in rat or pig urine.

Covalent organic framework as adsorbent for ultrasound-assisted dispersive (micro)solid phase extraction of polycyclic synthetic fragrances from seawater followed by fluorescent determination.

In this work, a new analytical approach based on ultrasound-assisted dispersive (micro)solid phase extraction (US-D-µSPE) using TpBD-Me2 covalent organic framework (COF) as adsorbent for simple, rapid and selective fluorescent determination of two polycyclic synthetic fragrances in seawater, i.e., 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta-(γ)-2-benzopyran (HHCB), branded galaxolide®, and 7-acetyl-1,1,3,4,4,6-hexamethyltetralin (AHTN), branded tonalide®, is proposed. Different parameters involved in both adsorption and desorption steps were optimized in order to obtain the best results. High adsorption efficiencies in the range of 91.2-97.8% were achieved for both analytes. Desorption efficiencies of ∼98% for AHTN and HHCB were obtained using methanol as solvent, rendering the material recyclable with merely minor losses in adsorption efficiency after five consecutive cycles of adsorption/desorption. Limits of detection (LODs) were 0.082 µg L-1 and 0.070 µg L-1 for AHTN and HHCB, respectively. The proposed method was successfully applied for the analysis of seawater without the need for a previous sample treatment, e.g., pH adjustment. Recoveries in the range of 90.4-101.2% with a relative standard deviation of 5.8% were obtained for both fragrances. The results proved the great capacity of TpBD-Me2 COF for the selective sorption of polycyclic fragrances in combination with fluorescent detection, being highly promising for application to environmental monitoring of other emerging organic pollutants.

Study of conformational and functional changes caused by binding of environmental pollutant tonalide to human serum albumin.

Tonalide (AHTN) is a new category of pollutants with a wide range of potential environmental and organismal hazards due to its persistence and lipophilicity, and the safety evaluation of this pollutant under physiological condition is a pressing issue. This study investigated the mechanism of interaction between AHTN and human serum albumin (HSA) that is an important transporter in plasma using multiple spectroscopic, molecular docking, and dynamics simulation methods. The steady-state fluorescence and fluorescence lifetime experiments showed that AHTN quenches the inherent fluorescence of HSA through a static quenching mechanism. Thermodynamic parameters exhibited that the binding constant of AHTN and HSA is of the order of 10^4 L/mol, and the binding is a spontaneous process of moderate strength with hydrophobic forces as the main driving force. Site competition revealed that AHTN binds to site I of HSA IIA subdomain, which was evidenced by the molecular docking results. AHTN altered the HSA amino acid microenvironment and conformation can be derived from three-dimensional fluorescence, circular dichroism spectroscopy, and molecular dynamics simulation. The computer simulations corroborate the experimental results positively. Moreover, AHTN acted as a competitive inhibitor to weaken the esterase-like activity of HSA, leading to impaired function of HSA. Results suggest that interactions between AHTN and HSA may affect the normal structure and activities of the protein, this insight will be helpful to provide some basic information to further explore the potential hazards of AHTN in humans.

Prolonged sub-lethal exposure to galaxolide (HHCB) and tonalide (AHTN) promotes the metastatic potential of glioblastoma tumor spheroids.

Galaxolide and tonalide are well-known polycyclic musks whose intensive use without limitations in numerous cleaning, hygiene, and personal care products has resulted in widespread direct human exposure via absorption, inhalation, and oral ingestion. Latest data shows that long-term, low-dose exposure to toxic chemicals can induce unpredictable harmful effects in a variety of living systems, however, interactions between synthetic musks and brain tumours remain largely unexplored. Glioblastoma (GB) accounts for nearly half of all tumours of the central nervous system and is characterized by very poor prognosis. The aims of this study were (1) to investigate the potential effect of long-term (20-generation) single and combined application of galaxolide and tonalide at sub-lethal doses (5-2.5 u M) on the angiogenesis, invasion, and migration of human U87 cells or tumour spheroids, and (2) to explore the underlying molecular mechanisms. Random amplified polymorphic DNA assays revealed significant DNA damage and increased total mutation load in galaxolide- and/or tonalide-treated U87 cells. In those same groups, we also detected remarkable tumour spheroid invasion and up-regulation of both HIF1-α/VEGF/MMP9 and IL6/JAK2/STAT3 signals, known to have important roles in hypoxia-related angiogenesis and/or proliferation. Prolonged musk treatment further altered angio-miRNA expression in a manner consistent with poor prognosis in GB. We also detected significant over-expression of the genes Slug, Snail, ZEB1, and Vimentin, which are biomarkers of epithelial to mesenchymal transition. In addition, matrigel, transwell, and wound healing assays clearly showed that long-term sub-lethal exposure to galaxolide and/or tonalide induced invasion and migration proposing a high metastatic potential. Our results suggest that assessing expression of HIF-1a, VEGF, STAT3, and the miR-17-92 cluster in biopsy samples of GB patients who have a history of possible long-term exposure to galaxolide or tonalide could be beneficial for deciding a therapy regime. Additionally, we recommend that extensively-used hygiene and cleaning materials be selected from synthetic musk-free products, especially when used in palliative care processes for GB patients.

Determination and environmental risk assessment of synthetic musks in the water and sediments of the Jiaozhou Bay wetland, China.

