Brian D. Laird

Bioaccessibility of mercury from traditional northern country foods measured using an in vitro gastrointestinal model is independent of mercury concentration

Human health risk assessment of dietary mercury (Hg) exposure in Canada assumes that all Hg from fish consumption is in the form of methylmercury (MeHg), the more bioavailable and hazardous form of Hg. In contrast, the risk assessment of dietary Hg to Inuit in northern Canada assumes that no more than two-thirds of dietary Hg is MeHg since mammal organs consumed by Inuit contain substantial concentrations of inorganic Hg. In vitro gastrointestinal models (e.g., the Simulator of the Human Intestinal Microbial Ecosystem) are often used for the evaluation of soil contaminant bioaccessibility, i.e., the fraction solubilized into gastrointestinal fluids, for use in site-specific human health risk assessment. In this research, we digested northern country foods using the SHIME for the measurement of Hg bioaccessibility, a novel approach for the assessment of dietary Hg bioavailability. We demonstrated that small intestinal Hg bioaccessibility from 16 fish, wild game, and marine mammal samples consumed by Inuit in northern Canada ranged between 1 and 93% and was independent of food HgT (MeHg+Hg(II)) concentration. Additionally, we demonstrated that gastrointestinal microbes may affect Hg bioaccessibility of the 16 country foods, either increasing or decreasing bioaccessibility depending upon the type of food. These results indicate that gastrointestinal absorption of Hg is not likely limited by the concentration of Hg in the food, which is in agreement with in vivo Hg bioavailability studies. Furthermore, these in vitro results support the hypothesis that the gastrointestinal absorption of Hg from Inuit country foods is dependent upon food type.

Human Exposure Assessment: A Case Study of 8 PAH Contaminated Soils Using in Vitro Digestors and the Juvenile Swine Model

In vitro digestors can be used to provide bioaccessibility values to help assess the risk from incidental human ingestion of contaminated soils. It has been suggested that these digestors may need to include a lipid sink to mimic human uptake processes. We compare the correspondence between in vivo polycyclic aromatic hydrocarbon (PAH) uptake for eight different PAH contaminated soils with PAH release in in vitro digestors in the presence and absence of a lipid sink. Lipid sinks were essential to the success of the in vitro digestors in predicting juvenile swine PAH uptake. In the presence of the lipid sink, results of the In Vitro Digestion model (IVD) closely corresponded with a slope of 0.85 (r(2) = 0.45, P < 0.07) to the in vivo results. The Relative Bioaccessibility Leaching Procedure (RBALP) results did not correspond to the in vivo study but did tightly reflect total soil PAH concentration. We conclude that the basis of this difference between digestors is that the RBALP used an aggressive extraction technique that maximized PAH release from soil. Systemic uptake in juvenile swine was not linked to soil PAH concentration but rather to the thermodynamic properties of the soil.

Dietary Advice on Inuit Traditional Food Use Needs to Balance Benefits and Risks of Mercury, Selenium, and n3 Fatty Acids

Elevated concentrations of mercury (Hg) are commonly found in the traditional foods, including fish and marine mammals, of Inuit living in Canadas Arctic. As a result, Inuit often have higher dietary Hg intake and elevated Hg blood concentrations. However, these same traditional foods are excellent sources of essential nutrients. The goals of this study were 1) to identify the traditional food sources of Hg exposure for Inuit, 2) to estimate the percentage of Inuit who meet specific nutrient Dietary Reference Intakes and/or exceed the Toxicological Reference Values (TRVs), and 3) to evaluate options that maximize nutrient intake while minimizing contaminant exposure. A participatory cross-sectional survey was designed in consultation with Inuit in 3 Canadian Arctic jurisdictions (Nunatsiavut, Nunavut, and the Inuvialuit Settlement Region). Estimated intakes for EPA (20:5n3) and DHA (22:6n3) met suggested dietary targets, and estimated selenium (Se) intake fell within the Acceptable Range of Oral Intake. Estimated intakes of Hg (rs = 0.41, P < 0.001), Se (rs = 0.44, P < 0.001), EPA (rs = 0.32, P < 0.001), and DHA (rs = 0.28, P < 0.001) were correlated with their respective blood concentrations. Mean estimated Hg intake (7.9 μg · kg(-1) · wk(-1)) exceeded the TRV of 5.0 μg · kg(-1) · wk(-1), with 35% of the population above this guideline. Because the estimated intakes of each of the nutrients were strongly correlated (Se: rs = 0.92, P < 0.001; EPA: rs = 0.82, P < 0.001; DHA: rs = 0.81, P < 0.001) with estimated Hg intake, efforts to decrease Hg exposure must emphasize the overall healthfulness of traditional foods and be designed to prevent concomitant harm to the nutrient intakes of Inuit.

Body burden of metals and persistent organic pollutants among Inuit in the Canadian Arctic.

