Environews
NIEHS NEWS | Growth Opportunities
The epidemic of childhood obesity is a health hazard that continues to affect more and more of our children. To combat the spread of this threat, stakeholders are joining forces to pool ideas and resources. One of two articles this month (p. A520) chronicles successful strategies used by local, state, and national programs and highlighted at June's Environmental Solutions to Obesity in America's Youth conference. In other news, the field of endocrine disruptor research continues to distinguish itself as a distinct discipline, as evidenced by studies presented at a workshop dedicated to that topic at the 87th annual Endocrine Society meeting in San Diego.
FOCUS | Bio(tech)feedback
When first introduced commercially in the 1990s, genetically modified (GM) foods appeared to be a great idea--they're resistant to pests and herbicides, so they help raise harvest yields, and they hold the promise of providing high-nutrition foods from even the poorest soils and harshest conditions. But the initial warm reception has been countered with public and scientific doubt and skepticism. This article (p. A526) examines some of the concerns contributing to the backlash and looks at future developments that could possibly make the idea of GM foods more palatable.
SPHERES OF INFLUENCE | Africa's Stake in Global Warming
Increased flooding and drought are challenges that are rising with global warming. While affluent countries frequently have relief measures and a cushion of resources to withstand the negative effects of climate change, other less-developed areas of the world are not so fortunate. Africa is one area that is in line to be the hardest hit by the effects of climate change. This article (p. A534) takes a look at how global warming is impacting the continent that has contributed the least to the problem, and discusses what can be done to help ease the burden.
INNOVATIONS | Adding Mussel to Soy Adhesives
Although a staple in adhesives used in the wood products industry, formaldehyde causes concern among those worried about possible health effects. Safer soybean-based wood adhesives have been used in the past, but were not as cost-efficient or convenient as those formulated with formaldehyde. This article (p. A538) describes a new take on soy-based adhesives, using proteins processed to resemble those that allow mussels to cling to rocks.
Commentaries
ASTHMA | Asthma and Climate Change
During the same period in which there has been a global increase in asthma incidence, atmospheric carbon dioxide and global average surface temperature have increased. Beggs and Bambrick (p. 915) hypothesize anthropogenic climate change as a contributor to the rise in asthma. Greater concentrations of CO2 and higher temperatures may increase pollen quantity and induce longer pollen seasons. As a result of these climate changes, pollen allergenicity can also increase. Exposure in early life to a more allergenic environment may provoke the development of other atopic conditions such as eczema and allergic rhinitis.
CANCER | Breast Cancer, the Environment, and Precaution
With prevention as the underlying goal, the precautionary principle calls for improved research processes that contribute to "strength of the evidence" assessments of health effects when scientific uncertainty is likely to persist. Brody et al. (p. 920) discuss how breast cancer studies have contributed to environmental programs and to application of geographic information systems for surveillance and historical exposure assessment. These methods also leave unanswered questions about when to invest in large epidemiologic studies, when negative results are sufficient, and how to pursue ambiguous positive results in further research and policy.
RISK ASSESSMENT | Bisphenol A Risk Assessment
On the basis of 19 studies, the Harvard Center for Risk Analysis concluded that evidence for low-dose effects of bisphenol A (BPA) is weak. However, vom Saal and Hughes (p. 926) propose that a new risk assessment for BPA is needed based on a) new literature reporting adverse effects in animals at doses below the current reference dose; b) a high rate of BPA leaching from food containers; c) reports that median BPA levels in human tissues are higher than levels causing adverse effects in mice; and d) epidemiologic evidence relating BPA to disease in women.
Reviews
RESPIRATORY DISEASE | Cardiovascular Health and PM
Cardiovascular hospital admissions and mortality are associated with outdoor air pollution, particularly mass concentrations of particulate matter (PM) ≤ 2.5 and ≤ 10 µm in diameter (PM2.5 and PM10, respectively). Delfino et al. (p. 934) review the likely causal components that may be driving PM associations with risk of cardiac ischemia and arrhythmias, increased blood pressure, decreased heart rate variability, and increased circulating markers of inflammation and thrombosis. High ultrafine particle (UFP) exposures may lead to systemic inflammation through oxidative stress responses to reactive oxygen species and thereby promote atherosclerosis and acute cardiovascular responses ranging from increased blood pressure to myocardial infarction.
EXPOSURE ASSESSMENT | Exposure Assessment for Atmospheric UFP
Exposure assessment issues for ultrafine particles (UFPs) are complex and need to be considered before undertaking epidemiologic investigations of UFP health effects. These issues include high spatial variability, indoor sources, variable infiltration of UFPs from a variety of outside sources, and meteorologic factors leading to high seasonal variability in concentration, composition, and volatility. To address these issues, investigators need to develop and validate the analytic technologies required to characterize the physical/chemical nature of UFPs in various environments. Sioutas et al. (p. 947) provide a detailed discussion of key characteristics of UFPs, their sources and formation mechanisms, and methodologic approaches to assessing population exposures.
