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

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

Arsenic, cadmium, lead, antimony bioaccessibility and relative bioavailability in legacy gold mining waste.

Bioaccessibility and relative bioavailability of As, Cd, Pb and Sb was investigated in 30 legacy gold mining wastes (calcine sands, grey battery sands, tailings) from Victorian goldfields (Australia). Pseudo-total As concentration in 29 samples was 1.45-148-fold higher than the residential soil guidance value (100 mg/kg) while Cd and Pb concentrations in calcine sands were up to 2.4-fold and 30.1-fold higher than the corresponding guidance value (Cd: 20 mg/kg and Pb: 300 mg/kg). Five calcine sands exhibited elevated Sb (31.9-5983 mg/kg), although an Australian soil guidance value is currently unavailable. Arsenic bioaccessibility (n = 30) and relative bioavailability (RBA; n = 8) ranged from 6.10-77.6% and 10.3-52.9% respectively. Samples containing > 50% arsenopyrite/scorodite showed low As bioaccessibility (<20.0%) and RBA (<15.0%). Co-contaminant RBA was assessed in 4 calcine sands; Pb RBA ranged from 73.7-119% with high Pb RBA associated with organic and mineral sorbed Pb and, lower Pb RBA observed in samples containing plumbojarosite. In contrast, Cd RBA ranged from 55.0-67.0%, while Sb RBA was < 5%. This study highlights the importance of using multiple lines of evidence during exposure assessment and provides valuable baseline data for co-contaminants associated with legacy gold mining activities.

Remediation options to reduce bioaccessible and bioavailable lead and arsenic at a smelter impacted site - consideration of treatment efficacy.

In this study, smelter contaminated soil was treated with various soil amendments (ferric sulfate [Fe2(SO4)3], triple superphosphate [TSP] and biochar) to determine their efficacy in immobilizing soil lead (Pb) and arsenic (As). In soils incubated with ferric sulfate (0.6M), gastric phase Pb bioaccessibility was reduced from 1939 ± 17 mg kg-1 to 245 ± 4.7 mg kg-1, while intestinal phase bioaccessibility was reduced from 194 ± 25 mg kg-1 to 11.9 ± 3.5 mg kg-1, driven by the formation of plumbojarosite. In TSP treated soils, there were minor reductions in gastric phase Pb bioaccessibility (to 1631 ± 14 mg kg-1) at the highest TSP concentration (6000 mg kg-1) although greater reductions were observed in the intestinal phase, with bioaccessibility reduced to 9.3 ± 2.2 mg kg-1. Speciation analysis showed that this was primarily driven by the formation of chloropyromorphite in the intestinal phase following Pb and phosphate solubilization in the low pH gastric fluid. At the highest concentration (10% w/w), biochar treated soils showed negligible decreases in Pb bioaccessibility in both gastric and intestinal phases. Validation of bioaccessibility outcomes using an in vivo mouse assay led to similar results, with treatment effect ratios (TER) of 0.20 ± 0.01, 0.76 ± 0.11 and 1.03 ± 0.10 for ferric sulfate (0.6M), TSP (6000 mg kg-1) and biochar (10% w/w) treatments. Results of in vitro and in vivo assays showed that only ferric sulfate treatments were able to significantly reduce As bioaccessibility and bioavailability with TER at the highest application of 0.06 ± 0.00 and 0.14 ± 0.04 respectively. This study highlights the potential application of ferric sulfate treatment for the immobilization of Pb and As in co-contaminated soils.

Alcohol consumption promotes arsenic absorption but reduces tissue arsenic accumulation in mice.

