Environews
NIEHS NEWS | Society Builds Sustainability in Africa
The numerous advantages and benefits of an urbanized and industrial global community often come at a high environmental price, particularly for countries in the developing world. In Africa, many countries are feeling the adverse public health effects of rapid growth, and with limited capacity and a scarcity of regulatory resources available, these nations are in need of comprehensive self-sustaining programs. This article (p. A246) takes a look at possible solutions discussed in a recent workshop of the African Society for Toxicological Sciences cosponsored by the NIEHS.
FOCUS | Perfluoroalkyl Acids: What Is the Evidence Telling Us?
Throughout the last decade, perfluoroalkyl acids and their chemical cousins have continued to garner the attention of environmental health scientists and toxicologists. Used to produce a variety of everyday products, these compounds are now ubiquitous in animals and humans, and have also been linked to adverse health effects in both, but questions remain regarding the mechanisms by which they influence health outcomes. This article (p. A250) discusses some of the latest toxicological research findings connecting the compounds to human and animal health effects.
INNOVATIONS | Radical Departure: Polymerization Does More With Less
Polymers provide a multitude of practical uses in our daily lives. A process known as atom transfer radical polymerization produces a polymer chain that grows slowly but steadily, and can be modified at various stages throughout the process to embody whatever characteristics the end user desires. This article (p. A258) describes a variation of this method that uses less catalyst and offers even greater flexibility.
Review
POPULATION HEALTH | Animal Feed Ingredients and Human Health
In the United States, animal feeding practices have changed considerably over the past century. As large-scale, concentrated production methods have become the predominant model for animal husbandry, animal feeds have been modified to include ingredients ranging from rendered animals and animal waste to antibiotics and organoarsenicals. Sapkota et al. (p. 663) review current U.S. animal feeding practices and etiologic agents that have been detected in animal feed and discuss how current feeding practices may lead to adverse human health outcomes.
Research
TOXICOLOGY | OECD Hershberger Bioassay Protocol Validation: Phase 2 Dose–Response Studies
The Organisation for Economic Co-operation and Development (OECD) Hershberger bioassay is designed to identify suspected androgens and antiandrogens based on changes in the weights of five androgen-responsive tissues: ventral prostate, paired seminal vesicles and coagulating glands, the levator ani and bulbocavernosus muscles, the glans penis, and paired Cowper's or bulbourethral glands. In phase 2, protocol sensitivity and reproducibility were evaluated by 16 laboratories from seven countries using two androgen agonists (17α-methyl testosterone and 17β-trenbolone), four antagonists (procymidone, vinclozolin, linuron, and p,p´-DDE), and a 5α-reductase inhibitor (finasteride). Owens et al. (p. 671) report that the Hershberger bioassay protocol is reproducible and transferable across laboratories with androgen agonists, weak androgen antagonists, and a 5α-reductase inhibitor.
RESPIRATORY DISEASE | Mortality Effects of a Copper Smelter Strike
Many studies have reported associations between fine particulate and sulfur oxide air pollution and human mortality. Pope et al. (p. 679) retrospectively explored a natural experiment associated with a copper smelter strike from 15 July 1967 through the beginning of April 1968. The results suggest that the 60% reduction in regional sulfate concentrations associated with the 8.5-month strike period produced improvements in visibility and in small but measureable reductions in mortality.
EXPOSURE ASSESSMENT | Linkage of Pesticide Use and Land Use Data
Nuckols et al.(p. 684)integrated crop maps from the California Department of Water Resources with a comprehensive Pesticide Use Reporting Database (CPUR) maintained by the State of California to more accurately locate where pesticides are applied, and they evaluated the effects for exposure assessment. The findings may have important implications for exposure classification in epidemiologic studies of agricultural pesticide use using CPUR. Environmental and biological measurements need to be conducted to ascertain which, if any, of these metrics best represent exposure.
