Emerging Chemicals in China:Historical Development,Current Situation,and Future Outlook

There has been a widespread international consensus to enhance the regulation of emerging chemicals in the 21st century.The substantial implementation work conducted over the past two decades has established a strong foundation for the control of emerging chemicals across the world.Nevertheless,distinct challenges confront countries and regions due to the ever-evolving diverse national conditions.China,as a developing nation and a major consumer of chemicals,is encountering particularly severe hurdles.This Perspective presents an overview encompassing the historical progression,current circumstances,and challenges confronted by China with regard to emerging chemicals.The central goal of these efforts is to prioritize the control of emerging chemicals and actively establish a monitoring mechanism.Additionally,it is necessary to develop a multistakeholder environmental risk prevention and control system.Ultimately,comprehensive efforts to enhance green substitution practices and active engagement of governance initiatives will be required.

Advancing Evaluation of Microplastics Thresholds to Inform Water Treatment Needs and Risks

Although human health impacts of microplastics are not well understood,concern regarding chemical contaminants retained on or within them is growing.Drinking water providers are increasingly asked about these risks,but strategies for evaluating them and the extent of treatment needed to manage them are currently lacking.Microplastics can potentially induce health effects if the concentration of contaminants adsorbed to them exceeds predetermined drinking water guidelines(e.g.,Maximum Contaminant Levels).The risk posed by microplastics due to adsorbed contaminants is difficult to determine,but a worst-case scenario can be evaluated by using adsorption capacity.Here,a“Threshold Microplastics Concentration”(TMC)framework is developed to evaluate whether waterborne microplastic concentrations can potentially result in the intake of regulated contaminants on/in microplastics at levels of human health concern and identify treatment targets for managing associated health risk.Exceeding the TMC does not indicate an immediate health risk;it informs the need for detailed risk assessment or further treatment evaluation to ensure particle removal targets are achieved.Thus,the TMC concept and framework provide an updateable,science-based screening tool to determine if there is a need for detailed risk assessment or treatment modification due to waterborne microplastics in supplies used for potable water production.

Unexpected Exposure Risks to Emerging Aromatic Amine Antioxidants and p‑Phenylenediamine Quinones to Residents:Evidence from External and Internal Exposure as Well as Hepatotoxicity Evaluation

Aromatic amine antioxidants(AAs),extensively used in rubber products,and their ozone-photolyzed product pphenylenediamine quinones(PPD-Qs)were found to be pervasive in various environments and with potential ecological and health risks.The relationship between external and internal exposure to these contaminants and their exposure risks to the general population remain poorly explored.Herein,dust−handwipe−urine samples(n=97 pairs)from families in Tianjin,China was collected for analyzing 20 AAs and 6 PPD-Qs(including self-synthesized emerging PPD-Qs).The median concentration ofΣ_(20)AAs(1310 ng/g,354 ng/m^(2),and 18.5 ng/mL,respectively)andΣ_(6)PPD-Qs(1645 ng/g,3913 ng/m^(2)and 3.76 ng/mL,respectively)in dust,handwipe,and urine samples indicated a non-negligible contamination of AAs and PPD-Qs in indoor environment.Notably,emerging DPPD-Q and DNPD-Q(oxidation products of DPPD and DNPD,respectively)were prominent,accounting for>90%of PPD-Qs.The correlation analysis and estimated daily intake(EDI)assessments indicated that neither dust ingestion nor dermal exposure may be the primary source of internal exposure to AAs and PPD-Qs in the general population,and other exposure pathways(e.g.,diet and inhalation)may exist.In vitro HepG2 cell experiments demonstrated that both PPD-Qs and PPDs may have potential exposure risk of hepatotoxicity.

