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.

Health risk assessment of heavy metal(loid)s in road dust via dermal exposure pathway from a low latitude plateau provincial capital city: The importance of toxicological verification.

The human health risk assessment through the dermal exposure of metal (loid)s in dust from low latitude and high geological background plateau cities was largely unknown. In this study, the road dust samples were harvested from a typical low-latitude plateau provincial capital city Kunming, Southwest China. The total concentration and dermal bioaccessibility of heavy metal (loid)s in road dust were determined, and their health risks as well as cytotoxicity on human skin keratinocytes were also assessed. The average concentrations of As (28.5 mg/kg), Cd (2.65 mg/kg), Mn (671 mg/kg), and Zn (511 mg/kg) exceeded the soil background values. Arsenic had the highest bioaccessibility after 2 h (3.79%), 8 h (4.24%), and 24 h (16.6%) extraction. The dermal pathway when bioaccessibility is considered has a higher hazard quotient than the conventional method using total metal(loid)s in the dust. In addition, toxicological verification suggested that the dust extracts suppressed the cell viability, increased the reactive oxygen species (ROS) level and DNA damage, and eventually activated the mitochondria-mediated apoptosis pathway, evidenced by the upregulation of Caspase-3/9, Bax, and Bak-1. Cadmium was positively correlated with the mRNA expression of Bax. Taken together, our data indicated that both dermal bioaccessibility and cytotoxicity should be considered for accurate human skin health risk assessment of heavy metal(loid)s in road dust, which may provide new insight for accurate human health risk assessment and environmental management.

A large-scale survey of urinary parabens and triclocarban in the Chinese population as well as the influencing factors and health risks.

Parabens and triclocarban are widely applied as antimicrobial preservatives in foodstuffs, pharmaceuticals, cosmetics, and personal care products. However, few studies have been conducted on large-scale biomonitoring of parabens and triclocarban in the Chinese general population. In the present study, there were 1157 urine samples collected from 26 Chinese provincial capitals for parabens and triclocarban measurement to evaluate the exposure levels, spatial distribution, and influencing factors, as well as associated health risks in the Chinese population. The median concentrations of Σparabens and triclocarban were 14.0 and 0.03 µg/L, respectively. Methyl paraben was the predominant compound. Subjects in western China were more exposed to parabens, possibly due to climate differences resulting in higher consumption of personal care products. Subjects who were female, aged 18-44 years, or had a higher education level were found to have higher paraben concentrations. The frequency of drinking bottled water was positively associated with paraben exposure. The assessment of health risk based on urinary paraben concentrations indicated that 0.8 % of the subjects had a hazard index exceeding one unit, while Monte Carlo analysis suggested that 3.6 % of the Chinese population exposure to parabens had a potential non-carcinogenic risk. This large-scale biomonitoring study will help to understand the exposure levels of parabens and triclocarban in the Chinese general population and provide supporting information for government decision-making.

Bisphenol chemicals in colostrum from Shanghai, China during 2006-2019: Concentration, temporal variation, and potential influence on birth parameters.

Bisphenol A (BPA) and its alternatives bisphenol S (BPS) and bisphenol F (BPF) are identified as endocrine disruptors that have negative impacts on infant growth. Their temporal variations in human milk and potential effects on fetal growth are not well known. In this study, colostrum collecting at four time points between 2006 and 2019 and paired urine in 2019 from Shanghai, China, were analyzed for eight bisphenols. The total concentrations in colostrum in 2019 were up to 3.43 ng/mL, with BPA being dominant, followed by BPS and BPF. BPA levels in colostrum noticeably decreased from 2010 to 2013. Additionally, obvious percentage changes in bisphenols were observed in 2019. The BPA concentrations in paired colostrum and urine were not significantly correlated. High levels of BPA in colostrum were linked to a significant reduction in birth head circumference in 2019 (p = 0.031). BPA and BPS in colostrum might have similar negative effect on fetal growth in 2019, but these effects were generally non-significant. Further studies are needed to testify the potential impact. The hazard indexes for infants in the first week of life were below 1, suggesting no obvious health risks. However, the high contribution from BPA still warrants further attention.

