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Methods promoting lead (Pb) phase transformation in soils are essential for decreasing Pb bioaccessibility/bioavailability and may offer an in situ, cost-efficient process for mitigating contaminant exposure. Recent plumbojarosite (PLJ) conversion methods have shown the greatest potential to reduce soil Pb bioaccessibility, an in vitro bioaccessibility assay measurement of the proportion of Pb solubilized under gastric chemical conditions. Soils tested utilizing the recent PLJ method were found to have a Pb bioaccessibility of1%, compared to original soils possessing bioaccessibility of70%. However, this technique requires heat (95-100 °C) to promote mineral transformation. Jarosite-group minerals may incorporate multiple interlayer cations; therefore, we probed the potential for jarosite to remediate Pb via intercalation by reacting presynthesized potassium (K)-jarosite with aqueous Pb and/or Pb-contaminated soil at room temperature. Both K-jarosite and heated PLJ-treated samples were investigated by pairing bioaccessibility analyses with advanced bulk and spatially resolved X-ray absorption spectroscopy analyses. Samples treated with K-jarosite promoted Pb transformation to low-bioaccessibility (10%) PLJ, with soil being converted to 100% PLJ using both heated and nonheated techniques. μ-X-ray fluorescence (μ-XRF) and μ-X-ray absorption near-edge structure (μ-XANES) showcase significant differences between elemental interactions for heated and nonheated PLJ-treated samples with anglesite impurities being found on the microscale. Although further development is necessary to accommodate for suitable field conditions, results indicate, for the first time, that K-jarosite may successfully convert soil Pb to PLJ without high-temperature conditions. The newfound utility of K-jarosite is expected to be key to future jarosite-based soil Pb remediation method development.

Purpose of Review The ubiquity of soil contamination by lead (Pb) and arsenic (As) has prompted the development of numerous techniques for its remediation. For human health exposure assessment, oral bioavailability-based methods are the most suitable to assess the efficacy of these treatment strategies, including in vivo relative bioavailability (systemic absorption relative to a toxicity reference) and in vitro bioaccessibility (dissolution in simulated gastrointestinal solutions). This paper provides a critical review of opportunities and challenges associated with the immobilization of Pb and As in contaminated soil. Recent Findings This review identified that the major inorganic and organic amendments used to reduce Pb and As exposure include phosphate, industrial by-products, metal oxides, organic matter, biochar, and treatment with iron sulphate to promote the formation of plumbojarosite in soil. In addition to RBA and IVBA assessment, investigating changes in Pb/As speciation in untreated vs treated soil can provide additional confirmation of treatment efficacy. The results of this review showed that immobilization efficacy may vary depending on amendment type, Pb, and As speciation in soil and the approach used for its assessment. Summary Reducing childhood exposure to Pb and As is a significant challenge, given the variety of contamination sources and treatment strategies. A lines-of-evidence approach using standardized methodologies is recommended for the assessment of immobilization efficacy to ensure exposure and risk reduction Graphical Abstract Bioavailability-based remediation strategies. Popular soil amendments to reduce Pb exposure include phosphate, industrial by-products, metal oxides, organic matter, and biochar; however, these may increase As exposure. The plumbojarosite formation technique has been recently developed to mitigate Pb and As exposure simultaneously. Multiple lines-of-evidence approach is recommended to assess treatment efficacy

Extensive research has examined arsenic (As) bioavailability in contaminated soils and is routinely assessed using in vitro bioaccessibility (IVBA) assays. Analysis of differences in bioaccessibility measurements across IVBA assays and phases is expected to provide valuable insights into geochemical mechanisms controlling soil As bioaccessibility and bioavailability. Soil iron (Fe) content and As speciation are expected to significantly influence IVBA gastric and intestinal phases due to fluctuations in precipitation-dissolution chemistry and sorption reactivity as pH and assay chemical complexity changes. The aim of this review was to examine these relationships by 1) conducting a meta-analysis (n = 47 soils) determining the influence of total Fe on As bioaccessibility measurements and 5 IVBA assays and 2) investigating the effect of As speciation on gastric/intestinal phase IVBA and in vitro-in vivo correlations. Our findings indicate that soil Fe content and As speciation heterogeneity are important in elucidating variability of bioaccessibility measurements across IVBA assays and gastrointestinal phases. Greater focus on coupled As speciation and Fe precipitation chemistry may (1) improve our understanding of soil geochemical factors and assay constituents that influence As in vitro-in vivo correlations and (2) resolve variability in the precision of oral relative bioavailability (RBA) estimated using IVBA assays for soils possessing heterogenous As speciation and Fe composition.

House dust and soils can be major sources of lead (Pb) exposure for children. The American Healthy Homes Survey (AHHS) was developed to estimate Pb exposure from house dust and soil, in addition to other potential household contaminants and allergens. We have combined X-ray absorption spectroscopic (XAS) fingerprinting and in vivo mouse relative bioavailability (RBA) measurements of a small set of house dust and residential soils collected in the AHHS, with the primary objective of gaining a better understanding of determinants of house dust Pb bioavailability. Lead speciation was well-related to variations in RBA results, and revealed that highly bioavailable Pb (hydroxy)carbonate (indicative of Pb-based paint) was the major Pb species present in house dusts. Measured Pb RBA was up to 100% and is likely driven by paint Pb. To our knowledge, this is the first report of in vivo Pb RBA in U.S. house dust contaminated in situ with paint Pb and corroborates results from a previous study that demonstrated high RBA of paint Pb added to soil. We also report a relatively low RBA (23%) in a residential soil where the major Pb species was found to be plumbojarosite, consistent with a previous report that plumbojarosite lowers Pb RBA in soils.

The relationship between ingestion of diets amended with a Pb-contaminated soil and the composition of the fecal microbiome was examined in a mouse model. Mice consumed diets amended with a Pb-contaminated soil in its native (untreated) state or after treatment for remediation with phosphoric acid or triple superphosphate alone or in combination with iron-waste material or biosolids compost. Subacute dietary exposure of mice receiving treated soil resulted in modulation of the fecal intestinal flora, which coincided with reduced relative Pb bioavailability in the bone, blood and kidney and differences in Pb speciation compared to untreated soil. Shifts in the relative abundance of several phyla including Verrucomicrobia, Tenericutes, Firmicutes, Proteobacteria, and TM7 (Candidatus Saccharibacteria) were observed. Because the phyla persist in the presence of Pb, it is probable that they are resistant to Pb. This may enable members of the phyla to bind and limit Pb uptake in the intestine. Families Ruminococcaceae, Lachnospiraceae, Erysipelotrichaceae, Verrucomicrobiaceae, Prevotellaceae, Lactobacilaceae, and Bacteroidaceae, which have been linked to health or disease, also were modulated. This study is the first to explore the relationship between the murine fecal microbiome and ingested Pb contaminated soils treated with different remediation options designed to reduce bioavailability. Identifying commonalities in the microbiome that are correlated with more positive health outcomes may serve as biomarkers to assist in the selection of remediation approaches that are more effective and pose less risk.

