Bioaccessibility and bioavailability of exogenous and endogenous toxic substances in traditional Chinese medicine and their significance in risk assessment.

Scientific risk assessment of exogenous and endogenous toxic substances in traditional Chinese medicine (TCM) is of great significance. The present review comprises a comprehensive summary of progress in the health risk assessment of harmful exogenous substances in TCMs. Such substances include heavy metals, pesticide residues, biotoxins, and endogenous toxic components involving pyrrolizidine alkaloids. The review also discusses the strengths and weaknesses of various bioaccessibility and bioavailability models, and their applications in risk assessment. Future avenues of risk assessment research are highlighted, including further exploration of risk assessment parameters, innovation of bioaccessibility and bioavailability techniques, enhancement of probabilistic risk assessment combined with bioavailability, improvement of cumulative risk assessment strategies, and formulation of strategies for reducing relative bioavailability (RBA) values in TCMs. Such efforts represent an attempt to develop a risk assessment system that is capable of evaluating the exogenous and endogenous toxic substances in TCMs to ensure its safe use in clinics, and to promote the sustainable development of the TCM industry.

Advances and challenges in ginseng research from 2011 to 2020: the phytochemistry, quality control, metabolism, and biosynthesis.

Covering: 2011 to the end of 2020Panax species (Araliaceae), particularly P. ginseng, P. quinquefolius, and P. notoginseng, have a long history of medicinal use because of their remarkable tonifying effects, and currently serve as crucial sources for various healthcare products, functional foods, and cosmetics, aside from their vast clinical preparations. The huge market demand on a global scale prompts the continuous prosperity in ginseng research concerning the discovery of new compounds, precise quality control, ADME (absorption/disposition/metabolism/excretion), and biosynthesis pathways. Benefitting from the ongoing rapid development of analytical technologies, e.g. multi-dimensional chromatography (MDC), personalized mass spectrometry (MS) scan strategies, and multi-omics, highly recognized progress has been made in driving ginseng analysis towards "systematicness, integrity, personalization, and intelligentization". Herein, we review the advances in the phytochemistry, quality control, metabolism, and biosynthesis pathway of ginseng over the past decade (2011-2020), with 410 citations. Emphasis is placed on the introduction of new compounds isolated (saponins and polysaccharides), and the emerging novel analytical technologies and analytical strategies that favor ginseng's authentic use and global consumption. Perspectives on the challenges and future trends in ginseng analysis are also presented.

[Form and valence of arsenic in dry and fresh Cordyceps breeding products based on HPLC-ICP-MS and its risk assessment].

A comparative study was conducted for the first time on the form and valence of arsenic in the dry and fresh Cordyceps breeding products to clarify the specific morphology and valence of arsenic in Cordyceps breeding products and its safety. Arsenic betai-ne(AsB), arsenite(AsⅢ), dimethyl arsenic(DMA), arsenocholine(AsC), monomethyl arsenic(MMA), and arsenate(AsⅤ) in the dry and fresh samples were investigated using a bionic extraction method combined with HPLC-ICP-MS. The HPLC separation was performed on a DioncxIonPac~(TM) AS7 anion exchange column with a mobile phase of 100 mmol·L~(-1) ammonium carbonate-water for gradient elution at room temperature and the flow rate of 0.8 mL·min~(-1). HPLC was coupled with ICP-MS for the determination. The arsenic content was characterized in combination with chemometrics. The health safety risk of inorganic arsenic in the samples was assessed using the margin of exposure(MOE). The results of methodological validation showed that the six arsenic compounds showed good linearity(R~2>0.999) from 10 to 500 ng·mL~(-1), with precision RSDs of 1.8%-3.0%, recoveries(n=6) of 84.15%-98.28%, reproducibility RSDs of 6.4%-7.7%, and sample stability RSDs of 8.3%-14% within 10 h. Trace AsⅢ and AsⅤ were detected in 30 batches of dry and fresh Cordyceps breeding products, while arsenic compounds in other forms and valence were not detected. In the dry products, AsⅢ was 0.019-0.040 mg·kg~(-1) and AsV was 0.024-0.061 mg·kg~(-1), while in the fresh products, AsⅢ was 0.002 3-0.006 1 mg·kg~(-1) and AsⅤ was 0.008-0.016 mg·kg~(-1). The risk assessment results showed that the MOE of inorganic arsenic was much higher than 1 in both dry and fresh products, and the potential health safety risk of inorganic arsenic was low. The HPLC-ICP-MS method established in this study was efficient, rapid, accurate, and stable for the determination of six arsenic compounds in Cordyceps breeding products. The results of this study provide a basis for the safety and quality control of Cordyceps breeding products.