Research
RESPIRATORY DISEASE | Transport of PAH from Particles into Cells
Butadiene soot (BDS), produced during combustion of 1,3-butadiene, is rich in polynuclear aromatic hydrocarbons (PAHs). Penn et al. (p. 956) characterize BDS with respect to particle size distribution, assembly, PAH composition, elemental content, and interaction with respiratory epithelial cells. Cells of a human bronchial epithelial cell line exhibit sequential fluorescent responses after BDS is added to medium overlying the cells. The ultrafine BDS particles move to the cell membrane, but do not cross into the cells. Fluorescent PAHs cross the membrane into the cytosol and accumulate in lipid vesicles, indicating that uptake of particles is not necessary for transfer of toxicants into the cells.
RESPIRATORY DISEASE | Mapping and Predicting Coal's Toxicity
Huang et al. (p. 964) show that the prevalence of coal workers' pneumoconiosis (CWP) in seven coal mine regions correlates with levels of bioavailable iron (BAI) in the coals from the particular regions. Using the linear fit of CWP prevalence and the calculated BAI in the seven coal mine regions, the pneumoconiotic potencies of 7,000 coal samples were derived and mapped. Results indicate that levels of BAI in the coals may be used to predict coal's toxicity, even before large-scale mining.
SIGNAL TRANSDUCTION | Xenoestrogen Regulation of Glucagon
Glucagon, secreted from pancreatic -cells, is involved in regulation of glucose metabolism by enhancing the synthesis and mobilization of glucose in the liver. Alonso-Magdalena et al. (p. 969) show that the endocrine disruptors bisphenol A (BPA) and diethylstilbestrol (DES), both at 10-9 M, suppressed low-glucose-induced intracellular calcium ion ([Ca2+]i) oscillations in -cells, the signal that triggers glucagon secretion. Competition studies indicate that 17β-estradiol (E2), BPA, and DES share a common membrane-binding site. The action of E2, BPA, and DES in pancreatic -cells may explain some effects of endocrine disruptors on metabolism of glucose and lipid.
Also see Science Selections, p. A544
CARDIOVASCULAR DISEASE | Air Pollution and MI Admissions
Results of studies in single locations that assess the effects of ambient particular matter on the risk of myocardial infarction (MI) differ widely. Zanobetti and Schwartz (p. 978) used a multicity case-crossover study to examine hospitalization associated with fine particulate matter with aerodynamic diameter < 10 µm (PM10) for > 300,000 MIs among elderly residents of 21 U.S. cities. Overall, they found a 0.65% increased risk of hospitalization for MI per 10 µg/m3 increase in ambient PM10 concentration. The exposure-response relationship between MI hospitalizations and PM10 is almost linear but with a steeper slope at levels of PM10 < 50 µg/m3.
DNA REPAIR | Keratinocyte Response to Arsenite and UVR
Arsenite increases the cancer rate caused by solar-simulation ultraviolet radiation (UVR) in the hairless mouse skin model. Wu et al. (p. 983) investigated how arsenite affected DNA photodamage repair and apoptosis after solar-simulation UVR in the mouse keratinocyte cell line 291.03C. Arsenite reduced the repair rate of 6-4 photoproducts at 5.0 µM and had no effect at 2.5 µM. UVR-induced apoptosis at 24 hr was decreased by 2.5 µM and by 5.0 µM arsenite. If these results are applicable in vivo, then inhibition of UVR-induced apoptosis may contribute to arsenite's enhancement of UVR-induced skin carcinogenesis.
EXPOSURE ASSESSMENT | Dispersion versus Stochastic Modeling of NO2 and PM
Cyrys et al. (p. 987) compared measured levels of nitrogen dioxide and PM2.5 (particulate matter < 2.5 µm in aerodynamic diameter) with levels predicted by stochastic and dispersion modeling (for 40 measurement sites), and they also compared the results of both approaches for all study sites (1,669). NO2 and PM2.5 concentrations obtained by the stochastic models were in the same range as the measured concentrations, whereas the NO2 and total suspended particle levels estimated by dispersion modeling were higher than the measured values. However, the correlation between stochastic- and dispersion-modeled concentrations was strong for both pollutants. Both models yield similar results regarding exposure estimation of the study cohort to traffic-related air pollutants.