Accurate assessment of adverse health effects attributable to ingestion of inorganic arsenic (As) present in contaminated soils requires determination of the internal dose of metal provided by ingested soil. This calculation requires estimation of the oral bioavailability of soil-borne (As). Animal models to assess the bioavailability of soil (As) are frequently used as surrogates for determination of this variable in humans. A mouse assay has been widely applied to estimate the bioavailability of As in soils at sites impacted by mining, smelting, and pesticides. In the mouse assay, the relative bioavailability (RBA) of soil (As) is determined as the ratio of the fraction of the ingested arsenic dose excreted in urine after consumption of diets containing a test soil or the soluble reference compound, sodium arsenate. The aim of the current study was to compare (As) bioavailability measured in the mouse assay with reported estimates in humans. Here, a pharmacokinetic model based on excretion of arsenic in urine and feces was used to estimate the absolute bioavailability (ABA) of As in mice that received an oral dose of sodium arsenate. Based upon this analysis, in mice that consumed diet amended with sodium arsenate, the ABA was 85%. This estimate of arsenic ABA for the mouse is comparable to estimates in humans who consumed (As) in drinking water and diet, and to estimates of ABA in monkeys and swine exposed to sodium arsenate. The concordance of estimates for ABA in mice and humans provides further support for use of the mouse model in human health risk assessment. Sodium arsenate ABA also provides a basis for estimating soil arsenic ABA from RBA estimates obtained in the mouse model.

Refereed/Peer-reviewed Lead (Pb) contamination of soils is of global concern due to the devastating impacts of Pb exposure in children. Because early-life exposure to Pb has long-lasting health effects, reducing exposure in children is a critical public health goal that has intensified research on the conversion of soil Pb to low bioavailability phases. Recently, plumbojarosite (PLJ) conversion of highly available soil Pb was found to decrease Pb relative bioavailability (RBA

Ulcerative dermatitis in laboratory mice remains an ongoing clinical problem and animal welfare issue. Many products have been used to treat dermatitis in mice, with varying success. Recently, the topical administration of healing clays, such as bentonite and green clays, has been explored as a viable, natural treatment. We found high concentrations of arsenic and lead in experimental samples of therapeutic clay. Given the known toxic effects of these environmental heavy metals, we sought to determine whether the topical administration of a clay product containing bioavailable arsenic and lead exerted a biologic effect in mice that potentially could introduce unwanted research variability. Two cohorts of 20 singly housed, shaved, dermatitis free, adult male CD1 mice were dosed daily for 2 wk by topical application of saline or green clay paste. Samples of liver, kidney and whole blood were collected and analyzed for total arsenic and lead concentrations. Hepatic and renal concentrations of arsenic were not different between treated and control mice in either cohort; however, hepatic and renal concentrations of lead were elevated in clay treated mice compared to controls in both cohorts. In addition, in both cohorts, the activity of δ-aminolevulinate acid dehydratase, an enzyme involved with heme biosynthesis and a marker of lead toxicity, did not differ significantly between the clay-treated mice and controls. We have demonstrated that these clay products contain high concentrations of arsenic and lead and that topical application can result in the accumulation of lead in the liver and kidneys; however, these concentrations did not result in measurable biologic effects. These products should be used with caution, especially in studies of lead toxicity, heme biosynthesis, and renal α2 microglobulin function.

Widespread contamination of soil, dust, and food with toxic metal(loid)s pose a significant public health concern. Only a portion of orally ingested metal(loid) contaminants are bioavailable, which is defined as the fraction of ingested metal(loid)s absorbed across the gastrointestinal barrier and into systemic circulation. Bioaccessibility tools are a class of in vitro assays used as a surrogate to estimate risk of oral exposure and bioavailability. Although development and use of bioaccessibility tools have contributed to our understanding of the factors influencing oral bioavailability of metal(loid)s, some of these assays may lack data that support their use in decisions concerning adverse health risks and soil remediation. This review discusses the factors known to influence bioaccessibility of metal(loid) contaminants and evaluates experimental approaches and key findings of SW-846 Test Method 1340, Unified BARGE Method, Simulated Human Intestinal Microbial Ecosystem, Solubility Bioaccessibility Research Consortium assay, In Vitro Gastrointestinal model, TNO-Gastrointestinal Model, and Dutch National Institute for Public Health and the Environment bioaccessibility models which are used to assess oral absolute bioavailability and relative bioavailability in solid matrices. The aim of this review was to identify emerging knowledge gaps and research needs with an emphasis on research required to evaluate these models on (1) standardization of assay techniques and methodology, and (2) use of common criteria for assessing the performance of bioaccessibility models.

Arsenic exposure has been reported to alter the gut microbiome in mice. Activity of the gut microbiome derived from fecal microbiota has been found to affect arsenic bioaccessibility in an in vitro gastrointestinal (GI) model. Only a few studies have explored the relation between arsenic exposure and changes in the composition of the gut microbiome and in arsenic bioaccessibility. Here, we used simulated GI model system (GIMS) containing a stomach, small intestine, colon phases and microorganisms obtained from mouse feces (GIMS-F) and cecal contents (GIMS-C) to assess whether exposure to arsenic-contaminated soils affect the gut microbiome and whether composition of the gut microbiome affects arsenic bioaccessibility. Soils contaminated with arsenic did not alter gut microbiome composition in GIMS-F colon phase. In contrast, arsenic exposure resulted in the decline of bacteria in GIMS-C, including members of Clostridiaceae, Rikenellaceae, and Parabacteroides due to greater diversity and variability in microbial sensitivity to arsenic exposure. Arsenic bioaccessibility was greatest in the acidic stomach phase of GIMS (pH 1.5-1.7); except for GIMS-C colon phase exposed to mining-impacted soil in which greater levels of arsenic solubilized likely due to microbiome effects. Physicochemical properties of different test soils likely influenced variability in arsenic bioaccessibility (GIMS-F bioaccessibility range: 8-37%, GIMS-C bioaccessibility range: 2-18%) observed in this study.