Simultaneous determination of eight pyrrolizidine alkaloids in various parts of Eupatorium lindleyanum by ultra high performance liquid chromatography tandem mass spectrometry and risk assessments based on a real-life exposure scenario.

Pyrrolizidine alkaloids are toxins having hepatotoxic and carcinogenic effects on human health. A ultra high performance liquid chromatography tandem mass spectrometry technique was developed for the first time for the simultaneous determination of eight pyrrolizidine alkaloids, including four diastereoisomers (intermedine, lycopsamine, rinderine, and echinatine) and their respective N-oxide forms, in different parts of Eupatorium lindleyanum. The risk assessment method for pyrrolizidine alkaloids in Eupatorium lindleyanum was explored using the margin of exposure strategy for the first time based on a real-life exposure scenario. Differences were found in all eight pyrrolizidine alkaloids in various parts of Eupatorium lindleyanum. Besides, the total levels of pyrrolizidine alkaloids in Eupatorium lindleyanum followed the order of root > flower > stem > leaf. Moreover, the risk assessment data revealed that the deleterious effects on human health were unlikely at exposure times of less than 200, 37, and 12 days during the lifetimes of Eupatorium lindleyanum leaves, stems, and flowers, respectively. This study reported both the contents of and risk associated with Eupatorium lindleyanum pyrrolizidine alkaloids. The comprehensive application of the novel ultra high performance liquid chromatography tandem mass spectrometry technique alongside the risk assessment approach provided a scientific basis for quality evaluation and rational utilization of toxic pyrrolizidine alkaloids in Eupatorium lindleyanum to improve public health safety.

Multifunctional ZnO@CuS nanoparticles cluster synergize chemotherapy and photothermal therapy for tumor metastasis.

The poor drug delivery and unsatisfying therapeutic effects remain to be the primary challenges for cancer therapy. Nanosystem that combines multiple functions into a single platform is an ideal strategy. Here, a smart drug delivery nanoplatform (Z@C-D/P) based on ZnO@CuS nanoparticles, loaded with doxorubicin (DOX) and pirfenidone (PFD) was constructed. Importantly, the ß-CD-DMA and PEG-DMA could be activated in the mild acidic tumor microenvironment, then the nanosystem underwent charge reversal and PFD release. PFD could inhibit cancer-associated fibroblasts (CAFs) activation and enhance tumor penetration. And the residual nanostructure ZnO@CuS could trigger cascade amplified ROS generation to induce tumor cell death. The photothermal effect further strengthened the anti-tumor efficacy. Finally, the nanosystem showed remarkable inhibition of tumor growth (89.7%) and lung metastasis. The innovatively designed nanosystem integrating chemotherapy and photothermal effect would provide a promising strategy in breast cancer therapy.

[Simultaneous determination of six pyrrolizidine alkaloids in different parts of Emilia sonchifolia by UPLC-MS/MS].