Alcohol consumption alters gut microflora and damages intestinal tight junction barriers, which may affect arsenic (As) oral bioavailability. In this study, mice were exposed to arsenate in the diet (6 µg/g) over a 3-week period and gavaged daily with Chinese liquor (0.05 or 0.10 mL per mouse per day). Following ingestion, 78.0% and 72.9% of the total As intake was absorbed and excreted via urine when co-exposed with liquor at daily doses of 0.05 or 0.10 mL, significantly greater than when As was supplied alone (44.7%). Alcohol co-exposure significantly altered gut microbiota but did not significantly alter As biotransformation in the intestinal tract or tissue. Significantly lower relative mRNA expression was observed for genes encoding for tight junctions in the ileum of liquor co-exposed mice, contributing to greater As bioavailability attributable to enhanced As absorption via the intestinal paracellular pathway. However, As concentration in the liver, kidney, and intestinal tissue of liquor-treated mice was decreased by 24.4%-42.6%, 27.5%-38.1%, and 28.1%-48.9% compared to control mice. This was likely due to greater renal glomerular filtration rate induced by alcohol, as suggested by significantly lower expression of genes encoding for renal tight junctions. In addition, in mice gavaged daily with 0.05 mL liquor, the serum antidiuretic hormone level was significantly lower than control mice (2.83 ± 0.59 vs. 5.40 ± 1.10 pg/mL), suggesting the diuretic function of alcohol consumption, which may facilitate As elimination via urine. These results highlight that alcohol consumption has a significant impact on the bioavailability and accumulation of As.

Dietary Galactooligosaccharides Supplementation as a Gut Microbiota-Regulating Approach to Lower Early Life Arsenic Exposure.

Prebiotics may stimulate beneficial gut microorganisms. However, it remains unclear whether they can lower the oral bioavailability of early life arsenic (As) exposure via regulating gut microbiota and altering As biotransformation along the gastrointestinal (GI) tract. In this study, weanling mice were exposed to arsenate (iAsV) via diet (7.5 µg As g-1) amended with fructooligosaccharides (FOS), galactooligosaccharides (GOS), and inulin individually at 1% and 5% (w/w). Compared to As exposure control mice, As concentrations in mouse blood, liver, and kidneys and As urinary excretion factor (UEF) were reduced by 43.7%-74.1% when treated with 5% GOS. The decrease corresponded to a significant proliferation of Akkermansia and Psychrobacter, reduced percentage of inorganic arsenite (iAsIII) and iAsV by 47.4% and 65.4%, and increased proportion of DMAV in intestinal contents by 101% in the guts of mice treated with 5% GOS compared to the As control group. In contrast, FOS and inulin either at l% or 5% did not reduce As concentration in mouse blood, liver, and kidneys or As UEF. These results suggest that GOS supplementation may be a gut microbiota-regulating approach to lower early life As exposure via stimulating the growth of Akkermansia and Psychrobacter and enhancing As methylation in the GI tract.

Chronic Exposure to Drinking Water As, Pb, and Cd at Provisional Guideline Values Reduces Weight Gain in Male Mice via Gut Microflora Alterations and Intestinal Inflammation.

Few studies have investigated the long-term effect of exposure to arsenic (As), lead (Pb), and cadmium (Cd) via drinking water at the provisional guideline values on gut microflora. In this study, male and female mice were exposed to water As, Pb, or Cd at 10, 10, or 5 µg L-1 for 6 months. At the end of the exposure, the net weight gain of male mice exposed to As and Pb (9.91 ± 1.35 and 11.2 ± 1.50 g) was significantly (p < 0.05) lower compared to unexposed control mice (14.1 ± 3.24 g), while this was not observed for female mice. Relative abundance of Akkermansia, a protective gut bacterium against intestinal inflammation, was reduced from 29.7% to 3.20%, 4.83%, and 17.0% after As, Pb, and Cd exposure in male mice, which likely caused chronic intestinal inflammation, as suggested by 2.81- to 9.60-fold higher mRNA levels of pro-inflammatory factors in ileal enterocytes of male mice. These results indicate that long-term exposure to drinking water As, Pb, and Cd at concentrations equivalent to the China provisional guideline values can cause loss of protective bacteria and lead to chronic intestinal inflammation, thereby affecting body weight gain in male mice.

Are PFBS, PFHxS, and 6:2FTSA more friendly to the soil environment compared to PFOS? A new insight based on ecotoxicity study in soil invertebrates (Eisenia fetida).