Human activity in estuarine areas has resulted in pollution of the aquatic environment, but little is known about the levels of synthetic musks (SMs) in river water and sediments in estuarine areas. This study investigated the concentrations and distribution of SMs in the Jiaozhou Bay wetland, including celestolide, phantolide, traseolide, galaxolide (HHCB), tonalide (AHTN), musk xylene and musk ketone (MK). The SMs HHCB, AHTN and MK were detected at concentrations of 10.7-208, not detected (ND)-59.2 and ND-13.6 ng/L, respectively, in surface water samples and 13.1-27.3, 3.06-14.5 and 1.33-18.8 ng/g (dry weight; dw), respectively, in sediment samples. Based on the calculated total organic carbon (TOC) concentrations, there was no significant correlation between SMs and TOC in sediment samples (p > 0.05). The hazard quotients were 0.204, 0.386 and 0.059 for AHTN, HHCB and MK, respectively, which indicated no serious environmental impact, because these values are all less than 1. The concentrations of SMs decreased as the distance to the Xiaojianxi refuse landfill increased in both surface water and sediments. Compared with previous studies, the concentration of SMs in the Jiaozhou Bay wetland was relatively high. Therefore, more attention should be paid to SMs because of their persistent impact on human health and the environment.

Effects of steaming on contaminants of emerging concern levels in seafood.

Seafood consumption is a major route for human exposure to environmental contaminants of emerging concern (CeCs). However, toxicological information about the presence of CeCs in seafood is still insufficient, especially considering the effect of cooking procedures on contaminant levels. This study is one among a few who evaluated the effect of steaming on the levels of different CeCs (toxic elements, PFCs, PAHs, musk fragrances and UV-filters) in commercially relevant seafood in Europe, and estimate the potential risks associated with its consumption for consumers. In most cases, an increase in contaminant levels was observed after steaming, though varying according to contaminant and seafood species (e.g. iAs, perfluorobutanoate, dibenzo(ah)anthracene in Mytilus edulis, HHCB-Lactone in Solea sp., 2-Ethylhexyl salicylate in Lophius piscatorius). Furthermore, the increase in some CeCs, like Pb, MeHg, iAs, Cd and carcinogenic PAHs, in seafood after steaming reveals that adverse health effects can never be excluded, regardless contaminants concentration. However, the risk of adverse effects can vary. The drastic changes induced by steaming suggest that the effect of cooking should be integrated in food risk assessment, as well as accounted in CeCs regulations and recommendations issued by food safety authorities, in order to avoid over/underestimation of risks for consumer health.

Bioconcentration of polycyclic musks in fathead minnows caged in a wastewater effluent plume.

The synthetic polycyclic musks HHCB (Galaxolide®) and AHTN (Tonalide®) were monitored in fathead minnows (FHMs) caged for a month at various locations in the North Saskatchewan River (NSR), upstream and downstream of the Gold Bar wastewater treatment plant that serves the city of Edmonton, AB, Canada. In addition, the distribution of these musk compounds in the river was predicted using the fugacity-based Quantitative Water Air Sediment Interface (QWASI) model. In FHMs caged 0.15 km downstream of the wastewater outfall, mean concentrations of HHCB and AHTN were 7.4 and 0.4 µg g-1 wet weight, respectively. These are among the highest reported concentrations of these musk compounds in fish exposed to treated wastewater. The musk concentrations in FHMs were significantly lower further downstream of the outfall. High bioconcentration factors (BCFs) in FHMs that exceeded 104 higher than estimated concentrations in water indicated that there were low rates of biotransformation of the musks in the fish. In the FHMs caged at the site closest to the wastewater outfall, HHCB concentrations in FHMs were comparable to the body burdens that have been reported to moderate expression of vitellogenin in female rainbow trout, indicating that fish in the NSR downstream of the wastewater outfall may be at risk of anti-estrogenic effects. The QWASI model applied to six individual river sections of the NSR predicted that the largest fluxes of HHCB and AHTN would be for downstream transport in water, which explains why FHMs accumulated elevated concentrations of the musks at the furthest downstream site, 9.9 km from the wastewater discharge.

Environmentally relevant concentrations of galaxolide (HHCB) and tonalide (AHTN) induced oxidative and genetic damage in Dreissena polymorpha.

Synthetic musk compounds (SMCs) are extensively used as fragrances in several personal care products and have been recognized as emerging aquatic pollutants. Among SMCs, galaxolide (HHCB) and tonalide (AHTN) are extensively used and have been measured in aquatic ecosystems worldwide. However, their potential risk to organisms remains largely unknown. The aim of this study was to investigate whether 21-day exposures to HHCB and AHTN concentrations frequently measured in aquatic ecosystems can induce oxidative and genetic damage in Dreissena polymorpha. The lipid peroxidation (LPO) and protein carbonyl content (PCC) were measured as oxidative stress indexes, while the DNA precipitation assay and the micronucleus test (MN test) were applied to investigate genetic injuries. HHCB induced significant increases in LPO and PCC levels, while AHTN enhanced only protein carbonylation. Moreover, significant increases in DNA strand breaks were caused by exposure to the highest concentrations of HHCB and AHTN tested in the present study, but no fixed genetic damage was observed.