CARDIOVASCULAR DISEASE | Chronic Arsenic Exposure and QT Prolongation
Chronic arsenic exposure is associated with cardiovascular abnormalities. Prolongation of the QT interval (time between initial deflections of QRS complex to the end of T wave) and profound repolarization changes on electrocardiograms have been reported in patients with acute promyelocytic leukemia who were treated with arsenic trioxide. This acquired form of long QT syndrome can result in life-threatening arrhythmias. Mumford et al.(p. 690) assessed the cardiac effects of arsenic by investigating QT interval alterations in a human population chronically exposed to arsenic and found a significant association between chronic arsenic exposure and QT interval prolongation in this population.
Also see Science Selections, p. A213
EXPOSURE ASSESSMENT | Lead in Washington, DC
In 2003, residents of the District of Columbia (DC) experienced an abrupt increase in lead levels in drinking water, which followed a change in water disinfection treatment in 2001 and which was attributed to consequent changes in water chemistry and corrosivity. To evaluate the public health implications of the increased lead levels, the DC Department of Health expanded the scope of its monitoring programs for blood lead levels in children. Guidotti et al.(p. 695) report that this expanded screening program revealed the continuing problem with sources of lead in homes, specifically lead paint.
REPRODUCTIVE HEALTH | THF-diols and LTX-diols and Rat Estrous Cycle
Ground corncob animal bedding and corn food products contain substances [tetrahydrofurandiols (THF-diols) and leukotoxindiols (LTX-diols)] that disrupt endocrine function in rats. THF-diols and LTX-diols have been shown to block sexual behavior in male rats and estrous cyclicity in female rats. Markaverich et al.(p. 702) examined the nature of the interaction of these compounds (additive or synergistic) and quantified the concentration of THF-diols in rat tissues. THF-diols, LTX-diols, and/or their metabolites likely act additively to disrupt endocrine function in male and female rats at concentrations of 0.5–1 ppm, concentrations 200-fold lower than those of classical phytoestrogen endocrine disruptors.
RESPIRATORY DISEASE | Coarse PM and Systemic Inflammation in Asthmatics
In a 12-week study of adult asthmatics living within a 30-mile radius of an atmospheric monitoring site in Chapel Hill, North Carolina, Yeatts et al.(p. 709) investigated whether markers of airway and systemic inflammation, as well as heart rate variability, change in response to fluctuations in ambient particulate matter (PM) in the coarse (aerodynamic diameter of 2.5–10 µm) and fine (aerodynamic diameter of 2.5 µm) size range. The data suggest that small temporal increases in ambient coarse PM are sufficient to affect important cardiopulmonary and lipid parameters in adults with asthma. Coarse PM may have underappreciated health effects in susceptible populations.
CANCER | Temporal Variability of Tungsten and Cobalt in Fallon, Nevada
Since 1997, Fallon, Nevada, has experienced a unique cluster of childhood leukemia. Multiple environmental studies have shown airborne tungsten and cobalt to be elevated within Fallon, but no study has evaluated whether the levels of these metals through time correspond with the onset of the leukemia cluster. Sheppard et al.(p. 715) used dendrochemistry, the study of element concentrations through time in tree rings, to assess temporal variability of airborne tungsten and cobalt in Fallon. Results suggest a temporal correspondence between the onset of excessive childhood leukemia and elevated levels of tungsten and cobalt.
Also see Science Selections, p. A213
REPRODUCTIVE HEALTH | Atrazine, Breast Cancer, and Prostate Cancer
Atrazine, a potent endocrine disruptor, increases aromatase expression in some human cancer cell lines by the inhibition of phosphodiesterase and the subsequent elevation of cAMP. Fan et al.(p. 720) compared steroidogenic factor 1 (SF-1) expression in atrazine-responsive and -nonresponsive cell lines and transfected SF-1 into nonresponsive cell lines to assess SF-1's role in atrazine-induced aromatase. Their findings are consistent with the endocrine-disrupting effects of atrazine in fish, amphibians, and reptiles; the induction of mammary and prostate cancer in laboratory rodents; and correlations between atrazine and similar reproductive cancers in humans. The results of this study raise concern for the impact of atrazine on environmental and public health.
