Changes in the Non-targeted Metabolomic Profile of Three-year-old Toddlers with Elevated Exposure to Polycyclic Aromatic Hydrocarbons.

Objective: To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons (PAHs) during critical brain development and explore their potential link with the intestinal microbiota. Methods: Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs (OH-PAHs) in 36-month-old children. Subsequently, 37 children were categorized into low- and high-exposure groups based on the sum of the ten OH-PAHs. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples. Furthermore, fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results: The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group (variable importance for projection > 1, P < 0.05). Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene, fluorine, and phenanthrene ( r = 0.336-0.531). The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states, including amino acid, lipid, and nucleotide metabolism. Additionally, these distinct metabolites were significantly associated with specific intestinal flora abundances ( r = 0.34-0.55), which were mainly involved in neurodevelopment. Conclusion: Higher PAH exposure in young children affected metabolic homeostasis, particularly that of certain gut microbiota-derived metabolites. Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

Identification of UDP-glucuronosyltransferase (UGT) isoforms involved in the metabolism of Chlorophenols (CPs).

Chlorophenols (CPs) are a group of pollutants that pose a great threat to the environment, they are widely used in industrial and agricultural wastes, pesticides, herbicides, textiles, pharmaceuticals and plastics. Among CPs, pentachlorophenol was listed as one of the persistent organic pollutants (POPs) by the Stockholm convention. This study aims to identify the UDP-glucosyltransferase (UGT) isoforms involved in the metabolic elimination of CPs. CPs' mono-glucuronide was detected in the human liver microsomes (HLMs) incubation mixture with co-factor uridine-diphosphate glucuronic acid (UDPGA). HLMs-catalyzed glucuronidation metabolism reaction equations followed Michaelis-Menten or substrate inhibition type. Recombinant enzymes and chemical reagents inhibition experiments were utilized to phenotype the main UGT isoforms involved in the glucuronidation of CPs. UGT1A6 might be the major enzyme in the glucuronidation of mono-chlorophenol isomer. UGT1A1, UGT1A6, UGT1A9, UGT2B4 and UGT2B7 were the most important five UGT isoforms for metabolizing the di-chlorophenol and tri-chlorophenol isomers. UGT1A1 and UGT1A3 were the most important UGT isoforms in the catalysis of tetra-chlorophenol and pentachlorophenol isomers. Species differences were investigated using rat liver microsomes (RLMs), pig liver microsomes (PLMs), dog liver microsomes (DLMs), and monkey liver microsomes (MyLMs). All these results were helpful for elucidating the metabolic elimination and toxicity of CPs.

Synthesis and characterization of iron oxide nanoparticles from Lawsonia inermis and its effect on the biodegradation of crude oil hydrocarbon.

Crude oil hydrocarbons are considered major environmental pollutants and pose a significant threat to the environment and humans due to having severe carcinogenic and mutagenic effects. Bioremediation is one of the practical and promising technology that can be applied to treat the hydrocarbon-polluted environment. In this present study, rhamnolipid biosurfactant (BS) produced by Pseudomonas aeruginosa PP4 and green synthesized iron nanoparticles (G-FeNPs) from Lawsonia inermis was used to evaluate the biodegradation efficiency (BE) of crude oil. The surface analysis of G-FeNPs was carried out by using FESEM and HRTEM to confirm the size and shape. Further, the average size of the G-FeNPs was observed around 10 nm by HRTEM analysis. The XRD and Raman spectra strongly confirm the presence of iron nanoparticles with their respective peaks. The BE (%) of mixed degradation system-V (PP4+BS+G-FeNPs) was obtained about 82%. FTIR spectrum confirms the presence of major functional constituents (C=O, -CH3, C-O, and OH) in the residual oil content. Overall, this study illustrates that integrated nano-based bioremediation could be an efficient approach for hydrocarbon-polluted environments. This study is the first attempt to evaluate the G-FeNPs with rhamnolipid biosurfactant on the biodegradation of crude oil.

Bioremediation of Hazardous Pollutants Using Enzyme-Immobilized Reactors.

