Environews
NIEHS NEWS | Children's Health Centers: Past, Present, and Future
Children's health researchers from a variety of disciplines are studying different agents and routes of exposure to determine the most effective avenues for future investigations. The future of children's environmental health research was a central theme at an NIEHS/EPA conference held in January 2007. This article (p. A192) looks at some of the issues discussed at the conference as scientists sought to chart the course for forthcoming NIEHS-funded children's environmental health research.
FOCUS | Driven to Extremes: Health Effects of Climate Change
Warmer winters, more intense flooding, increased drought, rising sea levels—the Earth is showing ever-increasing extreme climate patterns. This year, the Intergovernmental Panel on Climate Change is releasing its latest assessment of how human activities contribute to climate change and the resultant human and environmental health effects. This article (p. A196) discusses some of those health impacts.
SPHERES OF INFLUENCE | A Changing Climate of Litigation
Amid mounting concerns of climate change, environmental watchdogs have begun suing corporations on the grounds that their greenhouse gas emissions are causing undue harm, and governments for failing to regulate the corporations. Industry has responded with countersuits of its own. However, determining legal culpability has not proven to be simple or easy, nor is it clear how or even whether courtroom victories will have any effect on the course of climate change. This article (p. A204) examines some of the issues being debated in climate change litigation.
INNOVATIONS | Solar Thrill: Using the Sun to Cool Vaccines
Maintaining cool storage for vaccines is essential for those medicines to work properly, but in less developed areas of the world, reliable cooling can be hard to find. Now a joint partnership of international humanitarian agencies and private companies is developing a new concept using solar power to keep vaccines cool. This article (p. A208) discusses how the SolarChill refrigerator harnesses solar power to produce an ice-cooled vaccine storage unit.
Commentaries
POPULATION HEALTH | Nutrition Intervention against Environmental Toxicity
Nutrition and lifestyle are well-defined modulators of chronic diseases. Poor dietary habits and a sedentary lifestyle clearly contribute to the compromised quality of life in the United States. It is becoming increasingly clear that nutrition can modulate the toxicity of environmental pollutants. Hennig et al. (p. 493) recommend that future directions in environmental health research explore this nutritional paradigm that incorporates the relationships between nutrition and lifestyle, exposure to environmental toxicants, and disease. Nutritional interventions may provide the most sensible means to develop primary prevention strategies of diseases associated with many environmental toxic insults.
RISK ASSESSMENT | Biodiesel Research
Biodiesel is an alternative to diesel fuel that could become a commercially accepted part of the energy infrastructure in the United States. Biodiesel exhaust emission has been extensively characterized, but there have been limited cytotoxicity and mutagenicity studies on the effects of biodiesel exhaust in biologic systems. Swanson et al. (p. 496) reviewed pertinent medical literature and addressed recommendations on testing specific research needs in the field of biodiesel toxicity. Based on chemical composition, its exhaust emissions are less likely to present any risk to human health compared with petroleum diesel emissions; however, the reduced health effects of biodiesel are still speculative and should be investigated.
Review
RISK ASSESSMENT | Hormesis: Some Scientific Reality Checks
Hormesis, a biological phenomenon typically described as low-dose stimulation from substances producing higher-dose inhibition, has recently drawn attention. Mushak (p. 500) provides a critical assessment of current hormesis literature and discusses definitions, characterization, generalizability, mechanisms, and absence of empirical data specific for hormesis hypothesis testing. He also examines the disadvantages of using hormesis as the "default assumption" in risk assessment.
Research
RESPIRATORY DISEASE | Exhaled Nitric Oxide and Air Pollution
Airborne particles have been linked to pulmonary oxidative stress and inflammation. Because these effects may be particularly great for traffic-related particles, Adar et al. (p. 507) examined associations between particle exposures and exhaled nitric oxide (FeNO) in a study of 44 senior citizens; this involved repeated trips aboard a diesel bus. Samples of (FeNO) collected before and after the trips were regressed against microenvironmental and ambient particle concentrations using mixed models controlling for multiple variables. Fine particle exposures resulted in increased levels of (FeNO) in participants, suggesting increased airway inflammation. These associations were best assessed by microenvironmental exposure measurements during periods of high personal particle exposures.
