Objective ranges of soil-to-dust transfer coefficients for lead-impacted sites.

Residential yard soil and indoor dust datasets from eight communities near historical mining, smelting, and refining operations were used to quantify soil track-in, an important factor in evaluating indoor exposures to soil metals and to set residential soil cleanup levels. Regression analyses were used to derive slopes that represent mass soil-to-dust transfer coefficients or MSDs. Lead concentration data were available for all datasets. Arsenic data were available for six of the eight datasets. Cadmium and zinc data were available for one dataset, allowing limited comparison of MSDs for lead with other metals. Covariates that could indicate potential indoor sources of metals, such as house age and indoor heating source, were examined by multivariate regression analysis when available (three datasets). Covariates that could affect soil track-in, such as the amount of bare soil in the yard or having pets, were examined by stratified linear regression analysis when available (two datasets). Most of the R-squared values for lead, cadmium and zinc indicate a good to moderate fit (≥0.25), but for arsenic most indicate a poor fit (<0.25). Significant MSDs for models with a good to moderate fit range from 0.14 to 0.47 for lead, and 0.12 to 0.43 for the other metals (arsenic, cadmium, and zinc). The treatment of outliers was a significant methodological factor affecting the slope of the regressions. Substantial variability is expected among soils at residences due to both physical characteristics of each property and the ways in which residents interact with their home. Survey data providing information on various factors affecting soil track-in help to refine MSD estimates. For three of the datasets, covariate data were available that improved model fit by multivariate or stratified regression analysis for lead. When multivariate or stratified regression analyses were performed, the estimated MSD varied as little as <1% to as great as 200% depending on the dataset, but all estimates were below 0.4. Notably, the MSDs were lowest for the three datasets with the highest soil lead concentrations, i.e., those with average soil lead concentrations greater than 300 mg/kg after outlier removal. For five of the six datasets that had both arsenic and lead sampled, arsenic MSDs were much less than the lead MSDs; however, only two of the sites' arsenic models had significant MSDs and adequate fit. Cadmium and zinc were only included in one dataset, limiting our ability to draw any conclusions from comparison to those MSDs. The results of our study are consistent with prior studies suggesting that MSDs for metals without internal sources are 0.3-0.4, and application of MSDs in that range will provide more reliable exposure estimates than the 0.7 default value used by the United States Environmental Protection Agency in the Integrated Exposure Uptake Biokinetic (IEUBK) Model.

Absolute bioavailability of lead acetate and mining waste lead in rats.

The primary purpose of this study was to generate data that could be used to determine the absolute bioavailability of lead using data from a previous study in which soil containing lead from mining waste was mixed with feed. Young male and female Sprague-Dawley rats (7-8 weeks of age, five/sex/group) were given either soluble lead acetate mixed in a purified diet (AIN-76) at three different dose levels (1, 25, and 250 ppm Pb for 30 consecutive days) or intravenously at doses of 0.02, 0.20, and 2.0 mg Pb/kg BW for 29 days. A control group (purified diet only) was also included. The intravenous groups were used to provide maximal absorption (lead presumed to be 100% bioavailable) and accumulation data for lead in blood, bone, and liver. The lead acetate groups were used to evaluate the comparability of the present study with a previous study that compared bioavailable lead from ingested soil and lead acetate. Group mean whole blood, bone and liver lead concentration values increased with increasing dose levels for all treatment groups. A linear relationship was observed between blood lead concentration and dose following intravenous administration of lead and this provided empirical support for using blood lead concentrations at supposed steady state (approximately 30 days) to compute the bioavailability of lead administered by different routes and from different sources. The absolute bioavailability values of mining waste lead in soil were low based on the results for all tissue types. Absolute bioavailability values for lead acetate in dosed feed for blood, bone, and liver were approximately 6-, 19-, and 20-fold greater, respectively, than mining waste lead. Based on the current design and test system used, the absolute bioavailability of mining waste lead in soil administered in feed was approximately 3% based on blood data and less than 1% based on bone and liver data. These data are consistent with the low solubility of the constituent lead mineral phases in Butte soils.

A market basket survey of inorganic arsenic in food.