Significance As a strategy to stabilize soil Pb, we evaluated the effect of PLJ formation on the bioavailability of soil Pb. Our technology for PLJ formation resulted in >90% incorporation of soil Pb into the mineral structure of jarosite. This conversion decreased soil Pb bioavailability greater than 90%, even after pH neutralization to revitalize the soil to agronomic health. PLJ formation may be a more effective remediation method than other soil treatment technologies and may reduce removal clean-up efforts and costs. Because jarosite can sequester both cationic and anionic contaminants, it may be effective for both Pb and arsenic remediation. Furthermore, this treatment is not influenced by initial soil pH or organic matter content and uses an environmentally safe chemical., Exposure to lead (Pb) during early life has persistent adverse health effects. During childhood, ingestion of bioavailable Pb in contaminated soils can be a major route of Pb absorption. Remediation to alter physiochemical properties of soil-borne Pb can reduce Pb bioavailability. Our laboratory-based approach for soil Pb remediation uses addition of iron (Fe) sulfate and application of heat to promote formation of plumbojarosite (PLJ), a sparingly soluble Pb-Fe hydroxysulfate mineral. We treated two soils with anthropogenic Pb contamination and samples of clean topsoil spiked with various Pb compounds (i.e., carbonate, chloride, phosphate [P], or sulfate) to convert native Pb species to PLJ and used a mouse assay to assess relative bioavailability (RBA) of Pb in untreated (U) and remediated soils. Bone and blood Pb levels were significantly lower (P < 0.001, Student's t test) in mice that consumed diets amended with remediated soils than with U soils. Estimated RBA for Pb in both remediated natural soils and Pb-mineral spiked soils were reduced by >90% relative to Pb RBA for U soils, which is substantially more effective than other soil amendments, including P. X-ray absorption spectroscopy showed that >90% of all Pb species in remediated soils were converted to PLJ, and ingested PLJ was not chemically transformed during gastrointestinal tract transit. Post treatment neutralization of soil pH did not affect PLJ stability, indicating the feasibility in field conditions. These results suggest that formation of PLJ in contaminated soils can reduce the RBA of Pb and minimize this medium’s role as a source of Pb exposure for young children.

Children may be exposed to environmental contaminants through incidental ingestion of soil resulting from hand-to-mouth contact. We measured soil adherence to the skin among 86 children from four kindergartens and one elementary school in Taiwan. Rinse water samples were collected from the hands, forearms, feet and lower legs of children after they had engaged in assigned activity groups (pre-activity, indirect contact and direct contact) from two different soil textures groups: sand and clay. We found that the soil loadings significantly differed between the different soil textures, body parts, activities, and clothing groups. Measured soil loadings for hands of pre-activity, indirect contact activity, and direct contact activity groups were 0.0069, 0.0307 and 0.153 mg cm−2, respectively, for the group playing on sand and 0.0061, 0.0116 and 0.0942 mg cm−2, respectively, for the group playing on clay. To facilitate the use of soil adherence data in exposure assessments, we provided a new and simple way to group activities based on the intensity of children's interactions with soil. The adherence data from this study can help enhance existing information based on soil-to-skin adherence factors used to assess children's exposure to soil contaminants during their play activities.

Interest in improved understanding of relationships among soil properties and arsenic (As) bioaccessibility has motivated the use of regression models for As bioaccessibility prediction. However, limits in the numbers and types of soils included in previous studies restrict the usefulness of these models beyond the range of soil conditions evaluated, as evidenced by reduced predictive performance when applied to new data. In response, hierarchical models that consider variability in relationships among soil properties and As bioaccessibility across geographic locations and contaminant sources were developed to predict As bioaccessibility in 139 soils on both a mass fraction (mg/kg) and % basis. The hierarchical approach improved the estimation of As bioaccessibility in studied soils. In addition, the number of soil elements identified as statistically significant explanatory variables increased when compared to previous investigations. Specifically, total soil Fe, P, Ca, Co, and V were significant explanatory variables in both models, while total As, Cd, Cu, Ni, and Zn were also significant in the mass fraction model and Mg was significant in the % model. This developed hierarchical approach provides a novel tool to (1) explore relationships between soil properties and As bioaccessibility across a broad range of soil types and As contaminant sources encountered in the environment and (2) identify areas of future mechanistic research to better understand the complexity of interactions between soil properties and As bioaccessibility. Refereed/Peer-reviewed

Micronized copper azole (MCA) and micronized copper quaternary (MCQ) are the latest wood preservatives to replace the liquid alkaline copper and chromated copper arsenate preservatives due to concerns over the toxicity or lack of effectiveness of the earlier formulations. Today, the use of MCA has become abundant in the wood preservative industry with approximately 38millionlbs of copper carbonate being used to treat lumber each year. Despite this widespread usage, little information is available on the bioaccessibility of this preservative upon gastrointestinal exposure. Using a simulated hand-to-mouth/gastric system exposure study we investigated several types of commercially available copper-treated lumber products as-purchased and after exposure to outdoor weathering conditions. Soluble and particulate fractions of copper were measured after transfer to and release from surface wipes passed along copper-treated lumber and exposed to synthetic stomach fluid (SSF, pH1.5) or deionized (DI) water. Wipes passed along new boards contained greater amounts of copper than wipes from weathered boards. The total copper recovered from the wipes after microwave extraction varied among the different wood types. For all wood types the copper released into SSF was more soluble than what was soluble in DI water. The data suggest that copper from treated wood is highly bioaccessible in SSF regardless of wood type and weathering condition.

Relationships between total soil or bioaccessible lead (Pb), measured using an in vitro bioaccessibility assay, and children’s blood lead levels (BLL) were investigated in an urban neighborhood in Philadelphia, Pennsylvania, USA, with a history of soil Pb contamination. Soil samples from 38 homes were analyzed to determine whether accounting for the bioaccessible Pb fraction improves statistical relationships with children’s BLLs. Total soil Pb ranged from 58 to 2,821 mg/kg; the bioaccessible Pb fraction ranged from 47 to 2,567 mg/kg. Children’s BLLs ranged from 0.3 to 9.8 μg/dL. Hierarchical models were used to compare relationships between total or bioaccessible Pb in soil and children’s BLLs. Total soil Pb as the predictor accounted for 25% of the variability in child BLL; bioaccessible soil Pb as the predictor accounted for 28% of BLL variability. A bootstrapping analysis confirmed a significant increase in R2 for the model using bioaccessible soil Pb as the predictor with 99.3% of bootstraps showing a positive increase. Estimated increases of 1.4 μg/dL and 1.6 μg/dL in BLL per 1,000 mg/kg Pb in soil were observed for this study area using total and bioaccessible Pb, respectively. Children’s age did not contribute significantly to the prediction of BLLs.