Effects of extreme precipitation on bacterial communities and bioaerosol composition: Dispersion in urban outdoor environments and health risks.

Concerns about contaminants dispersed by seasonal precipitation have grown due to their potential hazards to outdoor environments and human health. However, studies on the crucial environmental factors influencing dispersion changes in bacterial communities are limited. This research adopted four-season in situ monitoring and sequencing techniques to examine the regional distribution profiles of bioaerosols, bacterial communities, and risks associated with extreme snowfall versus rainfall events in two monsoon cities. In the early-hours of winter snowfall, airborne cultivable bioaerosol concentrations were 4.1 times higher than the reference exposure limit (500 CFU/m3). The concentration of ambient particles (2.5 µm) exceeded 24,910 particles/L (97 µg/m3), positively correlating with the prevalence of cultivable bioaerosols. These bioaerosols contained cultivable bacterial species such as pathogenic Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Escherichia coli. Bioaerosol concentrations increased by 53.0% during 50-mm snow extremes. Taxonomic analysis revealed that Pseudomonas, Staphylococcus, and Veillonella were the most abundant bacterial taxa in the initial snowmelt samples during winter precipitation. However, their abundance decreased by 87.6% as snowing continued (24 h). Reduced water base cation concentration also led to a 1.15-fold increase in the Shannon index, indicating a similar yet heightened bacterial diversity. Seasonally, Pedobacter and Massilia showed higher relative abundance (25% and 18%, respectively), presenting increased bacterial transmission to the soil. Furthermore, Pseudomonas was identified in 60% of spring snowstorm samples, suggesting long-distance dispersal of pathogenic bacteria. When these atmospheric aerosol particles carrying biological entities (0.65-1.1 µm) penetrated human alveoli, the calculated hazard ratio was 0.55, which as observed in inhalation exposures. Consequently, this study underscores the risk of seasonal precipitation-enhanced ambient bacterial transmission.

Modeling and evaluation of biomechanics and hemodynamic based on patient-specific small intracranial aneurysm using fluid-structure interaction.

BACKGROUND AND OBJECTIVE: Rupture of small intracranial aneurysm (IA) often leads to the development of highly fatal clinical syndromes such as subarachnoid hemorrhage. Due to the patient specificity of small IA, there are many difficulties in evaluating the rupture risk of small IA such as multiple influencing factors, high clinical experience requirements and poor reusability. METHODS: In this study, clinical methods such as transcranial doppler (TCD) and magnetic resonance imaging (MRI) are used to obtain patient-specific parameters, and the fluid-structure interaction method (FSI) is used to model and evaluate the biomechanics and hemodynamics of patient-specific small IA. RESULTS: The results show that a spiral vortex stably exists in the patient-specific small IA. Due to the small size of the patient-specific small IA, the blood flow velocity still maintains a high value with maximum reaching 3 m/s. The inertial impact of blood flow and vortex convection have certain influence on hemodynamic and biomechanics parameters. They cause three high value areas of WSSM on the patient-specific small IA with maximum of 180 Pa, 130 Pa and 110 Pa, respectively. They also cause two types of WSS concentration points, positive normal stress peak value areas and negative normal stress peak value areas to appear. CONCLUSION: This paper found that the factors affecting hemodynamic parameters and biomechanical parameters are different. Unlike hemodynamic parameters, biomechanical parameters are also affected by blood pressure in addition to blood flow velocity. This study reveals the relationship between the flow field distribution and changes of patient-specific small IA, biomechanics and hemodynamics.

Transcriptome-based approach to identify mechanisms underlying locomotor abnormality induced by decabromodiphenyl ethane in zebrafish larvae.

