The effect of confounding variables in studies of lead exposure and IQ.

Methods proposed to address confounding variables frequently do not adequately distinguish confounding from covariation. A confounder is a variable that correlates both with the outcome and the major exposure variable. Accurate treatment of confounding is crucial to low dose extrapolation of the effects of chemical exposures based on epidemiology studies. This study explores the limitations of current regression models in extrapolation to the low dose region of the dose-response curve due to the existence of unrecognized and uncontrolled confounding, using epidemiological data for lead. Based on the reported data in analyses by Lanphear and colleagues and Crump and colleagues, and drawing on other studies, Wilson and Wilson considered maternal IQ, HOME score, SES, parental education, birthweight, smoking, and race as characteristic variables which may have interaction effects. This analysis identifies confounding variables based on the seven longitudinal cohorts in analyses conducted by Lanphear and colleagues and by Crump and colleagues and confirms maternal IQ, HOME score, maternal education and maternal marital status at birth are "Highly Likely" confounders, while race is a "Likely" confounder. The cohort data were reanalyzed using the methods presented by Crump and colleagues while also considering the interaction among the identified confounding variables. This analysis determined that confounders influence IQ estimates in a quantifiable way that may exceed or at least obscure previously-reported effects of blood lead on IQ with blood lead levels below 5 µg/dL; however, limitations in the datasets make predictions of the low dose dose-response analysis questionable.

Assessment of blood lead level declines in an area of historical mining with a holistic remediation and abatement program.

UNLABELLED: Lead exposure and blood lead levels (BLLs) in the United States have declined dramatically since the 1970s as many widespread lead uses have been discontinued. Large scale mining and mineral processing represents an additional localized source of potential lead exposure in many historical mining communities, such as Butte, Montana. After 25 years of ongoing remediation efforts and a residential metals abatement program that includes blood lead monitoring of Butte children, examination of blood lead trends offers a unique opportunity to assess the effectiveness of Butte's lead source and exposure reduction measures. This study examined BLL trends in Butte children ages 1-5 (n= 2796) from 2003-2010 as compared to a reference dataset matched for similar demographic characteristics over the same period. Blood lead differences across Butte during the same period are also examined. Findings are interpreted with respect to effectiveness of remediation and other factors potentially contributing to ongoing exposure concerns. REFERENCE POPULATION COMPARISON: BLLs from Butte were compared with a reference dataset (n=2937) derived from the National Health and Nutrition Examination Survey. The reference dataset was initially matched for child age and sample dates. Additional demographic factors associated with higher BLLs were then evaluated. Weights were applied to make the reference dataset more consistent with the Butte dataset for the three factors that were most disparate (poverty-to-income ratio, house age, and race/ethnicity). A weighted linear mixed regression model showed Butte geometric mean BLLs were higher than reference BLLs for 2003-2004 (3.48vs. 2.05µg/dL), 2005-2006 (2.65vs. 1.80µg/dL), and 2007-2008 (2.2vs. 1.72µg/dL), but comparable for 2009-2010 (1.53vs. 1.51µg/dL). This trend suggests that, over time, the impact of other factors that may be associated with Butte BLLs has been reduced. COMPARISON ACROSS BUTTE: Neighborhood differences were examined by dividing the Butte dataset into the older area called "Uptown", located at higher elevation atop historical mine workings, and "the Flats", at lower elevation and more recently developed. Significant declines in BLLs were observed over time in both areas, though Uptown had slightly higher BLLs than the Flats (2003-2004: 3.57vs. 3.45µg/dL, p=0.7; 2005-2006: 2.84vs. 2.52µg/dL, p=0.1; 2007-2008: 2.58vs. 1.99µg/dL, p=0.001; 2009-2010: 1.71vs. 1.44µg/dL, p=0.02). BLLs were higher when tested in summer/fall than in winter/spring for both neighborhoods, and statistically higher BLLs were found for children in Uptown living in properties built before 1940. Neighborhood differences and the persistence of a greater percentage of high BLLs (>5µg/dL) in Butte vs. the reference dataset support continuation of the home lead abatement program. CONCLUSIONS: Butte BLL declines likely reflect the cumulative effectiveness of screening efforts, community-wide remediation, and the ongoing metals abatement program in Butte in addition to other factors not accounted for by this study. As evidenced in Butte, abatement programs that include home evaluations and assistance in addressing multiple sources of lead exposure can be an important complement to community-wide soil remediation activities.

Dermal absorption of arsenic from soils as measured in the rhesus monkey.