This study aims to develop a UPLC-MS/MS method for simultaneous determination of six pyrrolizidine alkaloids(PAs)--intermedine N-oxide(ImNO), lycopsamine N-oxide(LyNO), seneciphylline(Sp), seneciphylline N-oxide(SpNO), senecionine N-oxide(SnNO), and senkirkine(Sk) in different parts of Emilia sonchifolia. UPLC conditions are as follows: ACQUITY UPLC HSS T3 column(2.1 mm×100 mm, 1.8 µm), mobile phase consisting of 0.05% formic acid and 2.5 mmol·L~(-1) ammonium formate in water(A)-0.05% formic acid and 2.5 mmol·L~(-1) ammonium formate in acetonitrile(B) for gradient elution. MS conditions are as below: electrospray ionization(ESI) in the positive ion mode, multiple reaction monitoring(MRM), and the content of the six PAs was calculated with the external standard method. The results suggested the differences in the six PAs among different parts of E. sonchifolia. Sk was detected in all the four parts, with similar content. SnNO also existed in all the four parts, but the content in roots was significantly higher than that in other parts. Sp and SpNO were found in both roots and flowers, with the content higher in the former than in the later. ImNO and LyNO were only found in leaves, and the content was low. Among the six components detected, ImNO, LyNO, and SpNO were found and determined for the first time, which enriched the toxic components and laid a scientific basis for the quality and safety evaluation of E. sonchifolia.

Innovative health risk assessment of heavy metals in Chinese herbal medicines based on extensive data.

In the present study, the concentrations of lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), and copper (Cu) in 2245 batches of Chinese herbal medicines (CHMs) were measured using inductively coupled plasma-mass spectroscopy (ICP-MS). We developed a risk assessment strategy that assessed the heavy metal-associated health risk of CHMs based on our large dataset. Using a combination of the mean and 95th percentile (P95) values of the chronic daily intake (CDI), hazard quotient (HQ), hazard index (HI), and lifetime cancer risk (CR), the health risks of the average exposure population and the high exposure population were estimated, respectively. To obtain a precise and realistic risk assessment, the exposure frequency and exposure duration were determined using questionnaire data from 20,917 randomly selected volunteers. Additionally, given the specific ingestion characteristics of CHMs, the safety factor and the transfer rates of heavy metals were highlighted as well. The concentrations of Pb, Cd, As, Hg, and Cu in 2245 batches of CHMs were 1.566, 0.299, 0.391, 0.074, and 8.386 mg/kg, respectively. The mean HI values indicated that consumption of most CHMs would not pose an unacceptable health risk to the average exposure population, except for argy wormwood leaf (1.326), morinda root (2.095), plantain herb (1.540), chrysanthemum flower (1.146), and Indian madder root (2.826). In addition, CR assessment for Pb and As revealed that, for the average exposure population, the risk of developing cancers was lower than the acceptable levels (1 × 10-4) in the clinic. However, the P95 of the HI and CR values indicated that more attention should be paid to the systemic effects of CHMs in terms of both non-carcinogenic and carcinogenic health risks for the high exposure population. Furthermore, in order to serve population health better, national and international guidelines have now been established. The risk assessment strategy developed in this study is the first of its kind, and contributed to the risk assessment, guidelines, and safety standards for heavy metals in CHMs.

In-depth profiling, characterization, and comparison of the ginsenosides among three different parts (the root, stem leaf, and flower bud) of Panax quinquefolius L. by ultra-high performance liquid chromatography/quadrupole-Orbitrap mass spectrometry.