The brominated flame retardant decabromodiphenyl ethane (DBDPE) has been extensively used following restrictions on BDE-209 and thus, been frequently detected in aquatic environment. However, information on impact of DBDPE on fish development and the potential mechanisms remains scarce. In present study, developing zebrafish were employed as a study model. Embryos were exposed until 5 d to DBDPE at concentrations of 0, 3, 30, and 300 µg/L, following which the impact on larval development was investigated. DBDPE bioaccumulation and locomotor hyperactivity were observed in developing zebrafish exposed to DBDPE. Transcriptome and bioinformatics analyses indicated that pathways associated with cardiac muscle contraction and retinol metabolism were notably affected. The mechanisms of DBDPE to induce locomotor abnormality were further investigated by analyzing levels of retinol and retinol metabolites, eye and heart histology, heart rates, and ATPase activity. Our results indicate that locomotor hyperactivity observed in larvae exposed to DBDPE results from abnormal heartbeat, which in turn is attributable to inhibition of Na+/K+-ATPase activity. Furthermore, DBDPE did not change larval eye histology and contents of retinoid (retinol, retinal, and retinoic acid). This study provides insight into the mechanisms underlying DBDPE-induced developmental toxicity and highlights the need for addressing the environmental risks for aquatic organisms.

Phthalate metabolites in breast milk from mothers in Southern China: Occurrence, temporal trends, daily intake, and risk assessment.

The extensive production and use of phthalates means that these compounds are now ubiquitous in the environment and various biota, which raises concerns about potential harmful health effects. In this study, phthalate metabolites (mPAEs) were measured in breast milk (n = 100) collected from mothers of southern China between 2014 - 2022. Of the nine target mPAEs, five were detected in all of the samples, including mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and mono-(2-ethylhexyl) phthalate (MEHP). The total levels of mPAEs in breast milk ranged from 4.76 to 51.6 ng/mL, with MiBP and MnBP being the predominant isomers (MiBP + MnBP > 48.3%). Increasing trends were observed in MMP (5.7%/year) and MEHP (7.1%/year) levels during the study period, while a decreasing trend were observed in MiBP (-6.6%/year); no clear temporal trends were found for the other metabolites and total mPAE levels. The results indicate that exposure to phthalates is still prevalent in southern China. Breastfeeding was found to contribute to estimated daily phthalate intakes of 0.383-6.95 µg/kg-bw/day, suggesting insignificant health risks to infants based on dietary exposure. However, the increasing exposure to MMP and MEHP calls for more research into the possible sources and potential risks.

Development of multi-generation lower respiratory tract model and insights into the transport and deposition characteristics of inhalable particles.

Airborne particles can spread quickly and enter human respiratory system via inhalation, causing chronic diseases, even cancer. Although recent studies have informed of toxicity of various pollutants, understanding the transport and deposition characteristics of particles in lower respiratory tract is still challenging. The current study proposes a novel model to simulate flow field change from the entrance of lower respiratory tract to pulmonary acinus, while studying particle transport and deposition characteristics. This model for lower respiratory tract with several bronchial extensions containing virtual pulmonary acinus is calculated using computational fluid dynamics and dynamics mesh. The results showed that in the first 10 generations of the lower respiratory tract, vortices and gravity interfered with particles' trajectory, affecting particle deposition distribution. For the first to the tenth-generation respiratory tract, coarse particles were deposited throughout almost the whole respiratory tract model. In contrast, ultrafine particles did not deposit in the higher-generation respiratory tract. The particle enrichment ability of various lobes was uneven with three particle deposition fraction variation patterns. Virtual pulmonary acinus influenced particle deposition and distribution because of vortex ring's trapped ability during expansion and contraction. This new attempt to build a virtual pulmonary acinus model to simulate particle deposition effects in human respiratory system may provide a reference for studying the toxicities of inhalable particles in the exposed human body.

A review on edible insects in China: Nutritional supply, environmental benefits, and potential applications.

