[Show abstract][Hide abstract] ABSTRACT: Populations:
Of the few U.S. studies available, the most rigorously conducted study did not find a consistent dose-response relationship between arsenic concentrations in tap water or toenails and decrements in IQ scores. Assuming that the strongest dose-response relationship from the most rigorous evidence from Bangladesh is generalizable to U.S. populations, possible reference doses were estimated in the range of 0.0004 to 0.001mg/kg-day. These doses are higher than the U.S. Environmental Protection Agency reference dose for chronic lifetime exposure, thus indicating protectiveness of the existing value for potential neurotoxicity in children. This reference dose is undergoing revision as EPA considers various health endpoints in reassessment of inorganic arsenic health risks.
[Show abstract][Hide abstract] ABSTRACT: Background:
Setting Spacecraft Water Exposure Guidelines (SWEGs) for lead (Pb) in spacecraft drinking water has special challenges related to estimating the increase in blood lead levels (PbB) due to the release of lead to systemic circulation via microgravity-induced bone loss.
The effects on the PbB of lead in drinking water (PbW) and lead released from bones, and changes in lead exposure before, during, and after spaceflight, were evaluated using a physiologically based pharmacokinetic model that incorporated environmental lead exposure on Earth and in flight and included temporarily increased rates of osteoporosis during spaceflight.
The model predicts that in 2030 (the earliest potential launch date for a long-duration mission), the average American astronaut would have a PbB of 1.7 microg x dl(-1) at launch and that, while in microgravity, PbB levels would decrease at PbW values less than about 9 microg L(-1) because of reduced exposure within the spacecraft to environmental lead. Astronauts with high concentrations of lead stored in bones could experience increases in PbB due to microgravity-accelerated release of lead from bones. While the resultant in-flight PbB would depend on their preflight bone lead levels, their PbB will not be significantly further elevated (< 1 microg x dl(-1)) by consuming water with a PbW of < or = 9 microg x dl(-1). Selection of a SWEG that would not result in an increase in blood lead is prudent given uncertainties about health effects at low exposures.
A SWEG of 9 microg x L(-1) would protect astronauts on long-duration spaceflights by ensuring that PbB values will not exceed prelaunch levels.
No preview · Article · Jul 2014 · Aviation Space and Environmental Medicine
[Show abstract][Hide abstract] ABSTRACT: The U.S. Environmental Protection Agency (EPA) is developing an integrated assessment of non-cancer and cancer risk assessment of inorganic arsenic (iAs). Cardiovascular disease (CVD) in association with iAs exposure has been examined in a number of studies and provides a basis for evaluating a reference dose (RfD) for assessing potential non-cancer health risks of arsenic exposure. In this systematic review of low-level iAs exposure (i.e., <100-150μg/L arsenic water concentration) and CVD in human populations, 13 cohort and case-control studies from the United States, Taiwan, Bangladesh, and China were identified and critically examined for evidence for derivation of a RfD. Eight cross-sectional and ecological studies from the United States were also examined for additional information. Prospective cohort data from Bangladesh provided the strongest evidence for determining the point of departure in establishing a candidate RfD based on a combined endpoint of mortality from "ischemic heart disease and other heart diseases." This study as well as the overall literature supported a no-observed-adverse-effect level of 100μg/L for arsenic in water, which was equivalent to an iAs dose of 0.009mg/kg-day (based on population-specific water consumption rates and dietary iAs intake). The study population was likely sensitive to arsenic toxicity because of nutritional deficiencies affecting arsenic methylation and one-carbon metabolism, as well as increasing CVD risk. Evidence is less clear on the interaction of CVD risk factors in the United States (e.g., diabetes, obesity, hypertension) with arsenic at low doses. Potential uncertainty factors up to 3 resulted in a RfD for CVD in the range of 0.003-0.009mg/kg-day. Although caution should be exercised in extrapolating these results to the U.S. general population, these doses allow a margin of exposure that is 10-30 times the current RfD derived by EPA (based on skin lesions in Southwest Taiwan). These findings suggest that the current EPA RfD is protective of CVD.