Despite Panax quinquefolius L. serving as a crucial source for food additives, healthcare products, and herbal medicines, unawareness of the metabolome differences among three parts (root, PQR; stem leaf, PQL; flower bud, PQF) seriously restricts its quality control. Ultra-high performance liquid chromatography/quadrupole-Orbitrap mass spectrometry (UHPLC/Q-Orbitrap-MS) was fully utilized to comprehensively identify and compare the ginsenoside compositions among PQR, PQL, and PQF. Metabolite profiling and characterization were performed by coupling reversed-phase UHPLC (a CSH C18 column) and improved untargeted data-dependent MS2 acquisition in the negative mode. A novel vehicle, "Ginsenoside Sieve," was proposed by developing fixed tolerance (± 10 mDa), discrete mass defect filtering (MDF) based on the m/z features of 499 known ginsenosides, which assisted in the screening of 71 (from 3453 ions), 89 (from 6842), and 84 (from 7369) target precursor masses for PQR, PQL, and PQF, respectively. The newly established data-dependent acquisition (DDA) approach exhibited 14% improvement in characterization of targeted components (using a PQL sample), and comparable performance in identifying the unknown, compared with conventional DDA. We could characterize 347 saponins (147 from PQR, 173 from PQL, and 195 from PQF), and 157 thereof not ever-isolated from the Panax genus. These potentially new saponins have 63 unknown masses. Subsequent untargeted metabolomics analysis unveiled 20 marker saponins, among which m-Rb1, Rb1, Ro, m-Rb2, and m-Rb1 isomer are the most important diagnostic for differentiating the three parts. Conclusively, the established improved DDA represents a potent ginsenoside characterization strategy, and the results obtained in this work would benefit better quality control of P. quinquefolius. Graphical abstract.

Simultaneous Profiling and Holistic Comparison of the Metabolomes among the Flower Buds of Panax ginseng, Panax quinquefolius, and Panax notoginseng by UHPLC/IM-QTOF-HDMSE-Based Metabolomics Analysis.

The flower buds of three Panax species (PGF: flower bud of P. ginseng; PQF: flower bud of P. quinquefolius; PNF: flower bud of P. notoginseng), widely consumed as healthcare products, are easily confused particularly in the extracts or traditional Chinese medicine (TCM) formulae. We are aimed to develop an untargeted metabolomics approach, by ultra-high performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS) to unveil the chemical markers diagnostic for the differentiation of PGF, PQF, and PNF. Key parameters affecting chromatographic separation and MS detection were optimized in sequence. Forty-two batches of flower bud samples were analyzed in negative high-definition MSE (HDMSE; enabling three-dimensional separations). Efficient metabolomics data processing was performed by Progenesis QI (Waters, Milford, MA, USA), while pattern-recognition chemometrics was applied for species classification and potential markers discovery. Reference compounds comparison, analysis of both HDMSE and targeted MS/MS data, and retrieval of an in-house ginsenoside library, were simultaneously utilized for the identification of discovered potential markers. Satisfactory conditions for metabolite profiling were achieved on a BEH Shield RP18 column and Vion™ IMS-QTOF instrument (Waters; by setting the capillary voltage of 1.0 kV and the cone of voltage 20 V) within 37 min. A total of 32 components were identified as the potential markers, of which Rb3, Ra1, isomer of m-Rc/m-Rb2/m-Rb3, isomer of Ra1/Ra2, Rb1, and isomer of Ra3, were the most important for differentiating among PGF, PQF, and PNF. Conclusively, UHPLC/IM-QTOF-MS-based metabolomics is a powerful tool for the authentication of TCM at the metabolome level.

Data-Dependent Acquisition and Database-Driven Efficient Peak Annotation for the Comprehensive Profiling and Characterization of the Multicomponents from Compound Xueshuantong Capsule by UHPLC/IM-QTOF-MS.

The state of the art ion mobility quadrupole time of flight (IM-QTOF) mass spectrometer coupled with ultra-high performance liquid chromatography (UHPLC) can offer four-dimensional information supporting the comprehensive multicomponent characterization of traditional Chinese medicine (TCM). Compound Xueshuantong Capsule (CXC) is a four-component Chinese patent medicine prescribed to treat ophthalmic disease and angina. However, research systematically elucidating its chemical composition is not available. An approach was established by integrating reversed-phase UHPLC separation, IM-QTOF-MS operating in both the negative and positive electrospray ionization modes, and a "Component Knockout" strategy. An in-house ginsenoside library and the incorporated TCM library of UNIFITM drove automated peak annotation. With the aid of 85 reference compounds, we could separate and characterize 230 components from CXC, including 155 ginsenosides, six astragalosides, 16 phenolic acids, 16 tanshinones, 13 flavonoids, six iridoids, ten phenylpropanoid, and eight others. Major components of CXC were from the monarch drug, Notoginseng Radix et Rhizoma. This study first clarifies the chemical complexity of CXC and the results obtained can assist to unveil the bioactive components and improve its quality control.