CARCINOGENESIS | Role of COX-2 Induction via IKKβ/NFκB in Resistance to Arsenite-Induced Apoptosis
Arsenic contamination has become a major public health concern worldwide, and epidemiologic data show that long-term arsenic exposure results in the risk of skin cancer. However, the mechanisms underlying carcinogenic effects of arsenite on skin remain to be studied. Ouyang et al. (p. 513) demonstrate that the IKKβ/NFκB pathway is required for COX-2 induction by arsenite, suggesting that the IKKβ/NFκB pathway may contribute to arsenite-induced carcinogenesis by protecting cells from apoptosis through inducing COX-2 expression.
HUMAN TOXICOLOGY | Cumulative Lead Exposure and Magnetic Resonance Spectroscopy
Exposure to lead has adverse effects on cognition in several different human populations, but little is known about the underlying structural and functional correlates of such exposure. Using magnetic resonance spectroscopy (MRS), Weisskopf et al. (p. 519) assessed the association between cumulative exposure to lead and levels of different brain metabolite ratios in vivo and determined that cumulative lead exposure is associated with an increase in the myoinositol-to-creatine ratio. These data suggest that glial effects may be more sensitive than neuronal effects as an indicator of cumulative exposure to lead in adults.
AGING | Air Pollution and Mortality in Chile
Because the estimated mortality rate associated with ambient air pollution based on general population studies may not be representative of the effects on certain subgroups, Cakmak et al. (p. 524) aimed to determine the influence of relatively high concentrations of air pollution on mortality in a general population sample and in the very elderly in Chilean urban centers during 1997–2003. The authors suggest that the very elderly (> 85 years of age) are more likely to die from air pollution than those who are younger. Concentrations deemed acceptable for the general population may not adequately protect the very elderly.
EPIDEMIOLOGY | Mortality and Chlorpyrifos Use
Chlorpyrifos is one of the most widely used organophosphate insecticides in the United States. Although the toxicity of chlorpyrifos has been extensively studied in animals, the epidemiologic data are limited. Lee et al. (p. 528) evaluated whether agricultural chlorpyrifos exposure is associated with mortality among pesticide applicators in the Agricultural Health Study, a prospective study of licensed pesticide applicators in Iowa and North Carolina. The findings of a possible association between chlorpyrifos use and external causes of death are based on small numbers. However, the findings may reflect a link between chlorpyrifos and depression or other neurobehavioral symptoms that deserves further evaluation.
CARDIOVASCULAR DISEASE | Up-regulation of Tissue Factor Due to UFP Exposure
Epidemiology studies have linked exposure to pollutant particles to increased cardiovascular mortality and morbidity, but the mechanisms remain unknown. Karoly et al. (p. 535) tested the hypothesis that the ultrafine fraction of ambient pollutant particles [ultrafine particles (UFPs)] would cause endothelial cell dysfunction. Using gene profiling, the authors found up-regulation of genes related to coagulation [tissue factor (F3) and coagulation factor II receptor-like 2] and differential regulation of genes related to F3 signaling. The results indicate that PM may cause adverse cardiovascular health effects by activating coagulation–inflammation circuitry.
TOXICOLOGY | Mammary Effects from Atrazine Metabolite Mixture
Atrazine, a widely used chlorotriazine herbicide, inhibits a number of endocrine-dependent processes, including gonadotrophin surges and mammary gland development in rats. Because chlorotriazine herbicide metabolites are present both in the environment and in exposed animals, Enoch et al. (p. 541) investigated whether a mixture of atrazine metabolites might produce developmental effects in rats after exposure in late pregnancy. The data suggest that acute exposure at levels as low as 0.09 mg/kg body weight during late pregnancy causes persistent alterations in mammary gland development of female offspring, and that these effects do not appear to be related to body weight or associated with pubertal timing.
ASTHMA | In Utero ETS Potentiates Adult Allergic Responses
Epidemiology studies have associated fetal exposure to maternal smoking and postnatal exposure to environmental tobacco smoke (ETS) with increased asthma risk. Using mice, Penn et al. (p. 548) tested the hypothesis that in utero ETS exposure alters airway function and respiratory immune responses in adults. At 6 weeks of age, there were no significant differences, but at 10 weeks, following exposure to OVA (ovalbumin) aerosol, ETS mice displayed greater airway hyperresponsiveness. At 15 weeks of age, mice that had inhaled saline in weeks 7–8 developed airway inflammation, whereas mice that had inhaled OVA in weeks 7–8 demonstrated no airway inflammation after sensitization and challenge. These results suggest that in utero ETS exposure exacerbates subsequent adult responses to initial allergen exposure.