This review explored the potential of edible insects to address the challenges of malnutrition and food security. Although grain production in China has met the Food and Agriculture Organization standards, the shortage of protein supply is still a big issue. Moreover, expanding livestock farming is considered unsustainable and environmentally unfriendly. Edible insects have become an alternative with higher sustainable and ecological properties. There are 324 species of insects currently consumed in China, and they have high nutritional value, with a rich source of protein and unsaturated fatty acids. Insect farming provides numerous benefits, including green feeds for livestock, poultry, and aquaculture, sustainable organic waste management, as well as industrial and pharmaceutical raw materials. The food toxicological evaluations conducted in China indicated that edible insects are safe for general consumption by the Chinese, but allergies and other related food safety issues should not be ignored. Consumer acceptance is another barrier to overcome, with different schemas between China and Western countries. More research on the potential functions of edible insects and their product development may enhance their acceptance in China. Overall, incorporating edible insects into our diet is a promising solution to address challenges related to protein supply and food security. To ensure safety and sustainability, appropriate legislation, quality regulations, large-scale insect farms, and acceptable processing techniques are necessary. Moreover, more scientific research and social awareness are required to promote the culture and utilization of edible insects in China.

Emission characteristics of (halogenated) polycyclic aromatic hydrocarbons during printed circuit board combustion and estimated emission intensity of a typical e-waste dismantling site in South China.

The pollution of polycyclic aromatic hydrocarbons (PAHs) and halogenated PAHs (Cl/Br-PAHs) caused by electronic waste dismantling activities have attracted considerable attention. The present study investigated the emissions and formation of PAHs and Cl/Br-PAHs based on the combustion of printed circuit boards simulating electronic waste dismantling process. The emission factor of ΣPAHs was 648 ± 56 ng/g, which was much lower than that of ΣCl/Br-PAHs (8.80 × 104 ± 9.14 × 103 ng/g). From 25 to 600 °C, the emission rate of ΣPAHs reached a sub-peak of 7.39 ± 1.85 ng/(g•min) at 350 °C, then increased gradually with the fastest rate of 19.9 ± 21.8 ng/(g•min) at 600 °C, whereas that of ΣCl/Br-PAHs was the fastest at 350 °C with a rate of 597 ± 106 ng/(g•min), then decreased gradually. The present study suggested that the formation pathways of PAHs and Cl/Br-PAHs are by de novo synthesis. Low molecular weight PAHs were readily partitioned into gas and particle phases, whereas high molecular weight fused PAHs were only detected in oil phase. However, the proportion of Cl/Br-PAHs in particle and oil phases were different from that of gas phase, whereas similar to that of the total emission. In addition, PAH and Cl/Br-PAH emission factors were used to estimate the emission intensity of pyrometallurgy project in Guiyu Circular Economy Industrial Park, and it was shown that approximately 1.30 kg PAHs and 176 kg Cl/Br-PAHs would be emitted annually. This study revealed that Cl/Br-PAHs would be formed by de novo synthesis, and for the first time provided the emission factors of Cl/Br-PAHs during the heat treatment process of printed circuit board, as well as estimated the contribution of pyrometallurgy, a new electronic waste recovery technology, to environmental Cl/Br-PAH pollution, which provides potential scientific information for governmental decision-making on the control of Cl/Br-PAHs.

Clinical Reasoning: A 17-Year-Old Girl With Progressive Cognitive Impairment.

A 17-year-old girl presented with a long history of cognitive impairment, personality and behavioral changes, dysarthria, and paroxysmal lower-extremity weakness. She was initially suspected of having mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes because of stroke-like symptoms, such as episodic lower-extremity weakness, as well as abnormal brain MRI findings of generalized cerebral atrophy, extensive high-intensity lesions in the cortex and subcortical white matter on fluid-attenuated inversion recovery images, decreased N-acetyl aspartate/creatine ratio, and a lactate peak in the focal area on spectrum images. However, there were no relatives with similar presentations in the family of the patient. The whole mitochondrial genome and whole-exome sequencing did not suggest pathogenic mutations, and no abnormalities were found in the blood or CSF lactate levels. In this case, we detail the clinical manifestations, diagnostic workup, and imaging findings. This case highlights the importance of assessing cognitive function and the relevant differential diagnoses in an adolescent with cognitive impairment.