Silica Nanoparticle Exposure Caused Brain Lesion and Underlying Toxicological Mechanism:Route-Dependent Bio-Corona Formation and GSK3βPhosphorylation Status

When nanoparticles(NPs)enter a physiological environment,they tend to adsorb proteins to form a so-called corona.A comprehensive understanding of the effect of protein corona on NPs’toxicity is required.Our previous study indicated that silica nanoparticles(SiO_(2)NPs)exposure with different routes resulted in distinct brain damage;however,an exact molecular mechanism of protein corona on the regulation of SiO_(2)NPsinduced damages needs further investigation.SiO_(2)NPs exposure via intravenous injection may encounter a protein-rich bio-matrix,which drives the adsorption of serum protein on their surface to form a stable SiO_(2)NPs@serum complex.On the contrary,SiO_(2)NPs exposure via intranasal instillation remained their original feature,due to a protein infertile environment of cerebrospinal fluid.Apparently,surface adsorption of proteinaceous substances altered inherent toxic behavior of SiO_(2)NPs.In addition,glycogen synthase kinase 3 beta(GSK3β)phosphorylate was found at different residues,which play an essential role in orchestrating apoptosis and autophagy threshold.Route-dependent corona formation determined GSK3βphosphorylation status and ultimately the toxic behavior of SiO_(2)NPs.This work presented the evidence of biocorona on the regulation of SiO_(2)NPs-induced toxicity,which can be used to guide risk assessment of environmental NPs.

Real-World Evidence of Multiple Air Pollutants and Mortality:A Prospective Cohort Study in an Oldest-Old Population

We aimed to report real-world longitudinal ambient air pollutants levels compared to WHO Air Quality Guidelines(AQG)and analyze multiple air pollutants’joint effect on longevity,and the modification and confounding from the climate and urbanization with a focus on the oldest-old.This study included 13,207 old participants with 73.3%aged 80 and beyond,followed up from 2008 to 2018 in 23 Chinese provinces.We used the Cox-proportional hazards model and quantile-based g-computation model to measure separate and joint effects of the multiple pollutants.We adjusted for climate and area economic factors based on a directed acyclic graph.In 2018,no participants met the WHO AQG for PM_(2.5) and O_(3),and about one-third met the AQG for NO_(2).The hazard ratio(HR)for mortality was 1.07(95%confidence interval-CI:1.05,1.09)per decile increase in all three pollutants,with PM_(2.5) being the dominant contributor according to the quantile-based g-computation model.In the three-pollutant model,the HRs(95%CI)for PM_(2.5) and NO_(2) were 1.27(1.25,1.3)and 1.08(1.05,1.12)per 10μg/m3 increase,respectively.The oldest-old experienced a much lower mortality risk from air pollution compared to the young-old.The mortality risk of PM_(2.5) was higher in areas with higher annual average temperatures.The adjustment of road density considerably intensified the association between NO_(2) and mortality.The ambient PM_(2.5) and O_(3) levels in China exceeded the WHO AQG target substantially.Multiple pollutants coexposure,confounding,and modification of the district economic and climate factors should not be ignored in the association between air pollution and mortality.

An In Vitro and In Vivo Study of Thyroid Disruption of 1,2-Bis(2,4,6-tribromophenoxy)ethane(BTBPE)�A Novel Brominated Flame Retardant

The novel brominated flame retardant,1,2-bis-(2,4,6-tribromophenoxy)ethane(BTBPE),is an emerging environ-mental pollutant with undetermined toxicity.We investigated how BTBPE causes thyroid endocrine disruption with integrated in silico,in vitro,and in vivo assays.In yeast two-hybrid and T-Screen assays,BTBPE interacted with zebrafish thyroid hormone receptors with binding energies weaker than the TR agonist-3,3′,5-Triiodo-L-thyronine(T3),and disrupted thyroid function as a thyroid receptor(TR)agonist.We examined the bioconcentra-tion,developmental toxicity,and thyroid endocrine disruption in zebrafish after a 14-day exposure to BTBPE(1,3,10μg/L).Thyroxine(T4)was lower in BTBPE-treated larvae,whereas corticotropin-releasing hormone(CRH)and thyroid-stimulating hormone(TSH)were higher.The gene transcription alterations along the hypothalamic-pituitary-thyroid(HPT)axis were observed.Furthermore,reduced locomotion suggested that BTBPE imparts developmental neurotoxicity at zebrafish early developmental stage.Establishing that BTBPE has thyroid endocrine-disrupting effects is an important step for understanding and managing BTBPE toxicity.

