Toxic Equivalency Factors Research Articles

Uptake, Elimination and Metabolism of Brominated Dibenzofurans in Mice.

Polybrominated dibenzofurans (PBDFs) are major brominated dioxins in the environment, but information on their bioaccumulation potential and toxicokinetics is limited. This study conducted oral exposure experiments with C57BL/6J mice to investigate the uptake ratios, distribution in the liver, plasma and brain, metabolism, and elimination kinetics of four bromine/chlorine-substituted dibenzofurans (TrBDF: 2,3,8-tribromo, TeBDF: 2,3,7,8-tetrabromo, PeBDF: 1,2,3,7,8-pentabromo, TrBCDF: 2,3,7-tribromo-8-chloro) in comparison with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The hepatic uptake ratios of 2,3,7,8-substituted dibenzofurans were lower than that of TCDD (up to 84% of the administered doses) and decreased with the number of Br substitutions (42%, 33%, and 29% for TrBCDF, TeBDF, and PeBDF, respectively). The brain uptake ratios of these dibenzofurans were less than 0.05%, and the plasma-to-brain transfer ratio also decreased with the Br number. All 2,3,7,8-substituted compounds were eliminated from the liver following first-order kinetics, with half-times in the order of TrBCDF (5.6 days) < TeBDF (8.8 days) ≈ TCDD (8.7 days) < PeBDF (13 days). The non-2,3,7,8-substituted TrBDF was poorly retained in the liver (<0.01% of the dose at 1 day) and rapidly eliminated following two-phase kinetics. All dibenzofurans were metabolised into monohydroxylated products in the liver, but the contribution of this metabolic pathway to hepatic elimination was only significant for TrBDF. As the toxic effects of dioxin-like compounds are influenced by their biological persistence, the slow elimination of TrBCDF, TeBDF, and PeBDF observed in this study suggests that exposure risk of brominated dibenzofurans may be underestimated using the toxic equivalency factors of the less persistent chlorinated analogues.

Concentration and health risk valuation of polycyclic aromatic hydrocarbons in Tilapia zilli in selected wetlands

Globally, food safety is growing, and the residues of PAHs (polycyclic aromatic hydrocarbons) in fish species above the standard threshold could elicit serious public and community health concerns. This study investigated the PAHs contamination concentrations of &lt;i&gt;Tilapia zilli&lt;/i&gt; in the wetlands of the Niger Delta. The study was conducted from March to August 2023, and fish samples were collected within these periods from 5 wetlands. The results obtained were as follows: pyrene; 2.46±0.11 µg/kg, chrysene; 2.54±0.12 µg/kg, BaP; 2.52±0.11 µg/kg, BaA; 2.54±0.13 µg/kg and BbF; 2.54±0.13 µg/kg. The mean results of characterising the PAHs in the fish were insignificant at &lt;i&gt;p&gt;0.05&lt;/i&gt;. The results of the health risk evaluation showed that Beneze (a) pyrene had the highest value (12.33 µg/kg), followed by Benzo (a) anthracene and Benzo (b) fluoranthene (1.51 and 1.20) of the toxicity equivalent factors. Meanwhile, the sum across the station was significantly higher than the standard limits. The CDI (chronic daily intake) results obtained in this study for each PAH (polycyclic aromatic hydrocarbon) congener were considerably high and fluctuated across the stations. However, the results for the ILCR (incremental life cancer risk) showed that the values were higher (1 × 10&lt;sup&gt;−2&lt;/sup&gt;) than the threshold set for this study (1 × 10&lt;sup&gt;−6&lt;/sup&gt; to 1 × 10&lt;sup&gt;−4&lt;/sup&gt;). The fish were thus contaminated above the acceptable limit; therefore, they are not fit for human consumption or for compounding animal feed.

Toxicity Equivalency Factors for Tetrodotoxin Analogues Determined with Automated Patch Clamp on Voltage-Gated Sodium Channels in Neuro-2a Cells.

Tetrodotoxin (TTX) is a potent marine neurotoxin, responsible for numerous poisoning incidents and some human fatalities. To date, more than 30 TTX analogues have been identified, but their individual toxicities and roles in poisoning remain largely unknown. In this work, the toxicity equivalency factors (TEFs) of five TTX analogues were determined by assessing the blockade of voltage-gated sodium channels in Neuro-2a cells using automated patch clamp (APC). All TTX analogues were less toxic than TTX. The derived TEFs were applied to the individual TTX analogues concentrations measured in pufferfish samples, using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). A comparison of these results with those obtained from APC analysis demonstrated that TEFs can be effectively used to translate LC-MS/MS analytical data into meaningful toxicological information. This is the first study to utilize APC device for the toxicological assessment of TTX analogues, highlighting its potential as a bioanalytical tool for seafood safety management and human health protection.