Dietary arsenic intake estimates based on surveys of total arsenic concentrations appear to be dominated by intake of the relatively non-toxic, organic arsenic forms found in seafood. Concentrations of inorganic arsenic in food have not been not well characterized. Accurate dietary intake estimates for inorganic arsenic are needed to support studies of arsenic's status as an essential nutrient, and to establish background levels of exposure to inorganic arsenic. In the market basket survey reported here, 40 commodities anticipated to provide at least 90% of dietary inorganic arsenic intake were identified. Four samples of each commodity were collected. Total arsenic was analysed using an NaOH digestion and inductively coupled plasma-mass spectrometry. Separate aliquots were analysed for arsenic species using an HCl digestion and hydride atomic absorption spectroscopy. Consistent with earlier studies, total arsenic concentrations (all concentrations reported as elemental arsenic per tissue wet weight) were highest in the seafoods sampled (ranging from 160 ng/g in freshwater fish to 2360 ng/g in saltwater fish). In contrast, average inorganic arsenic in seafood ranged from less than 1 ng/g to 2 ng/g. The highest inorganic arsenic values were found in raw rice (74 ng/g), followed by flour (11 ng/g), grape juice (9 ng/g) and cooked spinach (6 ng/g). Thus, grains and produce are expected to be significant contributors to dietary inorganic arsenic intake.

Topical application of a tumor promoter induces proliferation of an adherent cell population in murine spleen.

The tumor-promoting phorbol esters have proven to be potent immunomodulatory agents in vitro. It has not been possible to assess the role of phorbol ester-induced alterations of immune function in tumor promotion however, due to a lack of in vivo studies. Studies were therefore designed to assess proliferative responses of murine leukocytes after in vivo exposure to these agents. Topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) was found to cause an increase in division of murine spleen cells. The effect was dose-related up to 14 micrograms per application and generally reached a peak two days after TPA application. Cell separation experiments suggested TPA was acting on an adherent cell population distinct from splenic lymphocytes. Inflammatory reactions to TPA followed a similar time-course to that observed for spleen cell proliferation. The increased levels of proliferation observed could, therefore, be due to increased division of neutrophil and/or macrophage precursors residing in the murine spleen and appeared also to be associated with the inflammatory reaction induced by TPA.

Evaluation of methods for assessing the oral bioavailability of inorganic mercury in soil.

The risks associated with environmental exposures to inorganic mercury are typically assessed based on toxicity studies conducted with the soluble salt, mercuric chloride (HgCl2). Evidence indicates, however, that inorganic mercury is present in soil as a variety of compounds and that oral absorption of inorganic mercury decreases with a decrease in the solubility of the mercury compound being studied. Thus, while HgCl2 is approximately 15-20% bioavailable, the bioavailability of cinnabar (HgS) may be 30- to 60-fold less. The solubility and, hence, bioavailability of inorganic mercury in soil is expected to be substantially less than that of HgCl2 due to the presence of less soluble compounds and their interactions with soil constituents. Quantification of this difference in bioavailability is important in assessing potential risks associated with exposure to mercury-containing soil. A review of available studies supports the expectation that mercury bioavailability in soils will be reduced. This paper reviews methods for assessing soil metal absorption with consideration of the characteristics of the oral absorption of elemental and inorganic mercury that should be evaluated in designing additional studies. Because of the very slow elimination of mercury in some species, it is recommended that a repeated-dose study be conducted. Such a study would yield an estimate of relative bioavailability based on a comparison of tissue mercury concentrations in animals ingesting soil with those of animals receiving HgCl2. The dose, age, gender, and species of animal selected are not expected to affect relative bioavailability estimates; however, it is recommended that studies be conducted in two animal species. Rats should be used because they have been used in many studies of mercury absorption and toxicity. A species of large animals such as monkeys, swine, or dogs should also be used to provide confirmation in a species with greater similarities to humans in gastrointestinal physiology and anatomy. Other critical factors in designing these studies, such as selection and characterization of soil samples, are also addressed.

Use of a five-day test to predict the long-term effects of gastric antisecretory agents on serum gastrin in rats.

