Rosalind A. Schoof

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.

Estimation of Multimedia Inorganic Arsenic Intake in the U.S. Population

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 10th and 90th 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.

Risk characterization, assessment, and management of organic pollutants in beneficially used residual products

A wide array of organic chemicals occur in biosolids and other residuals recycled to land. The extent of our knowledge about the chemicals and the impact on recycling programs varies from high to very low. Two significant challenges in regulating these materials are to accurately determine the concentrations of the organic compounds in residuals and to appropriately estimate the risk that the chemicals present from land application or public distribution. This paper examines both challenges and offers strategies for assessing the risks related to the occurrence of organic compounds in residuals used as soil amendments. Important attributes that must be understood to appropriately characterize and manage the potential risks for organic chemicals in biosolids include toxicity and dose response, transport potential, chemical structure and environmental stability, analytical capability in the matrix of interest, concentrations and persistence in waste streams, plant uptake, availability from surface application versus incorporation, solubility factors, and environmental fate. This information is complete for only a few chemicals. Questions persist about the far greater number of chemicals for which toxicity and environmental behavior are less well understood. This paper provides a synopsis of analytical issues, risk assessment methodologies, and risk management screening alternatives for organic constituents in biosolids. Examples from experience in Wisconsin are emphasized but can be extrapolated for broader application.

Variation of Total and Speciated Arsenic in Commonly Consumed Fish and Seafood

ABSTRACT This article compiles available data and presents an approach for predicting human intakes of inorganic arsenic (Asi), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) from marine, estuarine, and freshwater seafood when only total arsenic (Astot) concentrations are reported. Twenty studies provided data on total arsenic (Astot) and Asi. Mean Asi concentrations were approximately 10 to 20 ng/g wet weight (ww) in freshwater, anadromous, and marine fish, whereas crustaceans and molluscs had mean Asi concentrations of 40 to 50 ng/g ww. Thirteen studies provided data for MMA and DMA. MMA was seldom detected, whereas DMA averaged 10 ng/g ww in freshwater fish, and 45 to 95 ng/g ww in anadromous fish, marine fish, crustaceans, and molluscs. There was little correlation between Astot concentrations and Asi concentrations; however, when only Astot data are available to assess health risks from arsenic in seafood, these data could support conservative, upper end estimates of the percent of Astot likely to be Asi. For marine and estuarine fish, and crustaceans and molluscs 2–3% of Astot was Asi at the 75th percentile of the dataset. For freshwater fish Asi was 10% of Astot at the 75th percentile. Due to the nonlinearity and low carcinogenic potency of DMA, the reported DMA concentrations should not contribute substantially to potential health risks from arsenic in seafood.

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.

Percutaneous absorption of arsenic from environmental media

Current knowledge of percutaneous absorption of arsenic is based on studies of rhesus monkeys using soluble arsenic in aqueous solution, and soluble arsenic mixed with soil (Wester et al., 1993). These studies produced mean dermal absorption rates in the range of 2.0-6.4% of the applied dose. Subsequently, questions arose as to whether these results represent arsenic absorption from environmental media. Factors such as chemical interactions, the presence of other metals, and the effects of weathering on environmental media all can affect the nature of arsenic and its potential for percutaneous absorption. Therefore, research specific to more relevant matrices is important. The focus of this effort is to outline study design considerations, including particle size, application rates, means of ensuring skin contact and appropriate statistical evaluation of the data. Appropriate reference groups are also important. The potential for background exposure to arsenic in the diet possibly obscuring a signal from a dermally applied dose of arsenic will also be addressed. We conclude that there are likely to be many site-or sample-specific factors that will control the absorption of arsenic, and matrix-specific analyses may be required to understand the degree of percutaneous absorption.

Arsenic Bioaccumulation in Freshwater Fishes

ABSTRACT The arsenic ambient water quality criterion (AWQC) for protection of human health via ingestion of aquatic organisms is currently 0.14 μ g/L. This AWQC is derived using a bioconcentration factor (BCF) of 44, which is a consumption-weighted average based on two data points for oysters and fish that was proposed by the U.S. Environmental Protection Agency in 1980 for broad application to freshwater and marine environments. This BCF is based on the assumption that bioaccumulation is a simple linear function of the exposure concentration. In the nearly quarter of a century since this BCF was promulgated, there have been additions to the arsenic bioaccumulation database and a broader scientific understanding of bioaccumulation mechanisms and how they can be applied to estimating tissue concentrations in aquatic organisms. From this database, we identified 12 studies of arsenic bioaccumulation in freshwater fishes in order to explore differences in laboratory-generated BCFs and field-generated bioaccumulation factors (BAFs) and to assess their relationship to arsenic concentrations in water. Our analysis indicates that arsenic concentrations in tissue and arsenic BAFs may be power functions of arsenic concentration in water. A power function indicates that the highest BCF values may occur at low background levels and may decrease as environmental concentrations increase above the ambient range.

Bioavailability of Soil-Borne Chemicals: Method Development and Validation

ABSTRACT Chemicals present in contaminated soils generally exhibit altered bioavailability compared to other vehicles used in studies of chemical toxicity. Methods used to assess the bioavailability of soil-borne chemicals have generally been modified versions of methods that are widely used in biomedical research. Oral and dermal bioavailability of semivolatile organic chemicals and metals in soil has been assessed by a variety of in vivo and in vitro methods. Due to variations in metabolism and excretion of different chemicals, approaches to measuring bioavailability must be selected with an understanding of disposition of the chemical being studied. Standard methods need to be modified due to constraints associated with doses relevant to environmental concentrations, the need to reflect weathering behavior in soils over time, and the need to generate data applicable to human health risk assessments. Estimates of relative bioavailability for chemicals in soil can be used directly to modify exposure estimates. Application of bioavailability data in a site-specific risk assessment requires regulatory acceptance of the data. Acceptance of the data will generally be dependent on either the use of a validated test method or a careful scientific review of the test method employed. A process for validating newly developed alternative toxicity methods for routine use developed by the Interagency Coordinating Committee on the Validation of Alternative Methods provides relevant guidance for assessing in vitro methods, but method validation should not be the only litmus test for inclusion of bioavailability data in risk assessments.

Issues in arsenic cancer risk assessment.

Efforts to develop effective therapeutic treatments for promoting fast wound healing after injury to the epidermis are hindered by a lack of understanding of the factors involved. Re-epithelialization is an essential step of wound healing involving the migration of epidermal keratinocytes over the wound site. Here, we examine genetic variants in the keratin-1 (KRT1) locus for association with migration rates of human epidermal keratinocytes (HEK) isolated from different individuals. Although the role of intermediate filament genes, including KRT1, in wound activated keratinocytes is well established, this is the first study to examine if genetic variants in humans contribute to differences in the migration rates of these cells. Using an in vitro scratch wound assay we observe quantifiable variation in HEK migration rates in two independent sets of samples; 24 samples in the first set and 17 samples in the second set. We analyze genetic variants in the KRT1 interval and identify SNPs significantly associated with HEK migration rates in both samples sets. Additionally, we show in the first set of samples that the average migration rate of HEK cells homozygous for one common haplotype pattern in the KRT1 interval is significantly faster than that of HEK cells homozygous for a second common haplotype pattern. Our study demonstrates that genetic variants in the KRT1 interval contribute to quantifiable differences in the migration rates of keratinocytes isolated from different individuals. Furthermore we show that in vitro cell assays can successfully be used to deconstruct complex traits into simple biological model systems for genetic association studies.