A novel approach to assess the health risk of aryl hydrocarbon receptor-bound contaminants via inhalation exposure using CYP1A1 expression as a biomarker

Polycyclic aromatic hydrocarbons (PAHs) and dioxins are potential causes of multiple diseases by activating the aryl hydrocarbon receptor (AhR) pathway. Health risk assessment of chemicals primarily relies on the relative potency factor (RPF), although its accuracy may be limited when solely using EC50 values. The induction of cytochrome P4501A1 (CYP1A1) serves as a biomarker for AhR activation and is an integrator of dioxin-like toxicity. Here, we present a method for evaluating the risks associated with AhR activation using mathematical models of dose-CYP1A1 induction. The dose-effect curves for certain PAHs and dioxins, including Ant, BghiP, 1,2,3,4,7,8-HxCDD, and others, exhibited a non-classical S-shaped form. The toxic equivalent factor (TEF) profiles revealed a broad range of toxic equivalent factor values. The TEFs for PAHs ranged from approximately 0.01 to 6, with higher values being observed when the concentration was less than 10−10 M, with the exceptions of Ace, Phe, and BghiP. Most congeners of dioxins got the lowest TEF value at around 10−10 M, ranging from 0.04 to 1.00. The binding affinity of AhR to ligands did not display a strong correlation with the EC50 of CYP1A1 expression, suggesting that the AhR-mediated effects of PAHs and dioxins are not fixed but instead fluctuate with the dose. Air samples acquired from a parking area were used to compare the proficiency of RPF and our current approach. In the current method, naphthalene and chrysene were the primary contributors of PAHs to AhR-mediated risks in parking lots air samples, respectively. However, the contributions of naphthalene and chrysene could be disregarded in the RPF approach.

Modeling PAH Mixture Interactions in a Human In Vitro Organotypic Respiratory Model.

One of the most significant challenges in human health risk assessment is to evaluate hazards from exposure to environmental chemical mixtures. Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous contaminants typically found as mixtures in gaseous and particulate phases in ambient air pollution associated with petrochemicals from Superfund sites and the burning of fossil fuels. However, little is understood about how PAHs in mixtures contribute to toxicity in lung cells. To investigate mixture interactions and component additivity from environmentally relevant PAHs, two synthetic mixtures were created from PAHs identified in passive air samplers at a legacy creosote site impacted by wildfires. The primary human bronchial epithelial cells differentiated at the air-liquid interface were treated with PAH mixtures at environmentally relevant proportions and evaluated for the differential expression of transcriptional biomarkers related to xenobiotic metabolism, oxidative stress response, barrier integrity, and DNA damage response. Component additivity was evaluated across all endpoints using two independent action (IA) models with and without the scaling of components by toxic equivalence factors. Both IA models exhibited trends that were unlike the observed mixture response and generally underestimated the toxicity across dose suggesting the potential for non-additive interactions of components. Overall, this study provides an example of the usefulness of mixture toxicity assessment with the currently available methods while demonstrating the need for more complex yet interpretable mixture response evaluation methods for environmental samples.

Polycyclic aromatic compounds (PACs) in industrial soils from northwestern of China: occurrence, distribution, exposure risk, and implications on risk-based controls.