RESPIRATORY DISEASE | Nanoparticles' Two-Way Transport across Lung Epithelium
Inhaled nanoparticles (NPs) may translocate from epithelial deposition sites of the lungs toward systemic circulation. Using healthy adult rats, Semmler-Behnke et al.(p. 728) studied the disappearance of NPs from the epithelium by sequential lung retention and clearance and bronchoalveolar lavage measurements. The authors found a strong size-selective difference in particle immobilization. Alveolar macrophage (AM)-mediated NP transport to the larynx originates not only from the NP fraction retained on the epithelium but also from NP being reentrained from the interstitium to the luminal side of epithelium. NPs are much less phagocytized by AMs than large particles but are effectively removed from the lung surface toward the interstitium.
DIABETES | Inhibition of Insulin Signal by Inorganic and Methyl Arsenic
Increased prevalences of diabetes mellitus have been reported among individuals chronically exposed to inorganic arsenic (iAs); however, the mechanisms underlying the diabetogenic effects of iAs have not been characterized. Paul et al.(p. 734) studied the molecular mechanisms responsible for the suppression of protein kinase B (PKB/Akt) phosphorylation by arsenite (iAsIII) and methylarsonous acid (MAsIII). The results suggest that inhibition of the 3-phosphoinositide-dependent kinase-1/PKB/Akt-mediated transduction step is the key mechanism for the inhibition of insulin-stimulated glucose uptake in adipocytes exposed to iAsIII or MAsIII, and possibly for impaired glucose tolerance associated with human exposures to iAs.
EXPOSURE ASSESSMENT | Efficiency and Equity of Power Plant Pollution Control
In deciding among competing approaches for emissions control, debates often hinge on the potential tradeoffs between efficiency and equity. However, previous health benefits analyses have not formally addressed both dimensions. Levy et al.(p. 743) modeled the public health benefits and the change in spatial inequality of health risk for a number of hypothetical control scenarios for power plants in the United States to determine optimal control strategies. The authors demonstrate an approach for formally quantifying both the magnitude and spatial distribution of health benefits of pollution-control strategies, allowing for joint consideration of efficiency and equity.
EXPOSURE ASSESSMENT | Traffic Pollution and Mortality in the Greater Boston Area
Airborne particles are associated with increased risk of death, but the differential toxicity of particles from different sources is gaining attention. Maynard et al.(p. 751) conducted a case–crossover analysis in which they analyzed approximately 100,000 deaths from all, cardiovascular, and respiratory causes for the years 1995–2002 using a geographic information system approach to improve exposure assessment. The authors concluded that particles from both traffic and coal-burning power plants are associated with increased deaths in Boston, Massachusetts, with larger effects for traffic particles.
Also see Science Selections, p. A213
TOXICOGENOMICS | Proteomic Analysis of Bronchoalveolar Lavage Fluid
Inhalation of diesel exhaust particles (DEP) is characterized by lung injury and inflammation with significant increases in the numbers of polymorphonuclear leukocytes and alveolar macrophages. This influx of cellular infiltrates is associated with the activation of multiple genes, including cytokines and chemokines, and the production of reactive oxygen species. Lewis et al.(p. 756) characterized alterations in the presence or abundance of a group of proteins in the lung and questioned whether additional changes could be discerned using modern proteomic techniques. The authors found a number of inflammatory response proteins that may be associated with the early phases of inflammation in response to DEP exposure.
EXPOSURE ASSESSMENT | TestSmart DNT Workshop
Developmental neurotoxicity testing (DNT) is perceived by many stakeholders to be an area in critical need of alternatives to current animal testing protocols and guidelines. Lein et al. (p. 764) report on a program called TestSmart DNT, in which the Johns Hopkins Center for Alternatives to Animal Testing, the U.S. Environmental Protection Agency, and the National Toxicology Program are collaborating. The goals of TestSmart DNT are to a) develop alternative methodologies for identifying and prioritizing chemicals and exposures that may cause developmental neurotoxicity in humans; b) develop policies for incorporating DNT alternatives into regulatory decision making; and c) identify opportunities for reducing, refining, or replacing the use of animals in DNT.