Integration of Data-Dependent Acquisition (DDA) and Data-Independent High-Definition MSE (HDMSE) for the Comprehensive Profiling and Characterization of Multicomponents from Panax japonicus by UHPLC/IM-QTOF-MS.

The complexity of herbal matrix necessitates the development of powerful analytical strategies to enable comprehensive multicomponent characterization. In this work, targeting the multicomponents from Panax japonicus C.A. Meyer, both data dependent acquisition (DDA) and data-independent high-definition MSE (HDMSE) in the negative electrospray ionization mode were used to extend the coverage of untargeted metabolites characterization by ultra-high-performance liquid chromatography (UHPLC) coupled to a VionTM IM-QTOF (ion-mobility/quadrupole time-of-flight) high-resolution mass spectrometer. Efficient chromatographic separation was achieved by using a BEH Shield RP18 column. Optimized mass-dependent ramp collision energy of DDA enabled more balanced MS/MS fragmentation for mono- to penta-glycosidic ginsenosides. An in-house ginsenoside database containing 504 known ginsenosides and 60 reference compounds was established and incorporated into UNIFITM, by which efficient and automated peak annotation was accomplished. By streamlined data processing workflows, we could identify or tentatively characterize 178 saponins from P. japonicus, of which 75 may have not been isolated from the Panax genus. Amongst them, 168 ginsenosides were characterized based on the DDA data, while 10 ones were newly identified from the HDMSE data, which indicated their complementary role. Conclusively, the in-depth deconvolution and characterization of multicomponents from P. japonicus were achieved, and the approaches we developed can be an example for comprehensive chemical basis elucidation of traditional Chinese medicine (TCM).

Refined assessment of heavy metal-associated health risk due to the consumption of traditional animal medicines in humans.

Little is known about the extent of heavy metal accumulation in traditional Chinese medicines (TCMs). In this study, the levels of lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg) in traditional animal medicines were monitored using inductively coupled plasma mass spectroscopy (ICP-MS). Additionally, for the first time, a heavy metal risk assessment strategy was used to evaluate the potential risks of traditional animal medicines by calculating estimated daily intake (EDI), target hazard quotient (THQ), and cancer risk (CR). To obtain a refined risk assessment, the frequency of exposure to traditional animal medicines was determined from questionnaire data, and the safe factor for TCM was applied. Based on the standard levels for leech, it was found that earthworm, hive, scorpion, and leech accumulated high levels of heavy metals. The combined THQ (cTHQ) values indicated that ingestion of most traditional animal medicines would not pose a risk to the health of either male or female human beings. However, it was indicated that attention should be paid to the potential risk associated with cicada slough, earthworm, scorpion, turtle shells, and hive. Among heavy metals, As and Hg contributed to a major extent to the risk to human health. The CR assessment for Pb and As indicated that, with the exception of earthworm, the cancer risk was less than the acceptable lifetime risk for both males and females. Owing to the higher body weight, both THQ and CR were generally lower for males than for females.

[Determination and risk assessment of heavy metals and harmful elements residues in Niuhuang Qingwei Pills based on ICP-MS].