NEURODEVELOPMENT | PCBs Disrupt Dendritic Development
Perinatal exposure to polychlorinated biphenyls (PCBs) is associated with decreased IQ scores, impaired learning and memory, psychomotor difficulties, and attentional deficits in children. To test the hypothesis that these neuropsychological deficits reflect altered patterns of neuronal connectivity, Lein et al. (p. 556) examined the effects of developmental PCB exposure on dendritic growth. The study demonstrates that developmental PCB exposure alters the ontogenetic profile of dendritogenesis in critical brain regions, supporting the hypothesis that disruption of
neuronal connectivity contributes to neuropsychological deficits seen in exposed children.
POPULATION HEALTH | NIEHS Portal
The NIEHS Portal was designed to provide decision makers with the data, information, and tools they need to monitor human and environmental health impacts of disasters; assess and reduce human exposures to contaminants; and develop science-based remediation, rebuilding, and repopulation strategies. Pezzoli et al. (p. 564) report that the NIEHS Portal is poised to serve as a national resource to track environmental hazards following natural and man-made disasters, focus medical and environmental response and recovery resources in areas of greatest need, and function as a test bed for technologies that will help advance environmental health sciences research into the modern scientific and computing era.
Also see Science Selections, p. A213
TOXICOGENOMICS | Toxicogenomics of Methapyrilene Hepatotoxicity
Toxicogenomics experiments often reveal thousands of transcript alterations that are related to multiple processes, making it difficult to identify key gene changes that are related to the toxicity of interest. Auman et al. (p. 572) compared gene expression changes between nontarget and target tissues for toxicity to help identify toxicity-related genes. By factoring in dose level, number of doses, and tissue into the analysis of gene expression elicited by methapyrilene, they identified genes unlikely to be implicated in toxicity, thus making it possible to focus on a subset of genes to identify toxicity-related processes.
RESPIRATORY DISEASE | Asbestos-Related Deaths in Libby Vermiculite Workers
Vermiculite from the mine near Libby, Montana, is contaminated with tremolite asbestos and other amphibole fibers (winchite and richterite). Asbestos-contaminated vermiculite was used in loose-fill attic insulation that remains in millions of homes in the United States, Canada, and other countries. Sullivan (p. 579) describes asbestos-related occupational respiratory disease mortality among workers who mined, milled, and processed the Libby vermiculite. The observed dose-related increases in asbestosis and lung cancer mortality highlight the need for better understanding and control of exposures that occur when homeowners or construction workers (including plumbers, cable installers, electricians, telephone repair personnel, and insulators) disturb loose-fill attic insulation made with asbestos-contaminated vermiculite.
BIOMONITORS | Pulmonary Protein Biomarkers of Arsenic Exposure
Environmental exposure to arsenic results in multiple adverse effects in the lung. Lantz et al. (p. 586) identified potential pulmonary protein biomarkers in the lung-lining fluid of mice chronically exposed to low-dose arsenic and validated these protein changes in human populations exposed to arsenic. The authors concluded that combinations of proteomic analyses of animal models, followed by specific analysis of human samples, provide an unbiased determination of important, previously unidentified putative biomarkers that may be related to human disease.
ENDOCRINE SYSTEM | Strain Differences and the Response to Estrogens
Studies of low-dose effects of xenoestrogens have yielded conflicting results that may be attributed to differences in estrogen sensitivity between rodent strains. Perinatal exposure of CD-1 mice to low doses of the xenoestrogen bisphenol A (BPA) alters peripubertal mammary gland development. Future studies of BPA action require estrogen receptor knock-out mice that were generated on a C57Bl6 background. Wadia et al. (p. 592) examined whether the mammary glands of CD-1 and C57Bl6 mice exhibited similar responses to 17β-estradiol (E2) and whether perinatal exposure to BPA equally enhanced sensitivity of the mammary glands to E2 at puberty.
GENE POLYMORPHISM | Genetic Polymorphisms Influencing Arsenic Metabolism
The susceptibility to arsenic-induced diseases differs greatly between individuals, possibly because of interindividual variations in arsenic metabolism affecting retention and distribution of toxic metabolites. To elucidate the role of genetic factors in arsenic metabolism, Schläwicke Engström et al. (p. 599) studied how polymorphisms in six genes affected the urinary metabolite pattern in a group of indigenous women in northern Argentina who were exposed to approximately 200 µg/L arsenic in drinking water. The findings indicate that polymorphisms in arsenic(+III)methyltransferase (AS3MT), and possibly glutathione S-transferases mu 1 (GSTM1) and theta (GSTT1), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and methylenetetrahydrofolate reductase (MTHFR) are responsible for a large part of the interindividual variation in arsenic metabolism and susceptibility.