Comparison of Air Pollution−Mortality Associations Using Observed Particulate Matter Concentrations and Reanalysis Data in 33 Spanish Cities

Air pollution poses a health hazard in all countries.However,complete data on ambient particulate matter(PM)concentrations are not available in all world regions.Reanalysis data is already a valuable source of exposure data in epidemiological studies examining the relationship between temperature and health.Nevertheless,the performance of reanalysis data in assessing the short-term health effects of particulate air pollution remains unclear.We assessed the performance of CAMS reanalysis(EAC4)data from the European Centre for Medium-Range Weather Forecasts,compared with daily PM concentrations from field monitoring stations,to estimate short-term exposure to PM with an aerodynamic diameter less than 10μm(PM_(10))on daily mortality in 33 Spanish provincial capital cities using a two-stage time series regression design.The shape of the PM_(10)distribution varied substantially between PM observations and CAMS global reanalysis of atmospheric composition(EAC4)reanalysis data,with correlation ranging from 0.21 to 0.58.The pooled mortality risk for a 10μg/m^(3)increase in PM_(10)showed similar estimates using PM concentrations{relative risks(RR)=1.007,95%confidence intervals(95%CI)=[1.002,1.011]}and EAC4 reanalysis data(RR=1.011,95%CI=[1.006,1.015]).However,the city-specific PM_(10)beta coefficients estimated using PM concentrations and EAC4 reanalysis data showed a low correlation(r=0.22).The use of reanalysis data should be approached with caution when assessing the association between particulate matter air pollution and health outcomes,particularly in cities with small populations.

Perspective: Dimensions of Environment and Health in Arctic Communities

In the Arctic,environment and health are linked in myriad ways.A key emphasis has been on numerous long-lived contaminants in traditional foods,particularly marine mammals,and their well-documented impacts on human,animal and environmental health(“One health approach”).More recent concerns for Indigenous communities focus on the(side)effects of the switch to a modern,processed diet,which is accompanied by a loss of tradition and emerging health impacts.Furthermore,the availability of traditional foods is increasingly threatened by the impacts of climate change,which also causes the emergence and spread of new and old diseases,such as anthrax.Climate change,including thawing permafrost and new forest fire regimes,threatens the built environment and infrastructure.In particular,well-built,planned,and healthy housing is urgently needed,given that much time is spent indoors.Health care,particularly for remote and Indigenous communities,is sparse,and often ignores traditional knowledge and local languages.Indigenous communities in the Arctic continue to suffer from marginalization,resource colonization/extraction,and the impacts of racism.Recent examples of the green energy transition,such as in Norway,continue a pattern of ignoring Indigenous rights and lifestyles.Overall,the connection between environment and health in the Arctic is multifaceted and complex,and investigations and solutions ought to embrace an interdisciplinary and holistic approach toward improving Environmental and Human Health in the region.

Canine on the Couch:The New Canary in the Coal Mine for Environmental Health Research

Human health is intimately connected and tied to the health of our environment and ecosystem,with only a very small fraction of the risk for chronic diseases explained by genetics alone.Companion animals are prone to disease types that are shared with people,including cancers and endocrine disorders,reinforcing the thought that environmental factors contribute to the risks for chronic diseases.These factors include air and water pollution and the built environment.As such,there is increasing interest in pursuing research with companion animals,and specifically dogs,as sentinel species to inform comparative health assessments and identify risk factors for disease.Of the canine diseases for which environmental exposure research has been published,cancers have received the most attention.This review summarizes two main aspects of this comparative approach:(1)cancers that occur in dogs and which are similar to humans and(2)research investigating environmental exposures and health outcomes in dogs.The goal of this review is to highlight the diverse conditions in which pet dogs may provide unique perspectives and advantages to examine relationships between environmental exposures and health outcomes,with an emphasis on chemical pollution and cancer.Furthermore,this review seeks to raise awareness and stimulate discussion around the best practices for the use of companion animals as environmental health sentinels.

