An activatable fluorescence probe for rapid detection and in situ imaging of ß-galactosidase activity in cabbage roots under heavy metal stress.

ß-Galactosidase (ß-gal), an enzyme related to cell wall degradation, plays an important role in regulating cell wall metabolism and reconstruction. However, activatable fluorescence probes for the detection and imaging of ß-gal fluctuations in plants have been less exploited. Herein, we report an activatable fluorescent probe based on intramolecular charge transfer (ICT), benzothiazole coumarin-bearing ß-galactoside (BC-ßgal), to achieve distinct in situ imaging of ß-gal in plant cells. It exhibits high sensitivity and selectivity to ß-gal with a fast response (8 min). BC-ßgal can be used to efficiently detect the alternations of intracellular ß-gal levels in cabbage root cells with considerable imaging integrity and imaging contrast. Significantly, BC-ßgal can assess ß-gal activity in cabbage roots under heavy metal stress (Cd2+, Cu2+, and Pb2+), revealing that ß-gal activity is negatively correlated with the severity of heavy metal stress. Our work thus facilitates the study of ß-gal biological mechanisms.

Global quantification of emerging and legacy per- and polyfluoroalkyl substances in indoor dust: Levels, profiles and human exposure.

This study investigated the occurrence and distribution of per- and polyfluoroalkyl substances (PFASs) in house dust samples from six regions across four continents. PFASs were detected in all indoor dust samples, with total median concentrations ranging from 17.3 to 197 ng/g. Among the thirty-one PFAS analytes, eight compounds, including emerging PFASs, exhibited high detection frequencies in house dust from all six locations. The levels of PFASs varied by region, with higher concentrations found in Adelaide (Australia), Tianjin (China), and Carbondale (United States, U.S.). Moreover, PFAS composition profiles also differed among regions. Dust from Australia and the U.S. contained high levels of 6:2 fluorotelomer phosphate ester (6:2 diPAP), while perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were predominant in other regions. Furthermore, our results indicate that socioeconomic factors impact PFAS levels. The assessment of human exposure through dust ingestion and dermal contact indicates that toddlers may experience higher exposure levels than adults. However, the hazard quotients of PFASs for both toddlers and adults were below one, indicating significant health risks are unlikely. Our study highlights the widespread occurrence of PFASs in global indoor dust and the need for continued monitoring and regulation of these chemicals.

Polylactic Acid Microplastics Do Not Exhibit Lower Biological Toxicity in Growing Mice Compared to Polyvinyl Chloride Microplastics.

Biomicroplastics (BMPs) will be produced during bioplastic degradation (i.e., polylactic acid), although bioplastics have been widely used for food packaging. Like conventional microplastics (MPs), BMPs would be mistakenly ingested into the body through diet or drinking water, but their health risks in vivo are poorly understood. Here, we deeply compared the toxicity difference between irregularly shaped polylactic acid (PLA-MPs, 16-350 µm) and polyvinyl chloride (PVC-MPs, 40-300 µm) MPs in growing mice. After six weeks of exposure, PLA-MP exposure resulted in more severe inhibition of the mice's weight gain than PVC-MPs did. Both PLA- and PVC-MPs significantly elevated the levels of oxidative stress. Moreover, significant changes including altered transcriptional profiles and significantly differentially expressed genes in liver and colon transcription levels were observed in the PVC- and PLA-MP groups. Compared with PVC-MPs, PLA-MPs have a stronger effect on lipid metabolism and digestive systems. PLA-MPs also caused gut microbiota dysbiosis, significantly interfering with the relative abundance of microbiota and altering microbial diversity. These findings indicated the toxicities of PLA-MPs in growing mice were not significantly reduced compared to PVC-MPs, which would also provide new insights for re-examining bioplastic safety.

A large Stokes shift NIR fluorescent probe for visual monitoring of mitochondrial peroxynitrite during inflammation and ferroptosis and in an Alzheimer's disease model.