Regulatory agencies have relied on dermal absorption data for soluble forms of arsenic as the technical basis for specific absorption values that are used to calculate exposure to arsenic in weathered soil. These evaluations indicate that percutaneous absorption of arsenic from soil ranges from 3.2 to 4.5% of the dermally applied dose, based on studies of arsenic freshly mixed with soil. When this value is incorporated into risk assessments and combined with other assumptions about dermal exposures to soil, the conclusion is often that dermal exposure to arsenic from soil may contribute significantly to overall exposure to arsenic in soil. Prior characterization research has indicated that the solubility of arsenic in soil varies, depending on the provenance of the soil, the source of the arsenic, and the chemical interaction of arsenic with other minerals present within the soil matrix. Weathering produces forms of arsenic that are more tightly bound within the soil and less available for absorption. Our research expands on prior in vivo studies to provide insights into the potential for dermal absorption of arsenic from the more environmentally relevant substrate of soil. Specifically, two soils with very high concentrations of arsenic were evaluated under two levels of skin hydration. One soil, containing 1400 mg/kg arsenic, was collected adjacent to a pesticide production facility in New York. The other soil, containing 1230 mg/kg arsenic, was collected from a residential area with a history of application of arsenical pesticides. Although the results of this research are constrained by the small study size dictated by the selection of an animal research model using monkeys, the statistical power was optimized by using a "crossover" study design, wherein each animal could serve as its own comparison control. No other models (animal or in vitro) were deemed adequate for studying the dermal absorption of soil arsenic. Our results show dermal absorption of soluble arsenic in solution to be 4.8 +/- 5.5%, which is similar to results reported earlier for arsenic in solution (and used by regulatory agencies in recommendations regarding dermal absorption of arsenic). Conversely, absorption following application of arsenic in the soil matrices resulted in mean estimated arsenic absorption of 0.5% or less for all soils, and all individual estimates were less than 1%. More specifically, following application of arsenic-bearing soils to the abdomens of monkeys, urinary arsenic excretion could not be readily distinguished from background. This was true across all five soil-dosing trials, including application of the two dry soils and three trials with wet soil. These findings are consistent with our understanding of the environmental chemistry of arsenic, wherein arsenic can be present in soils in complexed mineral forms. This research addresses an important component involved in estimating the true contribution of percutaneous exposures to arsenic in soil relative to exposures via ingestion. Our findings suggest that dermal absorption of arsenic from soil is truly negligible, and that EPA's current default assumption of 3% dermal absorption of arsenic from soils results in significant overestimates of exposure.

Microplastics in the context of regulation of commercial shellfish aquaculture operations.

Shellfish aquaculture in the Salish Sea (encompassing the Strait of Juan de Fuca, Puget Sound, and the Georgia Strait) is a major source of clams, oysters, and mussels in the United States and Canada. Plastic gear is necessary for the viability of many of these operations. During the past few years, shellfish farm permits issued in Washington State have been challenged on various bases that have included allegations that the plastic gear is releasing microplastics, commonly defined as particles less than 5 mm in diameter. Published survey data on sources of marine plastic debris demonstrate the very limited contribution of aquaculture gear. Both permits and industry codes of practice provide procedures to minimize loss of gear to the marine environment. Plastic gear is also designed specifically to maintain its integrity and not degrade in the marine environment. Plastic degradation is greatest on beaches with high UV exposure, whereas aquaculture gear is mostly underwater and/or covered by biofoulants. Available data for microplastics in water, sediment, and biota of the Salish Sea do not suggest significant release of microplastics from shellfish aquaculture operations. Integr Environ Assess Manag 2017;13:522-527. © 2017 SETAC.

The evolving science of chemical risk assessment for land-applied biosolids.

Biosolids, effluents, and manures are widely applied to agricultural land and other land with varying degrees of pretreatment or control. Regulations governing land application of biosolids take several broad forms in different countries, including limitations based on rates that do not lead to increases in background chemical concentrations or risk assessment approaches such as those used in the United States. Risk assessment is a process that is inherently limited by currently available information and practices, and consequently, risk-based land application limits must be reevaluated periodically. For complex mixtures such as biosolids, three principal categories of information will be affected by changing practices and scientific advances: (i) chemical constituents present in the material, (ii) the nature of expected exposures, and (iii) toxicity of the chemical constituents. New analytical methods and lower detection limits will affect chemical identification in wastes. Approaches to exposure assessment, such as increasing emphasis on probabilistic analyses, will continue to evolve, and exposure assumptions will change as new studies provide better data on factors such as soil ingestion, plant uptake of chemicals, and bioavailability of chemicals in soil. Similarly, toxicity assessments will be updated as new studies are conducted. The evolving science over the past decade is illustrated by comparing approaches used by the USEPA to assess human health and ecological risks for the Part 503 rule compared with the more recent evaluation of dioxins and related compounds in biosolids. While risks of chemicals in land-applied biosolids and other residuals need to be periodically re-evaluated, such re-evaluations may take forms other than full risk assessments.