Bioremediation uses the degradation abilities of microorganisms and other organisms to remove harmful pollutants that pollute the natural environment, helping return it to a natural state that is free of harmful substances. Organism-derived enzymes can degrade and eliminate a variety of pollutants and transform them into non-toxic forms; as such, they are expected to be used in bioremediation. However, since enzymes are proteins, the low operational stability and catalytic efficiency of free enzyme-based degradation systems need improvement. Enzyme immobilization methods are often used to overcome these challenges. Several enzyme immobilization methods have been applied to improve operational stability and reduce remediation costs. Herein, we review recent advancements in immobilized enzymes for bioremediation and summarize the methods for preparing immobilized enzymes for use as catalysts and in pollutant degradation systems. Additionally, the advantages, limitations, and future perspectives of immobilized enzymes in bioremediation are discussed.

The role of iron materials in the abiotic transformation and biotransformation of polybrominated diphenyl ethers (PBDEs): A review.

Polybrominated diphenyl ethers (PBDEs), widely used as flame retardants, easily enter the environment, thus posing environmental and health risks. Iron materials play a key role during the migration and transformation of PBDEs. This article reviews the processes and mechanisms of adsorption, degradation, and biological uptake and transformation of PBDEs affected by iron materials in the environment. Iron materials can effectively adsorb PBDEs through hydrophobic interactions, π-π interactions, hydrogen/halogen bonds, electrostatic interactions, coordination interactions, and pore filling interactions. In addition, they are beneficial for the photodegradation, reduction debromination, and advanced oxidation degradation and debromination of PBDEs. The iron material-microorganism coupling technology affects the uptake and transformation of PBDEs. In addition, iron materials can reduce the uptake of PBDEs in plants, affecting their bioavailability. The species, concentration, and size of iron materials affect plant physiology. Overall, iron materials play a bidirectional role in the biological uptake and transformation of PBDEs. It is necessary to strengthen the positive role of iron materials in reducing the environmental and health risks caused by PBDEs. This article provides innovative ideas for the rational use of iron materials in controlling the migration and transformation of PBDEs in the environment.

Exposure to environmental pollutants selects for xenobiotic-degrading functions in the human gut microbiome.

Environmental pollutants from different chemical families may reach the gut microbiome, where they can be metabolized and transformed. However, how our gut symbionts respond to the exposure to environmental pollution is still underexplored. In this observational, cohort study, we aim to investigate the influence of environmental pollution on the gut microbiome composition and potential activity by shotgun metagenomics. We select as a case study a population living in a highly polluted area in Campania region (Southern Italy), proposed as an ideal field for exposomic studies and we compare the fecal microbiome of 359 subjects living in areas with high, medium and low environmental pollution. We highlight changes in gut microbiome composition and functionality that were driven by pollution exposure. Subjects from highly polluted areas show higher blood concentrations of dioxin and heavy metals, as well as an increase in microbial genes related to degradation and/or resistance to these molecules. Here we demonstrate the dramatic effect that environmental xenobiotics have on gut microbial communities, shaping their composition and boosting the selection of strains with degrading capacity. The gut microbiome can be considered as a pivotal player in the environment-health interaction that may contribute to detoxifying toxic compounds and should be taken into account when developing risk assessment models. The study was registered at ClinicalTrials.gov with the identifier NCT05976126.

In Vitro and In Vivo Biotransformation Profiling of 6PPD-Quinone toward Their Detection in Human Urine.

The antioxidant N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its oxidized quinone product 6PPD-quinone (6PPD-Q) in rubber have attracted attention due to the ecological risk that they pose. Both 6PPD and 6PPD-Q have been detected in various environments that humans cohabit. However, to date, a clear understanding of the biotransformation of 6PPD-Q and a potential biomarker for exposure in humans are lacking. To address this issue, this study presents a comprehensive analysis of the extensive biotransformation of 6PPD-Q across species, encompassing both in vitro and in vivo models. We have tentatively identified 17 biotransformation metabolites in vitro, 15 in mice in vivo, and confirmed the presence of two metabolites in human urine samples. Interestingly, different biotransformation patterns were observed across species. Through semiquantitative analysis based on peak areas, we found that almost all 6PPD-Q underwent biotransformation within 24 h of exposure in mice, primarily via hydroxylation and subsequent glucuronidation. This suggests a rapid metabolic processing of 6PPD-Q in mammals, underscoring the importance of identifying effective biomarkers for exposure. Notably, monohydroxy 6PPD-Q and 6PPD-Q-O-glucuronide were consistently the most predominant metabolites across our studies, highlighting monohydroxy 6PPD-Q as a potential key biomarker for epidemiological research. These findings represent the first comprehensive data set on 6PPD-Q biotransformation in mammalian systems, offering insights into the metabolic pathways involved and possible exposure biomarkers.

