https://stacks.cdc.gov/view/cdc/37676/cdc_37676_DS1.pdf

Toxicological Profile for Lead

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 (r2 = 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% whe...

Estimation of lead and arsenic bioavailability using a physiologically based extraction test

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 ...

Advances in evaluating the oral bioavailability of inorganics in soil for use in human health risk assessment

Soil ingestion can be a major route of human exposure to many immobile soil contaminants. The present risk assessment is based on toxicity studies in which contaminants are typically ingested in liquid or food matrices. The difference in bioavailability of contaminants ingested in a soil matrix is not taken into account. To become bioavailable, contaminants first need to become bioaccessible, i.e., they must be mobilized from the soil during digestion. Soil contaminants may be less bioaccessible than contaminants from liquid or food, so that the risks can be overestimated. This article describes the development of an in vitro human digestion model that is physiologically based. It can be used as a tool to assess bioaccessibility. We explain the rationale behind the experimental design of the model. We address the aspects of the simulated compartments of the gastrointestinal tract, temperature, soil-to-fluid ratio, ratio of digestive juices, transit times, centrifugation, pH values, mixing, constituents and their concentrations, and bile. The optimized in vitro digestion model was applied in a case study. The bioaccessibility of lead in pottery flakes with glazing was determined and compared to the bioaccessibility of lead in the soil from which the pottery flakes were removed. The data indicate that pottery flake lead is considerably less bioaccessible (0.3 +/- 0.2%) than lead in soil without pottery flakes (42-66% at the same site, and 28-73% at other sites in the same town). Furthermore, bioaccessibility values of lead in soil appear to be less than calculated bioaccessibility values for dietary lead (which are based on the criterion used by the Dutch risk assessment and on literature absorption data). This indicates that accounting for the matrix of ingestion can affect the exposure assessment for lead. The in vitro digestion model is a promising tool for studying the effect of the ingestion matrix on bioaccessibility.

https://www.bgs.ac.uk/barge/docs/Oomen_et_al_2003.pdf

Development of an in vitro digestion model for estimating the bioaccessibility of soil contaminants

Chemical immobilization, an in situ remediation method where inexpensive chemicals are used to reduce contaminant solubility in contaminated soil, has gained attention. We investigated the effectiveness of lime-stabilized biosolid (LSB), N-Viro Soil (NV), rock phosphate (RP), and anaerobic biosolid (AB) to reduce extractability and plant and gastrointestinal (GI) bioavailability in three Cd-, Pb-, and Zn-contaminated soils from smelter sites. Treated (100 g kg(-1) soil) and control soils were incubated at 27 degrees C and -0.033 MPa (0.33 bar) water content for 90 d. The effect of soil treatment on metal extractability was evaluated by sequential extraction, on phytoavailability by a lettuce bioassay (Lactuca sativa L.), on human GI availability of Pb from soil ingestion by the Physiologically Based Extraction Test. The largest reductions in metal extractability and phytoavailability were from alkaline organic treatments (LSB and NV). Phytotoxic Zn [1188 mg Zn kg(-1) extracted with 0.5 M Ca(NO3)2] in Blackwell soil (disturbed soil) was reduced by LSB, NV, and RP to 166, 25, and 784 mg Zn kg(-1), respectively. Rock phosphate was the only treatment that reduced GI-available Pb in both gastric and intestinal solutions, 23 and 92%, respectively. Alkaline organic treatments (LSB, NV) decreases Cd transmission through the food chain pathway, whereas rock phosphate decreases risk from exposure to Pb via the soil ingestion pathway. Alkaline organic treatments can reduce human exposure to Cd and Pb by reducing Zn phytotoxicity and revegetation of contaminated sites.

Chemical Immobilization of Lead, Zinc, and Cadmium in Smelter-Contaminated Soils Using Biosolids and Rock Phosphate

An animal model using rats was developed to initiate investigations on the bioavailability of different sources of environmental lead. Lead must be absorbed and transported to target organs like brain, liver, kidney, and bone, before susceptible cells can be harmed. The bioavailability and therefore the toxicity of lead are dependent upon the route of exposure, dose, chemical structure, solubility, particle size, matrix incorporation, and other physiological and physicochemical factors. In the present study male F344 rats were fed < or = 38 microns size particles of lead sulfide, lead oxide, lead acetate, and a lead ore concentrate from Skagway, Alaska, mixed into the diet at doses of 0, 10, 30, and 100 ppm as lead for 30 d. No mortality or overt symptoms of lead toxicity were observed during the course of the study. Maximum blood lead concentrations attained in the 100 ppm groups were approximately 80 micrograms/dl in rats fed lead acetate and lead oxide, and were approximately 10 micrograms/dl in those fed lead sulfide and lead ore concentrate. Maximum bone lead levels in rats fed soluble lead oxide and lead acetate were much higher (approximately 200 micrograms/g) than those seen in rats fed the less soluble lead sulfide and lead ore (approximately 10 micrograms); kidney lead concentrations were also about 10-fold greater in rats fed the more soluble compared to the less soluble lead compounds. However, strong correlations between dose and tissue lead concentrations were observed in rats fed each of the four different lead compounds. Kidney lesions graded as minimal occurred in 7/10 rats fed 30 ppm and in 10/10 rats fed 100 ppm lead acetate, but not at lower doses or from other lead compounds. Similarly, urinary aminolevulinic acid excretion, a biomarker for lead toxicity, was increased in rats fed 100 ppm lead acetate or lead oxide, but was unaffected at lower doses or by the less soluble lead compounds. Although the histological and biochemical responses to lead toxicity were restricted to the more soluble lead compounds in this study, lead from Skagway lead ore concentrate and lead sulfide was also bioavailable, and accumulated in proportion to dose in vulnerable target organs such as bone and kidney. Longer-term studies with different mining materials are being conducted to determine if tissue lead continues to increase, and whether the levels attained are toxic. Data from such studies can be used to compare the toxicity and bioavailability of lead from different sources in the environment.

R. A. Jeffcoat

Papers

Comparison of lead bioavailability in F344 rats fed lead acetate, lead oxide, lead sulfide, or lead ore concentrate from Skagway, Alaska