Some Polycyclic Aromatic Compounds (PACs) such asnitrated-PAHs (NPAHs), oxygenated-PAHs (OPAHs) and methyl-PAHs (MPAHs) have attracted significant concern due to derivatives have greater potential to be more toxic at low environmental concentrations compared to their PPAHs, particularly in petrochemical industrial region and its surrounding areas surface soils in China.Hence, this article provides an insight into the fate, sources, impacts, and relevance to the external environment of PAH-derivatives based on important emissions source. Moreover, prospective health risk due to their exposure has also been discussed. In this study, the concentration (10-3ng/g) of Ʃ18PPAHs, Ʃ11MPAHs, Ʃ12NPAHs, and Ʃ4OPAHs in the park were 9.67 ± 1.40, 3.24 ± 0.54, 0.03 ± 0.02 and 0.19 ± 0.65, respectively, which were 4.47, 3.89, 2.04 and 1.17 times than of them surrounding the region. A decreasing trend of the low molecular weight (2-4Rings) contribution to the total amount of PAHs, while the fraction of high molecular weight (5-6Rings) species showed the opposite trend. According to the principal component analysis (PCA) and diagnostic ratios indicated PAHs in the soil samples have mixed sources from industrial activities, solid fuel combustion, and heavy traffic. Despite the high concentrations of MPAHs and OPAHs, the toxicity equivalency quotients (TEQs) of them were not calculated due to the lack of toxic equivalent factors (TEF), thus current studies on PAH and derivatives could have underestimated their exposure risks. The quality and sustainable management of soils are crucial for human health and sustainable development, while there is lack of public awareness of the severe issue of soil pollution. It is recommended to conduct more intensive monitoring and regional assessments in the future.

Anticoagulant Rodenticide Toxicity in Terrestrial Raptors: Tools to Estimate the Impact on Populations in North America and Globally.

Anticoagulant rodenticides (ARs) have caused widespread contamination and poisoning of predators and scavengers. The diagnosis of toxicity proceeds from evidence of hemorrhage, and subsequent detection of residues in liver. Many factors confound the assessment of AR poisoning, particularly exposure dose, timing and frequency of exposure, and individual and taxon-specific variables. There is a need, therefore, for better AR toxicity criteria. To respond, we compiled a database of second-generation anticoagulant rodenticide (SGAR) residues in liver and postmortem evaluations of 951 terrestrial raptor carcasses from Canada and the United States, 1989 to 2021. We developed mixed-effects logistic regression models to produce specific probability curves of the toxicity of ∑SGARs at the taxonomic level of the family, and separately for three SGARs registered in North America, brodifacoum, bromadiolone, and difethialone. The ∑SGAR threshold concentrations for diagnosis of coagulopathy at 0.20 probability of risk were highest for strigid owls (15 ng g-1 ) lower and relatively similar for accipitrid hawks and eagles (8.2 ng g-1 ) and falcons (7.9 ng g-1 ), and much lower for tytonid barn owls (0.32 ng g-1 ). These values are lower than those we found previously, due to compilation and use of a larger database with a mix of species and source locations, and also to refinements in the statistical methods. Our presentation of results on the family taxonomic level should aid in the global applicability of the numbers. We also collated a subset of 440 single-compound exposure events and determined the probability of SGAR-poisoning symptoms as a function of SGAR concentration, which we then used to estimate relative SGAR toxicity and toxic equivalence factors: difethialone, 1, brodifacoum, 0.8, and bromadiolone, 0.5. Environ Toxicol Chem 2024;00:1-11. © 2024 His Majesty the King in Right of Canada and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC Reproduced with the permission of the Minister of Environment and Climate Change Canada.

Source Apportionment and Health Risk of Some Organic Contaminants in Water and Suspended Particulate Matter from Imo River, Nigeria

The objective of this study was to provide the source identification and assessment of potential health associated with some organic contaminant detected in water and suspended particle matter (SPM) from the Imo River, Nigeria using gas chromatography with a flame ionization detector (GC/FID) after 1:1 ratio solvent mixture (n-hexane and dichloromethane) extraction. The findings on SPM revealed the values; pH (5.42±0.097-5.567±0.057), conductivity (74.58±5.390-87.6±0.9 uS/cm), and total organic carbon (TOC) (3.626±0.366-6.143±0.176), and surface water; pH (6.077±0.049-6.46±0.52), conductivity (49.03±1.430- 58.12±0.553 uS/cm). The total concentrations of both low and high molecular PAHs in SPM recorded at stations1-3 were 4.384 mg/kg, 16.87 mg/kg, and (22.69 mg/kg); surface water 2.329 mg/L, 7.428 mg/L and 6.657 mg/L. The source apportionment of PAHs in SPM and surface water via molecular diagnostic ratios identified both petrogenic source (crude oil, petroleum spillages, and seepages) and pyrogenic sources (combustion of grass, wood, coal, and gas flaring). A further analysis with Principal Component Analysis (PCA) revealed two principal components, with 65.568% for component 1 and 34.432% for component 2 for SPM, and 62.80% for principal components and 37.2% for principal component 2 for surface water. The correlation analysis of PAHs affirmed common sources such as petrogenic and pyrogenic origins. The toxic equivalent factor of total benzo(a)pyrene for 6 ∑PAHs in SPM was recorded as 3.693 mg/kg, 1.605 mg/kg, and 0.453 mg/kg; surface water was recorded as 0.823 mg/L, 1.858 mg/L, and 0.353 mg/L, while the mutagenic equivalency quantities of SPM were recorded as 3.693mg/kg, 1.146 mg/kg, and 0.316 mg/kg; surface water 0.739 mg/L, 0.938, and 0.577 for stations 1-3. The effect of carcinogenic PAHs in SPM was higher in adults than in children, with regards to ILCR analysis. Users of Imo Rivers should be guided on the exposure of SPM and surface water since the toxic, mutagenic, and cancer risk levels of the river are above the permissible limit in some stations.