Inuit living in the Arctic are exposed to elevated levels of environmental contaminants primarily due to long-range atmospheric transport. Blood sampling and contaminant biomonitoring was conducted as part of the International Polar Year Inuit Health Survey in 2007-2008. The body burden of metals (e.g. Cd, Pb) and persistent organic pollutants (e.g. PCBs, DDT & DDE, toxaphene, chlordane, PBDEs) were measured for Inuit participants (n=2172) from 36 communities in Nunavut, Nunatsiavut, and the Inuvialuit Settlement Region, in Canada. The geometric mean of blood concentrations for Cd, Pb, PCBs, DDE & DDT, toxaphene, and chlordane were higher than those in the Canadian general population. A total of 9% of study participants exceeded the intervention guideline of 100μgL(-1) for Pb, 11% of participants exceeded the trigger guideline of 5μgL(-1) for Cd, and 1% exceeded the intervention guideline of 100μgL(-1) for PCBs. Also, 3% of women of child-bearing age exceeded blood Pb of 100μgL(-1) while 28% of women of child-bearing age exceeded 5μgL(-1) of PCBs. This work showed that most Inuit Health Survey participants were below blood contaminant guidelines set by Health Canada but that metal and POP body burdens commonly exceed exposures observed in the general population of Canada.

Polycyclic aromatic hydrocarbons are enriched but bioaccessibility reduced in brownfield soils adhered to human hands.

The health risk associated with exposure to urban brownfields is often driven by the incidental ingestion of soil by humans. Recent evidence found that humans likely ingest the fraction of soil that passes a 45-microm sieve, which is the particle size adhered to the hands. We evaluated if PAH concentrations were enriched in this soil fraction compared to the bulk soil and if this enrichment lead to an increase in bioaccessibility and thus an increase in incremental lifetime cancer risk for exposed persons. Soils (n=18) with PAH concentrations below the current Canadian soil quality guidelines for human health were collected from an Arctic urban site and were sieved to pass a 45-microm sieve. Soil PAH profiles were measured and bioaccessibility was assessed using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). PAHs were significantly enriched in the <45 microm size fraction (3.7-fold) and this enrichment could be predicted according to the fugacity capacity of soil (Enrichment=2.18-0.055Zsoil, r2=0.65, p<0.001). PAH release in the stomach and small intestine compartments of the SHIME was low (8%) and could not be predicted by PAH concentrations in 45-microm sieved soil. In fact, PAH release in the SHIME was lower from the <45 microm size fraction despite the fact that this fraction had higher levels of PAHs than the bulk soil. We postulate that this occurs because PAHs adsorbed to soil did not reach equilibrium with the small intestinal fluid. In contrast, PAH release in the colonic compartment of the SHIME reached equilibrium and was linked to soil concentration. Bioaccessibility in the SHIME colon could be predicted by the ratio of fugacity capacity of soil to water for a PAH (Bioaccessibility=0.15e(-6.4x10E-7Zsoil/Zwater), r2=0.53, p<0.01). The estimated incremental lifetime cancer risk was significantly greater for the <45 microm soil fraction compared to the bulk fraction; however, when bioaccessible PAH concentrations in a simulated small intestine were used in the risk assessment calculations, cancer risk was slightly lower in the <45 microm soil fraction for these soils. Our results highlight the importance of using a small soil size fraction, e.g. 45 microm, for contaminated site human health risk assessment. However, further work is needed to estimate the bioavailability of this size fraction in an in vivo model and to assess the correlation between in vitro and in vivo gastrointestinal models.

Bioaccessibility of metals in fish, shellfish, wild game, and seaweed harvested in British Columbia, Canada

Fish, shellfish, wild game, and seaweed are important traditional foods that are essential to the physical and cultural well-being of Indigenous peoples in Canada. The goal of this study was to measure the concentration and bioaccessibility of As, Cd, Hg, Se, Cu and Mn in 45 commonly consumed traditional foods collected by harvested by the First Nations Food, Nutrition, and Environment Study (FNFNES) from 21 First Nations communities in British Columbia, Canada, in 2008-2009. A significant and negative correlation was observed between Hg concentration and Hg bioaccessibility. Metal bioaccessibility tended to be high; median values ranging between 52% (Mn) and 83% (Cu). The notable exceptions were observed for As in wild game organs (7-19%) and rabbit meat (4%) as well as Hg in salmon eggs (10%). Results of Principal Components Analysis confirmed the unique pattern of bioaccessibility of As and Hg in traditional foods, suggesting that, unlike other metals, As and Hg bioaccessibility are not simply controlled by food digestibility under the operating conditions of the in vitro model. These data provide useful information for dietary contaminant risk assessment and intake assessments of essential trace elements.