Hand-to-mouth activity in children can be an important route for ingestion of soil and dust contaminated with inorganic arsenic. Estimating the relative bioavailability of arsenic present in these media is a critical element in assessing the risks associated with aggregate exposure to this toxic metalloid during their early life. Here, we evaluated the performance of a mouse assay for arsenic bioavailability in two laboratories using a suite of 10 soils. This approach allowed us to examine both intralaboratory and interlaboratory variations in assay performance. Use of a single vendor for preparation of all amended test diets and of a single laboratory for arsenic analysis of samples generated in the participating laboratories minimized contributions of these potential sources of variability in assay performance. Intralaboratory assay data showed that food and water intake and cumulative urine and feces production remained stable over several years. The stability of these measurements accounted for the reproducibility of estimates of arsenic bioavailability obtained from repeated intralaboratory assays using sodium arsenate or soils as the test material. Interlaboratory comparisons found that estimates of variables used to evaluate assay performance (recovery and urinary excretion factor) were similar in the two laboratories. For all soils, estimates of arsenic relative bioavailability obtained in the two laboratories were highly correlated (r2 = 0.94 and slope = 0.9) in a linear regression model. Overall, these findings show that this mouse assay for arsenic bioavailability provides reproducible estimates using a variety of test soils. This robust model may be adaptable for use in other laboratory settings. Refereed/Peer-reviewed

Effects of dietary P level on the oral bioavailability of Pb present in soil were examined in a mouse model. Adult female C57BL/6 mice had free access to AIN-93G purified rodent diet amended with Pb as a soluble salt, Pb acetate, or in a soil matrix (NIST SRM 2710a). In these studies, the basal diet contained P at a nutritionally sufficient level (0.3% w/w) and the modified diets contained P at a lower (0.15%) or a higher (1.2%) level. For either dietary Pb source (Pb acetate or NIST SRM 2710a), low dietary P level markedly increased accumulation of Pb in bone, blood, and kidney. Tissue Pb levels in mice fed a high P in diet were not different from mice fed the basal P diet. Dietary P and Pb interacted to affect body weight change and feed efficiency in mice. The relative contribution of different Pb species in diet and feces was also affected by dietary P level. Differences in Pb species between diet and feces indicated that transformation of Pb species can occur during gastrointestinal tract transit. These interactions between Pb and P that alter Pb speciation may be important determinants of the bioavailability of Pb ingested in soil.

For much of the world's population, food is the major source of exposure to arsenic. Exposure to this non-essential metalloid at relatively low levels may be linked to a wide range of adverse health effects. Thus, evaluating foods as sources of exposure to arsenic is important in assessing risk and developing strategies that protect public health. Although most emphasis has been placed on inorganic arsenic as human carcinogen and toxicant, an array of arsenic-containing species are found in plants and animals used as foods. Here, we 2evaluate the contribution of complex organic arsenicals (arsenosugars, arsenolipids, and trimethylarsonium compounds) that are found in foods and consider their origins, metabolism, and potential toxicity. Commonalities in the metabolism of arsenosugars and arsenolipids lead to the production of di-methylated arsenicals which are known to exert many toxic effects. Evaluating foods as sources of exposure to these complex organic arsenicals and understanding the formation of reactive metabolites may be critical in assessing their contribution to aggregate exposure to arsenic.

Lead (Pb) in soil is an important exposure source for children. Thus, determining bioavailability of Pb in soil is critical in evaluating risk and selecting appropriate strategies to minimize exposure. A mouse model was developed to estimate relative bioavailability of Pb in NIST SRM 2710a (Montana 1 Soil). Based on Pb levels in tissues, the mean relative bioavailability of this metal in this soil was 0.5. Estimates of relative bioavailabilities derived from mouse compared favorably with those obtained in juvenile swine. The mouse model is thus an efficient and inexpensive method to obtain estimates of relative bioavailability of soil Pb.

Background: Exposure to inorganic and organic arsenic compounds is a major public health problem that affects hundreds of millions of people worldwide. Exposure to arsenic is associated with cancer and noncancer effects in nearly every organ in the body, and evidence is mounting for health effects at lower levels of arsenic exposure than previously thought. Building from a tremendous knowledge base with > 1,000 scientific papers published annually with “arsenic” in the title, the question becomes, what questions would best drive future research directions? Objectives: The objective is to discuss emerging issues in arsenic research and identify data gaps across disciplines. Methods: The National Institutes of Health’s National Institute of Environmental Health Sciences Superfund Research Program convened a workshop to identify emerging issues and research needs to address the multi-faceted challenges related to arsenic and environmental health. This review summarizes information captured during the workshop. Discussion: More information about aggregate exposure to arsenic is needed, including the amount and forms of arsenic found in foods. New strategies for mitigating arsenic exposures and related health effects range from engineered filtering systems to phytogenetics and nutritional interventions. Furthermore, integration of omics data with mechanistic and epidemiological data is a key step toward the goal of linking biomarkers of exposure and susceptibility to disease mechanisms and outcomes. Conclusions: Promising research strategies and technologies for arsenic exposure and adverse health effect mitigation are being pursued, and future research is moving toward deeper collaborations and integration of information across disciplines to address data gaps. Citation: Carlin DJ, Naujokas MF, Bradham KD, Cowden J, Heacock M, Henry HF, Lee JS, Thomas DJ, Thompson C, Tokar EJ, Waalkes MP, Birnbaum LS, Suk WA. 2016. Arsenic and environmental health: state of the science and future research opportunities. Environ Health Perspect 124:890–899; http://dx.doi.org/10.1289/ehp.1510209

Lumber pressure-treated with micronized copper was examined for the release of copper and copper micro/nanoparticles using a surface wipe method to simulate dermal transfer. In 2003, the wood industry began replacing CCA treated lumber products for residential use with copper based formulations. Micronized copper (nano to micron sized particles) has become the preferred treatment formulation. There is a lack of information on the release of copper, the fate of the particles during dermal contact, and the copper exposure level to children from hand-to-mouth transfer. For the current study, three treated lumber products, two micronized copper and one ionic copper, were purchased from commercial retailers. The boards were left to weather outdoors for approximately 1year. Over the year time period, hand wipe samples were collected periodically to determine copper transfer from the wood surfaces. The two micronized formulations and the ionic formulation released similar levels of total copper. The amount of copper released was high initially, but decreased to a constant level (~1.5mgm(-2)) after the first month of outdoor exposure. Copper particles were identified on the sampling cloths during the first two months of the experiment, after which the levels of copper were insufficient to collect interpretable data. After 1month, the particles exhibited minimal changes in shape and size. At the end of 2-months, significant deterioration of the particles was evident. Based on the wipe sample data, a playground visit may result in a potential exposure to 2.58mg of copper, which is near or exceeds the daily tolerable upper intake limits for children under the age of 8, if completely ingested through hand-to-mouth transfer. While nanoparticles were found, there is not enough information to estimate the exposure from the released particles due to a lack of published literature on copper carbonate.