To achieve a comprehensive understanding of heavy metals and harmful elements residues in Niuhuang Qingwei Pills,49 samples from 18 manufactures were collected from 31 provinces in China.Risk assessment and control preparations were applied innovatively in evaluation of exogenous pollution in traditional Chinese Medicine.Determination methods for Pb,Cd,As,Hg and Cu were established by inductively coupled plasma mass spectrometry(ICP-MS).Based on the procedures including hazard identification,hazard characterization,exposure assessment and risk characterization,risk assessment was performed and residual limits for Pb,Cd,As,Hg and Cu in the drug were formulated.The results showed that the hazardous quotients(HQ) of the elements were decreased in the following order:Pb>As>Cu>Hg>Cd,and the total hazardous index(HI) of heavy metals and harmful elements in Niuhuang Qingwei Pills was above 1,implying health risk of the drug.Under the proposed limits,5 elements in the control preparation as well as Cd and Cu in the samples were within the limits range,but the excess rates of Pb,As and Hg in the samples were 12%,12% and 14%,respectively.For the first time,basic steps for risk assessment of Chinese patent medicine were established,which provided model and reference for risk assessment and limit formulation of other drugs.

Inhibiting pulmonary metastasis of breast cancer based on dual-targeting graphene oxide with high stability and drug loading capacity.

In this study, heparin and polyethyleneimine-folic acid modified graphene oxide was designed and synthesized as a dual-targeting biomaterial to load doxorubicin (DOX@GPFH) with high loading capacity for enhanced cellular uptake. GDC0941, a phosphatidylinositide 3-kinase/Akt phosphorylation inhibitor, was selected to enhance anti-metastasis effect of DOX@GPFH via down-regulating expression of matrix metalloproteinase. Modified with heparin, the stability of DOX@GPFH was significantly enhanced and the drug loading ratio increased largely from 64.4% to 125.1%. The inhibition rates of the mixture of DOX@GPFH and GDC0941 in vitro by wound healing, cell migration and invasion assays were 61.2%±13.9%, 81.0%±3.6% and 76.8%±5.2%, respectively, while the tumor and the pulmonary anti-metastasis rates tested in vivo were 77.0%±7.6% and 73.7%±9.6%, respectively. Our findings illustrated an effective approach for developing dual-targeting graphene oxide with high drug loading for pulmonary anti-metastasis of breast cancer.

Systematic Profiling of the Multicomponents and Authentication of Erzhi Pill by UHPLC/Q-Orbitrap-MS Oriented Rapid Polarity-Switching Data-Dependent Acquisition and Selective Monitoring of the Chemical Markers Deduced from Fingerprint Analysis.

The analytical platform UHPLC/Q-Orbitrap-MS offers a solution to quality investigation of TCM with high definiteness. Using Erzhi Pill (EZP) as a case, we developed UHPLC/Q-Orbitrap-MS based approaches to achieve systematic multicomponent identification and rapid authentication. Comprehensive multicomponent characterization of EZP was performed by negative/positive switching data-dependent high-energy collision-induced dissociation-MS² (HCD-MS²) after 25 min chromatographic separation. By reference compounds comparison, elemental composition analysis, fragmentation pathways interpretation, and retrieval of an in-house library, 366 compounds were separated and detected from EZP, and 96 thereof were structurally characterized. The fingerprints of two component drugs (Ligustri Lucidi Fructus, LLF; Ecliptae Herba, EH) for EZP were analyzed under the same LC-MS condition by full scan in negative mode. In combination with currently available pharmacological reports, eight compounds were deduced as the 'identity markers' of EZP. Selective ion monitoring (SIM) of eight marker compounds was conducted to authenticate six batches of EZP samples. Both LLF and EH could be detected from all EZP samples by analyzing the SIM spectra, which could indicate their authenticity. Conclusively, UHPLC/Q-Orbitrap-MS by rapid polarity switching could greatly expand the potency of untargeted profiling with high efficiency, and SIM of multiple chemical markers rendered a practical approach enabling the authentication of TCM formulae.

Insights into Euphorbia diversity: Probing the contrasts between Euphorbia fischeriana Steud and Euphorbia ebracteolata Hayata.

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A novel bioaccessibility-based probabilistic risks assessment of potentially toxic elements (PTEs) in earthworm.