Distribution of phthalate metabolites, benzophenone-type ultraviolet filters, parabens, triclosan and triclocarban in paired human hair, nail and urine samples.

In this study, the distribution of nineteen ingredients of personal care product (PCPs), including seven metabolites of phthalates (mPAEs), five benzophenone-type ultraviolet filters (BPs), and seven antimicrobial agents (AAs), were investigated in paired human hair, nail and urine samples. The median concentrations of ΣmPAEs, ΣBPs and ΣAAs were 135, 2.76 and 179 ng/g in hair, 37.3, 2.95 and 297 ng/g in nails, and 345, 4.03 and 50.1 ng/mL in urine, respectively. Mono-methyl phthalate (49%), 2,4-dihydroxybenzophenone (45%) and triclosan (71%) were the most abundant mPAE, BP and AA in hair samples, respectively, and had similar abundance in nail samples. In contrast, mono-n-butyl phthalate (45%), 4-hydroxy benzophenone (29%) and methyl paraben (54%) were the predominant mPAE, BP and AA in urine samples, respectively. Significant differences in the concentrations of some target compounds were observed between male and female but inconsistent across different matrices. Moreover, most compounds with significant correlations had quite different correlation coefficients in each matrix. No significant correlations were found between hair, nail and urine samples for most of the target analytes. These results suggest these analytes have matrix-specific distribution, and it is necessary to use multiple matrices to comprehensively assess the risk of ingredients of PCPs to human health.

A large-scale nationwide study of urinary phenols in the Chinese population.

Bisphenol A (BPA), tetrabromobisphenol A (TBBPA), and their substitutes are commonly used in everyday products. However, large-scale internal exposure levels of them in China, the factors influencing on them, and the associated health risks were not systematically investigated still. In the present study, there were 1157 morning urine samples collected from residents of 26 provincial capitals in China for the measurement of BPA and seven bisphenol analogues, as well as TBBPA and its substitutes, i.e., tetrachlorobisphenol A and 4,4'-sulphonylbis(2,6-dibromophenol). The concentrations of Σ8bisphenols and Σ3TBBPAs ranged from

Maternal transfer of resorcinol-bis(diphenyl)-phosphate perturbs gut microbiota development and gut metabolism of offspring in rats.

Resorcinol-bis(diphenyl)-phosphate (RDP), an emerging organophosphate flame retardant, is increasingly used as a primary alternative for decabromodiphenyl ether and is frequently detected in global environmental matrices. However, the long-term effects of its exposure to humans remain largely unknown. To investigate its intergenerational transfer capacity and health risks, female Sprague Dawley rats were orally exposed to RDP from the beginning of pregnancy to the end of the lactation period. The RDP content, gut microbiota homeostasis, and metabolic levels were determined. RDP accumulation occurred in the livers of maternal rats and offspring and increased with exposure time. 16S rRNA gene sequencing showed that exposure to RDP during pregnancy and/or lactation significantly disrupted gut microbiota homeostasis, as evidenced by decreased abundance and diversity. In particular, the abundance of Turicibacter, Adlercreutzia, and YRC22 decreased, correlating significantly with glycollipic metabolism. This finding was consistent with the reduced levels of short-chain fatty acids, the crucial gut microbial metabolites. Meanwhile, RDP exposure resulted in changes in gut microbiome-related metabolism. Nine critical overlapping KEGG metabolic pathways were identified, and the levels of related differential metabolites decreased. Our results suggest that the significant adverse impacts of RDP on gut microbiota homeostasis and metabolic function may increase the long-term risks related to inflammation, obesity, and metabolic diseases.

Emission and gas-particle partitioning characteristics of atmospheric halogenated and organophosphorus flame retardants in decabromodiphenyl ethane-manufacturing functional areas.