The Southeast Missouri Lead District is among the most productive lead deposits exploited in modern times. Intensive mining conducted prior to regulations resulted in a legacy of lead contaminated soil, large piles of mine tailings and elevated childhood blood lead levels. This study seeks to identify the source of the lead contamination in the Big River and inform risk to the public. Isotopic analysis indicated the mine tailing piles at the head of the Big River are the primary source of the lead contamination. The isotopic signature of the lead in these mine tailings matched the lead over 100 km downstream. All of the other potential lead sources investigated had different isotopic signatures. Lead concentrations in soils and sediments decrease with distance downstream of the mine tailings piles. Additionally, the speciation of the lead changes from predominantly mineralized forms, such as galena, to adsorbed lead. This is reflected in the in-vitro bioaccessibility assay (IVBA) analysis which shows higher bioaccessibility further downstream, demonstrating the importance of speciation in risk evaluation.

The use of colloidal silver-containing products as dietary supplements, immune boosters and surface disinfectants has increased in recent years which has elevated the potential for human exposure to silver nanoparticles particles and ions. Product mislabeling and long-term use of these products may put consumers at risk for adverse health outcomes including argyria. This study assessed several physical and chemical characteristics of five commercial products as well as their cytotoxicity using a rat intestinal epithelial cell (IEC-6) model. Concentrations of silver were determined for both the soluble and particulate fractions of the products. Primary particle size distribution and elemental composition were determined by transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS), respectively. Hydrodynamic diameters were measured using nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS). The effect of gastrointestinal (GI) simulation on the colloidal silver products was determined using two systems. First, physical and chemical changes of the silver nanoparticles in these products was assessed after exposure to Synthetic Stomach Fluid (SSF) resulting in particle agglomeration, and the appearance of AgCl on the surfaces and between particles. IEC-6 cells were exposed for 24 h to dilutions of the products and assessed for cell viability. The products were also treated with a three-stage simulated GI system (stomach and intestinal fluids) prior to exposure of the IEC-6 cells to the isolated silver nanoparticles. Cell viability was affected by each of the consumer products. Based on the silver nitrate and commercial silver nanoparticle dose response, the cytotoxicity for each of the colloidal silver products was attributed to the particulate silver, soluble silver or non-silver matrix constituents.

Human oral exposure to copper oxide nanoparticles (NPs) may occur following ingestion, hand-to-mouth activity, or mucociliary transport following inhalation. This study assessed the cytotoxicity of Cupric (II) oxide (CuO) and Cu2O-polyvinylpyrrolidone (PVP) coated NPs and copper ions in rat (intestine epithelial cells; IEC-6) and human intestinal cells, two- and three-dimensional models, respectively. The effect of pretreatment of CuO NPs with simulated gastrointestinal (GI) fluids on IEC-6 cell cytotoxicity was also investigated. Both dose- and time-dependent decreases in viability of rat and human cells with CuO and Cu2O-PVP NPs and Cu2+ ions was observed. In the rat cells, CuO NPs had greater cytotoxicity. The rat cells were also more sensitive to CuO NPs than the human cells. Concentrations of H2O2 and glutathione increased and decreased, respectively, in IEC-6 cells after a 4-h exposure to CuO NPs, suggesting the formation of reactive oxygen species (ROS). These ROS may have damaged the mitochondrial membrane of the IEC-6 cells causing a depolarization, as a dose-related loss of a fluorescent mitochondrial marker was observed following a 4-h exposure to CuO NPs. Dissolution studies showed that Cu2O-PVP NPs formed soluble Cu whereas CuO NPs essentially remained intact. For GI fluid-treated CuO NPs, there was a slight increase in cytotoxicity at low doses relative to non-treated NPs. In summary, copper oxide NPs were cytotoxic to rat and human intestinal cells in a dose- and time-dependent manner. The data suggests Cu2O-PVP NPs are toxic due to their dissolution to Cu ions, whereas CuO NPs have inherent cytotoxicity, without dissolving to form Cu ions.

The storage of coal combustion residue (CCR) in surface water impoundments may have an impact on nearby water quality and aquatic ecosystems. CCR contains leachable trace elements that can enter nearby waters through spills and monitored discharge. It is important, therefore, to understand their environmental fate in affected systems. This experiment examined trace element leachability into freshwater from fly ash (FA), the most common form of CCR. The effects on water quality of FA derived from both high and low sulfur coal sources as well as the influences of two different emergent macrophytes, Juncus effusus and Eleocharis quadrangulata, were evaluated in wetland microcosms. FA leachate dosings increased water electric conductivity (EC), altered pH, and, most notably, elevated the concentrations of boron (B), molybdenum (Mo), and manganese (Mn). The presence of either macrophyte species helped reduce elevated EC, and B, Mo, and Mn concentrations over time, relative to microcosms containing no plants. B and Mo appeared to bioaccumulate in the plant tissue from the water when elevated by FA dosing, while Mn was not higher in plants dosed with FA leachates. The results of this study indicate that emergent macrophytes could help ameliorate downstream water contamination from CCR storage facilities and could potentially be utilized in wetland filtration systems to treat CCR wastewater before discharge. Additionally, measuring elevated B and Mo in aquatic plants may have potential as a monitoring tool for downstream CCR contamination.

Effects of different treatments on the bioavailability of lead (Pb) in soil from a smelter emission contaminated site in Joplin, Missouri, were evaluated in a mouse model. Similar estimates of relative bioavailability for Pb in untreated or treated soil were obtained in mice and in the well-established juvenile swine model. In the mouse model, treatments that used phosphate (phosphoric acid or triple superphosphate) combined with iron oxide or biosolids compost significantly reduced soil Pb bioavailability. Notably, effects of these remediation procedures were persistent, given that up to 16 years had elapsed between soil treatment and sample collection. Remediation of soils was associated with changes in Pb species present in soil. Differences in Pb species in ingested soil and in feces from treated mice indicated that changes in Pb speciation occurred during transit through the gastrointestinal tract. Use of the mouse model facilitates evaluation of remediation procedures and allows monitoring of the performance of procedures under laboratory and field conditions.

