The physiologically based extraction test (PBET) is an in vitro test system for predicting the bioavailability of metals from a solid matrix and incorporates gastrointestinal tract parameters representative of a human (including stomach and small intestinal pH and chemistry, soil-to-solution ratio, stomach mixing, and stomach emptying rates). For lead (Pb), the results of the PBET are linearly correlated with results from a Sprague-Dawley rat model (r 2 ) 0.93 between in vitro and in vivo results, n ) 7). For arsenic (As), the results of the PBET are overpredicting bioavailability study results in rabbit and primate models (2-11% difference between in vitro and in vivo results, depending on the animal model). The PBET was not designed to supplant bioavailability studies using animal models, but rather to estimate Pb and As bioavailability when animal study results are not available. Dissolution of Pb in the acidic stomach environment was strongly pH dependent; the extent of dissolution decreased by 65% when stomach pH was increased from 1.3 to 2.5. Arsenic solubility decreased by only 16% over the same pH range. Lead was removed from solution to a greater extent than As by neutralization during the small intestinal simulation, consistent with adsorption and precipitation reactions occurring for Pbsbut not Assat neutral pH values. In addition to providing mechanistic explanations for controls on Pb and As bioavailability, the PBET allows estimates of site-specific Pb and As bioavailability from soil for the purpose of exposure assessment.
Cleanup goals for sites affected by inorganic contaminants
often are established on the basis of risk assessments,
and these assessments rely on the estimated oral toxicity
of the substances of concern. These toxicity estimates
typically are based on historical studies in which a soluble
salt of the metal was dissolved in water or mixed in
food and then ingested by an animal or human. However,
these toxicity studies do not account for the characteristics
of a metal in soil or the limitations that these characteristics
place on enteric absorption of that metal. Therefore, a
more accurate risk assessment must account for the
bioavailability of the metal in site-specific soil, relative to
the bioavailability of the metal in the form administered in the
toxicity study (i.e., the relative bioavailability of the
element in soil). Historically, relative bioavailability estimates
for metals in soil have been based on in vivo studies in
laboratory animals. Given the costs and time constraints
associated with such studies, it is clear that a more efficient
alternative is desirable. The most promising option
involves the development and validation of in vitro extraction
tests that are predictive of oral metals bioavailability
from soil. Such tests would provide a rapid and inexpensive
method for developing more accurate exposure estimates
for use in human health risk assessments. This paper
reviews the site-specific in vivo studies that have been
conducted to estimate the relative bioavailability of arsenic
and lead in soil, discusses the soil and mineralogical
factors that influence the bioavailability of these elements,
and reviews the research to date on the development of
bioavailability-predictive extraction tests for metals in soil.
Finally, this paper outlines an ongoing collaborative
research project to formally validate an in vitro extraction
test for use in estimating the oral bioavailability of
arsenic and lead in soil.
A screening-level in vitro test was developed to evaluate the relative solubility of ingested lead (Pb) from different mine wastes in the gastrointestinal (GI) tract. The in vitro method, modeled after assay methods for available iron from food, used a laboratory digestion procedure designed to reproduce GI tract chemistry and function. The in vitro method was independently calibrated against a rabbit feeding study, demonstrating that only 1-6% of the total Pb in four mine-waste samples with disparate Pb mineralogy was bioaccessible. In vitro method development tests indicated that H+ concentration and Clc omplexation control dissolution of Pb-bearing minerals in the stomach and that both GI tract enzymes and organic acids are necessary to maintain Pb in the soluble form on entering the small intestine. The experimental results indicate that ingestion of Pb-bearing mine wastes results in limited Pb solubility and that the in vitro test provides a screening-level estimate of the maximum available Pb from mine wastes.
Arsenic is widely distributed in the environment by natural and human means. The potential for adverse health effects from inorganic arsenic depends on the level and route of exposure. To estimate potential health risks of inorganic arsenic, the apportionment of exposure among sources of inorganic arsenic is critical. In this study, daily inorganic arsenic intake of U.S. adults from food, water, and soil ingestion and from airborne particle inhalation was estimated. To account for variations in exposure across the U.S., a Monte Carlo approach was taken using simulations for 100,000 individuals representing the age, gender, and county of residence of the U.S. population based on census data. Our analysis found that food is the greatest source of inorganic arsenic intake and that drinking water is the next highest contributor. Inhalation of airborne arsenic-containing particles and ingestion of arsenic-containing soils were negligible contributors. The exposure is best represented by the ranges of inorganic arsenic intake (at the 10 th and 90 th percentiles), which were 1.8 to 11.4 µg/day for males and 1.3 to 9.4 µg/day for females. Regional differences in inorganic arsenic exposure were due mostly to consumption of drinking water containing differing inorganic arsenic content rather than to food preferences.
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