The excessive formation of peroxynitrite (ONOO-) in mitochondria has been implicated in various pathophysiological processes and diseases. However, owing to short emission wavelengths and small Stokes shifts, previously reported fluorescent probes pose significant challenges for mitochondrial ONOO- imaging in biological systems. In this study, a near-infrared (NIR) fluorescent probe, denoted as DCO-POT, is designed for the visual monitoring of mitochondrial ONOO-, displaying a remarkable Stokes shift of 170 nm. The NIR fluorophore of DCO-CHO is released by DCO-POT upon the addition of ONOO-, resulting in off-on NIR fluorescence at 670 nm. This phenomenon facilitates the high-resolution confocal laser scanning imaging of ONOO- generated in biological systems. The practical applications of DCO-POT as an efficient fluorescence imaging tool are verified in this study. DCO-POT enables the fluorometric visualization of ONOO- in organelles, cells, and organisms. In particular, ONOO- generation is analyzed during cellular and organism-level (zebrafish) inflammation during ferroptosis and in an Alzheimer's disease mouse model. The excellent visual monitoring performance of DCO-POT in vivo makes it a promising tool for exploring the pathophysiological effects of ONOO-.

Genomic epidemiological analysis of county-scale Yersinia pestis spread pattern over 50 years in a Southwest Chinese prefecture.

Plague, one of the most devastating infectious diseases in human history, is caused by the bacterium Yersinia pestis. Since the 1950s, the Dehong Dai-Jingpo Autonomous Prefecture (DH) in Yunnan Province, China, has recorded plague outbreaks that have resulted in 1,153 human cases and 379 deaths. The genetic diversity and transmission characteristics of Y. pestis strains in this region remain unknown. Here, we performed high-resolution genomic epidemiological analysis of 175 Y. pestis strains isolated from five counties and 19 towns in DH between 1953 and 2007. Phylogenetic analysis revealed that most DH strains were located in lineage 1.ORI2, which could be further subdivided into seven sub-phylogroups (SPG1-SPG7). The dominant sub-phylogroups of Y. pestis in DH varied during different periods and presented a population shift. Genomic evidence showed that plague might have emerged from the southwest of DH (e.g., Longchuan or Ruili counties) or its bordering countries, and subsequently spread to the northeast in multiple waves between 1982 and 2007. Our study infers a fine-scale phylogeny and spread pattern of the DH Y. pestis population, which extends our knowledge regarding its genetic diversity and provides clues for the future prevention and control of plague in this region.

Large polystyrene microplastics results in hepatic lipotoxicity in mice.

Like small microplastics (MPs), recent studies reveal that large MPs could cause health risks in mice, even if they are not enriched in tissues. However, potential hepatoxicity following large MPs exposure and the underlying mechanisms have not been thoroughly investigated. In the present study, we explored the disruption of hepatic lipid metabolism and potential underlying toxic mechanisms in mice caused by long-term exposure to large polystyrene MPs (40-100 µm) based on a multi-omic approach. After 21 weeks of feeding foods containing MPs (50 and 500 mg/kg food), lipidomic revealed that environmentally relevant and higher doses MP exposures resulted in significant changes in a total of 20 lipid classes. Ceramide (Cer) and dihydroceramide (dhCer) were significantly reduced, while cholesteryl ester (CE), lysoalkylphosphatidylcholine (LPCO), lysophosphatidylethanolamine (LPE) and total glyceride (TG) were all elevated by MPs. The transcriptomic and other physiological data suggested that the potential toxic mechanisms may be related to disorders of fatty acid and cholesterol synthesis and metabolism disorders, and transporting of TG. Our findings demonstrate the hepatic lipotoxicity following exposure to environmentally relevant and higher doses of large MPs, calling for future research and management of the environmental risks of MPs with relatively large particle sizes.

Neonatal exposure to bisphenol analogues disrupts genital development in male mice.

The public concern and governmental regulations on bisphenol A (BPA) have stimulated the development and production of alternative analogues to replace BPA in a myriad of applications. Given the endocrine disrupting activities of BPA and potentially other analogues, the present study investigated and compared the effects of neonatal exposure to BPA, BPB, BPE, BPF, and BPS on the genital development in male mice. Pups were injected subcutaneously on the right shoulder in the mornings of postnatal days P0.5, P2, P4, and P6, resulting in a low dose of 0.05 µg/g body weight (bw)/day and a high dose of 10 µg/g bw/day. Mice were sacrificed at predetermined time and evaluated for gene expression levels (3 days after birth or P3), steroid hormone levels (P5), and morphological changes (P21). The results demonstrated that BPA, BPB, BPE, or BPF significantly shortened glans penis length and anogenital distance, while BPS didn't. Testis weight and anogenital distance were also significantly affected by BPA, BPE or BPF. The results also revealed that bisphenol analogues exposure significantly reduced testosterone levels, and altered the expression levels of developmental genes networks in developing penis of mice. Our data demonstrate that selected bisphenol analogues may possess similar endocrine disrupting effects compared to BPA, and exposure to these analogues could affect reproductive development of male mice. This raises the concern on the environmental and health safety of bisphenol analogues applied as industrial BPA replacements.