Toxicity source apportionment of fugitive dust PM2.5-bound polycyclic aromatic hydrocarbons using multilayer perceptron neural network analysis in Guanzhong Plain urban agglomeration, China

Polycyclic aromatic hydrocarbons (PAHs) in urban fugitive dust, known for their toxicity and ability to generate reactive oxygen species (ROS), are a major public health concern. This study assessed the spatial distribution and health risks of 15 PAHs in construction dust (CD) and road dust (RD) samples collected from June to November 2021 over the cities of Tongchuan (TC), Baoji (BJ), Xianyang (XY), and Xi'an (XA) in the Guanzhong Plain, China. The average concentration of ΣPAHs in RD was 39.5 ± 20.0 μg g−1, approximately twice as much as in CD. Four-ring PAHs from fossil fuels combustion accounted for the highest proportion of ΣPAHs in fugitive dust over all four cities. Health-related indicators including benzo(a)pyrene toxic equivalency factors (BAPTEQ), oxidative potential (OP), and incremental lifetime cancer risk (ILCR) all presented higher risk in RD than those in CD. The multilayer perceptron neural network algorithm quantified that vehicular and industrial emissions contributed 86 % and 61 % to RD and CD BAPTEQ, respectively. For OP, the sources of biomass and coal combustion were the key generator which accounted for 31–54 %. These findings provide scientific evidence for the direct efforts toward decreasing the health risks of fugitive dust in Guanzhong Plain urban agglomeration, China.

Leaching characteristics of metals and Polycyclic Aromatic Hydrocarbons (PAHs) from asphalt paving materials

Asphalt pavement, a major type of road surface, may contain hazardous elements depending on its specific composition. A growing concern has developed regarding the potential leaching of these hazardous constituents from asphalt pavements, particularly when incorporating waste materials and additives. This study investigates the presence of heavy metals and polycyclic aromatic hydrocarbons (PAHs) in leachates from six commonly employed asphalt paving materials. A comprehensive laboratory leaching experiment was conducted on three key sample scales: asphalt binder, asphalt mortar, and asphalt mixture. The impact of the leachates was assessed by the heavy metal pollution index and the toxic equivalency factor based on the benzo[a]pyrene equivalent concentration. The results reveal that leaching tests at the binder and mortar scales provided fundamental insights into leaching characteristics within a relatively short timeframe, while the mixture-scale test was more capable of representing pollutant leaching in near-true scenarios. In addition, the results indicate potential adverse health implications associated with the incorporation of hazardous waste, such as bottom ash, into asphalt pavement. These findings hold significant implications for promoting environmentally responsible practices of asphalt pavement.

Evaluating contamination of seafood purchased from U.S. retail stores by persistent environmental pollutants, pesticides and veterinary drugs

Studies have reported health risks associated with seafood contamination, but few data exist on levels in commercially available seafood in the US. To better understand, the magnitude of foodborne exposure and identify vulnerable populations in the US, we measured concentrations of veterinary drugs, persistent organic pollutants (POPs) (polycyclic aromatic hydrocarbons [PAHs], polybrominated diphenyl ethers [PBDEs] and polychlorinated biphenyls [PCBs]), and legacy and current-use pesticides in 46 seafood samples purchased from retail outlets. Measured levels were used to estimate risk based on available maximum residue limits (MRLs) and toxic equivalence (TEQ) factors for analytes. Only seventeen of the 445 analytes were detected, at low substance frequencies. However, half of the samples tested positive for one or more analyte, with total concentrations ranging from below the limit of detection (LOD) to as high as 156 µg/kg wet weight. Based on the risk assessment for individual pesticides and veterinary drugs, the hazard quotients (HQ) were all <1, indicating no risk. However, for the sum of PCB126 and PCB167, two dioxin-like PCBs detected in our samples, the TEQ was nearly two orders of magnitude higher than the WHO limits in one catfish sample. Moreover, vulnerable groups with higher rates of consumption of specific fish types may face higher risks.