Regulating the absorption and excretion of perfluorooctane sulfonate and its alternatives through influencing enterohepatic circulation.

Enterohepatic circulation has been reported to play a significant role in the bioaccumulation of PFASs. In this study, the tissue distribution and excretion of PFOS and its alternatives, namely 6:2 and 8:2 fluorotelomer sulfonic acid (FTSA) was investigated using a mouse assay with a focus on role of enterohepatic circulation. Liver was the primarily accumulating organ for PFOS and 8:2 FTSA (33.4 % and 25.8 % of total doses absorbed after 14 days), whereas 65 % of 6:2 FTSA was excreted via urine within 24 h. Peak levels of 8:2 FTSA and PFOS were found in the gallbladder, implying the important role of enterohepatic circulation in PFASs reabsorption. The role of enterohepatic circulation was further evaluated through co-exposure of 8:2 FTSA and PFOS with medicines (namely metformin (MET) and ursodeoxycholic acid (UDCA)). MET reduced accumulation of 8:2 FTSA and PFOS in the liver by 68.6 % and 65.8 %, through down-regulation of bile acid transporter (Asbt) and enhancement of fecal excretion. Conversely, UDCA raised their concentrations by 21.9 % and 34.6 % compared to that exposed solely to PFASs. A strong positive correlation was identified between PFASs serum levels and Asbt expression. This study illuminated PFAS bioaccumulation mechanisms and suggested potential strategies to mitigate the exposure risks.

Comparison of in vitro membrane permeabilities of diverse environmental chemicals with in silico predictions.

The parallel artificial membrane permeability assay (PAMPA) is widely used for estimating biomembrane permeabilities of experimental drugs in pharmaceutical research. However, there are few reports of studies using PAMPA to measure membrane permeabilities of chemicals of environmental concern (CECs) outside the pharmaceutical domain, many of which differ substantially from drugs in their physicochemical properties. We applied PAMPA methods simulating gastrointestinal (PAMPA-GIT) and blood-brain barrier (PAMPA-BBB) membranes under consistent conditions to 51 CECs, including some pharmaceuticals. A backward stepwise multivariate linear regression was implemented to explore the correlation between the differences of measured permeabilities from PAMPA-GIT and PAMPA-BBB and Abraham solute descriptors. In addition, a previously reported in silico model was evaluated by comparing predicted and measured permeability results. PAMPA-GIT and PAMPA-BBB experimental permeability results agreed relatively well. The backward stepwise multivariate linear regression identified excess molar refraction and polarizability to be significant at the 0.10 level in predicting the differences between PAMPA-GIT and PAMPA-BBB. The in silico model performed well - with predicted permeability of most compounds within two-fold of experimentally measured values. We found that CECs pose experimental challenges to the PAMPA method in terms of having lower solubility and lower stability compared to most drugs.

Accumulation of persistent organic pollutants in the kidneys of pet cats (Felis silvestris catus) and the potential implications for their health.