Environmental Medicine
RISK ASSESSMENT | Potential Arsenic Toxicity from Kelp Supplements
Medicinal use of herbal dietary supplements is a potential cause of inadvertent arsenic toxicity. To evaluate the extent of arsenic contamination in commercially available kelp, Amster et al. (p. 606) analyzed nine samples randomly obtained from local health food stores. Eight of the nine samples showed detectable levels of arsenic higher than the Food and Drug Administration tolerance level of 2 ppm. None of the supplements contained information regarding the possibility of contamination with arsenic or other heavy metals. The authors recommend that clinicians should inquire about use of dietary supplements as a part of the patient's medical history.
Also see Science Selections, p. A212
Children's Health
NEURODEVELOPMENT | Dose Response for Mercury and IQ
Prenatal exposure to mercury has been associated with adverse childhood neurologic outcomes in epidemiologic studies; dose–response information for this relationship is useful for estimating benefits of reduced mercury exposure. Axelrad et al. (p. 609) estimated a dose–response relationship between maternal mercury body burden and subsequent childhood decrements in intelligence quotient (IQ). IQ is a useful end point for estimating neurodevelopmental effects, but it may not fully represent cognitive deficits associated with mercury exposure and it does not represent deficits related to attention and motor skills. Nevertheless, the integrated IQ coefficient provides a more robust description of the dose–response relationship for prenatal mercury exposure and cognitive functioning.
Also see Science Selections, p. A212
ASTHMA | Parental Smoking, TNF, and Asthma
Polymorphisms in the proinflammatory cytokine genes tumor necrosis factor-α (TNF) and lymphotoxin-α (LTA, also called TNF-β) have been associated with asthma and atopy in some studies. Parental smoking is a consistent risk factor for childhood asthma. Secondhand smoke and ozone both stimulate TNF production. Wu et al. (p. 616) investigated whether genetic variations in TNF and LTA are associated with asthma and atopy and whether the association is modified by parental smoking in a Mexican population with high ozone exposure. The results suggest that genetic variation in TNF may contribute to childhood asthma and that associations may be modified by parental smoking.
Also see Science Selections, p. A213
NEURODEVELOPMENT | Maternal Smoking and Speech Perception in Newborns
Tobacco smoking during pregnancy is known to adversely affect development of the central nervous system in babies of smoking mothers by restricting utero–placental blood flow and the amount of oxygen available to the fetus. Behavioral data associate maternal smoking with lower verbal scores and poorer performance on specific language/auditory tests. Key et al. (p. 623) examined the effects of maternal smoking during pregnancy on newborns' speech discrimination ability. The findings indicate that prenatal exposure to tobacco smoke in otherwise healthy babies is linked with significant changes in brain physiology associated with basic perceptual skills that could place the infant at risk for later developmental problems.
RISK ASSESSMENT | Blood Lead and Vitamin D Deficiency in Children
Blood lead concentrations are higher in summer than in winter. Although the effects of some environmental factors (e.g., lead in dust) on this phenomenon have been studied, relationships to sunlight-induced vitamin D synthesis have not been adequately investigated. Kemp et al. (p. 630) report that the higher summertime serum 25-hydroxy-vitamin D concentrations in 4- to 8-year-old children are likely caused by increased sunlight-induced vitamin D synthesis and may contribute to the seasonal increase in blood lead. Age and race/ethnicity are key factors that affect blood lead concentration and vitamin D intake, as well as their interactions, in young urban children.
Mini-Monograph
RISK ASSESSMENT | Arsenic in China: Occurrence and Health Effects
China has well-documented arsenic exposure, with approximately 5% of wells tested in 20,517 villages in China in 2001–2005 containing > 50 µg/L arsenic. High prevalence rates of arsenicosis are likely caused by exposure to As through drinking contaminated water and burning high As–content coal in unventilated indoor stoves. The Mini-Monograph (p. 636) discusses the effects of these long-term As exposures, focusing on children's intelligence and growth, urinary As metabolites in both children and adults, cellular and genetic damage in arsenicosis patients, and the reduction of As exposure through health education.