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Title: Comparison of the bioavailability of elemental waste laden soils using in vivo and in vitro analytical methodology and refinement of exposure/dose models. 1998 annual progress report

Abstract

'The authors hypotheses are: (1) the more closely the synthetic, in vitro, extractant mimics the extraction properties of the human digestive bio-fluids, the more accurate will be the estimate of an internal dose; (2) performance can be evaluated by in vivo studies with a rat model and quantitative examination of a mass balance, calculation and dose estimates from model simulations for the in vitro and in vivo system; and (3) the concentration of the elements Pb, Cd, Cr and selected Radionuclides present in the bioavailable fraction obtained with a synthetic extraction system will be a better indicator of contaminant ingestion from a contaminated soil because it represents the portion of the mass which can yield exposure, uptake and then the internal dose to an individual. As of April 15, 1998, they have made significant progress in the development of a unified approach to the examination of bioavailability and bioaccessibility of elemental contamination of soils for the ingestion route of exposure. This includes the initial characterization of the soil, in vitro measurements of bioaccessibility, and in vivo measurements of bioavailability. They have identified the basic chemical and microbiological characteristics of waste laden soils. These have been used to prioritize the soilsmore » for potential mobility of the trace elements present in the soil. Subsequently they have employed a mass balance technique, which for the first time tracked the movement and distribution of elements through an in vitro or in vivo experimental protocol to define the bioaccessible and the bioavailable fractions of digested soil. The basic mass balance equation for the in vitro system is: MT = MSGJ + MIJ + MR. where MT is the total mass extractable by a specific method, MSGJ, is the mass extracted by the saliva and the gastric juices, MIJ is the mass extracted by the intestinal fluid, and MR is the unextractable portion of the initial mass. The above is based upon the use of a synthetic digestive bio-fluids model that includes the saliva, gastric juices, and intestinal fluids. The system has been devised to sequentially extract elements from soil by starting with an extraction by the saliva and carrying the entire mixture to the subsequent bio-fluids for further extraction. The residence time of the soil in each extractant and the liquid to mass ratio in the gastric juices are based upon typical values known for the human digestive system. Experiments were conducted to examine the sensitivity of the extractions to changes in these major variables. The results indicated the lack of significant extraction after 2 h of residence in gastric fluid. The range of variation of the liquid to mass ratio was element dependent over the interval 100:1 and 5,000:1. The final values used for the extraction protocol were: 2 h residence time , and a ratio of 1,000:1. Details of the chemical composition of the extraction protocol are found in Hamel, 1998.'« less

Authors:
; ;  [1]; ;  [2]
  1. Univ. of Medicine and Dentistry of New Jersey, Piscataway, NJ (US). Exposure Measurement and Assessment Div.
  2. Rutgers, The State Univ. of New Jersey, New Brunswick, NJ (US)
Publication Date:
Research Org.:
Univ. of Medicine and Dentistry of New Jersey, Environmental and Occupational Health Sciences Institute, Piscataway, NJ (US)
Sponsoring Org.:
USDOE Office of Environmental Management (EM), Office of Science and Risk Policy
OSTI Identifier:
13580
Report Number(s):
EMSP-54584-98
ON: DE00013580
Resource Type:
Technical Report
Country of Publication:
United States
Language:
English
Subject:
56; Progress Report; Biophysics; Doses; Health Hazards; Ecology; Risk Assessment; PROGRESS REPORT; BIOPHYSICS; DOSES; HEALTH HAZARDS; ECOLOGY; RISK ASSESSMENT