[Show abstract][Hide abstract] ABSTRACT: While exposures to high levels of arsenic in drinking water are associated with excess cancer risk (e.g., skin, bladder, and lung), exposures at lower levels (e.g., <100-200μg/L) generally are not. Lack of significant associations may result from methodological issues (e.g., inadequate statistical power, exposure misclassification), or a different dose-response relationship at low exposures, possibly associated with a toxicological mode of action that requires a sufficient dose for increased tumor formation. The extent to which bladder cancer risk for low-level arsenic exposure can be statistically measured by epidemiological studies was examined using an updated meta-analysis of bladder cancer risk with data from two new publications. The summary relative risk estimate (SRRE) for all nine studies was elevated slightly, but not significantly (1.07; 95% confidence interval [CI]: 0.95-1.21, p-Heterogeneity [p-H]=0.543). The SRRE among never smokers was 0.85 (95% CI: 0.66-1.08, p-H=0.915), whereas the SRRE was positive and more heterogeneous among ever smokers (1.18; 95% CI: 0.97-1.44, p-H=0.034). The SRRE was statistically significantly lower than relative risks predicted for never smokers in the United States based on linear extrapolation of risks from higher doses in southwest Taiwan to arsenic water exposures >10μg/L for more than one-third of a lifetime. By contrast, for all study subjects, relative risks predicted for one-half of lifetime exposure to 50μg/L were just above the upper 95% CI on the SRRE. Thus, results from low-exposure studies, particularly for never smokers, were statistically inconsistent with predicted risk based on high-dose extrapolation. Additional studies that better characterize tobacco use and stratify analyses of arsenic and bladder cancer by smoking status are necessary to further examine risks of arsenic exposure for smokers.
[Show abstract][Hide abstract] ABSTRACT: Most astronauts experiencing prolonged microgravity undergo accelerated bone loss at a whole-body rate of 0.5-1% per month, with some load-bearing bones losing mass at normalized rates up to about 2.6% per month. The accompanying release of lead (Pb) stored in bones would increase the concentration of Pb in the blood (PbB), thereby complicating efforts to set acceptable Pb concentrations for spacecraft drinking water (PbW).
A physiologically based pharmacokinetic (PBPK) model was modified to permit modeling the effects on PbB of temporarily increased rates of bone loss and various PbW concentrations.
The model predicts that, for the average American astronaut, the increase in PbB due to Pb released from bones would be more than offset by decreases in ingested or inhaled spacecraft environmental Pb, so that calculated PbB levels actually decrease in microgravity when PbW < about 9 microg Pb x L(-1). Measured PbB in astronauts before and immediately after 6-mo stays on the International Space Station (ISS) support these results. Currently, PbW on the ISS averages 0.6 microg Pb x L(-1) and PbW on Earth at the Johnson Space Center averages about 5 microg Pb x L(-1).
Most astronauts on long spaceflights will not be adversely affected by the release of lead from bones into the blood. A small percentage of astronauts (assuming there could be any who would have high concentrations of lead in their bones) could be at risk of experiencing elevated levels of PbB due to microgravity-accelerated release of Pb from their bones, depending on their individual rate of bone loss.
No preview · Article · Dec 2013 · Aviation Space and Environmental Medicine
[Show abstract][Hide abstract] ABSTRACT: The recent EPA Framework for Metals Risk Assessment provides the opportunity for contextual risk assessment for sites impacted by metals (such as the depicted Dauntless Mine in Colorado).
No preview · Article · Nov 2009 · Environmental Science and Technology
[Show abstract][Hide abstract] ABSTRACT: Although exposure to high levels of arsenic in drinking water is associated with excess cancer risk (e.g., skin, bladder, and lung), lower exposures (e.g., <100-200 microg/L) generally are not. Lack of significant associations at lower exposures may be attributed to methodologic issues (e.g., inadequate statistical power, exposure misclassification), or to differences in the dose-response relationship at high versus low exposures. The objectives of this review and meta-analysis were to evaluate associations, examine heterogeneity across studies, address study design and sample size issues, and improve the precision of estimates. Eight studies of bladder cancer and low-level arsenic exposure met our inclusion criteria. Meta-analyses of never smokers produced summary relative risk estimates (SRREs) below 1.0 (highest versus lowest exposure). The SRRE for never and ever smokers combined was elevated slightly, but not significantly (1.11; 95% CI: 0.95-1.30). The SRRE was somewhat elevated among ever smokers (1.24; 95% CI: 0.99-1.56), and statistical significance was observed in some subgroup analyses; however, heterogeneity across studies was commonly present. Although uncertainties remain, low-level arsenic exposure alone did not appear to be a significant independent risk factor for bladder cancer. More studies with detailed smoking history will help resolve whether smoking is an effect modifier.