Arsenic (As) and lead (Pb) are two contaminants of concern associated with urban gardening. In Puerto Rico, data currently is limited on As and Pb levels in urban garden soils, soil metal (loid) bioaccessibility, and uptake of As and Pb in soil by edible plants grown in the region. This study examined total and bioaccessible soil As and Pb concentrations and accumulation in 10 commonly grown garden plants collected from three urban community gardens in Puerto Rico. Bioavailability values were predicted using bioaccessibility data to compare site-specific bioavailability estimates to commonly used default exposure assumptions. Total and bioaccessible As levels in study soils ranged from 2 to 55 mg/kg and 1 to 18 mg/kg, respectively. Total and bioaccessible Pb levels ranged from 19 to 172 mg/kg and 17 to 97 mg/kg, respectively. Measured bioaccessibility values corresponded to 19% to 42% bioaccessible As and 61% to 100% bioaccessible Pb when expressed as a percent of total As and Pb respectively. Predicted relative percent bioavailability of soil As and Pb based on measured bioaccessibility values ranged from 18% to 36% and 51% to 85% for As and Pb respectively. Transfer factors (TFs) measuring uptake of As in plants from soil ranged from 0 to 0.073 in the edible flesh (fruit or vegetable) of plant tissues analyzed and 0.073 to 0.444 in edible leaves. Pb TFs ranged from 0.002 to 0.012 in flesh and 0.023 to 0.204 in leaves. Consistent with TF values, leaves accumulated higher concentrations of As and Pb than the flesh, with the highest tissue concentrations observed in the culantro leaf (3.2 mg/kg dw of As and 8.9 mg/kg dw of Pb). Leaves showed a general but not statistically-significant (α = 0.05) trend of increased As and Pb concentration with increased soil levels, while no trend was observed for flesh tissues. These findings provide critical data that can improve accuracy and reduce uncertainty when conducting site-specific risk determination of potential As and Pb exposure while gardening or consuming garden produce in the understudied region of Puerto Rico.

The widespread use of copper in treated lumber may result in a potential for human exposure. Due to a lack of information concerning the release of copper from treated wood particles following oral ingestion, the in vitro bioaccessibility of copper from copper-treated wood dust in synthetic stomach fluid (SSF) and DI water was investigated. Copper-containing particles ranging in size from nano-scale to micron-scale were observed by transmission electron microscopy (TEM) in thin sections of these micronized copper-treated wood products. Three copper-treated wood products (liquid alkali copper quaternary and two micronized copper quarternary products) from different manufacturers were incubated in the extraction media. The released copper was then fractionated by centrifugation and filtration through 0.45 μm and 10 kDa filters, respectively. Soluble copper released into isolated fractions was measured using Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES). Total copper from each wood product was also determined using microwave-assisted acid digestion of dried wood samples and ICP-OES. The bioaccessible copper released into SSF was between 83 and 90% for all wood types. However, the percent of copper released in DI water was between 14 and 25% for all wood products. These data suggest that copper is highly bioaccessible at the low pH values present in the stomach and may pose a potential exposure risk upon ingestion.

In vitro bioaccessibility (IVBA) assays estimate arsenic (As) relative bioavailability (RBA) in contaminated soils to improve accuracy in human exposure assessments. Previous studies correlating soil As IVBA with RBA have been limited by the use of few soil types and sources of As, and the predictive value of As IVBA has not been validated using an independent set of As-contaminated soils. In this study, a robust linear model was developed to predict As RBA in mice using IVBA, and the predictive capability of the model was independently validated using a unique set of As-contaminated soils. Forty As-contaminated soils varying in soil type and contaminant source were included in this study, with 31 soils used for initial model development and nine soils used for independent model validation. The initial model reliably predicted As RBA values in the independent data set, with a mean As RBA prediction error of 5.4%. Following validation, 40 soils were used for final model development, resulting in a linear model with the equation RBA = 0.65 × IVBA + 7.8 and an R2 of 0.81. The in vivo-in vitro correlation and independent data validation presented provide critical verification necessary for regulatory acceptance in human health risk assessment. Refereed/Peer-reviewed

Evaluation of soil arsenic (As) relative bioavailability (RBA) is essential to accurately assess human exposure to As contaminated soils via the incidental ingestion pathway. A variety of animal bioassays have been developed to estimate As RBA in contaminated soils and dusts, with uncertainty regarding how physiological differences between animal models or differences in assay methodologies may influence As RBA estimates. This study compared As RBA estimates across 20 As pesticide and mineimpacted soils in two commonly utilized animal bioassays, a mouse model based on steady state urinary excretion factor (UEF) and two swine models based on UEF and area under the curve (AUC), to elucidate factors influencing As RBA estimates. Multiple regression analysis supported combining the RBAs from swine UEF and swine AUC assays into a single regression model. The weighted least squares regression model derived from these data was as follows: swine RBA (%) = 1.23$ mouse RBA (%) - 0.80 (R-2 = 0.50). The mean relative percent difference between swine and mouse RBAs was +13%. This study extends and confirms conclusions from previous smaller studies to indicate that mouse and swine As RBA assays yield similar RBA estimates when applied to the same soils, although there appears to be a trend for the swine assay to predict higher RBAs than the mouse UEF assay. (C) 2017 Published by Elsevier Ltd. Refereed/Peer-reviewed

Arsenic (As) is the most frequently occurring contaminant on the Priority List of Hazardous Substances, which lists substances of greatest public health concern to people living at or near U.S. National Priorities List sites. Human exposure to arsenic via ingestion of arsenic-contaminated soils can have serious health impacts including increased cancer risk. Accurate assessment of human health risks from exposure to arsenic-contaminated soils depends on estimating its bioavailability, defined as the fraction of ingested arsenic absorbed across the gastrointestinal barrier and available for systemic distribution and metabolism. Arsenic bioavailability varies among soils and is influenced by site-specific soil physical and chemical characteristics and internal biological factors. This review describes the state-of-the science that supports our understanding of oral bioavailability of soil arsenic, the methods that are currently being explored for estimating soil arsenic relative bioavailability (RBA), and future research areas that could improve our prediction of the oral RBA of soil arsenic in humans. The following topics are addressed: (1) arsenic soil geochemistry; (2) arsenic toxicology; (3) in vivo models for estimating arsenic RBA; (4) in vitro bioaccessibility methods; and (5) conclusions and research needs.

Hand-pressing trials and hand-to-mouth soil transfer experiments were conducted to better understand soil loadings, soil transfer ratios for three mouthing activities, and variations in particle size distributions under various conditions. Results indicated that sand caused higher soil loadings on the hand than clay. When the moisture level of clay soil exceeded its liquid limit, soil loadings also increased. Greater pressing pressures also led to larger clay loadings. Clay with a moisture content close to its plastic limit caused the smallest soil loadings due to strong soil cohesion. Particle sizes of the transferred clay were larger than that of the original clay, indicating that hand-pressing and the pressure exerted may have enhanced clay particles of larger sizes adhering onto the hand. Nevertheless, the sizes of most particles that adhered to the hand were still smaller than 150 μm. Higher pressing pressures and greater moisture contents resulted in larger soil loadings on the hand, and transfer ratios became smaller. Transfer ratios from palm-licking with clay particles were smaller than those from finger-mouthing, which may have been due to finer particles that more readily adhered to the skin of the palm and that were transferred from the hand to the mouth with greater difficulty.