As alternatives to perfluorooctane sulfonate (PFOS) with shorter carbon chains or lower proportion of fluorine atoms, perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), and 6:2 fluorotelomer sulfonic acid (6:2FTSA) have been detected in various environmental media. However, it is unclear whether the toxicity of these alternatives is lower than that of PFOS. Therefore, this study investigated the toxicity and differences in PFBS, PFHxS, 6:2FTSA, and PFOS (0.2 mg/kg) after 56 d of exposure using the common invertebrate Eisenia fetida in soil as the test organism. The results showed that although PFOS, PFBS, PFHxS, and 6:2FTSA induced oxidative stress and apoptosis in earthworms and led to developmental and reproductive toxicity in terms of comprehensive toxicity, PFHxS > PFOS > PFBS >6:2FTSA. To reveal the mechanisms underlying the differences in toxicity between the alternatives and PFOS, we conducted molecular docking and transcriptomic analyses. The results indicated that, unlike PFOS, PFBS, and PFHxS, 6:2FTSA did not cause significant changes in antioxidant enzyme activity at the molecular level. Furthermore, PFOS exposure caused disorder in the nervous and metabolic systems of earthworms, and PFHxS disrupted energy balance and triggered inflammatory responses, which may be important reasons for the higher toxicity of these compounds. In contrast, exposure to 6:2FTSA did not result in adverse transcriptomic effects, suggesting that 6:2FTSA exerted the least molecular-scale toxicity in earthworms. The results of this study provide new insights into the environmental safety of using PFBS, PFHxS, and 6:2FTSA as alternatives to PFOS.

Effect of Microplastic Types on the In Vivo Bioavailability of Polychlorinated Biphenyls.

As MPs are released into the soil, various equilibrium statuses are expected. MPs could play roles as a "source," a "cleaner," or a "sink" of HOCs. Three types of MPs (LDPE, PLA, and PS) were selected to study their effect on polychlorinated biphenyl (PCBs) relative bioavailability (RBA) measured by a mouse model. As a "source" of HOCs, exposure to MP-sorbed PCBs resulted in their accumulation in adipose tissue with PCB RBA as 101 ± 6.73% for LDPE, 76.2 ± 19.2% for PLA, and 9.22 ± 2.02% for PS. The addition of 10% MPs in PCB-contaminated soil led to a significant (p < 0.05) reduction in PCB RBA (52.2 ± 16.7%, 49.3 ± 4.85%, and 47.1 ± 5.99% for LDPE, PLA, and PS) compared to control (75.0 ± 4.26%), implying MPs acted as "cleaner" by adsorbing PCBs from the digestive system and reducing PCB accumulation. MPs acted as a "sink" for PCBs in contaminated soil after aging, but the sink effect varied among MP types with more pronounced effect for LDPE than PLA and PS. Therefore, the role played by MPs in bioavailability of HOCs closely depended on the MP types as well as the equilibrium status among MPs, soil, and HOCs.

Impact of precursors and bioaccessibility on childhood PFAS exposure from house dust.

This study investigated the impact of precursors and bioaccessibility on childhood per- and polyfluoroalkyl substances (PFAS) exposure in house dust (n = 28) from Adelaide, Australia. Sum PFAS concentration (∑38) ranged from 3.0 to 2640 µg kg-1 with PFOS (1.5-675 µg kg-1), PFHxS (1.0-405 µg kg-1) and PFOA (1.0-155 µg kg-1) constituting the major perfluoroalkyl sulfonic (PFSA) and carboxylic acids (PFCA). The total oxidizable precursor (TOP) assay was applied to estimate concentrations of unmeasurable precursors that may undergo oxidation to measurable PFAS. Sum PFAS concentration post-TOP assay changed 3.8-112-fold (91.5-62,300 µg kg-1) with median post-TOP assay PFCA (C4-C8) concentrations (92.3-170 µg kg-1) increasing significantly (13.7-48.5-fold). As incidental dust ingestion is a significant exposure pathway for young children, PFAS bioaccessibility was determined using an in vitro assay. Sum PFAS bioaccessibility ranged from 4.6 to 49.3 % with significantly (p < 0.05) higher PFCA (10.3-83.4 %) bioaccessibility compared to PFSA (3.5-51.5 %). When in vitro extracts were assessed post-TOP assay, PFAS bioaccessibility changed (7-1060 versus 137-3900 µg kg-1) although percentage bioaccessibility decreased (2.3-14.5 %) due to the disproportionately higher post-TOP assay PFAS concentration. PFAS estimated daily intake (EDI) was calculated for a 'stay-at-home' 2-3-year-old child. Inclusion of dust specific bioaccessibility values resulted in a 1.7-20.5-fold decrease in ∑PFOA, PFOA and PFHxS EDI (0.02-1.23 ng kg bw-1 day-1) compared to default absorption assumptions (0.23-5.4 ng kg bw-1 day-1). However, when 'worst-case scenario' precursor transformation was considered, EDI calculations were 4.1-187-fold higher that the EFSA tolerable weekly intake value (equivalent to 0.63 ng kg bw-1 day-1), although this was moderated when exposure parameters were refined through PFAS bioaccessibility incorporation (0.35-17.0-fold higher than the TDI). Irrespective of exposure scenario, EDI calculations were below the FSANZ tolerable daily intake values for PFOS (20 ng kg bw-1 day-1) and PFOA (160 ng kg bw-1 day-1) for all dust samples analysed.