Persistent organic pollutants (POPs), such as polychlorinated diphenyls (PCBs) and brominated diphenyl ethers (PBDEs), are ubiquitous in the pet cat's living environment and are ingested through dietary intake and environmental exposure such as house dust. Cats are known to be susceptible to chronic kidney disease (CKD) and exposure to POPs may be associated with CKD. However, no studies have been conducted on the renal accumulation and health effects of POPs in cats. The objective of this study was to elucidate the accumulation of PCBs, PBDEs, and organochlorine pesticides (OCPs) in the kidneys of domestic cats and discuss their potential impact on feline health. We report here that cats specifically accumulate POPs in their kidneys. Tissue samples were collected from the kidneys, livers, and muscles of cats and the concentrations of POPs in these tissues were analyzed in this study. The results showed that these compounds accumulated significantly higher in the kidney compared to other tissues. In addition, the ability to accumulate in the kidney was higher in cats than in other animals, suggesting that cats have a unique pattern of POPs accumulation in their kidneys, which is thought to occur because cats store a significant number of lipid droplets in the proximal tubules of the kidneys. This unique feature suggests that lipophilic POPs may accumulate in these lipid droplets during the excretory process. Accumulation of certain POPs in the kidneys causes necrosis and sloughing of renal tubular epithelial cells, which may be associated with CKD, a common disease in cats. This study provides valuable insight into understanding the renal accumulation and risk of POPs in cats and provides essential knowledge for developing strategies to protect the health and welfare of domestic cats.

Mercury Concentrations in Feathers of Albatrosses and Large Petrels at South Georgia: Contemporary Patterns and Comparisons with Past Decades.

Mercury (Hg) is an environmental contaminant that can negatively impact the health of humans and wildlife. Albatrosses and large petrels show some of the highest levels of Hg contamination among birds, with potential repercussions for reproduction and survival. Here, body feather total Hg (THg) concentrations were determined in breeding adults of five species of albatrosses and large petrels in the foraging guild at South Georgia during the mid-2010s. We tested the effects of species, sex and trophic ecology (inferred from stable isotopes) on THg concentrations and compared our results with published values from past decades. Feather THg concentrations differed significantly among species (range: 1.9-49.6 µg g-1 dw), and were highest in wandering albatrosses Diomedea exulans, intermediate in black-browed albatrosses Thalassarche melanophris and northern giant petrels Macronectes halli, and lowest in southern giant petrels M. giganteus and white-chinned petrels Procellaria aequinoctialis. Females were more contaminated than males in all species, potentially due to differences in distributions and diet composition. Across species, THg concentrations were not correlated with feather δ13C or δ15N values, implying that species effects (e.g., breeding and moulting frequencies) may be more important than trophic effects in explaining feather THg concentrations in this foraging guild. Within species, the only significant correlation was between THg and δ13C in wandering albatrosses, which could reflect higher Hg exposure in subtropical waters. Comparisons with THg concentrations from past studies, which reflect contamination from 10 to > 60 years ago, revealed considerable annual variation and some evidence for increases over time for wandering and black-browed albatrosses since before 1950 and from the late 1980s, respectively.

Towards process-based modelling and parameterisation of bioaccumulation in humans across PFAS congeners.

Per- and polyfluoroalkyl substances (PFAS) are a large class of stable toxic chemicals which have ended up in the environment and in organisms in significant concentrations. Toxicokinetic models are needed to facilitate extrapolation of bioaccumulation data across PFAS congeners and species. For the present study, we carried out an inventory of accumulation processes specific for PFAS, deviating from traditional Persistent Organic Pollutants (POPs). In addition, we reviewed toxicokinetic models on PFAS reported in literature, classifying them according to the number of compartments distinguished as a one-compartment model (1-CM), two-compartment model (2- CM) or a multi-compartment model, (multi-CM) as well as the accumulation processes included and the parameters used. As the inventory showed that simple 1-CMs were lacking, we developed a generic 1-CM of ourselves to include PFAS specific processes and validated the model for legacy perfluoroalkyl acids. Predicted summed elimination constants were accurate for long carbon chains (>C6), indicating that the model properly represented toxicokinetic processes for most congeners. Results for urinary elimination rate constants were mixed, which might be caused by the exclusion of reabsorption processes (renal reabsorption, enterohepatic circulation). The 1-CM needs to be improved further in order to better predict individual elimination pathways. Besides that, more data on PFAS-transporter specific processes are needed to extrapolate across PFAS congeners and species.

Dermal bioavailability of perfluoroalkyl substances using in vitro 3D human skin equivalent models.