Environmental Medicine
CARDIOVASCULAR DISEASE | Air Pollution and MI Survival
Several studies have examined the effect of particulate pollution (PM) on survival in general populations, but less is known about susceptible groups. Moreover, previous cohort studies have been cross-sectional and subject to confounding by uncontrolled differences between cities. Zanobetti and Schwartz (p. 769) investigated whether PM was associated with progression of disease or reduced survival in a study of 196,000 persons from 21 U.S. cities discharged alive following an acute myocardial infarction (MI), using within-city, between-year exposure to PM. This study shows a significant association between particle exposure and adverse post-MI outcomes in persons who survived an MI.
Children's Health
RISK ASSESSMENT | Fetal Death and Proximity to Hazardous Waste Sites
The effects of prenatal exposure to environmental toxicants on various adverse pregnancy outcomes, including fetal death, are not well understood. Mueller et al.(p. 776) examined the risk of fetal death in relation to maternal residential proximity to hazardous waste sites. The risk of fetal death for women residing near a hazardous waste site (≤ 0.5 miles) was not increased. The results do not suggest that fetal death is associated with residential proximity to hazardous waste sites overall; however, close proximity to pesticide-containing sites may increase the risk of fetal death.
Also see Science Selections, p. A213
EXPOSURE ASSESSMENT | Children's Arsenic Exposures from CCA-Treated Wood
Lumber treated with chromated copper arsenate (CCA) compounds has been used in residential outdoor wood structures and public playgrounds. Recent analyses of arsenic hand-loading data indicate that the transfer efficiency coefficient and hand-loading estimates significantly overestimate the amount of transfer that occurs during actual play. Barraj et al. (p. 781) assess the feasibility of using the children's hand-loading data in the SHEDS-Wood model and their impact on exposure estimates. The analysis indicates that data from observational studies of children can be used in SHEDS-Wood. The estimates of the mean (and 95th percentile) lifetime average daily dose and average daily dose were 27% (10%) and 29% (15%) of the estimates derived by the U.S. Environmental Protection Agency.
EPIDEMIOLOGY | Farmworkers Who Gave Birth to Infants with Birth Defects
In February 2005, three infants with congenital anomalies were identified in Collier County, Florida; the infants were born within 8 weeks of one another, and their mothers worked for the same tomato grower. During the period of organogenesis, all three women worked in fields recently treated with several pesticides. Calvert et al. (p. 787) report thatdespite the suggestive evidence, a causal link could not be established between pesticide exposures and the birth defects in the three infants. Nonetheless, the prenatal pesticide exposures experienced by the mothers of these three infants is cause for concern. Results of this study support the need for epidemiologic studies to examine the role of pesticide exposure in the etiology of congenital anomalies.
NEURODEVELOPMENT | Organophosphate Pesticides and Neurodevelopment
Organophosphate (OP) pesticides are widely used in agriculture and in homes. Although animal studies suggest that even moderate doses of OP pesticides are neurodevelopmental toxicants, there have been few studies in humans. In a longitudinal birth cohort of primarily Latino farmworker families in California, Eskenazi et al. (p. 792) investigated the relationship of prenatal and child OP urinary metabolite levels with children's neurodevelopment. The authors report adverse associations of prenatal dialkyl phosphates (DAPs) with mental development and pervasive developmental problems at 24 months of age. Because of the observed positive relationship with postnatal DAPs, the results should be interpreted with caution.
Mini-Monograph
RISK ASSESSMENT | Cumulative Risk Assessment
Cumulative risk refers to the combined threats from exposure via all relevant routes to multiple stressors. The Mini-Monograph (p. 799) examines the assessment of cumulative risks through the development of guidelines for cumulative risk assessment by the U.S. Environmental Protection Agency that take a broader, more holistic approach—approaches that take into account the effects of physical, biological, chemical, and psychosocial stressors; the key challenges in determining whether and to what degree differential exposure to environmental mixtures contributes to increased vulnerability of exposed populations; and the relationship between environmental exposures and health outcomes as mitigated by differential susceptibility in individuals or populations.