Microplastics affect arsenic bioavailability by altering gut microbiota and metabolites in a mouse model.

Microplastics exposure is a new human health crisis. Although progress in understanding health effects of microplastic exposure has been made, microplastic impacts on absorption of co-exposure toxic pollutants such as arsenic (As), i.e., oral bioavailability, remain unclear. Microplastic ingestion may interfere As biotransformation, gut microbiota, and/or gut metabolites, thereby affecting As oral bioavailability. Here, mice were exposed to arsenate (6 µg As g-1) alone and in combination with polyethylene particles of 30 and 200 µm (PE-30 and PE-200 having surface area of 2.17 × 103 and 3.23 × 102 cm2 g-1) in diet (2, 20, and 200 µg PE g-1) to determine the influence of microplastic co-ingestion on arsenic (As) oral bioavailability. By determining the percentage of cumulative As consumption recovered in urine of mice, As oral bioavailability increased significantly (P < 0.05) from 72.0 ± 5.41% to 89.7 ± 6.33% with PE-30 at 200 µg PE g-1 rather than with PE-200 at 2, 20, and 200 µg PE g-1 (58.5 ± 19.0%, 72.3 ± 6.28%, and 69.2 ± 17.8%). Both PE-30 and PE-200 exerted limited effects on pre- and post-absorption As biotransformation in intestinal content, intestine tissue, feces, and urine. They affected gut microbiota dose-dependently, with lower exposure concentrations having more pronounced effects. Consistent with the PE-30-specific As oral bioavailability increase, PE exposure significantly up-regulated gut metabolite expression, and PE-30 exerted greater effects than PE-200, suggesting that gut metabolite changes may contribute to As oral bioavailability increase. This was supported by 1.58-4.07-fold higher As solubility in the presence of up-regulated metabolites (e.g., amino acid derivatives, organic acids, and pyrimidines and purines) in the intestinal tract assessed by an in vitro assay. Our results suggested that microplastic exposure especially smaller particles may exacerbate the oral bioavailability of As, providing a new angle to understand health effects of microplastics.

Development toxicity and cytotoxicity of pyroxsulam on embryos and adults of zebrafish (Danio rerio).

Pyroxsulam is a typical triazolopyrimidine sulfonamide herbicide, which plays a vital role in weed control for wheat production. Previous studies on pyroxsulam have mainly focused on weed resistance, control effects, and soil microorganisms, however, research on aquatic ecotoxicity is lacking. This study evaluated the toxicity of pyroxsulam in zebrafish embryos (120 h) and adults (14 and 28 d). Chronic exposure to pyroxsulam (0.2, 2, and 10 µg L-1) reduced reactive oxygen species (ROS) content in embryos but increased ROS content in adults. Pyroxsulam caused lipid peroxidation and DNA damage in embryos and adults. The expression of p53, bcl-2/bax, and caspase 3/8/9 indicated that pyroxsulam inhibited apoptosis in embryos but induced apoptosis in adults. By calculating integrated biomarker response, apoptosis was more readily affected than oxidative damage in embryos and adults. The toxicity of pyroxsulam increased with increasing concentration, however, with increasing exposure time, the toxicity of pyroxsulam to adults decreased. Pyroxsulam exerted toxic effects on zebrafish at different life stages (embryos and adults), and different stages had different toxicity. These results indicate that in future studies on the toxicity of pyroxsulam to zebrafish, different life stages (embryos and adults) need to be studied. The present study evaluated the toxicity of environmentally relevant concentrations of pyroxsulam to zebrafish embryos and adults, providing worthy data for assessing its effects on aquatic ecosystems.