Introduction: Early risk assessment studies usually based on total heavy metal (loid) contents, inevitably leading to an overestimation of the health risks. In addition, inputs are represented as single-point estimates in deterministic models, leading to underestimation or overestimation of the health risks. Methods: To overcome these barriers, a novel probabilistic risk assessment strategy based on the combinational use of bioaccessibility and Monte Carlo simulation was developed to assess heavy metal (loid) associated health risks of earthworms in this study. To obtain a realistic and robust probabilistic risk assessment, heavy metal (loid) exposure duration and frequency were determined using our questionnaire data. Results: As a result, the mean gastrointestinal bioaccessibility was in the order: Cd > As > Cu > Hg. The mean hazard index (HI) values for investigated metal (loid)s were 0.65 and 0.59 for male and female, respectively, demonstrating an acceptable health risk in an average community. However, the 90th percentile of HI values was 1.87 and 1.65 for male and female, respectively. And the total non-cancer risks of heavy metal (loid) exposure exceeded the acceptable threshold for 19.9% and 17.8% of male and female, respectively. In addition, the total cancer risk (TCR) value through co-exposure to As and Cd suggested that the carcinogenic risks may be of concern for average exposure population. Sensitivity analyses revealed that the exposure frequency and bioaccessible As concentration were the dominant contributors to the total risk variance, which provided meaningful implications for environmental management. Conclusion: Altogether, the refined strategy based on bioaccessibility and Monte Carlo simulation is the first of its kind, such effort attempts to scientifically guide the rational clinic use of TCM and the improvement of population-health.

Refined Cumulative Risk Assessment of Pb, Cd, and as in TCM Decoction Based on Bioavailability through In Vitro Digestion/MDCK Cells.

In this study, the oral bioavailability of Pb, Cd, and As in three types of traditional Chinese medicines (TCMs) and TCM decoctions were investigated through in vitro PBET digestion/MDKC cell model. Furthermore, a novel cumulative risk assessment model associated with co-exposure of heavy metal(loid)s in TCM and TCM decoction based on bioavailability was developed using hazard index (HI) for rapid screening and target organ toxicity dose modification of the HI (TTD) method for precise assessment. The results revealed that the bioavailability of Pb, Cd, and As in three types of TCM and TCM decoction was 5.32-72.49% and 4.98-51.97%, respectively. After rapid screening of the co-exposure health risks of heavy metal(loid)s by the HI method, cumulative risk assessment results acquired by TTD method based on total metal contents in TCMs indicated that potential health risks associated with the co-exposure of Pb, Cd, and As in Pheretima aspergillum (E. Perrier) and Oldenlandia diffusa (Willd.) Roxb were of concern. However, considering both the factors of decoction and bioavailability, TTD-adjusted HI outcomes for TCMs in this study were <1, indicating acceptable health risks. Collectively, our innovation on cumulative risk assessment of TCM and TCM decoction provides a novel strategy with the main purpose of improving population health.

Progress in quality control, detection techniques, speciation and risk assessment of heavy metals in marine traditional Chinese medicine.

Marine traditional Chinese medicines (MTCMs) hold a significant place in the rich cultural heritage in China. It plays an irreplaceable role in addressing human diseases and serves as a crucial pillar for the development of China's marine economy. However, the rapid pace of industrialization has raised concerns about the safety of MTCM, particularly in relation to heavy metal pollution. Heavy metal pollution poses a significant threat to the development of MTCM and human health, necessitating the need for detection analysis and risk assessment of heavy metals in MTCM. In this paper, the current research status, pollution situation, detection and analysis technology, removal technology and risk assessment of heavy metals in MTCM are discussed, and the establishment of a pollution detection database and a comprehensive quality and safety supervision system for MTCM is proposed. These measures aim to enhance understanding of heavy metals and harmful elements in MTCM. It is expected to provide a valuable reference for the control of heavy metals and harmful elements in MTCM, as well as the sustainable development and application of MTCM.