[Biomechanical analysis of four internal fixations for Pauwels â ¢ femoral neck fractures with defects].

OBJECTIVE: To investigate the biomechanical characteristics of different internal fixations for Pauwels type Ⅲ femoral neck fracture with defect, and provide reference for the treatment of femoral neck fracture. METHODS: Three-dimensional (3D) finite element models of femoral neck fractures were established based on CT images, including fracture and fracture with defects. Four internal fixations were simulated, namely, inverted cannulated screw(ICS), ICS combined with medial buttress plate, the femoral neck system (FNS) and FNS combined with medial buttress plate. The von Mises stress, model stiffness and fracture displacements of fracture models under 2 100 N axial loads were measured and compared. RESULTS: When femoral neck fracture was fixed by ICS and FNS, the peak stress was mainly concentrated on the surface of the screw near the fracture line, and the peak stress of FNS is higher than that of ICS;When the medial buttress plate was combined, the peak stress was increased and transferred to medial buttress plate, with more obvious of ICS fixation. For the same fracture model, the stiffness of FNS was higher than that of ICS. Compared with femoral neck fracture with defects, fracture model showed higher stiffness in the same internal fixation. The use of medial buttress plate increased model stiffness, but ICS increased more than FNS. The fracture displacement of ICS model exceeded that of FNS. CONCLUSION: For Pauwels type Ⅲ femoral neck fracture with defects, FNS had better biomechanical properties than ICS. ICS combined with medial buttress plate can better enhance fixation stability and non-locking plate is recommended. FNS had the capability of shear resistance and needn't combine with medial buttress plate.

Nonphthalate Plasticizers in House Dust from Multiple Countries: An Increasing Threat to Humans.

Along with the restrictions of phthalate esters (PAEs), a variety of nonphthalate plasticizers (NPPs) have been increasingly used for industrial needs. Knowledge remains limited on the environmental occurrences, fate, and human exposure risks of many emerging NPPs. In this study, we investigated a suite of 45 NPPs along with the major PAEs in house dust from five regions in the Asia-Pacific region and the United States. The findings clearly demonstrated ubiquitous occurrences of many NPPs in the home environment, particularly acetyl tributyl citrate (ATBC), tricapryl trimellitate (TCTM), trioctyl trimellitate (TOTM), glycerol monooleate (GMO), methyl oleate (MO), and diisobutyl adipate (DiBA). The median total concentrations of NPPs ranged from 17.8 to 252 µg/g in the study regions, while the mean ratios of ΣNPPs to ΣPAEs ranged from 0.19 (Hanoi) to 0.72 (Adelaide). Spatial differences were observed not only for the chemical abundances but also for the composition profiles and the hazard quotient (HQ) prioritization of individual chemicals. Although the current exposure may unlikely cause significant health risks according to the HQ estimation, potential exposure risks cannot be overlooked, due to the lack of appropriate toxic threshold data, the existence of additional exposure pathways, and possible cocktail effects from coexisting NPPs and PAEs.

Sorption of representative organic contaminants on microplastics: Effects of chemical physicochemical properties, particle size, and biofilm presence.