Perfluoroalkyl substances (PFAS) have been identified in various products that come in contact with human skin, ranging from school uniforms to personal care products. Despite this, knowledge on human dermal uptake of PFAS is lacking. Thus, the human dermal absorption of 17 PFAS was assessed, for the first time, using in vitro 3D-human skin equivalent models exposed to 500 ng/cm2 PFAS dissolved in methanol over 24-36 h. The distribution of target PFAS is presented, based on three fractions: absorbed, un-absorbed, and retained within skin tissue (absorbable dose). Perfluoropentanoic acid (PFPeA) and perfluorobutane sulfonate (PFBS) had the highest absorbed fraction, 58.9 % and 48.7 % respectively, with the absorbed fraction decreasing with increasing carbon chain length of the studied perfluorocarboxylic acids (PFCAs) (r = 0.97, p = 0.001) and perfluorosulfonic acids (PFSAs) (r = 0.97, p = 0.004). Interestingly, while longer chain PFAS (Cn ≥ 9) were not directly absorbed, a large fraction of the exposure dose was detected within the skin tissue at the end of the exposure. This was most apparent for perfluoroundecanoic acid (PFUnDA) and perfluorononane sulfonate (PFNS) for which 66.5 % and 68.3 % of the exposure dose was found within the skin tissue, while neither compound was detected in the absorbed fraction. For compounds with a carbon chain length > 11, the fraction found within the skin tissue, decreases with increasing chain length. Physicochemical properties played a role in dermal permeation of PFAS, with a clear inverse correlation between logKOW and absorbed fraction for both PFCAs (r = -0.97; p ≤ 0.001) and PFSAs (r = -0.99; p ≤ 0.001). Steady-state flux (JSS) and permeation coefficients (Papp) were determined for target compounds with significant permeation after 36 h exposure (C5-C8 PFCAs and C4-C7 PFSAs). In general, both the flux and permeation coefficient decreased with increasing chain length.

Defluorination as the key trait to gauge the biodegradability of fluorinated pollutants in environmental microbial communities.

Research on microbial defluorination is largely centred on controlled experiments using axenic or well defined microbial inocula. These approaches serve a relevant purpose in the field, offering fundamental biochemical and mechanistic insights on the intricacies of biological defluorination. However, they fail to account for the effective contribution of environmental microbial communities in the recycling of fluoroorganic pollutants, a highly relevant perspective from an environmental risk assessment standpoint, while also missing an important outlook on how community-wide dynamics can leverage the breakdown of C─F bonds in these recalcitrant compounds. With that in mind, this chapter provides experimental and methodological insights on the study of microbial defluorination in wild environmental communities, using this critical catabolic step as the de facto endpoint to evolve, select and cultivate microorganisms with improved defluorination performances.

Multiomics Analysis of PCB126's Effect on a Mouse Chronic-Binge Alcohol Feeding Model.

BACKGROUND: Environmental pollutants, including polychlorinated biphenyls (PCBs) have been implicated in the pathogenesis of liver disease. Our group recently demonstrated that PCB126 promoted steatosis, hepatomegaly, and modulated intermediary metabolism in a rodent model of alcohol-associated liver disease (ALD). OBJECTIVE: To better understand how PCB126 promoted ALD in our previous model, the current study adopts multiple omics approaches to elucidate potential mechanistic hypotheses. METHODS: Briefly, male C57BL/6J mice were exposed to 0.2mg/kg polychlorinated biphenyl (PCB) 126 or corn oil vehicle prior to ethanol (EtOH) or control diet feeding in the chronic-binge alcohol feeding model. Liver tissues were collected and prepared for mRNA sequencing, phosphoproteomics, and inductively coupled plasma mass spectrometry for metals quantification. RESULTS: Principal component analysis showed that PCB126 uniquely modified the transcriptome in EtOH-fed mice. EtOH feeding alone resulted in >4,000 differentially expressed genes (DEGs), and PCB126 exposure resulted in more DEGs in the EtOH-fed group (907 DEGs) in comparison with the pair-fed group (503 DEGs). Top 20 significant gene ontology (GO) biological processes included "peptidyl tyrosine modifications," whereas top 25 significantly decreasing GO molecular functions included "metal/ion/zinc binding." Quantitative, label-free phosphoproteomics and western blot analysis revealed no major significant PCB126 effects on total phosphorylated tyrosine residues in EtOH-fed mice. Quantified hepatic essential metal levels were primarily significantly lower in EtOH-fed mice. PCB126-exposed mice had significantly lower magnesium, cobalt, and zinc levels in EtOH-fed mice. DISCUSSION: Previous work has demonstrated that PCB126 is a modifying factor in metabolic dysfunction-associated steatotic liver disease (MASLD), and our current work suggests that pollutants also modify ALD. PCB126 may, in part, be contributing to the malnutrition aspect of ALD, where metal deficiency is known to contribute and worsen prognosis. https://doi.org/10.1289/EHP14132.