The emission and gas-particle partitioning characteristics in various functional areas of production lines are still unknown. However, flame-retardant manufacturing activities are the primary emission source of flame retardants. Thus, fine particles and gases were investigated in three functional areas of a decabromodiphenyl ethane production line, i.e., polybrominated diphenyl ethers (PBDEs), novel brominated flame retardants (NBFRs), dechlorane plus (DPs), and organophosphorus flame retardants (OPFRs) in a flame-retardant manufacturing factory. High levels of PBDEs (8.02 × 103-4.16 × 104 pg/m3), NBFRs (6.05 × 103-1.92 × 105 pg/m3), and DPs (89.5-5.20 × 103 pg/m3) were found in various functional areas, suggesting manufacturing activities were a primary emission source. In contrast, OPFRs were derived from long-range transport or other non-industrial sources. Varied concentrations of PBDEs, NBFRs, and DPs were observed in different production lines, higher in the reaction zone area than others. As the predominant compounds, decabromodiphenyl ether, decabromodiphenyl ethane, syn-DP, and tris(chloropropyl) phosphate accounted for 54.7%, 89.3%, 93.4%, and 34.7% of PBDEs, NBFRs, DPs, and OPFRs, respectively. Three models were used to predict the gas-particle partitioning of the halogenated flame retardants emitted from manufacturing activities. The Li-Jia Empirical Model predicted the gas-particle partitioning behavior well. This research shows that the adsorption-desorption process of the halogenated flame retardants between the gaseous and particulate phases did not reach equilibrium.

Polybrominated diphenyl ethers and bromophenols in paired serum, hair, and urine samples of e-waste dismantlers: Insights into hair as an indicator of endogenous exposure.

Polybrominated diphenyl ethers (PBDEs) are important pollutants during dismantling activities of electronic waste (e-waste) in China due to its large production and usage. Bromophenols (BPs), which are a kind of flame retardants and diphenyl ether bond cleavage metabolites of PBDEs, are often neglected in the assessment of human exposure to e-waste. Herein, 22 PBDEs and 19 BPs were determined in paired serum, hair, and urine samples collected from workers and residents of a typical e-waste dismantling site in southern China. Both PBDE and BP congeners were more frequently detected in hair than serum and urine samples. The medians of ΣPBDEs and ΣBPs were 350 and 547 ng/g dw in hair internal (hair-In) of occupational population, respectively, which were significantly higher than non-occupational population. However, a non-significant difference was found in levels of ΣPBDEs and ΣBPs in serum and urine between occupational and non-occupational populations, suggesting that hair analysis could easily differentiate between the exposure intensities of PBDEs and BPs to populations than serum and urine analyses. Moreover, levels of BPs in hair-In were 1-2 orders of magnitude higher than those in hair external (hair-Ex), while a non-significant difference was found in the levels of PBDEs. This result indicated that BPs might have originated from endogenous contribution. Notably, as the predominant congeners, the level of 2,4,6-tribromophenol (2,4,6-TBP) in hair-In was 3-8 times higher than that of BDE-209, while level of 2,4,6-TBP in hair-Ex was 1-3 times lower than that of BDE-209. Furthermore, in vivo experiments performed on Sprague-Dawley rats following a 28-day oral treatment with BDE-209 and 2,4,6-TBP verified that endogenous accumulation of 2,4,6-TBP in hair could be attributed to the metabolism of BDE-209 and exposure to 2,4,6-TBP. In conclusion, compared with PBDEs, biomonitoring phenolic compounds or metabolites with hair could better reflect human endogenous exposure.

Proliferation toxicity and mechanism of novel mixed bromine/chlorine transformation products of tetrabromobisphenol A on human embryonic stem cell.