Given the potential for human exposure to silver nanoparticles from spray disinfectants and dietary supplements, we characterized the silver-containing nanoparticles in 22 commercial products that advertised the use of silver or colloidal silver as the active ingredient. Characterization parameters included: total silver, fractionated silver (particulate and dissolved), primary particle size distribution, hydrodynamic diameter, particle number, and plasmon resonance absorbance. A high degree of variability between claimed and measured values for total silver was observed. Only 7 of the products showed total silver concentrations within 20% of their nominally reported values. In addition, significant variations in the relative percentages of particulate vs. soluble silver were also measured in many of these products reporting to be colloidal. Primary silver particle size distributions by transmission electron microscopy (TEM) showed two populations of particles - smaller particles (

In 2008, the United States Environmental Protection Agency (USEPA) set a new National Ambient Air Quality Standard (NAAQS) for lead in total suspended particulate matter (Pb-TSP) which called for significant decreases in the allowable limits. The Federal Reference Method (FRM) for Pb-TSP promulgated in 1978 prescribes analysis of Pb by flame atomic absorption spectroscopy (FAAS), but the new limits approach the limits of quantitation of FAAS. On August 2, 2013, the USEPA finalized a new FRM for Pb-TSP. This new FRM describes two extraction methods and analysis by inductively coupled plasma-mass spectrometry (ICP-MS). The study described here was performed to evaluate the use of ICP-MS in the analysis of Pb-TSP for implementation of this new FRM. A multi-laboratory study of the new FRM demonstrated acceptable intra- and inter-laboratory precision and comparability for glass fiber, quartz, and PTFE filters, and acceptable accuracy for the analysis of three National Institute of Standards and Technology (NIST) Standard Reference Materials (SRMs). A comparison was made between analytical results obtained using the 1978 FRM and those obtained using the new FRM. The results demonstrate that the ICP-MS method performs acceptably for the determination of Pb-TSP with lower limits of quantitation and strong inter- and intra-laboratory precision.

Exposure to contaminated soil and dust is an important pathway in human health risk assessment. Physical and chemical characteristics and biological factors determine the bioaccessibility/bioavailability of soil and dust contaminants. Within a single sample, contamination may arise from multiple sources of toxic elements that may exist as different species that impact bioavailability. In turn, the bioaccessibility/bioavailability of soil and dust contaminants directly impacts human health risk. Research efforts focusing on development and application of in vitro and in vivo methods to measure the bioaccessibility/bioavailability of metal-contaminated soils have advanced in recent years. The objective of this workshop was to focus on developments in assessing the bioaccessibility/bioavailability of arsenic-contaminated soils, metals’ contamination in urban Canadian residences and potential children's exposures to toxic elements in house dust, an urban community-based study (i.e., West Oakland Resi...

The significant rise in consumer products and applications utilizing the antibacterial properties of silver nanoparticles (AgNPs) has increased the possibility of human exposure. The mobility and bioavailability of AgNPs through the ingestion pathway will depend, in part, on properties such as particle size and the surface chemistries that will influence their physical and chemical reactivities during transit through the gastrointestinal tract. This study investigates the interactions between synthetic stomach fluid and AgNPs of different sizes and with different capping agents. Changes in morphology, size and chemical composition were determined during a 30 min exposure to synthetic human stomach fluid (SSF) using Absorbance Spectroscopy, High Resolution Transmission Electron and Scanning Electron Microscopy (TEM/SEM), Dynamic Light Scattering (DLS), and Nanoparticle Tracking Analysis (NTA). AgNPs exposed to SSF were found to aggregate significantly and also released ionic silver which physically associated with the particle aggregates as silver chloride. Generally, the smaller sized AgNPs (

The U.S. Department of Housing and Urban Development in collaboration with the United States Environmental Protection Agency conducted a survey measuring lead, allergens, and insecticides in a randomly selected nationally representative sample of residential homes. Multistage sampling with clustering was used to select the 1131 homes of which a subset of 500 randomly selected homes included the collection of hard surface floor wipes. Samples were collected by trained field technicians between June 2005 and March 2006 using isopropanol wetted wipes. Samples were analyzed for a suite of 24 compounds which included insecticides in the organochlorine, organophosphate, pyrethroid and phenylpyrazole classes, and the insecticide synergist piperonyl butoxide. The most commonly detected were permethrin (89%), chlorpyrifos (78%), chlordane (64%), piperonyl butoxide (52%), cypermethrin (46%), and fipronil (40%). Mean and geometric mean (GM) concentrations varied widely among compounds, but were highest for trans-permethrin (mean 2.22 ng/cm2 and GM 0.14 ng/ cm2) and cypermethrin (mean 2.9 ng/cm2 and GM 0.03 ng/ cm2). Results show that most floors in occupied homes in the U.S. have measurable levels of insecticides that may serve as sources of exposure to occupants.

Several investigations have been conducted to develop in vitro bioaccessibility (IVBA) assays that reliably predict in vivo oral relative bioavailability (RBA) of arsenic (As). This study describes a meta-regression model relating soil As RBA and IVBA that is based upon data combined from previous investigations that examined the relationship between As IVBA and RBA when IVBA was determined using an extraction of soil in 0.4 M glycine at pH 1.5. Data used to develop the model included paired IVBA and RBA estimates for 83 soils from various types of sites such as mining, smelting, and pesticide or herbicide application. The following linear regression model accounted for 87% of the observed variance in RBA (R2 = .87): RBA(%) = 0.79 × IVBA(%) + 3.0. This regression model is more robust than previously reported models because it includes a larger number of soil samples, and also accounts for variability in RBA and IVBA measurements made on samples collected from sites contaminated with different As sources and conducted in different labs that have utilized different experimental models for estimating RBA.

The objective of this study was to establish a national relative moldiness index for homes in the United States.As part of the Housing and Urban Development's American Healthy Homes Survey, dust samples were collected by vacuuming 2 m in the bedrooms plus 2 m in the living rooms from a nationally representative 1096 homes in the United States using the Mitest sampler. Five milligrams of sieved (300 mum pore, nylon mesh) dust was analyzed by mold-specific quantitative polymerase chain reaction for the 36 indicator species in 1096 samples.On the basis of this standardized national sampling and analysis, an "Environmental Relative Moldiness Index" was created with values ranging from about -10 to 20 or above (lowest to highest).The Environmental Relative Moldiness Index scale may be useful for home mold-burden estimates in epidemiological studies.