Microplastic pollution has attracted mounting concerns worldwide. Microplastics may concentrate organic and metallic contaminants; thus, affecting their transport, fate and organismal exposure. To better understand organic contaminant-microplastic interactions, our study explored the sorption of selected polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), α-hexabromocyclododecane (α-HBCDD), and organophosphate flame retardants (OPFRs) on high-density polyethylene (HDPE) and polyvinylchloride (PVC) microplastics under saline conditions. Sorption isotherms determined varied between chemicals and between HDPE and PVC microplastics. Log Freundlich sorption coefficients (Log KF) for the targeted chemicals ranged from 2.01 to 5.27 L kg-1 for HDPE, but were significantly lower for PVC, i.e., ranging from Log KF data (2.84 - 8.58 L kg-1). Significant correlations between chemicals' Log KF and Log Kow (octanol-water partition coefficient) indicate that chemical-dependent sorption was largely influenced by their hydrophobicity. Sorption was evaluated using three size classes (< 53, 53 - 300, and 300 - 1000 µm) of lab-fragmented microplastics. Particle size did not significantly affect sorption isotherms, but influenced the time to reach equilibrium and the predicted maximum sorption, likely related to microplastic surface areas. The presence of biofilms on HDPE particles significantly enhanced contaminant sorption capacity, indicating more complex sorption dynamics in the chemical-biofilm-microplastic system. Our findings offer new insights into the chemical-microplastic interactions in marine environment.

Emerging Plasticizers in South China House Dust and Hand Wipes: Calling for Potential Concern?

Following regulations on legacy plasticizers, a large variety of industrial chemicals have been employed as substitutes to manufacture consumer products. However, knowledge remains limited on their environmental distributions, fate, and human exposure risks. In the present work, we screened for a total of 34 emerging plasticizers in house dust from South China and matched hand wipes collected from volunteers (n = 49 pairs). The results revealed a frequent detection of 27 emerging plasticizers in house dust, with the total concentrations reaching a median level of 106 700 ng/g. Thirteen of them had never been investigated by any environmental studies prior to our work, which included glycerol monooleate (median: 61 600 ng/g), methyl oleate (16 400 ng/g), butyl oleate (411 ng/g), 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate (341 ng/g), 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (105 ng/g), isopropyl myristate (154 ng/g), di(2-ethylhexyl) sebacate (69.1 ng/g), triisononyl trimellitate (64.4 ng/g), as well as a few others. Emerging plasticizers were also frequently detected in hand wipes, with a median total level of 4680 ng, indicating potential exposure via hand-to-mouth contact. Several chemicals, including acetyl tributyl citrate, tributyl citrate, di-n-butyl maleate, isopropyl myristate, and isopropyl palmitate, exhibited significant correlations between dust and hand wipe. However, other plasticizers did not follow this pattern, and the chemical compositional profiles differed between dust and hand wipe, suggesting chemical-specific sources and exposure pathways. Although the estimation of daily intake (EDI) indicated no substantial risks through dust ingestion or hand-to-mouth transfer of emerging plasticizers, continuous monitoring is needed to explore whether some of the important plasticizers are safe replacements or regrettable substitutions of the legacy ones.

Occupational exposure to rare earth elements: Assessment of external and internal exposure.

Our study investigated occupational exposure to rare earth elements (REEs) in a major REE processing plant from North China by assessing both external exposure and internal exposure in the workers. An exposure group, including 50 workers in the processing plant, and a control group, including 50 workers from a liquor factory located 150 km away from the exposure group, were recruited in the study. Portable air sampler was employed to accurately measure individual exposure to the external environment, and the data demonstrating significantly higher contamination in the REE processing plant compared with the control group (i.e., 87.5 versus 0.49 µg/m3 of ΣREEs). Blood concentrations were also significantly higher in the exposure group (3.47 versus 2.24 µg/L of ΣREEs). However, the compositional profiles of REEs resembled between the exposure and control group in blood or air particles, indicating the influence of mining/processing activities on the surrounding regions. External exposure in the occupational environment appeared to significantly influence internal REE exposure in the REE processing workers. Some other sociodemographic and occupational factors, including the residence time and the type of work, could also influence occupational exposure to selected REEs. Our data clearly demonstrated the highly elevated REE contamination in both working environment and human bodies compared with the control subjects, raising the critical need for better assessing the health risks from occupational REE exposure and efficient management for occupational hazards.

Low-level alternative halogenated flame retardants (AHFRs) in indoor dust from Adelaide, South Australia decades since national legislative control on polybrominated diphenyl ethers (PBDEs).