Probing the Affinity of Coronavirus with Contact Surfaces in Simulated Body Fluids

Transmission of viral pathogens has raised serious public health concerns,but the affinity and strength of viruses adhering to hightouch surfaces are not clear.We systematically investigated the propensities of a coronavirus,Murine hepatitis virus A59(MHV),adhering onto and releasing from four representative contact surfaces,silica,stainless steel,cellulose,and polystyrene,in simulated saliva and urine using quartz crystal microbalance with dissipation monitoring(QCM-D).We also quantified the interactions between MHV and contact surfaces using atomic force microscopy(AFM).Both initial adhesion rates and saturated adhesion mass of MHV were higher in urine buffer than in saliva buffer,which is attributed to the higher repulsions between the virus and surfaces in the presence of mucin.The maximum adhesion mass of MHV follows the order of stainless steel>silica>cellulose≈polystyrene in both urine and saliva buffers.Stainless steel and silica are surfaces with likely higher risks of virus contamination due to their highest maximum adhesion mass in both urine and saliva buffers and lower virus release percentages upon water rinse.The results of this study will provide insights into risk assessment and control of pathogens associated with contact surfaces.

Establishing a Multifaceted Comprehensive Maternity Cohort Facilitates Understanding of How Environmental Exposures Impact Perinatal Health

China’s“three-child policy”,implemented in response to population aging,has made the protection of maternal and infant health an urgent priority.In this environmental and medical big-data era,the Zhejiang Environmental and Birth Health Research Alliance(ZEBRA)maternity cohort was established with the aim of identifying risk factors for perinatal morbidity and mortality from the perspectives of both observational epidemiology and experimental etiology.Compared with conventional birth cohorts,the inclusion of a maternity cohort allows greater scope for research and places an emphasis on maternal health.In particular,it allows us to focus on pregnant women with a history of pregnancy-related illnesses and those planning to have a second or third child.There are currently many pressing issues in perinatal health,including the risk associations between exogenous together with endogenous factors and the occurrence of perinatal abnormalities,pregnancy complications,and adverse pregnancy outcomes.It is crucial to explore the interaction between environmental exposures and genetic factors affecting perinatal health if we are to improve it.It is also worthwhile to assess the feasibility of the early stage prediction of major perinatal abnormalities.We hope to study this in the ZEBRA cohort and also seek nationwide and international collaborations to establish a multicenter cohort consortium,with the ultimate goal of contributing epidemiological evidence to literature and providing evidence-based insights for global maternal and child healthcare.

An Overview of Adverse Outcome Pathway Links between PM_(2.5)Exposure and Cardiac Developmental Toxicity

Fine particulate matter(PM_(2.5))is a significant risk factor for birth defects.As the first and most important organ to develop during embryogenesis,the heart’s potential susceptibility to PM_(2.5)has attracted growing concern.Despite several studies supporting the cardiac developmental toxicity of PM_(2.5),the diverse study types,models,and end points have prevented the integration of mechanisms.In this Review,we present an adverse outcome pathway framework to elucidate the association between PM_(2.5)-induced molecular initiating events and adverse cardiac developmental outcomes.Activation of the aryl hydrocarbon receptor(AhR)and excessive generation of reactive oxygen species(ROS)were considered as molecular initiating events.The excessive production of ROS induced oxidative stress,endoplasmic reticulum stress,DNA damage,and inflammation,resulting in apoptosis.The activation of the AhR inhibited the Wnt/β-catenin pathway and then suppressed cardiomyocyte differentiation.Impaired cardiomyocyte differentiation and persistent apoptosis resulted in abnormalities in the cardiac structure and function.All of the aforementioned events have been identified as key events(KEs).The culmination of these KEs ultimately led to the adverse outcome,an increased morbidity of congenital heart defects(CHDs).This work contributes to understanding the causes of CHDs and promotes the safety evaluation of PM_(2.5).