Systematic update to the mammalian relative potency estimate database and development of best estimate toxic equivalency factors for dioxin-like compounds

The World Health Organization (WHO) assesses potential health risks of dioxin-like compounds using Toxic Equivalency Factors (TEFs). This study systematically updated the relative potency (REP) database underlying the 2005 WHO TEFs and applied advanced methods for quantitative integration of study quality and dose-response. Data obtained from fifty-one publications more than doubled the size of the previous REP database (∼1300 datasets). REP quality and relevance for these data was assessed via application of a consensus-based weighting framework. Using Bayesian dose-response modeling, available data were modeled to produce standardized dose/concentration-response Hill curves. Study quality and REP data were synthesized via Bayesian meta-analysis to integrate dose/concentration-response data, author-calculated REPs and benchmark ratios. The output is a prediction of the most likely relationship between each congener and its reference as model-predicted TEF uncertainty distributions, or the ‘best estimate TEF’ (BE-TEF). The resulting weighted BE-TEFs were similar to the 2005 TEFs, though provide more information to inform selection of TEF values as well as to provide risk assessors and managers with information needed to quantitatively characterize uncertainty around TEF values. Collectively, these efforts produce an updated REP database and an objective, reproducible approach to support development of TEF values based on all available data.

The occurrence, sources, and health risks of substituted polycyclic aromatic hydrocarbons (SPAHs) cannot be ignored

Similar to parent polycyclic aromatic hydrocarbons (PPAHs), substituted PAHs (SPAHs) are prevalent in the environment and harmful to humans. However, they have not received much attention. This study investigated the occurrence, distribution, and sources of 10 PPAHs and 15 SPAHs in soil, water, and indoor and outdoor PM2.5 and dust in high-exposure areas (EAH) near industrial parks and low-exposure areas (EAL) far from industrial parks. PAH pollution in all media was more severe in the EAH than in the EAL. All SPAHs were detected in this study, with alkylated and oxygenated PAHs being predominant. Additionally, 3-OH-BaP and 1-OH-Pyr were detected in all dust samples in this study, and 6-N-Chr, a compound with carcinogenicity 10 times higher than that of BaP, was detected at high levels in all tap water samples. According to the indoor-outdoor ratio, PAHs in indoor PM2.5 in the EAH mainly originated from indoor pollution sources; however, those in the EAL were simultaneously affected by indoor-outdoor air exchange and indoor sources. Most target PAHs tended to deposit from air to dust, and this tendency was significantly negatively associated with the octanol-air partitioning coefficient of PAHs. SPAHs in the environment are primarily derived from the petroleum industry and the mixed combustion of gasoline, biomass, and coal. The toxicity equivalence factors of SPAHs were predicted using QSAR models to assess their lifetime carcinogenic risk (ILCR). The ILCRtotal from PAHs for adults in the EAH was >10−4. Though the levels of 6-N-Chr and 1-Me-Pyr in the environment were markedly lower than those of PPAHs, their ILCRs from PM2.5 inhalation and dermal contact with water exceeded 10−6. This study is significant for recognizing and controlling the health risks associated with SPAHs in humans.

The 2022 world health organization reevaluation of human and mammalian toxic equivalency factors for polychlorinated dioxins, dibenzofurans and biphenyls

In October 2022, the World Health Organization (WHO) convened an expert panel in Lisbon, Portugal in which the 2005 WHO TEFs for chlorinated dioxin-like compounds were reevaluated. In contrast to earlier panels that employed expert judgement and consensus-based assignment of TEF values, the present effort employed an update to the 2006 REP database, a consensus-based weighting scheme, a Bayesian dose response modeling and meta-analysis to derive “Best-Estimate” TEFs. The updated database contains almost double the number of datasets from the earlier version and includes metadata that informs the weighting scheme. The Bayesian analysis of this dataset results in an unbiased quantitative assessment of the congener-specific potencies with uncertainty estimates. The “Best-Estimate” TEF derived from the model was used to assign 2022 WHO-TEFs for almost all congeners and these values were not rounded to half-logs as was done previously. The exception was for the mono-ortho PCBs, for which the panel agreed to retain their 2005 WHO-TEFs due to limited and heterogenous data available for these compounds. Applying these new TEFs to a limited set of dioxin-like chemical concentrations measured in human milk and seafood indicates that the total toxic equivalents will tend to be lower than when using the 2005 TEFs.