Since commercial polybrominated diphenyl ethers (PBDEs) have been globally banned or restricted in 2000s, alternative halogenated flame retardants (AHFRs) appear increasingly dominant over PBDEs in many countries/regions. In this study, low levels of AHFRs were unexpectedly observed in the indoor dust from Adelaide, South Australia. Anti-dechlorane plus (anti-DP) was the most frequently detected AHFR with a median concentration of 1.28 ng/g, while other AFHRs were less detected (detection frequency < 50%). The levels of ΣPBDEs (496 ng/g, median) and ΣAHFRs (160 ng/g) and the ratio of ΣAHFRs/ΣPBDEs (0.32) were much lower than those investigated in Australian indoor dust previously. The findings were different to the trend for PBDEs and AHFRs from other countries over the past two decades. No significant correlation was determined between DP and PBDE congeners, indicating their different sources in dust. The human exposure assessment suggested that dust ingestion was the predominant pathway of PBDEs and AHFRs exposure for toddlers, while dermal absorption may be the dominant pathway for adults. The estimated daily intake (EDI) suggested low health risks via dust ingestion and dermal contact for general populations in Adelaide. This study contributes to the knowledge on region-specific FR contamination in indoor environments and related human exposure risk.

Quantitative fatty acid signature analysis (QFASA) in indoor dust: Implication for tracking indoor source accumulation of organic pollutant exposure.

Indoor dust has been used as a proxy for estimating human indoor pollutant exposure risks, yet source identification remains challenging. This study tentatively investigated whether quantitative fatty acid signature analysis (QFASA) of dust, could be applied to indicate sources and their respective contributions for a major class of indoor organic pollutants organophosphate flame retardants (OPFRs). We observed significant correlations between OPFR concentrations and lipid content (p < 0.05) in house dusts. Using 15 signature fatty acids (FAs) in various indoor sources and the QFASA model, we found that clothing (39.1% in Australia and 36.5% in China) was the predominant contributing vector of dust OPFR followed by cooking oil and pet hair. Among these sources, clothing materials were proposed to be important vectors introducing organic pollutants to the indoor environment. Our QFASA contribution estimation analyses allowed for accurate prediction of most OPFR concentrations in clothing, validating our findings that clothing materials may serve as important carrier for OPFRs in indoor migration. This is the first study attempting to identify sources of organic pollutants using QFASA in an indoor setting and will provide important insight into the transfer of organic pollutants in indoor environment.

[Characterization and Exposure Risk Assessment of Non-phthalate Plasticizers in House Dust from Guangzhou].

Although non-phthalate plasticizers are widely used in various consumer products as substitutes for phthalates, currently little is known about their environmental occurrence and the risks of human exposure. To characterize the pollution and human exposure risk in indoor environments, house dust samples collected from 83 households in Guangzhou were analyzed for twelve typical non-phthalate plasticizers. Results showed that dioctyl terephthalate (DEHT), trioctyl trimellitate (TOTM), acetyl lemon tributyl ester (ATBC), heptylnonyl adipate, di(2-ethylhexyl) adipate, and trioctyl trimellitate were detected in all samples. The total concentrations of non-phthalate plasticizers ranged from 22.4 to 615 µg ·g-1 with a median of 101 µg ·g-1. DEHT had the highest concentrations (9-487 µg ·g-1), followed by TOTM (0.3-87 µg ·g-1) and ATBC (1.7-50 µg ·g-1). Daily intakes via dust ingestion for adults and children were estimated based on the dust concentrations. The total daily intake of children was 367 ng ·(kg ·d)-1, which was 8-9 times higher than that of adults[43 ng ·(kg ·d)-1]. Further risk assessment through the hazard quotient approach showed that the exposure of adults and children to non-phthalic plasticizers via dust ingestion was within an acceptable risk range.

"Novel" Synthetic Antioxidants in House Dust from Multiple Locations in the Asia-Pacific Region and the United States.