Thyroid Hormone Biomonitoring:A Review on Their Metabolism and Machine-Learning Based Analysis on Effects of Endocrine Disrupting Chemicals

The thyroid is an essential endocrine organ in human body,and thyroid hormones(THs)are pivotal signaling molecules and mediators in various physiological processes.THs,particularly in their free form,play a critical role in regulating body temperature and in the metabolism of lipid and glucose,making the maintenance of TH levels crucial for human health.THs undergo a series of metabolic processes,producing TH metabolites(THMs).THMs are significant in endocrine regulation,such as 3,5-diiothyronine(3,5-T2)and 3-iodothyronamine(3-T1AM),which exhibit activities akin to THs.The production and distribution of THMs are intricately linked to the function of specific organs and tissues,highlighting the need for advanced research into the determination and mechanisms of THMs in body.Exposure to endocrine disrupting chemicals(EDCs)can significantly affect the levels of thyroid stimulating hormone(TSH)and THs.This review utilizes machine learning to analyze epidemiological data,identifying potential EDCs that pose risks of hyperthyroidism and hypothyroidism.Additionally,it delves into the toxicological mechanisms of these EDCs,examining their effects on TH production,binding processes,related proteins,and metabolic enzymes.This approach effectively bridges the gap between epidemiological studies and toxicological researches,laying the groundwork for future research trends.By integrating epidemiological studies with machine learning,this review offers insightful perspectives on the potential risks associated with chemical exposure and underscores the necessity for further research in understanding the impact of EDCs on TH metabolism and TH-related health effects.

Effect of Elevated Temperatures on Inflammatory Cytokine Release:An In Vitro and Population-Based Study

Extreme high temperatures in the summer have become a global concern,and their risks to the inflammatory system have been largely unknown.Here we appraised the exposure risks of summer heatwaves by comparing the sera cytokine levels in healthy individuals under high and normal temperatures.In addition,we established a cell model with a 1.5°C temperature increase to investigate the regulatory mechanisms of temperature-related cytokines.Our results suggest that elevated temperatures enhance the release of interleukin-6(IL-6)and interleukin-8(IL-8)via the aryl hydrocarbon receptor(AhR)pathway and augment the proinflammatory effects of other factors.This suggests that we may have underestimated the impact of high temperatures on the health of individuals beyond just mortality rates.Moreover,seemingly minor temperature increases of just 1.5℃ can still pose a challenge to cells.

Cross-Cutting Approach for the Characterization of Microbial Emerging Hazards in Agriculture Settings from Circular Economy-Driven Wastewater Streams

The recycling of biowaste from municipal wastewater treatment plants(WWTPs)in agriculture represents a circular economy-driven source of water and nutrients to support food system sustainability.However,biowaste may represent the source of emerging hazards of anthropogenic and animal origin that can transfer from agricultural soils to related food production,posing a risk to consumers’health,as in the case of outbreaks due to the consumption of ready-to-eat leafy vegetables contaminated with pathogenic E.coli.From this perspective,we propose a combined strategy based on both classical methods and culture-independent metagenomics approaches to identify microbial hazards relevant to foodborne diseases in WWTP-related biowastes.The virulence genes targeted by real-time PCR,performed before and after the enrichment of the raw samples,may represent a proxy for the viability of pathogens,the presence of which is then confirmed via classical microbiological methods.Bioinformatics analysis of shotgun metagenomic sequences could assess the presence of genes associated with resistance to specific antimicrobials followed by phenotypic confirmation via cultivation of the raw samples in the presence of the predicted molecules.Bacterial 16S rDNA analysis supports biowaste traceability based on their taxonomic composition.This strategy would support a“One Health”Action based on a cross-cutting assessment of emerging food-borne risks along the food chain.