Modelling of PFAS-surface interactions: Effect of surface charge and solution ions.

PER-: and poly-fluoroalkyl substances (PFAS) are a class of substances of increasing concern as environmental contaminants. The interactions between PFAS and surfaces play an important role in PFAS transport and remediation. Previous studies have found PFAS adsorption to be dependent upon properties including pH, organic matter and particle size, along with PFAS functional group and carbon chain length. It is hypothesised that a theoretical examination of PFAS-surface interactions, via Monte Carlo molecular simulation, would show differences resulting from changes in surface charge, H+, OH-, Ca2+ concentrations and PFAS carbon chain length. Monte Carlo molecular simulations of perfluorooctane and perfluorobutane sulfonic acids interacting with a graphite surface in an aqueous medium were performed. Variations in surface charge, H+, OH- and Ca2+ concentrations were made. The distance-dependent density of molecules from the surface was analysed as a proxy for PFAS adsorption to the surface. Simulation results showed differences in surface behaviour that depended on surface charge, H+, OH- and Ca2+ concentrations, along with carbon chain length, with surface charge playing the most prominent role in controlling PFAS adsorption. For negatively charged surfaces, adsorption due to divalent cation bridging was observed in Ca2+ solutions. Modelling, such as in this study, of the thermodynamic equilibrium behaviour of low concentrations of molecules, in scenarios where both adsorption and mobility of PFAS occur, can aid in the design and testing of sorptive surfaces for amendment-based PFAS remediation.

Arsenic Ingested Early in Life Is More Readily Absorbed: Mechanistic Insights from Gut Microbiota, Gut Metabolites, and Intestinal Morphology and Functions.

Early-life arsenic (As) exposure is a particular health concern. However, it is unknown if As ingested early in life is more readily absorbed from the gastrointestinal (GI) tract, i.e., higher in oral bioavailability. Here, weanling (3-week) and adult (6-week-old) female mice were exposed to arsenate in the diet (10 µg g-1) over a 3-week period with As oral bioavailability estimated using As urinary excretion as the bioavailability endpoint. The As urinary excretion factor was 1.54-fold higher in weanling mice compared to adult mice (82.2 ± 7.29 versus 53.1 ± 3.73%), while weanling mice also showed 2.28-, 1.50-, 1.48-, and 1.89-fold higher As concentration in small intestine tissue, blood, liver, and kidneys, demonstrating significantly higher As oral bioavailability of early-life exposure. Compared to adult mice, weanling mice significantly differed in gut microbiota, but the difference did not lead to remarkable differences in As biotransformation in the GI tract or tissue and in overall gut metabolite composition. Although the expression of several metabolites (e.g., atrolactic acid, hydroxyphenyllactic acid, and xanthine) was up-regulated in weanling mice, they had limited ability to elevate As solubility in the intestinal tract. Compared to adult mice, the intestinal barrier function and intestinal expression of phosphate transporters responsible for arsenate absorption were similar in weanling mice. However, the small intestine of weanling mice was characterized by more defined intestinal villi with greater length and smaller width, providing a greater surface area for As to be absorbed across the GI barrier. The results highlight that early-life As exposure can be more readily absorbed, advancing the understanding of its health risk.

Effect of florasulam on oxidative damage and apoptosis in larvae and adult zebrafish (Danio rerio).

Florasulam is widely used for weed control in wheat fields due to its high activity and low dosage. Previous studies on florasulam have focused on soil microbial and residue determination, however, its ecotoxicity to aquatic organisms is unclear. The toxicity of florasulam was evaluated in larvae (120 h) and adult (14 and 28 d) zebrafish. After florasulam (0.1 and 1 µg L-1) exposure, reactive oxygen species levels in larvae and adult zebrafish significantly increased and antioxidant system was activated. Florasulam induced lipid peroxidation in larvae and adult zebrafish. Florasulam did not cause DNA damage to larvae but caused DNA damage to adult zebrafish. Changes in caspase 3/8/9 genes indicated that apoptosis was induced in larvae but inhibited in adult zebrafish. By calculating integrated biomarker response, caspase 3 and malondialdehyde could be used as early warning indicators of florasulam effect on larvae and adult zebrafish, respectively. The higher the exposure concentration, the greater the toxicity of florasulam to larvae and adult zebrafish. Increasing exposure time resulted in higher toxicity to adult zebrafish. Florasulam has different toxicity at larvae and adult zebrafish. In future studies to investigate florasulam toxicity to zebrafish, different zebrafish life stages (larvae and adult) need to be studied.