Mixed bromine/chlorine transformation products of tetrabromobisphenol A (ClyBrxBPAs) are mixed halogenated-type compounds recently identified in electronic waste dismantling sites. There are a lack of toxicity data on these compounds. To study their development toxicity, the proliferation toxicity was investigated using human embryonic stem cells (hESC) exposed to the lowest effective dose of two ClyBrxBPA analogues (2-chloro-2',6-dibromobisphenol A and 2,2'-dichloro-6-monobromobisphenol A). For comparison, tetrabromobisphenol A, 2,2',6-tribromobisphenol A, and bisphenol A were also assessed. It was observed that ClyBrxBPAs inhibited hESCs proliferation in a concentration-dependent manner. The cell bioaccumulation efficiency of ClyBrxBPAs was higher than that of tetrabromobisphenol A. Also, ClyBrxBPAs were more toxic than tetrabromobisphenol A, with 2,2'-dichloro-6-monobromobisphenol A exhibiting the most potent toxicity. Furthermore, flow cytometry and oxidative stress results showed that increased reactive oxygen species raised the degree of apoptosis and reduced DNA synthesis. Metabolomics analysis on the effect of ClyBrxBPAs on metabolic pathway alteration showed that ClyBrxBPAs mainly interfered with four metabolic pathways related to amino acid metabolism and biosynthesis. These results provide an initial perspective on the proliferation toxicity of ClyBrxBPAs, indicating development toxicity in children.

Associated long-term effects of decabromodiphenyl ethane on the gut microbial profiles and metabolic homeostasis in Sprague-Dawley rat offspring.

Decabromodiphenyl ethane (DBDPE) as a widely used brominated flame retardant is harmful to human health due to its toxicity, including cardiovascular toxicity, reproductive toxicity, and hepatotoxicity. However, the knowledge of the long-term effects and structural and metabolic function influence on gut microbiota from DBDPE exposure remains limited. This study was mainly aimed at the gut microbiome and fecal metabolome of female rats and their offspring exposed to DBDPE in early life. 16S rRNA gene sequencing demonstrated that maternal DBDPE exposure could increase the α-diversity of gut microbiota in immature offspring while decreasing the abundance of Bifidobacterium, Clostridium, Muribaculum, Escherichia, and Lactobacillus in adult offspring. The nonmetric multidimensional scaling showed a consistency in the alternation of ß-diversity between pregnant rats and their adult offspring. Furthermore, the short-chain fatty acids produced by gut microbiota dramatically increased in adult offspring after maternal DBDPE exposure, revealing that DBDPE treatment disrupted the gut microbial compositions and altered the gut community's metabolic functions. Untargeted metabolomics identified 41 differential metabolites and seven metabolic pathways between adult offspring from various groups. Targeted metabolomic showed that maternal high dose DBDPE exposure obviously decreased the level of glutathione, taurine, and l-carnitine in their adult offspring, which verified the correlation between weight loss and amino acid metabolites. An interesting link between some gut bacteria (especially the Firmicutes) and fecal metabolites demonstrated the shifts in gut microbiota may drive the metabolic process of fecal metabolites. The current findings provide new insight into long-term effects on human health.

Associations between urinary monohydroxylated polycyclic aromatic hydrocarbons and unexplained recurrent spontaneous abortion and health risk assessment in a large case-control study in China.

Polycyclic aromatic hydrocarbons (PAHs) are a group of environmental endocrine disruptors with known carcinogenic, reproductive, and developmental toxicity. Important knowledge gaps remain regarding the relationship between PAH exposure and unexplained recurrent spontaneous abortion (URSA). In the present study, twelve monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) were measured in the urine of 413 URSA cases and 434 controls. The main OH-PAHs measured in this study were monohydroxy metabolites of naphthalene, followed by fluorene and phenanthrene. After the creatinine correction, the median concentration of urinary OH-PAHs in the control group (17.4 µg/g Creatinine) was higher than that in the case group (14.2 µg/g Creatinine). There was no positive relationship between PAH exposure and URSA using binary logistic regression analysis. Among 847 Chinese women of childbearing age, residential environment, type of drinking water, and education level were the influencing factors of PAH exposure. The health risk assessment showed that over 98% of women had a carcinogenic risk with carcinogenic risk values above the acceptable level (10-6). Although this large-scale case-control study did not observe an association between PAH exposure and URSA, more attention should be paid to the high carcinogenic risk due to PAH exposure in women of reproductive age.