Associations of Gestational Exposure to Air Pollution and Polycyclic Aromatic Hydrocarbons with Placental Inflammation

Restricted fetal growth(RFG)is a leading contributor to perinatal mortality and has been associated with gestational exposure to air pollution,such as fine particulate matter(PM_(2.5)),nitrogen dioxide(NO2),and polycyclic aromatic hydrocarbons(PAHs).This study examines the association between trimester-specific and weekly means of air pollution throughout gestation and placental inflammatory markers at delivery.In a prospective cohort study of 263 pregnant women in Rochester,NY,we measured interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)in placental tissue and estimated gestational exposure to PM_(2.5)and NO_(2)using a high-resolution spatial-temporal model.Exposure to PAHs was estimated using urinary 1-hydroxypyrene(1-OHP)concentrations collected once per trimester.Using distributed lag models with a penalized spline function,each interquartile range(2.6μg/m^(3))increase in PM_(2.5)concentration during gestational weeks 6−11 was associated with decreased placental IL-6 levels(−22.2%,95%CI:−39.0%,−0.64%).Using multiple linear regression models,each interquartile range increase of 1-OHP was associated with an increase in TNF-αin the first trimester(58.5%,95%CI:20.7%,74.2%),third trimester(22.9%,95%CI:0.04%,49.5%),and entire pregnancy(29.6%,95%CI:3.9%,60.6%).Our results suggest gestational exposure to air pollution may alter the inflammatory environment of the placenta at delivery.

Discharges of Wastewater Treatment Plants Needed Further Monitoring to Minimize Potential Risk of Entamoeba and Blastocystis for Public Health

The protozoan parasites Entamoeba histolytica and Blastocystis hominis are responsible for causing human amebiasis and hominis infections,respectively.These infections are highly prevalent and are often linked to waterborne diseases.Due to the absence of regulations for monitoring these protozoa at the discharge points of wastewater treatment plants(WWTPs),the effluents reaching surface waters contribute to waterborne transmission.This underscores the significance of the removal capacities of WWTPs in reducing the spread of these infectious parasites.Therefore,this study examined five different types of WWTPs in Ankara,Turkey,over a year to assess their capacities to remove E.histolytica and B.hominis.The seasonal abundances of genes specific to these protozoa in both the influents and effluents of each WWTP were measured using a quantitative polymerase chain reaction.The reduction in the number of protozoan rDNA copies between the influent and effluent samples was evaluated as the removal capacity,expressed in log10 reduction(LRV)values.The results elucidated that the removal of E.histolytica and B.hominis was highly affected by the process used.Membrane bioreactor systems displayed the highest removal capacity with LRV>3.Therefore,discharges of WWTPs with other processes could need further monitoring to minimize the potential risk for public health.

Tracking Source Variations of Inhalation Cancer Risks and Ozone Formation Potential in Hong Kong over Two Decades(2000−2020)Using Toxic Air Pollutant Monitoring Data