Metallic mangroves: Sediments and in situ diffusive gradients in thin films (DGTs) reveal Avicennia marina (Forssk.) Vierh. lives with high contamination near a lead­zinc smelter in South Australia.

From 1889, aerial emissions and effluent from a coastal lead­zinc smelter at Port Pirie, South Australia, have led to the accumulation of lead (Pb), zinc (Zn), arsenic (As), cadmium (Cd) and copper (Cu) in the surrounding marine environment. Despite this, extensive stands of grey mangrove (Avicennia marina) inhabit coastal areas at Port Pirie, right up to the smelter's boundary. To understand the contamination level the mangroves are living in there, elemental concentrations were measured in mangrove sediments, leaves, pneumatophores and fruits at sites 0.30-43.0 km from the smelter. Plant health was assessed via leaf chlorophyll content at four sites with contrasting contamination, as well as in situ labile elemental concentration using diffusive gradients in thin films (DGT). Sites < 1.7 km of the smelter exceeded Australian and New Zealand Environment and Conservation Council (ANZECC) & Agriculture and Resource Management Council of Australia and New Zealand (ARMCANZ) (2000) sediment quality guideline values for As (78.3-191 mg/kg), Cd (5.17-151 mg/kg), Cu (80.7-788 mg/kg), Pb (2,544-14,488 mg/kg) and Zn (281-62,097 mg/kg), while sites further away showed less enrichment above background. Similarly, elevated elemental concentrations in leaves and pneumatophores occurred closer to the smelter (up to 319 mg/kg Pb; 1,033 mg/kg Zn), while fruits had little contamination of non-essential elements (≤ 5.23 mg/kg). Relationship between sediment and leaf elemental concentration was isometric for Pb and anisometric for others. Labile As, Cd, Cu, Pb and Zn exceeded the 95% and 80% level of species protection in marine water by ANZECC & ARMCANZ (2000) near the smelter, but chlorophyll content did not vary significantly among sites (p > 0.05). These results reveal that A. marina tolerate high elemental contamination at Port Pirie, contributing to lesser but still high contamination in plants, warranting further investigation into non-lethal impacts on mangroves or additional biota inhabiting this ecosystem.

Ca Minerals and Oral Bioavailability of Pb, Cd, and As from Indoor Dust in Mice: Mechanisms and Health Implications.

BACKGROUND: Elevating dietary calcium (Ca) intake can reduce metal(loid)oral bioavailability. However, the ability of a range of Ca minerals to reduce oral bioavailability of lead (Pb), cadmium (Cd), and arsenic (As) from indoor dust remains unclear. OBJECTIVES: This study evaluated the ability of Ca minerals to reduce Pb, Cd, and As oral bioavailability from indoor dust and associated mechanisms. METHODS: A mouse bioassay was conducted to assess Pb, Cd, and As relative bioavailability (RBA) in three indoor dust samples, which were amended into mouse chow without and with addition of CaHPO4, CaCO3, Ca gluconate, Ca lactate, Ca aspartate, and Ca citrate at 200-5,000µg/g Ca. The mRNA expression of Ca and phosphate (P) transporters involved in transcellular Pb, Cd and As transport in the duodenum of mice was quantified using real-time polymerase chain reaction. Serum 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], parathyroid hormone (PTH), and renal CYP27B1 activity controlling 1,25(OH)2D3 synthesis were measured using ELISA kits. Metal(loid) speciation in the feces of mice was characterized using X-ray absorption near-edge structure (XANES) spectroscopy. RESULTS: In general, mice exposed to each of the Ca minerals exhibited lower Pb-, Cd-, and As-RBA for three dusts. However, RBAs with the different Ca minerals varied. Among minerals, mice fed dietary CaHPO4 did not exhibit lower duodenal mRNA expression of Ca transporters but did have the lowest Pb and Cd oral bioavailability at the highest Ca concentration (5,000µg/g Ca; 51%-95% and 52%-74% lower in comparison with the control). Lead phosphate precipitates (e.g., chloropyromorphite) were observed in feces of mice fed dietary CaHPO4. In comparison, mice fed organic Ca minerals (Ca gluconate, Ca lactate, Ca aspartate, and Ca citrate) had lower duodenal mRNA expression of Ca transporters, but Pb and Cd oral bioavailability was higher than in mice fed CaHPO4. In terms of As, mice fed Ca aspartate exhibited the lowest As oral bioavailability at the highest Ca concentration (5,000µg/g Ca; 41%-72% lower) and the lowest duodenal expression of P transporter (88% lower). The presence of aspartate was not associated with higher As solubility in the intestine. DISCUSSION: Our study used a mouse model of exposure to household dust with various concentrations and species of Ca to determine whether different Ca minerals can reduce bioavailability of Pb, Cd, and As in mice and elucidate the mechanism(s) involved. This study can contribute to the practical application of optimal Ca minerals to protect humans from Pb, Cd, and As coexposure in the environment. https://doi.org/10.1289/EHP11730.