Synthetic antioxidants represent a complex group of additive chemicals broadly used in consumer products. While traditional antioxidants such as 2,6-di-tert-butyl-4-methylphenol (BHT) have been well studied, a variety of "novel" antioxidants have emerged with extensive applications but received much less attention. Our study aimed to explore a suite of 34 emerging antioxidants in house dust from four different regions, including Guangzhou (China), Adelaide (Australia), Carbondale (Illinois), and Hanoi (Vietnam). The results revealed broad occurrence of several rarely investigated chemicals in house dust across regions, including triethylene glycol bis(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate (AO245), 2,6-di-tert-butyl-4-(dimethylamino)methylphenol (AO4703), 2,2'-thiene-2,5-diylbis(5-tert-butyl-1,3-benzoxazole) (BBOT), 1,3-diphenylguanidine (DPG), 2,4-bis(1,1-dimethylethyl)phenol (2,4DtBP), and 2,6-bis(1,1-dimethylethyl)phenol (2,6DtBP). In particular, DPG exhibited a median concentration of 5030-11 400 ng/g in house dust from the studied regions except for Hanoi (305 ng/g), generally 1 order of magnitude greater than that of BHT (890-1060 ng/g) and dominating the compositional profiles of antioxidants. Estimated intake of target antioxidants by toddlers via dust ingestion, even under the high exposure scenario, was determined to be 2-4 orders of magnitude lower than the reference doses of selected antioxidants. However, potential risks from long-term exposure to a cocktail of antioxidants under environmentally relevant concentrations merit further investigations due to insufficient knowledge on the sources, fate, and toxicokinetics of these chemicals to date.

Prenatal exposure to atrazine induces cryptorchidism and hypospadias in F1 male mouse offspring.

The main objective of the present study was to determine whether prenatal exposure to atrazine could affect testicle descent and penile masculinization. Atrazine has been demonstrated with a variety of endocrine disrupting activities and reproductive toxicities. However, the effects of prenatal atrazine exposure on male offspring's genital malformation, such as hypospadias and cryptorchidism, remain poorly understood. In this study, pregnant ICR mice were gavaged from gestational day 12.5-16.5 with different doses of atrazine. Although no sign of systemic toxicity was observed in F1 male pups, prenatal exposure to 100 mg/kg/day atrazine affected penile morphology, urethral meatus position and descent of testis, and reduced anogenital distance and penile size in postnatal day 21 F1 male pups. The comparative study with an androgen receptor (AR) antagonist vinclozolin suggested that these effects of atrazine on male genital development may not be through antagonism of AR. The results also revealed that atrazine exposure significantly reduced maternal serum testosterone levels, decreased AR nuclear translocation, and altered the expression levels of developmental gene networks in developing penis of mice. Atrazine exposure also affected the expression of insulin-like 3 (Insl3) and steroidogenic gene expression in developing reproductive tract. Therefore, our data indicate that prenatal atrazine exposure can induce hypospadias in F1 mice, likely through disruption of testosterone production, decreasing genomic androgen action, and then altering expression of developmental genes during sexual differentiation. Our data also suggest that prenatal atrazine exposure can induce cryptorchidism in F1 mice, possibly through down regulation of Insl3.

Emerging and legacy per- and polyfluoroalkyl substances in house dust from South China: Contamination status and human exposure assessment.

Our study investigated a large variety of per- and polyfluoroalkyl substances (PFASs) in house dust collected from Guangzhou, South China during 2015-2018. The perfluorobutane sulfonic acid (PFBS) exhibited the highest median concentration (17.6 ng/g), followed by linear perfluorooctanoic acid (L-PFOA; 4.8 ng/g), linear perfluorooctane sulfonic acid (L-PFOS; 4.2 ng/g), 6:2 fluorotelomer phosphate diester (6:2 diPAP; 3.4 ng/g), perfluorodecanoic acid (PFDA; 1.2 ng/g) and perfluoroundecanoic acid (PFUdA; 1.2 ng/g), and 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA; 1.1 ng/g). Total concentrations of PFASs (median: 53 ng/g) were generally within the 25-50 percentile of the concentration range reported in global studies. However, our samples exhibited composition profiles different from those reported in many other regions. Analysis based on this and previous studies revealed that the compositions in house dust from East Asia, North America, and Europe exhibit a region-specific pattern. This may indicate region-specific market demands, application patterns, as well as associated human exposure risks. Exploration of dwelling characterizations suggested that renovation history appeared to be a significant factor influencing PFAS concentrations in house dust, although other factors may exist and play a role. Estimation of daily intakes via dust ingestion and dermal contact indicates low exposure risks from these two pathways. However, the PFAS chemical-specific biological effects, possible mixture effects, as well as additional exposure pathways, imply that the risk from indoor PFAS exposure should not be overlooked.