Higher Toxicity of Gaseous Organics Relative to Particulate Matters Emitted from Typical Cooking Processes.

Cooking emission is known to be a significant anthropogenic source of air pollution in urban areas, but its toxicities are still unclear. This study addressed the toxicities of fine particulate matter (PM2.5) and gaseous organics by combining chemical fingerprinting analysis with cellular assessments. The cytotoxicity and reactive oxygen species activity of gaseous organics were ∼1.9 and ∼8.3 times higher than those of PM2.5, respectively. Moreover, these values of per unit mass PM2.5 were ∼7.1 and ∼15.7 times higher than those collected from ambient air in Shanghai. The total oleic acid equivalent quantities for carcinogenic and toxic respiratory effects of gaseous organics, as estimated using predictive models based on quantitative structure-property relationships, were 1686 ± 803 and 430 ± 176 μg/mg PM2.5, respectively. Both predicted toxicities were higher than those of particulate organics, consistent with cellular assessment. These health risks are primarily attributed to the high relative content and toxic equivalency factor of the organic compounds present in the gas phase, including 7,9-di-tert-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione, 2-ethylhexanoic acid, and 2-phenoxyethoxybenzene. Furthermore, these compounds and fatty acids were identified as prominent chemical markers of cooking-related emissions. The obtained results highlight the importance of control measures for cooking-emitted gaseous organics to reduce the personal exposure risks.

Development and application of a systematic and quantitative weighting framework to evaluate the quality and relevance of relative potency estimates for dioxin-like compounds (DLCs) for human health risk assessment

The toxic equivalency factors (TEFs) approach for dioxin-like chemicals (DLCs) is currently based on a qualitative assessment of a heterogeneous data set of relative estimates of potency (REPs) spanning several orders of magnitude with highly variable study quality and relevance. An effort was undertaken to develop a weighting framework to systematically evaluate and quantitatively integrate the quality and relevance for development of more robust TEFs. Six main-study characteristics were identified as most important in characterizing the quality and relevance of an individual REP for human health risk assessment: study type, study model, pharmacokinetics, REP derivation method, REP derivation quality, and endpoint. Subsequently, a computational approach for quantitatively integrating the weighting framework parameters was developed and applied to the REP2004 database. This was accomplished using a machine learning approach which infers a weighted TEF distribution for each congener. The resulting database, weighted for quality and relevance, provides REP distributions from >600 data sets (including in vivo and in vitro studies, a range of endpoints, etc.). This weighted database provides a flexible platform for systematically and objectively characterizing TEFs for use in risk assessment, as well as providing information to characterize uncertainty and variability. Collectively, this information provides risk managers with information for decision making.

Okadaic Acid Is at Least as Toxic as Dinophysistoxin-1 after Repeated Administration to Mice by Gavage.

Okadaic acid (OA) and its analogues cause diarrhetic shellfish poisoning (DSP) in humans, and risk assessments of these toxins require toxicity equivalency factors (TEFs), which represent the relative toxicities of analogues. However, no human death by DSP toxin has been reported, and its current TEF value is based on acute lethality. To properly reflect the symptoms of DSP, such as diarrhea without death, the chronic toxicity of DSP toxins at sublethal doses should be considered. In this study, we obtained acute oral LD50 values for OA and dinophysistoxin-1 (DTX-1) (1069 and 897 μg/kg, respectively) to set sublethal doses. Mice were treated with sublethal doses of OA and DTX-1 for 7 days. The mice lost body weight, and the disease activity index and intestinal crypt depths increased. Furthermore, these changes were more severe in OA-treated mice than in the DTX-1-treated mice. Strikingly, ascites was observed, and its severity was greater in mice treated with OA. Our findings suggest that OA is at least as toxic as DTX-1 after repeated oral administration at a low dose. This is the first study to compare repeated oral dosing of DSP toxins. Further sub-chronic and chronic studies are warranted to determine appropriate TEF values for DSP toxins.