No preview · Article · Sep 2008 · Regulatory Toxicology and Pharmacology
[Show abstract][Hide abstract] ABSTRACT: Background exposures provide perspective for interpreting calculated health risks associated with naturally occurring substances such as arsenic. Background inorganic arsenic intake from diet and water for children (ages 1-6 years) and all ages of the U.S. population was modeled stochastically using consumption data from USDA, published data on inorganic arsenic in foods, and EPA data on arsenic in drinking water. Mean and 90th percentile intakes for the U.S. population were 5.6 and 10.5 microg/day, assuming nationwide compliance with the 10 microg/L U.S. drinking water standard. Intakes for children were slightly lower (3.5 and 5.9 microg/day). Based on the current EPA cancer slope factor for arsenic, estimated lifetime risks associated with background diet and water at the mean and 90th percentile are 1 per 10,000 and 2 per 10,000, respectively. By comparison, reasonable maximum risks for arsenic in soil at 20 (higher typical background level) and 100mg/kg are 4 per 100,000 and 2 per 10,000, using EPA default exposure assumptions. EPA reasonable maximum estimates of arsenic exposure from residential use of treated wood are likewise within background intakes. These examples provide context on how predicted risks compare to typical exposures within the U.S. population, thereby providing perspective for risk communication and regulatory decision-making on arsenic in the environment and in consumer products.
No preview · Article · Jul 2007 · Regulatory Toxicology and Pharmacology
[Show abstract][Hide abstract] ABSTRACT: Lumber treated with chromated copper arsenate (CCA) compounds has been used in residential outdoor wood structures and public playgrounds. The U.S. Environmental Protection Agency (EPA) has conducted a probabilistic assessment of children's exposure to arsenic using the Stochastic Human Exposure and Dose Simulation model for the wood preservative scenario (SHEDS-Wood). The assessment relied on data derived from an experimental study conducted using adult volunteers and designed to result in maximum hand and wipe loadings to estimate the residue-skin transfer efficiency. Recent analyses of arsenic hand-loading data generated by studies of children actively involved in playing on CCA-treated structures indicate that the transfer efficiency coefficient and hand-loading estimates derived from the experimental study significantly overestimate the amount that occurs during actual play.
Our goal was to assess the feasibility of using child hand-loading data in the SHEDS-Wood model and their impact on exposure estimates.
We used data generated by the larger of the studies of children in SHEDS-Wood, instead of the distributions used by U.S. EPA. We compared our estimates of the lifetime average daily dose (LADD) and average daily dose (ADD) with those derived by the U.S. EPA.
Our analysis indicates that data from observational studies of children can be used in SHEDS-Wood. Our estimates of the mean (and 95th percentile) LADD and ADD were 27% (10%) and 29% (15%) of the estimates derived by U.S. EPA.
We recommend that the SHEDS-Woods model use data from studies of children actively playing on playsets to more accurately estimate children's actual exposures to CCA.
Preview · Article · Jun 2007 · Environmental Health Perspectives
[Show abstract][Hide abstract] ABSTRACT: Engineered nano-scale materials are increasingly being used in a variety of consumer products. Health risk assessments are critical to evaluate the potential hazards associated with release of these materials and to ensure regulatory and public acceptance. Exposure and toxicity comprise the main components of risk. Materials science evaluations of nano-engineered particle exposures during production and throughout product lifetime may involve relatively simple tribology and reliability testing, and long-term stability assessment. Even without testing, existing knowledge of the properties of resins and binders can be used to formulate durable products that retain nanomaterials. Standard screening tests for toxicity are currently under development. Research has focused on some of the most common types of nanomaterials in or destined for products. A wealth of related information is also available from ultrafine particles (UFPs), metal fumes, volatile organic compounds, and mineral fibers. The presented approach describes the interplay between exposure, materials science, and toxicity, which when taken together, can aid in characterizing risk of products, engineering "safety" in products containing nanomaterials.
[Show abstract][Hide abstract] ABSTRACT: Nanoparticles are small-scale substances (<100 nm) with unique properties and, thus, complex exposure and health risk implications.