Effects of various Fe compounds on the bioavailability of Pb contained in orally ingested soils in mice: Mechanistic insights and health implications.

Reducing lead (Pb) exposure via oral ingestion of contaminated soils is highly relevant for child health. Elevating dietary micronutrient iron (Fe) intake can reduce Pb oral bioavailability while being beneficial for child nutritional health. However, the practical performance of various Fe compounds was not assessed. Here, based on mouse bioassays, ten Fe compounds applied to diets (100-800 mg Fe kg-1) reduced Pb oral relative bioavailability (RBA) in two soils variedly depending on Fe forms. EDTA-FeNa was most efficient, which reduced Pb-RBA in a soil from 79.5 ± 14.7 % to 23.1 ± 2.72 % (71 % lower) at 100 mg Fe kg-1 in diet, more effective than other 9 compounds at equivalent or higher doses (3.6-68 % lower). When EDTA-FeNa, ferrous gluconate, ferric citrate, and ferrous bisglycinate were supplemented, Fe-Pb co-precipitation was not observed in the intestinal tract. EDTA-FeNa, ferrous gluconate, ferric citrate, and ferrous sulfate suppressed duodenal divalent metal transporter 1 (DMT1)mRNA relative expression similarly (27-68 % lower). In comparison, among ten compounds, EDTA-FeNa elevated Fe concentrations in mouse liver, kidney, and blood (1.50-2.69-fold higher) most efficiently, suggesting the most efficient Fe absorption that competed with Pb. In addition, EDTA was unique from other organic ligands, ingestion of which caused 12.0-fold higher Pb urinary excretion, decreasing Pb concentrations in mouse liver, kidney, and blood by 68-88 %. The two processes (Fe-Pb absorption competition and Pb urinary excretion with EDTA) interacted synergistically, leading to the lowest Pb absorption with EDTA-FeNa. The results provide evidence of a better inhibition of Pb absorption by EDTA-FeNa, highlighting that EDTA-FeNa may be the most appropriate supplement for intervention on human Pb exposure. Future researches are needed to assess the effectiveness of EDTA-FeNa for intervention on human Pb exposure.

Impact of smelter re-development on spatial and temporal airborne Pb concentrations.