Toxic air pollutants(TAPs)are a class of airborne chemicals known or suspected to cause serious health issues.This study,applying positive matrix factorization and inhalation unit risk estimates of TAPs,quantifies the changes in significant sources contributing to inhalation cancer risks(ICRs)from 2000 to 2020 in Hong Kong,China.Total ICR decreased from 1701 to 451 cases per million between 2000−2004 and 2016−2020,largely attributed to the reduction in diesel particulate matter(DPM),gasoline and solvent use-related volatile organic compounds(VOCs),and coal/biomass combustion-related polycyclic aromatic hydrocarbons and metal(loid)s.The regional contribution of VOCs associated with industrial and halogenated solvent sources increased substantially,representing the largest non-DPM ICR contributor(37%)in 2016−2020,stressing the need for a more comprehensive risk evaluation across the fast-growing and densely populated Greater Bay Area(GBA).ICRs in Hong Kong and the GBA will likely remain over 100 cases per million by 2050.The contributions to ozone formation potential of VOC/carbonyl sources were quantified,which show a notable shift from being solvent/gasoline-dominant in 2000−2004 to being more evenly shared by various sources in 2016−2020.Establishing a similar TAP monitoring network in the GBA is anticipated to provide the monitoring data needed to facilitate the development of more informed air quality management strategies.

Prenatal Environmental Antibiotic Exposure and Autism Spectrum Disorder Symptoms in Children at 3 Years of Age:Findings from the Ma’anshan Birth Cohort Study

ABSTRACT:Antibiotic exposure during pregnancy may affect the neurodevelopment of children,but biomonitoring-based population studies on this class of new pollutants are lacking.We conducted a prospective birth cohort study of 2860 mother−child pairs,measured the urinary concentrations of 41 antibiotics and their two metabolites over three trimesters,and assessed children’s autism spectrum disorder(ASD)symptoms at 3 years of age.We examined the associations between prenatal antibiotic exposure and children’s ASD symptoms.The least absolute shrinkage and selection operator regression screened for Tetracycline and Ofloxacin as important predictors of ASD symptoms.Modified Poisson regression models revealed that maternal Tetracycline exposure throughout pregnancy increased the risk of ASD symptoms(RR:1.66,95%CI:1.14,2.40).Maternal Tetracycline exposure during the first(RR:1.74,95%CI:1.13,2.68)and third trimesters(RR:1.86,95%CI:1.16,3.00)increased the risk of ASD symptoms in boys,and Ofloxacin exposure during the first trimester(RR:1.47,95%CI:1.07,2.02)increased the risk of ASD symptoms in girls.No dose-dependent relationships between prenatal antibiotic exposure and ASD symptoms were validated by restricted cubic splines.Prenatal exposure to Tetracycline and Ofloxacin may increase the risk of ASD symptoms in children,and the first and third trimesters might be the key windows.

PFOA/PFOS Facilitated Intestinal Fatty Acid Absorption by Activating the PPARα Pathway:Insights from Organoids Model

Perfluorooctanoic acid(PFOA)and perfluorooctanesulfonate(PFOS)continue to be extensively present in the natural environment and seriously threaten human health.The intestinal tract is the primary organ of PFOA/PFOS exposure due to the consumption of contaminated food and drinking water.However,it remains unclear how PFOA/PFOS affects intestinal function and overall health.The aim of this study was to investigate the influence of PFOA/PFOS on the absorption of fatty acids in the intestine and the underlying mechanisms using three-dimensional(3D)intestinal organoids.Our results showed that PFOS,but not PFOA,could significantly enhance the fatty acid uptake capacity without obvious damage to the organoids.Furthermore,PFOS markedly reduced the protein levels of ChgA in enteroendocrine cells,but with no observed impact on aldolase B+enterocytes.Mechanistically,exposure to PFOS induced the activation of the peroxisome proliferator-activated receptor(PPAR)αpathway in intestinal organoids,with enhanced expression of PPARαtarget genes associated with fatty acid metabolism,such as Fabp1 and Cd36(fatty acid transporter genes),Acox1 and Pdk4(fatty acid oxidation genes),and Plin2 and Plin3(lipid droplet synthesis genes).These data suggest that PFOS have the potential to affect the absorption function of the intestinal epithelium through the PPARαpathway,and its effect is much stronger than that of PFOA.Our findings also highlight that organoids can be used as a valuable model for conducting toxicological research on environmental chemicals.