Bioaccessibility of Metal Cations in Soil Is Linearly Related to Its Water Exchange Rate Constant

Site-specific risk assessments often incorporate the concepts of bioaccessibility (i.e., contaminant fraction released into gastrointestinal fluids) or bioavailability (i.e., contaminant fraction absorbed into systemic circulation) into the calculation of ingestion exposure. We evaluated total and bioaccessible metal concentrations for 19 soil samples under simulated stomach and duodenal conditions using an in vitro gastrointestinal model. We demonstrated that the median bioaccessibility of 23 metals ranged between <1 and 41% under simulated stomach conditions and < 1 and 63% under simulated duodenal conditions. Notably, these large differences in metal bioaccessibility were independent of equilibrium solubility and stability constants. Instead, the relationship (stomach phase R = 0.927; duodenum phase R = 0.891) between bioaccessibility and water exchange rates of metal cations (k(H₂O)) indicated that desorption kinetics may influence if not control metal bioaccessibility.

The effect of residence time and fluid volume to soil mass (LS) ratio on in vitro arsenic bioaccessibility from poorly crystalline scorodite

Percent arsenic bioaccessibility is occasionally dependent upon arsenic concentration; however, the mechanism(s) of this relationship has not yet been defined. To evaluate the mechanism of this relationship, the arsenic bioaccessibility from freshly synthesized poorly crystalline scorodite was measured in the stomach, small intestine, and colon stages of the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). The shape of the arsenic dissolution isotherms were different between stages (stomach: linear; small intestine: exponential rise to maxima; colon: sigmoidal). These results indicate that arsenic bioaccessibility may be limited by either in vitro GI fluid saturation or in vitro GI model residence time, depending upon the chemical/microbiological conditions of the model. Gastrointestinal microorganisms increased arsenic bioaccessibility of scorodite up to two-fold in the SHIME colon; however, this was dependent upon the sample arsenic concentration. Up to 40% of the bioaccessible arsenic was reduced to arsenite; however this process was neither mediated by GI microorganisms nor associated with increased arsenic bioaccessibility.

Nutritional Status and Gastrointestinal Microbes Affect Arsenic Bioaccessibility from Soils and Mine Tailings in the Simulator of the Human Intestinal Microbial Ecosystem

In vitro gastrointestinal models, used to measure the metal(loid) bioaccessibility for site specific risk assessment, are typically operated under fasted conditions. We evaluated the hypothesis that fed conditions increase arsenic bioaccessibility on three reference soils (NIST 2711, NIST 2709, and BGS 102) and the bulk and <38 mum size fractions of a mine tailing. The three nutritional states included a fed state with a carbohydrate mixture, a second fed state with homogenized crowberries (Empetrum nigrum), and a fasted state. The carbohydrate mixture increased arsenic bioaccessibility from four of five samples in the simulator of the human intestinal microbial ecosystem (SHIME) stomach but only three of five samples in the SHIME small intestine and colon. In contrast, crowberries increased arsenic bioaccessibility from four of five samples in the SHIME small intestine but had variable affects in the SHIME stomach and colon. The effect of nutritional status on arsenic bioaccessibility was potentially mediated via ligand-promoted dissolution in the SHIME stomach and small intestine. The displacement of arsenic with phosphate was potentially present in the SHIME small intestine but not the SHIME stomach. Microbial activity increased arsenic bioaccessibility relative to sterile conditions from four of five samples under fasted conditions and three of the five samples under fed conditions, which may suggest that in vitro gastrointestinal (GI) models operated under fed conditions and with microbes provide a more conservative estimate of in vitro bioaccessibility. However, for some samples, the arsenic bioaccessibility in the SHIME colon (with microbial activity) was equivalent to values observed in a separate physiologically based extraction test under small intestinal conditions (without microbial activity). These results suggest that the incorporation of microbial activity into in vitro GI models does not necessarily make estimates of arsenic bioaccessibility more protective than those generated using in vitro models that do not include microbial activity.

Assessing the Bioavailability and Risk from Metal-Contaminated Soils and Dusts

ABSTRACT Exposure to contaminated soil and dust is an important pathway in human health risk assessment. Physical and chemical characteristics and biological factors determine the bioaccessibility/bioavailability of soil and dust contaminants. Within a single sample, contamination may arise from multiple sources of toxic elements that may exist as different species that impact bioavailability. In turn, the bioaccessibility/bioavailability of soil and dust contaminants directly impacts human health risk. Research efforts focusing on development and application of in vitro and in vivo methods to measure the bioaccessibility/bioavailability of metal-contaminated soils have advanced in recent years. The objective of this workshop was to focus on developments in assessing the bioaccessibility/bioavailability of arsenic-contaminated soils, metals’ contamination in urban Canadian residences and potential childrens exposures to toxic elements in house dust, an urban community-based study (i.e., West Oakland Residential Lead Assessment), bioavailability studies of soil cadmium, chromium, nickel, and mercury and human exposures to contaminated Brownfield soils. These presentations covered issues related to human health and bioavailability along with the most recent studies on community participation in assessing metals’ contamination, studies of exposures to residential contamination, and in vitro and in vivo methods development for assessing the bioaccessibility/bioavailability of metals in soils and dusts.