Total suspended particulate (TSP) and PM10 filters collected from two ambient air monitoring stations in Port Pirie were analysed to determine the impact of a lead (Pb) smelter redevelopment on air quality parameters including total elemental concentration, Pb isotopic ratio, Pb bioaccessibility and Pb speciation. Filters from 2009 to 2020 were analysed with a focus on samples from 2017 (immediately prior to smelter redevelopment) and 2020 (post-smelter redevelopment). Lead concentration in 2009-2020 TSP was variable ranging up to 6.94 µg m-3 (mean = 0.57 µg m-3), however, no significant decrease in Pb concentration was observed at either Port Pirie West (p = 0.56, n = 34) or Oliver Street (p = 0.32, n = 28) monitoring stations when 2017 and 2020 TSP values were compared. Similarly, no significant difference (p = 0.42) in PM10 Pb concentration was observed in 2017 (mean = 0.80 µg m-3) and 2020 (0.60 µg m-3) Oliver Street filters. Although no change in percentage Pb bioaccessibility was observed when 2017 and 2020 Port Pirie West TSP samples were compared (mean of 88.7% versus 88.0%), Pb bioaccessibility was lower (p < 0.005) in both 2020 TSP (mean of 83.9% versus 62.9%) and PM10 (mean of 70.8% versus 58.3%) Oliver Street filters compared to 2017. While scanning electron microscopy, energy dispersive x-ray spectroscopy identified a number of Pb phases within filters (galena, anglesite, cerussite, conglomerates), differences in Pb speciation between 2017 and 2020 filters could not be identified although it was presumed that this influenced Pb bioaccessibility outcomes at Oliver Street. Data from this study suggests that recent smelter redevelopments have not significantly decreased the concentrations of airborne Pb in Port Pirie although re-entrainment of soil-Pb from historical impact may also be a contributing Pb source.

In vivo relative bioavailability of perfluorooctanoic acid (PFOA) and its alternative hexafluoropropylene oxide trimer acid (HFPO-TA): Influence of food and mechanisms exploration.

The extensive use of perfluorooctanoic acid (PFOA), and its substitute hexafluoropropylene oxide trimer acid (HFPO-TA) has resulted in their frequent detection in environmental samples. However, little is known of their bioavailability via oral ingestion and the influence of food co-ingestion on absorption. Here, the relative bioavailability (RBA) of PFOA and HFPO-TA in soil was measured using an in vivo mouse model in the presence of food with different nutritional statuses (n = 11). PFOA and HFPO-TA RBA in soil was variable depending on nutrient co-administration, ranging from 29.8-95.5 % and 43.9-68.0 %, respectively. For both PFOA and HFPO-TA, a significantly negative correlation was observed between RBA and protein content in food (r = 0.57-0.72), while a positive correlation was observed with carbohydrate content (r = 0.51-0.57). Mechanistic studies showed that protein in food decreased PFOA and HFPO-TA RBA by down-regulating the expression of fatty acid binding protein 1 (FABP1) and up-regulating the expression of multidrug resistance associated protein 4 (Mrp4) in the liver, which are responsible for the absorption and efflux of PFOA and HFPO-TA. Dietary carbohydrates promoted albumin synthesis and up-regulated FABP1 expression thereby enhancing absorption and increasing PFOA and HFPO-TA RBA. This study provides an insight into potential dietary strategies for reducing exposure to per- and polyfluoroalkyl substances.

Modelling polycyclic aromatic hydrocarbon bioavailability in historically contaminated soils with six in-vitro chemical extractions and three earthworm ecotypes.

Accurate prediction of organic contaminant bioavailability for risk assessment in ecological applications is hindered by limited validation on relevant bioassay species. Here, six in-vitro chemical extraction methods (butanol, non-buffered and buffered hydroxypropyl-ß-cyclodextrin (HPCD, Buf-HPCD), Tenax, potassium persulfate oxidation, polyoxymethylene solid phase extraction (POM)) were tested for PAH bioaccumulation prediction in three earthworm ecotypes with dissimilar exposures, Amynthas sp., Eisenia fetida, and Lumbricus terrestris, in historically contaminated soils from manufactured gas plant (MGP) sites. Extractions were compared directly and modelled in a calculation approach using equilibrium partitioning theory (EqPT) with a novel combination of different organic carbon/octanol-water partitioning parameters (KOC and KOW). In the direct comparison approach Buf-HPCD showed the closest prediction of accumulation for burrowing Amynthas sp. and L. terrestris (within 1.5 and 3.1, respectively), but Tenax and POM showed the closest approximation for E. fetida (within 1.1 and 0.9, respectively). The optimum method for predicting PAH bioaccumulation in the calculation approach depended on earthworm species and the partitioning parameters used in equations of the four models, but overall POM, which was independent of KOC, showed the closest approximation of accumulation, within a factor of 2.5 across all species. This work effectively identifies the optimum in-vitro based approaches for PAH bioavailability prediction in earthworms as a model soil health indicator for ecological risk assessment within regulatory and remediation decision frameworks.