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.

Arsenic relative bioavailability from diet and airborne exposures: Implications for risk assessment.

Major human environmental health concern has been associated with inorganic arsenic (iAs) in drinking water in which dissolved iAs is highly bioavailable. More recently health concerns have been raised regarding the extent of iAs exposure via food and other potential sources. Arsenic relative bioavailability (RBA) in soil is known to be variable; the extent and role of iAs bioavailability in food are not well characterized. iAs in coal fly ash and bottom ash are other potential exposure media for which RBA has not been well characterized. A comprehensive literature search was conducted to support evaluation of the contribution of food and coal fly ash to iAs exposure. Few studies were found that investigated bioavailability associated with As-containing coal ash or airborne As-containing particles; estimated bioavailability in these studies ranged from 11% to 50%. The implications and potential usefulness of iAs bioavailability associated with inhalation exposure to human health risk assessment remain unknown at this time. Main sources of dietary iAs intake in the U.S. include rice and other grains, vegetables, and fruits. Due to low concentrations of iAs, seafood is not a primary contributor to dietary iAs intake. Three general kinds of food studies were identified: studies of As bioaccessibility in composites, As bioavailability and bioaccessibility in specific foods, and As consumption and urinary excretion in human volunteers. One in vivo study was identified that examined As bioavailability in food. A variety of experimental in vitro gastro-intestinal protocols have been used, however, few studies have included As speciation before and after the in vitro extraction. Current data suggest that the bioaccessibility of iAs in rice is quite high, typically 70% or more indicating that iAs in rice is highly bioavailable. Adjusting for RBA may not have a meaningful impact on iAs exposure estimates for rice-based foods.

In vivo percutaneous absorption of arsenic from water and CCA-treated wood residue.

This study was conducted to evaluate the dermal absorption of arsenic from residues present on the surface of wood preserved with chromated copper arsenate (CCA). The research reported herein used methods parallel to those of earlier research on the dermal absorption of radiolabeled arsenic (R. C. Wester et al., 1993, Fund. Appl. Toxicol. 20, 336-340), with modifications to allow use of environmental matrices that are not radiolabeled. These modifications include the surface area of application and dietary intake of arsenic, thus maximizing the potential for detection of dermally absorbed arsenic in exposed animals above diet-associated background levels of exposure. Two forms of arsenic were administered in this work. The first, arsenic in solution, was applied to the skin of monkeys to calibrate the model against prior absorption research and to serve as the basis of comparison for absorption of arsenic from CCA-treated wood residues. The second substrate was residue that resides on the surface of CCA-treated wood. Results from this research indicate that this study methodology can be used to evaluate dermally absorbed arsenic without the use of a radiolabel. Urinary excretion of arsenic above background levels can be measured following application of soluble arsenic, and absorption rates (0.6-4.4% absorption) are consistent with prior research using the more sensitive, radiolabeled technique. Additionally, the results show that arsenic is poorly absorbed from CCA-treated wood residues (i.e., does not result in urinary arsenic excretion above background levels).

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.

Health effect levels for risk assessment of childhood exposure to arsenic.

Health risks to children from chemicals in soil and consumer products have become a regulatory focus in the U.S. This study reviews short-term health effect levels for arsenic exposure in young children (i.e., 0-6 years old). Acute health effects are described mostly in adults in case reports of arsenic poisoning from water or food and in studies of medicinal arsenic treatment. Several epidemiological studies report health effects from subchronic arsenic exposure in children primarily from drinking water in developing countries. Acute health effects typically include gastrointestinal, neurological, and skin effects, and in a few cases facial edema and cardiac arrhythmia. Dermatoses are most consistently reported in both adults and children with subchronic exposure. With low exposure, the prevalence and severity of disease generally increases with age (i.e., length of exposure) and arsenic dose. The available data collectively indicate a lowest-observed-adverse-effect level around 0.05mg/kg-day for both acute and subchronic exposure. At low doses, children do not appear to be more sensitive than adults on a dose-per-body-weight basis, although data for acute exposures are limited and uncertainties exist for quantifying potential neurological or vascular effects at low-level subchronic exposures. Based on these data, possible reference levels for acute and subchronic exposure in young children are 0.015 and 0.005mg/kg-day, respectively.