For children, ingestion of soils and house dusts can be an important exposure pathway for regulated organic compounds. Following ingestion, the extent to which compounds desorb and become bioaccessible is a critical determinant of systemic adsorption. We characterized the physicochemical properties of 37 soil and house dust pairs collected during a national survey of United States homes. For each sample, we measured the bioaccessibility of fipronil, a phenylpyrazole insecticide using an in vitro, three- compartment digestive system, then modeled the physicochemical predictors of fipronil bioaccessibility. The properties of the soils and dusts were not correlated and percent carbon was the only significant predictor of bioaccessibility for both soils (p0.001) and dusts (p0.001). The carbon content of the soils (3.1±2.4%) was lower than that of the dusts (18.6±6.9%) Due to the lower carbon content, soil sorbed fipronil was more bioaccessible than dust sorbed fipronil. However, the slope of the bioaccessibility carbon regression line was steeper for the soils than for the house dusts. This suggested that, for soils having carbon percentages greater than those in this study, fipronil bioaccessibility may be less than that of house dusts having equal carbon content.

Soil and dust ingestion rates by children are among the most critical exposure factors in determining risks to children from exposures to environmental contaminants in soil and dust. We believe this is the first published soil ingestion study for children in Taiwan using tracer element methodology. In this study, 66 children under 3 years of age were enrolled from Taiwan. Three days of fecal samples and a 24-h duplicate food sample were collected. The soil and household dust samples were also collected from children's homes. Soil ingestion rates were estimated based on silicon (Si) and titanium (Ti). The average soil ingestion rates were 9.6±19.2 mg/day based on Si as a tracer. The estimated soil ingestion rates based on Si did not have statistically significant differences by children's age and gender, although the average soil ingestion rates clearly increased as a function of children's age category. The estimated soil ingestion rates based on Si was significantly and positively correlated with the sum of indoor and outdoor hand-to-mouth frequency rates. The average soil ingestion rates based on Si were generally lower than the results from previous studies for the US children. Ti may not be a suitable tracer for estimating soil ingestion rates in Taiwan because the Ti dioxide is a common additive in food. To the best of our knowledge, this is the first study that investigated the correlations between soil ingestion rates and mouthing behaviors in Taiwan or other parts of Asia. It is also the first study that could compare available soil ingestion data from different countries and/or different cultures. The hand-to-mouth frequency and health habits are important to estimate the soil ingestion exposure for children. The results in this study are particularly important when assessing children's exposure and potential health risk from nearby contaminated soils in Taiwan.

In the terrestrial environment, standardized protocols are available for measuring the exposure and effects of contaminants to invertebrates, but none currently exist for vertebrates. In an effort to address this, we proposed that developing lizard embryos may be used as a terrestrial vertebrate model. Lizard eggs may be particularly susceptible to soil contamination and in ovo exposure may affect hatchling size, mortality, as well as thyroid function. Toxicant-induced perturbations of thyroid function resulting from in ovo chemical exposure may result in toxicity during the critical perinatal period in reptiles. Fertilized Eastern fence lizard (Sceloporus undulatus) eggs were placed in cadmium (Cd)-spiked expanded perlite (0, 1.48, 14.8, 148, 1480, 14,800 microg Cd/g, nominal concentrations), artificially incubated at 28 degrees C, and examined daily for mortality. Whole lizard hatchlings as well as failed hatches were homogenized in ethanol and the homogenate was divided for Cd body residue analysis and thyroid hormone (triiodothyronine (T3) and thyroxine (T4)) analyses. Acute mortality was observed in the two highest doses (1480 and 14800 microg Cd/g). Cadmium body residues showed a higher internal concentration with increasing exposure concentration indicating uptake of Cd. There was a decrease in T3:T4 ratio at the highest surviving dose (148 microg Cd/g), however, there were no differences observed in hatchling size measured as weight and snout-vent length, or in whole body thyroid hormone levels. In summary, this study has shown Cd amended to a solid phase representing soil (perlite) can traverse the thin, parchment-like shell membrane of the fence lizard egg and bioaccumulate in lizard embryos. We believe this study is a good first step in investigating and evaluating this species for use as a model.

To evaluate the capabilities of in vitro assays to predict arsenic (As) relative bioavailability (RBA), we examined the relationship between As bioaccessibility, determined using a number of in vitro bioaccessibility (IVBA) methodologies (SBRC, IVG, PBET, DIN and UBM) and As RBA determined in a mouse assay for nine As-contaminated soils and 1 NIST reference material (2710a). Significant differences (P < 0.05) in As IVBA were observed within and between assays indicating that different IVBA methodologies may not produce congruent data, as a result of variability in the extracting medium constituents and/or differences in the pH of gastric and intestinal phases. When results of in vivo determinations of As RBA were compared with As IVBA results, there was no significant difference in slopes of the relationships (P = 0.49-0.88) when SBRC, IVG, PBET, DIN, and UBM gastric and intestinal phase data were used. A significantly (P < 0.05) smaller y-intercept was, however, determined for the in vivo-SBRC gastric phase correlation compared to SBRC, IVG, PBET, and DIN intestinal phase, a factor that may influence prediction of As RBA, especially for soils with low As RBA. When in vivo-in vitro relationships were compared to previously derived correlations from the literature, some differences were observed. These differences may be attributed to factors affecting both in vivo and in vitro data including physiological differences in animal models (e.g., mouse versus swine), which may influence As absorption, differences in the approach used to estimate As RBA, and variability arising from subtle interoperator differences in performance of in vitro assays Refereed/Peer-reviewed

A mouse assay for measuring the relative bioavailability (RBA) of arsenic (As) in soil was developed. In this study, results are presented of RBA assays of 16 soils, including multiple assays of the same soils, which provide a quantitative assessment of reproducibility of mouse assay results, as well as a comparison of results from the mouse assay with results from a swine and monkey assay applied to the same test soils. The mouse assay is highly reproducible; three repeated assays on the same soils yielded RBA estimates that ranged from 1 to 3% of the group mean. The mouse, monkey, and swine models yielded similar results for some, but not all, test materials. RBA estimates for identical soils (nine test soils and three standard reference materials [SRM]) assayed in mice and swine were significantly correlated (r = 0.70). Swine RBA estimates for 6 of the 12 test materials were higher than those from the mouse assay. RBA estimates for three standard reference materials (SRM) were not statistically different (mouse/swine ratio ranged from 0.86-1). When four test soils from the same orchard were assessed in the mouse, monkey, and swine assays, the mean soil As RBA were not statistically different. Mouse and swine models predicted similar steady state urinary excretion fractions (UEF) for As of 62 and 74%, respectively, during repeated ingestion doses of sodium arsenate, the water-soluble As form used as the reference in the calculation of RBA. In the mouse assay, the UEF for water soluble As(V) (sodium arsenate) and As(III) (sodium [meta] arsenite) were 62% and 66%, respectively, suggesting similar absolute bioavailabilities for the two As species. The mouse assay can serve as a highly cost-effective alternative or supplement to monkey and swine assays for improving As risk assessments by providing site-specific assessments of RBA of As in soils.