DNA adduct formation in Saccharomyces cerevisiae following exposure to environmental pollutants, as in vivo model for molecular toxicity studies.

DNA adduction in the model yeast Saccharomyces cerevisiae was investigated after exposure to the fungicide penconazole and the reference genotoxic compound benzo(a)pyrene, for validating yeasts as a tool for molecular toxicity studies, particularly of environmental pollution. The effect of the toxicants on the yeast's growth kinetics was determined as an indicator of cytotoxicity. Fermentative cultures of S. cerevisiae were exposed to 2 ppm of Penconazole during different phases of growth; while 0.2 and 2 ppm of benzo(a)pyrene were applied to the culture medium before inoculation and on exponential cultures. Exponential respiratory cultures were also exposed to 0.2 ppm of B(a)P for comparison of both metabolisms. Penconazole induced DNA adducts formation in the exponential phase test; DNA adducts showed a peak of 54.93 adducts/109 nucleotides. Benzo(a)pyrene induced the formation of DNA adducts in all the tests carried out; the highest amount of 46.7 adducts/109 nucleotides was obtained in the fermentative cultures after the exponential phase exposure to 0.2 ppm; whereas in the respiratory cultures, 14.6 adducts/109 nucleotides were detected. No cytotoxicity was obtained in any experiment. Our study showed that yeast could be used to analyse DNA adducts as biomarkers of exposure to environmental toxicants.

Identification of Bromophenols' glucuronidation and its induction on UDP- glucuronosyltransferases isoforms.

Bromophenols (BPs) are prominent environmental pollutants extensively utilized in aquaculture, pharmaceuticals, and chemical manufacturing. This study aims to identify UDP- glucuronosyltransferases (UGTs) isoforms involved in the metabolic elimination of BPs. Mono-glucuronides of BPs were detected in human liver microsomes (HLMs) incubated with the co-factor uridine-diphosphate glucuronic acid (UDPGA). The glucuronidation metabolism reactions catalyzed by HLMs followed Michaelis-Menten or substrate inhibition kinetics. Recombinant enzymes and inhibition experiments with chemical reagents were employed to phenotype the principal UGT isoforms participating in BP glucuronidation. UGT1A6 emerged as the major enzyme in the glucuronidation of 4-Bromophenol (4-BP), while UGT1A1, UGT1A6, and UGT1A8 were identified as the most essential isoforms for metabolizing 2,4-dibromophenol (2,4-DBP). UGT1A1, UGT1A8, and UGT2B4 were deemed the most critical isoforms in the catalysis of 2,4,6-tribromophenol (2,4,6-TBP) glucuronidation. Species differences were investigated using the liver microsomes of pig (PLM), rat (RLM), monkey (MyLM), and dog (DLM). Additionally, 2,4,6-TBP effects on the expression of UGT1A1 and UGT2B7 in HepG2 cells were evaluated. The results demonstrated potential induction of UGT1A1 and UGT2B7 upon exposure to 2,4,6-TBP at a concentration of 50 µM. Collectively, these findings contribute to elucidating the metabolic elimination and toxicity of BPs.

Penetration pathways, influencing factors and predictive models for dermal absorption of exobiotic molecules: A critical review.