Characteristics, Source and Risk Assessment of Soil Polycyclic Aromatic Hydrocarbons around Oil Wells in the Yellow River Delta, China

The Yellow River Delta (YRD) is the most complete wetland ecosystem in the warm temperate zone of China and is rich in oil resources. However, with petroleum extraction and the development of the economy, pollution of the YRD has been paid increasing attention, in particular, pollution via polycyclic aromatic hydrocarbons (PAHs), as they have caused great harm to human health and the ecosystem balance. Based on the investigations of a research group in 2009, this study re-collected samples according to the same sampling points and analyzed the concentration, composition, source, ecological risk and health risk of PAHs in 2021. The concentration of ΣPAH16 in the surface soil of YRD in 2009 ranged from 2.6 to 8275.46 ng/g, with an average of 1744.41 ng/g. The concentration of ΣPAH16 in 2021 ranged from 56.25 to 582.56 ng/g, with an average of 149.63 ng/g. Therefore, the pollution situation in the YRD in 2021 was significantly improved compared with 2009. The composition of PAHs in soil in 2009 and 2021 was similar, which was dominated by low-ring PAHs. The evaluation results of the toxicity equivalent factor method showed that there was no potential ecological risk in the soil in 2009 and 2021. The evaluation results of the lifetime cancer risk increment model showed that the incremental lifetime cancer risk models (ILCRs) of soil PAHs in 2009 and 2021 were lower than the safety threshold of 10−6; therefore, there was no carcinogenic risk. The existing management measures for oil wells need to be further promoted to protect the regional ecological environment in the YRD.

The Simultaneous Determination of Nine Furocoumarins in Angelica dahurica Using UPLC Combined with the QAMS Approach and Novel Health Risk Assessment Based on the Toxic Equivalency Factor

Objective: This study aimed to provide data for the type and content of linear furocoumarins (FCs) in Angelica dahurica (AD) in order to assess their cumulative risks and provide a scientific basis for the rational use and quality evaluation of the medicinal AD to improve public health. Methods: A UPLC method was developed for the simultaneous determination of nine FCs initially by using imperatorin (Im) as the internal standard substance, including Im, phellopterin (Ph), isoimperatorin (Is), oxypeucedanin hydrate (Oh), byakangelicin (Bn), xanthotoxin (8-MOP), bergapten (5-MOP), byakangelicol (Bl), and oxypeucedanin (Op) in two species of Angelica dahurica (AD). And, the risk assessment for the total FCs in AD was explored using the hazard index combined with the toxic equivalency factor (TEF-HI) strategy for the first time. Results: The established method revealed acceptable applicability, and there were no significant differences compared with the external standard method (ESM). The quantitative results demonstrated that the total content of FCs in Angelica dahurica (BZ) were higher than that in Angelica dahurica var. formosana (HBZ), and there was a great difference between the Bl and Op. Moreover, the risk assessment data revealed that the risk of total FCs in AD to human health was low. Conclusions: The established UPLC method that determined nine FCs in AD using a single marker could solve the problem of difficulty in obtaining a chemical reference substance with high purity and requiring a long determination time. And, the TEF-HI risk assessment approach associated with FCs in ADs could guide the rational utilization of toxic FCs in ADs in the progress of improving public health safety. In short, the whole systematic strategy provides a scientific basis for rational quality evaluation and the healthy use of related herbal medicines.

Evaluation of Toxicity Equivalency Factors of Tetrodotoxin Analogues with a Neuro-2a Cell-Based Assay and Application to Puffer Fish from Greece.

Tetrodotoxin (TTX) is a potent marine neurotoxin involved in poisoning cases, especially through the consumption of puffer fish. Knowledge of the toxicity equivalency factors (TEFs) of TTX analogues is crucial in monitoring programs to estimate the toxicity of samples analyzed with instrumental analysis methods. In this work, TTX analogues were isolated from the liver of a Lagocephalus sceleratus individual caught on South Crete coasts. A cell-based assay (CBA) for TTXs was optimized and applied to the establishment of the TEFs of 5,11-dideoxyTTX, 11-norTTX-6(S)-ol, 11-deoxyTTX and 5,6,11-trideoxyTTX. Results showed that all TTX analogues were less toxic than the parent TTX, their TEFs being in the range of 0.75-0.011. Then, different tissues of three Lagocephalus sceleratus individuals were analyzed with CBA and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The obtained TEFs were applied to the TTX analogues' concentrations obtained by LC-MS/MS analysis, providing an indication of the overall toxicity of the sample. Information about the TEFs of TTX analogues is valuable for food safety control, allowing the estimation of the risk of fish products to consumers.