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Decreasing renal glomerular filtration rate (GFR) in association with increasing blood cadmium levels was reported in epidemiological studies of general populations. Dependence of cadmium clearance on GFR has implications for interpreting causation in these studies. Associations between cadmium clearance and creatinine clearance, a metric of GFR, were evaluated in a sample of the U.S. population. Blood to urine cadmium clearance and serum creatinine clearance were estimated in approximately 6000 individuals included in the National Health and Nutrition Examination Survey (NHANES 2009–2016). Linear regression models explained approximately 45% of variance in cadmium clearance in adults, with 74% of the explained variance attributed to creatinine clearance and 25% explained by age. In adolescents (12–99% of the explained variance attributed to creatinine clearance. The models predicted that halving creatinine clearance would result in a 40% decrease in cadmium clearance and a 20% rise in blood cadmium. Dependence of cadmium clearance on GFR has implications for assigning causation to studies in which increasing blood cadmium levels have been associated with increasing risk of low GFR. Statistical associations between blood cadmium and low GFR, such as elevated odds ratios in upper percentile strata of populations, may be partially a consequence of lower cadmium clearance in association with low GFR that is reverse causation.

Refereed/Peer-reviewed Lead (Pb) contamination of soils is of global concern due to the devastating impacts of Pb exposure in children. Because early-life exposure to Pb has long-lasting health effects, reducing exposure in children is a critical public health goal that has intensified research on the conversion of soil Pb to low bioavailability phases. Recently, plumbojarosite (PLJ) conversion of highly available soil Pb was found to decrease Pb relative bioavailability (RBA

Hand-to-mouth activity in children can be an important route for ingestion of soil and dust contaminated with inorganic arsenic. Estimating the relative bioavailability of arsenic present in these media is a critical element in assessing the risks associated with aggregate exposure to this toxic metalloid during their early life. Here, we evaluated the performance of a mouse assay for arsenic bioavailability in two laboratories using a suite of 10 soils. This approach allowed us to examine both intralaboratory and interlaboratory variations in assay performance. Use of a single vendor for preparation of all amended test diets and of a single laboratory for arsenic analysis of samples generated in the participating laboratories minimized contributions of these potential sources of variability in assay performance. Intralaboratory assay data showed that food and water intake and cumulative urine and feces production remained stable over several years. The stability of these measurements accounted for the reproducibility of estimates of arsenic bioavailability obtained from repeated intralaboratory assays using sodium arsenate or soils as the test material. Interlaboratory comparisons found that estimates of variables used to evaluate assay performance (recovery and urinary excretion factor) were similar in the two laboratories. For all soils, estimates of arsenic relative bioavailability obtained in the two laboratories were highly correlated (r2 = 0.94 and slope = 0.9) in a linear regression model. Overall, these findings show that this mouse assay for arsenic bioavailability provides reproducible estimates using a variety of test soils. This robust model may be adaptable for use in other laboratory settings. Refereed/Peer-reviewed

Arsenic (As) is the most frequently occurring contaminant on the Priority List of Hazardous Substances, which lists substances of greatest public health concern to people living at or near U.S. National Priorities List sites. Human exposure to arsenic via ingestion of arsenic-contaminated soils can have serious health impacts including increased cancer risk. Accurate assessment of human health risks from exposure to arsenic-contaminated soils depends on estimating its bioavailability, defined as the fraction of ingested arsenic absorbed across the gastrointestinal barrier and available for systemic distribution and metabolism. Arsenic bioavailability varies among soils and is influenced by site-specific soil physical and chemical characteristics and internal biological factors. This review describes the state-of-the science that supports our understanding of oral bioavailability of soil arsenic, the methods that are currently being explored for estimating soil arsenic relative bioavailability (RBA), and future research areas that could improve our prediction of the oral RBA of soil arsenic in humans. The following topics are addressed: (1) arsenic soil geochemistry; (2) arsenic toxicology; (3) in vivo models for estimating arsenic RBA; (4) in vitro bioaccessibility methods; and (5) conclusions and research needs.

Several investigations have been conducted to develop in vitro bioaccessibility (IVBA) assays that reliably predict in vivo oral relative bioavailability (RBA) of arsenic (As). This study describes a meta-regression model relating soil As RBA and IVBA that is based upon data combined from previous investigations that examined the relationship between As IVBA and RBA when IVBA was determined using an extraction of soil in 0.4 M glycine at pH 1.5. Data used to develop the model included paired IVBA and RBA estimates for 83 soils from various types of sites such as mining, smelting, and pesticide or herbicide application. The following linear regression model accounted for 87% of the observed variance in RBA (R2 = .87): RBA(%) = 0.79 × IVBA(%) + 3.0. This regression model is more robust than previously reported models because it includes a larger number of soil samples, and also accounts for variability in RBA and IVBA measurements made on samples collected from sites contaminated with different As sources and conducted in different labs that have utilized different experimental models for estimating RBA.