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Arsenic relative bioavailability in contaminated soils: comparison of animal models, dosing schemes and biological endpoints Jie Li, Chao Li, Hong-Jie Sun, Albert L. Juhasz, Jun Luo, Hong-bo Li, and Lena Q. Ma Environ. Sci. Technol., Just Accepted Manuscript • DOI: 10.1021/acs.est.5b04552 • Publication Date (Web): 23 Nov 2015 Downloaded from http://pubs.acs.org on November 23, 2015
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Arsenic relative bioavailability in contaminated soils: comparison of
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animal models, dosing schemes and biological endpoints
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Jie Li,† Chao Li,† Hong-Jie Sun,† Albert L. Juhasz,‡ Jun Luo,† Hong-Bo Li,*,† and Lena Q.
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Ma*,†,§
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†
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Nanjing University, Nanjing 210023, China
State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment,
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‡
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Mawson Lakes, South Australia 5095, Australia
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§
Centre for Environmental Risk Assessment and Remediation, University of South Australia,
Soil and Water Science Department, University of Florida, Gainesville, FL 32611, USA
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*
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School of the Environment, Nanjing University, Nanjing 210023, China; Tel./fax: +86 025
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8968 0637, E-mail:
[email protected] Corresponding author, State Key Laboratory of Pollution Control and Resource Reuse,
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TABLE OF CONTENT
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ABSTRACT: Different animals and biomarkers have been used to measure arsenic (As)
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relative bioavailability (RBA) in contaminated soils. However, there is a lack of As-RBA
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comparison based on different animals (i.e., swine and mouse) and biomarkers [area under
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blood As concentration curve (AUC) after a single gavaged-dose vs. steady state As urinary
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excretion (SSUE) and As accumulation in liver and kidneys after multiple doses via diet]. In
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this study, As-RBA in 12 As-contaminated soils with known As-RBA via swine blood AUC
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model were measured using mouse blood AUC, SSUE, liver and kidneys analyses.
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Arsenic-RBA for the four mouse assays was 2.8–61, 3.6–64, 3.9–74, and 3.4–61%.
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Compared to swine blood AUC assay (7.0–81%), though well correlated (R2=0.83), the
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mouse blood AUC assay yielded lower values (2.8–61%). Similarly, strong correlations of
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AS-RBA were observed between mouse blood AUC and mouse SSUE (R2=0.86) and
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between urine, liver, and kidneys (R2=0.75–0.89), suggesting As-RBA was congruent among
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different animals and endpoints. Different animals and biomarkers had little impact on the
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outcome of in vivo assays to validate in vitro assays. Based on its simplicity, mouse liver or
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kidney assay following repeated doses of soil-amended diet is recommended for future
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As-RBA studies.
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INTRODUCTION Arsenic (As) is ubiquitous in the environment including soils.1 As a carcinogen, it can
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cause adverse effects to human health including cancer.2 Incidental ingestion of contaminated
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soil has been identified as an important pathway for human exposure to As. Reliable
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assessment of human health risk from the ingestion of As-contaminated soil depends not only
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on total As concentration, but also its bioavailability (i.e., the proportion of soil-borne As that
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is absorbed into the systemic circulation following ingestion). As such, various animal assays
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have been developed to quantify As relative bioavailability (RBA, relative to the absorption
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of sodium arsenate) in contaminated soils.3-7
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As a measure of As-RBA, different biomarkers (As concentration in blood, kidneys,
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liver, or urine) have been used to determine As absorption following a single gavaged dose or
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multiple repeated doses of As-contaminated soil via diet. At present, the majority of As-RBA
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studies have utilized swine and mouse bioassays, with either area under the blood As
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concentration time curve (AUC) or steady state As urinary excretion (SSUE) being used as
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the endpoint of As exposure.5,8,9 Swine shares many similarities with humans (i.e., As and
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mineral metabolism, and bone development), which is the preferred animal model to assess
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As-RBA. 10-12 Compared to swine, mouse is cost-effective and easy to handle, and has the
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potential to be utilized in many labs.6,13-16 In addition, large sample size can be
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accommodated to ensure the robustness of As-RBA results. However, these animal models
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differ in physiological parameters, which may influence As absorption from contaminated
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soil, thereby influencing As-RBA measurement. To date, a dearth of information is available
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comparing As-RBA derived using different animal models, with only one study comparing
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As-RBA results from mouse and swine models in 12 As-contaminated soils.17
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In addition to different animal models, varying feeding schemes have been employed to
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measure As-RBA in contaminated soil. A steady state dosing approach has been utilized
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where animals are exposed to As-contaminated soil incorporated into feed for up to 10–14
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days. In this approach, either As excreted in urine during the exposure period or the last two
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days, or As concentration in liver or kidneys was used to determine As-RBA.6,7,18 This 4
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approach provides the advantage of mimicking daily continuous exposure to contaminated
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soil, however, feed is included in the methodology, which may influence As absorption.17 For
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example, inorganic phosphate may out compete arsenate for phosphate transporters in the
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gastrointestinal barrier, thereby reducing As absorption and As-RBA. To overcome this issue,
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alternative approaches have been used to assess As-RBA following administeration of a
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single gavaged dose of contaminated soil to fasted animals with area under the blood As
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concentration time curve (AUC) as the biomarker.4,5,8,19 With the exclusion of feed and under
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fasted conditions, this approach may provide a worst case scenario of As absorption. While
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different animal models and feeding schemes have been used to assess As-RBA, comparison
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studies detailing the influences of these parameters on As-RBA measurement are lacking.
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Therefore, the objective of this study was to compare As-RBA in contaminated soils
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determined using different animal models (i.e., mouse vs. swine), different feeding schemes
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(i.e., single gavaged dose vs. multiple diet doses), and different biomarkers (blood, urine,
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liver, and kidneys) to determine how these operational parameters impact As-RBA
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determination. In addition, a secondary objective was to determine how the different in vivo
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methods of As-RBA determination influenced the relationships between As-RBA and As
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bioaccessibility determined using common in vitro assays. This study will help to select a
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robust, easy, and inexpensive approach to measure As-RBA for large numbers of soil samples
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and for its use in validation studies of in vitro bioaccessibility assays.
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MATERIALS AND METHODS
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Arsenic-Contaminated Soils. In a previous study, Juhasz et al.5 determined As-RBA in
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12 contaminated soils (42 to 1114 mg As kg–1) using swine incorporating a single gavaged
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dose and AUC analysis. In these soils, As-RBA in the