This review provides a comprehensive summary of the skin penetration pathways of xenobiotics, including metals, organic pollutants, and nanoparticles (NPs), with a particular focus on the methodologies employed to elucidate these penetration routes. The impacts of the physicochemical properties of exogenous substances and the properties of solvent carriers on the penetration efficiencies were discussed. Furthermore, the review outlines the steady-state and transient models for predicting the skin permeability of xenobiotics, emphasizing the models which enable realistic visualization of pharmaco-kinetic phenomena via detailed geometric representations of the skin microstructure, such as stratum corneum (SC) (bricks and mortar) and skin appendages (hair follicles and sebaceous gland units). Limitations of published research, gaps in current knowledge, and recommendations for future research are highlighted, providing insight for a better understanding of the skin penetration behavior of xenobiotics and associated health risks in practical application contexts.

Gender-specific abdominal fat distribution and insulin resistance associated with organophosphate esters and phthalate metabolites exposure.

The worldwide prevalence of obesity highlights the potential contribution of endocrine-disrupting chemicals (EDCs). However, common epidemiological measures such as body mass index and waist circumference may misrepresent the intricate obesity risks these chemicals pose across genders. This study delves deeper into abdominal fat by differentiating between subcutaneous and visceral regions by analyzing data from National Health and Nutrition Examination Surveys (NHANES). We particularly investigated the gender-specific associations between organophosphorus flame-retardant metabolites (mOPFRs), phthalates (mPAEs) and accumulated fat indexes from 2536 people. Aiding by Bayesian Kernel Machine Regression (BKMR), we found while co-exposure to mOPFRs and mPAEs was linked to general and abdominal obesity across the entire and gender-specific populations, a gender-specific fat distribution emerged. For women, urinary BDCPP and MBzP were linked to an increased subcutaneous fat index (SFI) [BDCPP OR: 1.12 (95% CI: 1.03-1.21), MBzP OR: 1.09 (95% CI: 1.01-1.18)], but not to visceral fat index (VFI). These metabolites had a combined linkage with SFI, with BDCPP (weighting 22.0%) and DPHP (weighting 31.0%) being the most influential in Quantile g-computation model (qgcomp) model. In men, BCEP exposure exclusively associated with the elevated VFI [OR: 1.14 (95% CI: 1.03-1.26)], a trend further highlighted in mixture models with BCEP as the predominant association. Intriguingly, only males displayed a marked correlation between these metabolites and insulin resistance in subpopulation. An attempted mediation analysis revealed that elevated C-reactive protein mediated 12.1% of the association between urinary BCEP and insulin resistance, suggesting a potential role of inflammation. In conclusion, the gender-specific fat distribution and insulin resistance that associated with mOPFRs represented the potential risk of these chemicals to man.

Effects of micro-nano plastics on the environmental biogeochemical cycle of nitrogen: A comprehensive review.

Micro-nano plastics (MNPs; size <5 mm), ubiquitous and emerging pollutants, accumulated in the natural environment through various sources, and are likely to interact with nutrients, thereby influencing their biogeochemical cycle. Increasing scientific evidences reveal that MNPs can affect nitrogen (N) cycle processes by affecting biotopes and organisms in the environmental matrix and MNPs biofilms, thus plays a crucial role in nitrous oxide (N2O) and ammonia (NH3) emission. Yet, the mechanism and key processes behind this have not been systematically reviewed in natural environments. In this review, we systematically summarize the effects of MNPs on N transformation in terrestrial, aquatic, and atmospheric ecosystems. The effects of MNPs properties on N content, composition, and function of the microbial community, enzyme activity, gene abundance and plant N uptake in different environmental conditions has been briefly discussed. The review highlights the significant potential of MNPs to alter the properties of the environmental matrix, microbes and plant or animal physiology, resulting in changes in N uptake and metabolic efficiency in plants, thereby inhibiting organic nitrogen (ON) formation and reducing N bioavailability, or altering NH3 emissions from animal sources. The faster the decomposition of plastics, the more intense the perturbation of MNPs to organisms in the natural ecosystem. Findings of this provide a more comprehensive analysis and research directions to the environmentalists, policy makers, water resources planners & managers, biologists, and biotechnologists to do integrate approaches to reach the practical engineering solutions which will further diminish the long-term ecological and climatic risks.