This symposium review summarizes recent findings in exposure and toxicity of nanoparticles and their application for assessing
human health risks. Characterization of airborne particles indicates that exposures will depend on particle behavior (e.g.,
disperse or aggregate) and that accurate, portable, and cost-effective measurement techniques are essential for understanding
exposure. Under many conditions, dermal penetration of nanoparticles may be limited for consumer products such as sunscreens,
although additional studies are needed on potential photooxidation products, experimental methods, and the effect of skin
condition on penetration. Carbon nanotubes apparently have greater pulmonary toxicity (inflammation, granuloma) in mice than
fine-scale carbon graphite, and their metal content may affect toxicity. Studies on TiO2 and quartz illustrate the complex relationship between toxicity and particle characteristics, including surface coatings,
which make generalizations (e.g., smaller particles are always more toxic) incorrect for some substances. These recent toxicity
and exposure data, combined with therapeutic and other related literature, are beginning to shape risk assessments that will
be used to regulate the use of nanomaterials in consumer products.
Full-text · Article · Jan 2006 · Toxicological Sciences
[Show abstract][Hide abstract] ABSTRACT: Nanotechnology has enormous potential for creating cost-effective, simple, and efficient tools for addressing water-supply challenges while preventing the creation of potentially toxic byproducts. The success of these tech-nologies using nanomaterials, however, will depend on whether the nanoparticles and fibers can be confined and isolated from human and environmental receptors and on assessments of the potential health and environmental risks if exposures do occur. To truly qualify as "green" technol-ogy, applications of nanotechnology will need to demon-strate that such exposures and potential concerns for health and environmental risk can be managed adequately. This paper describes some of these technologies, focusing on nanofiltration and disinfection, desalination, and environ-mental remediation, as well as implications to human health and the environment.
[Show abstract][Hide abstract] ABSTRACT: In response to concerns regarding arsenic in soil from a pesticide manufacturing plant, we conducted a biomonitoring study on children younger than 7 years of age, the age category of children most exposed to soil. Urine samples from 77 children (47% participation rate) were analyzed for total arsenic and arsenic species related to ingestion of inorganic arsenic. Older individuals also provided urine (n = 362) and toenail (n = 67) samples. Speciated urinary arsenic levels were similar between children (geometric mean, geometric SD, and range: 4.0, 2.2, and 0.89-17.7 microg/L, respectively) and older participants (3.8, 1.9, 0.91-19.9 microg/L) and consistent with unexposed populations. Toenail samples were < 1 mg/kg. Correlations between speciated urinary arsenic and arsenic in soil (r = 0.137, p = 0.39; n = 41) or house dust (r = 0.049, p = 0.73; n = 52) were not significant for children. Similarly, questionnaire responses indicating soil exposure were not associated with increased urinary arsenic levels. Relatively low soil arsenic exposure likely precluded quantification of arsenic exposure above background.
Full-text · Article · Dec 2005 · Environmental Health Perspectives
[Show abstract][Hide abstract] ABSTRACT: Arsenic is a natural component of the environment and is ubiquitous in soils, water, and the diet. Because dietary intake can be a significant source of background exposure to inorganic arsenic (the most toxicologically significant form), accurate intake estimates are needed to provide a context for risk management of arsenic exposure. Intake of inorganic arsenic by adults is fairly well characterized, but previous estimates of childhood intake were based on inorganic arsenic analyses in a limited number of foods (13 food types). This article estimates dietary intake for U.S. children (1 to 6 years of age) based on reported inorganic arsenic concentrations in 38 foods and in water used in cooking those foods (inorganic arsenic concentration of 0.8 μg/L), and U.S. Department of Agriculture food consumption data. This information is combined using a probabilistic software model to extract food consumption patterns and compute exposure distributions. The mean childhood dietary intake estimate for inorganic arsenic was 3.2 μg/day with a range of 1.6 to 6.2 μg/day for the 10th and 95th percentiles, respectively. For both the mean and 95th percentile inorganic arsenic intake rates, intake was predominantly contributed by grain and grain products, fruits and fruit juices, rice and rice products, and milk.
Full-text · Article · Jun 2004 · Human and Ecological Risk Assessment
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · May 2004 · Regulatory Toxicology and Pharmacology