Citation Formats

Lioy, P.J., Gallo, M., Georgopoulos, P., Tate, R., and Buckley, B.. Comparison of the bioavailability of elemental waste laden soils using in vivo and in vitro analytical methodology and refinement of exposure/dose models. 1998 annual progress report. United States: N. p., 1998. Web. doi:10.2172/13580.
Lioy, P.J., Gallo, M., Georgopoulos, P., Tate, R., & Buckley, B.. Comparison of the bioavailability of elemental waste laden soils using in vivo and in vitro analytical methodology and refinement of exposure/dose models. 1998 annual progress report. United States. doi:10.2172/13580.
Lioy, P.J., Gallo, M., Georgopoulos, P., Tate, R., and Buckley, B.. Mon . "Comparison of the bioavailability of elemental waste laden soils using in vivo and in vitro analytical methodology and refinement of exposure/dose models. 1998 annual progress report". United States. doi:10.2172/13580. https://www.osti.gov/servlets/purl/13580.
@article{osti_13580,
title = {Comparison of the bioavailability of elemental waste laden soils using in vivo and in vitro analytical methodology and refinement of exposure/dose models. 1998 annual progress report},
author = {Lioy, P.J. and Gallo, M. and Georgopoulos, P. and Tate, R. and Buckley, B.},
abstractNote = {'The authors hypotheses are: (1) the more closely the synthetic, in vitro, extractant mimics the extraction properties of the human digestive bio-fluids, the more accurate will be the estimate of an internal dose; (2) performance can be evaluated by in vivo studies with a rat model and quantitative examination of a mass balance, calculation and dose estimates from model simulations for the in vitro and in vivo system; and (3) the concentration of the elements Pb, Cd, Cr and selected Radionuclides present in the bioavailable fraction obtained with a synthetic extraction system will be a better indicator of contaminant ingestion from a contaminated soil because it represents the portion of the mass which can yield exposure, uptake and then the internal dose to an individual. As of April 15, 1998, they have made significant progress in the development of a unified approach to the examination of bioavailability and bioaccessibility of elemental contamination of soils for the ingestion route of exposure. This includes the initial characterization of the soil, in vitro measurements of bioaccessibility, and in vivo measurements of bioavailability. They have identified the basic chemical and microbiological characteristics of waste laden soils. These have been used to prioritize the soils for potential mobility of the trace elements present in the soil. Subsequently they have employed a mass balance technique, which for the first time tracked the movement and distribution of elements through an in vitro or in vivo experimental protocol to define the bioaccessible and the bioavailable fractions of digested soil. The basic mass balance equation for the in vitro system is: MT = MSGJ + MIJ + MR. where MT is the total mass extractable by a specific method, MSGJ, is the mass extracted by the saliva and the gastric juices, MIJ is the mass extracted by the intestinal fluid, and MR is the unextractable portion of the initial mass. The above is based upon the use of a synthetic digestive bio-fluids model that includes the saliva, gastric juices, and intestinal fluids. The system has been devised to sequentially extract elements from soil by starting with an extraction by the saliva and carrying the entire mixture to the subsequent bio-fluids for further extraction. The residence time of the soil in each extractant and the liquid to mass ratio in the gastric juices are based upon typical values known for the human digestive system. Experiments were conducted to examine the sensitivity of the extractions to changes in these major variables. The results indicated the lack of significant extraction after 2 h of residence in gastric fluid. The range of variation of the liquid to mass ratio was element dependent over the interval 100:1 and 5,000:1. The final values used for the extraction protocol were: 2 h residence time , and a ratio of 1,000:1. Details of the chemical composition of the extraction protocol are found in Hamel, 1998.'},
doi = {10.2172/13580},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Mon Jun 01 00:00:00 EDT 1998},
month = {Mon Jun 01 00:00:00 EDT 1998}
}

Technical Report:

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  • 'The bioavailability study has made significant progress in developing in vitro methodology, and the authors have completed the time course in vivo studies. The in vitro studies have been conducted to establish the major digestive variables of concern and the values to be used in application of both the saliva/gastric juice and intestinal fluid components of a synthetic digestive extraction. In vitro and in vivo experiments have been conducted on the 575 urn particle fraction of a soil sample collected in a Jersey City State Park. Five Jersey City soil samples were first characterized for physical and chemical characteristics. Basedmore » upon the composition of the five soils, one was selected for use in the first series of experiments. The second set of in vivo studies are to be conducted on a standard NIST Montana soil. It has already been examined for bioaccessibility and availability with the in vitro methodology. A sample has been collected in Bayonne to obtain an urban background soil. Surficial soil samples have been acquired from the Savannah River Site of the DOE. These are not radioactive but are contaminated with heavy metals, e.g. arsenic, and are being analyzed by both the in vivo and in vitro methodology. During this past summer a second set of soil samples were collected at Savannah River Site. These contain levels of both heavy metals and radionuclides. Recently, a special extraction laboratory has been constructed at EOHSI, with resources made available from the organization. It will handle the extraction and measurement of the radio activity of the soil, and extracts obtained by the in vivo techniques. It is anticipated that the SRS samples collected this summer will be available for analysis in both the in vivo and in vitro systems this fall. The initial characterization will be for soil, physical and chemical content, and microbial characteristics. The samples will be analyzed for the 5 75 urn particle size fraction, and the total mass 5 250 urn in particle size. Previous experience has suggested a preferential distribution of toxic materials in the small size fraction of soils, and that these particles will define the majority of the potential bioavailabiity of the soil. Initial mass balance experiments have been completed on the in vitro methodology, and they are attempting to optimize the recovery of total mass of each metal or radionuclide present in a soil. The mass balance studies have proceeded with the use of test soils from a home in Califon that has known arsenic contamination, and a lead contaminated soil from Columbia Univ. which has been used in human feeding studies. The plans for next year intend to focus on the analysis of the SRS samples, radioactive and non-radioactive and soils from other DOE sites and pharmacokinetic modeling. The technique development has moved to the point where the applications can be made using a reproducible protocol.'« less
  • The bioavailability of soil contaminants can be measured using in vitro or in vivo techniques. Since there was no standard method for intercomparison among laboratories, we compared two techniques for bioavailability estimation: in vitro dissolution and in vivo rat feeding model for a NIST-traceable soil material. Bioaccessibility was measured using a sequential soil extraction in synthetic analogues of human saliva, gastric and intestinal fluids. Bioavailability was measured in Sprague Dawley rats by determining metal levels in the major organs and urine, feces, and blood. Bioaccessibility was found to be a good indicator of relative metal bioavailability. Results are presented frommore » bioaccessible experiments with Cesium in contaminated DOE soils, and total alpha and beta bioaccessibility. The results indicate that the modified methodology for bioaccessibility can be used for specific radionuclide analysis.« less
  • 'The purpose of this study is to determine the bioavailability of organic solvents following dermal exposures to contaminated soil and water. Breath analysis is being used to obtain real-time measurements of volatile organics in expired air following exposure in rats and humans. Rhesus monkeys will be used as surrogates for humans in benzene exposures. The exhaled breath data is being analyzed using physiologically based pharmacokinetic (PBPK) models to determine the dermal bioavailability of organic solvents under realistic exposure conditions. The end product of this research will be a tested framework for the rapid screening of real and potential exposures whilemore » simultaneously developing physiologically based pharmacokinetic (PBPK) models to comprehensively evaluate and compare exposures to organics from either contaminated soil or water. This report summarizes work 7 months into a 3-year project. Method development has produced systems for solvent exposure from soil and water which mimic actual exposure, and for which animals and human volunteers can be safely tested. Soil exposure is generally open to the air (working the soil) while water exposure is generally immersion. For 6--8 hour test exposure, a patch has been developed where soil is contained against the skin by a non-occlusive membrane, while simultaneously allowing volatilization of test solvent to the environment (activated charcoal). The water counterpart is an occlusive glass culture dish, sealed to skin with silicone adhesive. Shorter term exposure is done by one hand immersion in a bucket containing circulating water or soil, the volunteer instructed to move fingers through the water or soil. Human volunteers and animals breathe fresh air via a new breath-inlet system that allows for continuous real-time analysis of undiluted exhaled air. The air supply system is self-contained and separated from the exposure solvent-laden environment. The system uses a Teledyne 3DQ Discovery ion trap mass spectrometer (MS/MS) equipped with an atmospheric sampling glow discharge ionization source (ASGDI). The MS/MS system provides an appraisal of individual chemical components in the breath stream in the single-digit parts-per-billion (ppb) detectable range for each of the compounds proposed for study, while maintaining linearity of response over a wide dynamic range.'« less
  • 'Increased risk of malignancy following exposure to genotoxic agents in the environment is a major public concern. Exposure to radiation, benzene, and organic solvents is associated with an increased risk of leukemia; however the mechanism of leukemogenesis is unknown. The authors postulate that chemical(s) that increase the rate of genomic instability and induce hematotoxicity will promote accumulation of genetically-damaged hematopoietic stem cells (hsc), and thus contribute towards development of environmentally-induced hematologic malignancy. They will use molecular and cellular approaches to establish the relationship between hematoxicity, genomic instability and production of genetically aberrant hsc and progeny in mice exposed to radiation,more » benzene and trichloroethylene (TCE). The goals of this project are to (1) determine whether recruitment of hsc into cycle by agents that induce hematotoxicity (i.e., pancytopenia, anemia) facilitates fixation of genetic damage in hsc exposed to environmental genotoxins in vivo. (2) Determine whether environmental genotoxins with leukemogenic potential disrupt hsc genomic integrity by inactivating cell cycle checkpoints. (3) Determine whether low dose exposures to agents that induce chronic pancytopenia/anemia and/or cyclic hemopoiesis increase fixation of genetic damage in hsc. Increased understanding of the relationship between genotoxicity, hematotoxicity and genomic instability will (a) lend insight into mechanisms underlying environmental-induction of leukemic progression, (b) facilitate development of a rationale to identify chemical combinations which synergize to increase or decrease leukemogenic potential, and (c) provide opportunities to optimize approaches for biomonitoring and risk assessment. This report summarizes work after 1.5 year of a 3 year project. Accomplishments to-date include demonstration that the cycling status of hemopoietic stem cells at the time of genotoxin exposure alters the frequency and persistence of genetically damaged hemopoietic stem cells and associated progeny (Aim 1), development of assays to measure genomic instability in hemopoietic stem cells and associated progenitors (Aim 2) and quantification of genomically aberrant hsc and progeny following radiation, benzene and TCE exposures (Aim 2). Mice with varying susceptibility to leukemogenesis have been exposed to combinations of radiation, benzene and TCE to allow assessment of the cellular and genomic perturbations associated with leukemogenesis.'« less
  • 'This EMSP research endeavors to understand fundamental laser-ablation sampling processes and to determine the influence of these processes on analytical characterization of EM waste-site samples. The issues germane to the EMSP are sensitivity and accuracy of analysis. These issues are researched by studying fractionation, sample transport, mass loading, and analytical system optimization. Inductively coupled plasma-mass spectroscopy (ICP-MS) is emphasized in this research because of its use throughout the DOE labs and sites. This report summarizes research performed over the first half of this three-year program. Four issues were emphasized to improve analytical sensitivity and accuracy, including the time dependent lasermore » removal of mass from a solid sample, fractionation, particle generation and transport, and optimization of the ICP-MS for laser ablation sampling. This research has led to six journal publications.'« less