It has been hypothesized that prolonged achlorhydria causes compensatory elevation of serum gastrin, and that there is an association in rats between sustained hypergastrinemia, hyperplasia of gastric enterochromaffin-like cells, and subsequent formation of gastric carcinoids in 2-year carcinogenicity studies. The present study examined whether daily administration of gastric antisecretory drugs in rats for 4 days could cause hypergastrinemia associated with inhibition of acid output. Rats were dosed orally for 4 days with the histamine H2-receptor antagonist ranitidine or the H+,K+-sensitive ATPase inhibitor omeprazole, and examined on day 5 for effects on gastric acid secretion and serum gastrin. Omeprazole (138 mg/kg/day significantly inhibited gastric acid secretion and increased serum gastrin levels. Large, single daily doses of ranitidine (1000-2000 mg/kg/day) had no effect on 24-hr acid or gastrin secretion; however, ranitidine did inhibit next-day acid secretion with associated increases in serum gastrin when administered in three divided doses. These results with ranitidine support the hypothesis that a sustained gastric antisecretory action will cause a compensatory hypergastrinemia, regardless of the antisecretory agent used. The ability to detect increased serum gastrin levels associated with inhibition of acid secretion, after administration of antisecretory agents for only 4 days, suggest that this short 5-day test may be useful for determining the potential of antisecretory agents to cause hypergastrinemia due to 24-hr inhibition of acid secretion and may be predictive of long-term hyperplastic changes.

An assessment of lead absorption from soil affected by smelter emissions.

The purpose of this study was to assess the oral bioavailability of lead in soil collected from a former smelter site in Sandy, Utah, USA. Sprague-Dawley rats (approximately 4 weeks of age, 5 of each sex in group) were given either soil lead or lead acetate mixed in a purified diet (AIN-93G ™) at four different concentrations for 31 consecutive days. Food consumption measurements were used to compute mean daily lead exposures for the soil lead and lead acetate groups. The lead acetate treatment yielded higher concentrations of lead in the blood and bone than the soil lead treatment. Mean blood lead values ranged from below the detection limit (3 µg dL(-1)) to 27.25 µg lead dL(-1) for the lead acetate groups at dose levels of 0.10-2.91 mg lead kg body weight(-1) and from below the detection limit to 8.8 µg lead dL(-1) for the soil lead groups at doses of 0.11-3.43 mg lead kg body weight(-1). At these same doses, mean bone values ranged from 0.52 to 26.92 µg lead g(-1) for the lead acetate groups and from 0.64 to 13.1 µg lead g(-1) for the soil lead groups. Relative per cent bioavailability was estimated by modelling the dose-blood concentration curves for the lead acetate treatment and the dosed soil lead treatment, and then comparing doses that produce an equivalent blood lead concentration. The ratio of the doses of lead acetate and soil lead that produced the same tissue response (i.e., concentration) provided an index of relative bioavailability. For lead, the bioavailability of soil lead relative to lead acetate was 41% at a blood concentration of 6 µg lead dL(-1).

Bioavailability of arsenic in soil and house dust impacted by smelter activities following oral administration in cynomolgus monkeys.

This study was conducted to determine the extent of arsenic (As) absorption from soil and house dust impacted by smelter activities near Anaconda, Montana. Female cynomolgus monkeys were given a single oral administration via gelatin capsules of soil (0.62 mg As/kg body wt) or house dust (0.26 mg As/kg body wt), or soluble sodium arsenate by the gavage or intravenous route of administration (0.62 mg As/kg body wt) in a crossover design with a minimum washout period of 14 days. Urine, feces, and cage rinse were collected at 24-hr intervals for 168 hr. Blood was collected at specified time points and area under the curves (AUCs) was determined. Arsenic concentrations for the first 120 hr, representing elimination of greater than 94% of the total administered dose for the three oral treatment groups, were < 0.021 to 4.68 micrograms/ml for the urine and < 0.24 to 31.1 micrograms/g for the feces. In general, peak concentrations of As in the urine and feces were obtained during the collection intervals of 0-24 and 24-72 hr, respectively. The main pathway for excretion of As for the intravenous and gavage groups was in the urine, whereas for the soil and dust groups, it was in the feces. Mean absolute percentage bioavailability values based on urinary excretion data were 68, 19, and 14% for the gavage, house dust, and soil treatments, respectively, after normalization of the intravenous As recovery data to 100%. Corresponding absolute bioavailability values based on blood were 91, 10, and 11%. The bioavailability of soil and house dust As relative to soluble As (by gavage) was between 10 and 30%, depending upon whether urinary or blood values were used. These findings suggest that risks associated with the ingestion of As in soil or dust will be reduced compared to ingestion of comparable quantities of As in drinking water.