CANCER | Agricultural Pesticides and Breast Cancer Incidence
Reynolds et al. (p. 993) evaluated whether California breast cancer rates were elevated in areas with recent high agricultural pesticide use. The rate ratios and 95% confidence intervals were calculated using Poisson regression models, adjusting for age, race/ethnicity, and neighborhood socioeconomic status and urbanization. The aggregative analysis included 176,302 invasive breast cancer cases and 70,968,598 person-years of observation. The results provide no evidence that California women living in areas of recent, high agricultural pesticide use experience higher rates of breast cancer.
RISK ASSESSMENT | Benchmark Calculations for Perchlorate
The National Academy of Sciences recently reported that the perchlorate dose required to cause hypothyroidism in adults would be > 0.40 mg/kg-day for months or longer. Crump and Gibbs (p. 1001) calculated benchmark doses for perchlorate from thyroid-stimulating hormone (TSH) and free thyroxine (T4) serum indicators from two occupational cohorts with long-term exposure to perchlorate and from a clinical study of volunteers. The lower 95% statistical confidence limits on benchmark doses estimated from a combined analysis of the two occupational studies ranged from 0.21 to 0.56 mg/kg-day for free T4 index and from 0.36 to 0.92 mg/kg-day for TSH.
RESPIRATORY DISEASE | Particles and Angiotensin
Exposure to particulate matter (PM) is associated with acute cardiovascular mortality and morbidity. Li et al. (p. 1009) hypothesized that PM may activate the angiotensin type 1 receptor (AT1R), a G protein-coupled receptor that regulates inflammation and vascular function. They investigated the acute effects of urban particles (Standard Reference Material 1648) on the constriction of rat pulmonary artery rings and the activation of extracellular signal-regulated kinases 1 and 2 and p38 mitogen-activated protein kinases in human pulmonary artery endothelial cells. Results indicate that activation of the local renin-angiotensin system may play an important role in cardiovascular effects induced by PM.
NEURODEVELOPMENT | Thimerosal and Blood and Brain Mercury
Reports have indicated that infants can receive ethylmercury (in the form of thimerosal used in vaccines) at or above methylmercury exposure guidelines. Burbacher et al. (p. 1015) compared the systemic disposition and brain distribution of total and inorganic mercury in infant monkeys exposed to thimerosal with those exposed to MeHg. Initial and terminal half-lives of blood Hg after thimerosal exposure were shorter than the elimination half-life of Hg after MeHg exposure. Brain concentrations of total Hg were lower in the thimerosal-exposed monkeys than in the MeHg-exposed monkeys; a higher percentage of total Hg in the brains of thimerosal-exposed monkeys was inorganic Hg. The results indicate that MeHg is not a suitable reference for risk assessment from exposure to thimerosal-derived Hg.
Also see Science Selections, p. A543
CANCER | Developmental Carcinogenic Effects of OH-PCBs
Martinez et al. (p. 1022) examine the relationship between estrogenicity and carcinogenicity of 2´,4´,6´-trichloro-4-biphenylol (OH-PCB-30) and 2´,3´,4´,5´-tetrachloro-4-biphenylol (OH-PCB-61) congeners. The hydroxylated PCBs (OH-PCBs) were tested individually and in combination to determine whether effects of combined OH-PCBs differed from those of these OH-PCBs alone. Results indicate that the individual OH-PCBs tested were estrogenic and tumorigenic in mice exposed during reproductive tract development. Data also support the hypothesis that mixtures may act differently, and unexpectedly, than individual compounds.
NEURODEVELOPMENT | Developmental Chlorpyrifos Exposure
Aldridge et al. (p. 1027) exposed developing rats to chlorpyrifos (CPF) regimens below the threshold for systemic toxicity on gestational days 17-20, postnatal days (PN) 1-4, or PN11-14. Basal neurotransmitter content and synaptic activity (turnover) in brain regions containing the major 5HT and dopamine projections were assessed in early adulthood (PN60). Results indicate that, in a critical developmental period, apparently nontoxic exposures to CPF produce lasting activation of 5HT systems in association with 5HT-associated behavioral anomalies.
RESPIRATORY DISEASE | Seasonal Effects of PM
Health effects associated with particulate matter (PM) show seasonal variations possibly related to differences in the elemental composition. Becker et al. (p. 1032) exposed normal human bronchial epithelial cells and alveolar macrophages to equal mass of seasonal coarse [PM diameter of 2.5-10 µm (PM2.5-10)], fine (PM2.5), and ultrafine (PM< 0.1) ambient PM. Elemental constituents were measured along with variation in production of interleukin (IL)-8, IL-6, and reactive oxygen species. Results indicate that elemental constituents of PM may in part account for the seasonal variations in PM-induced adverse health effects related to lung inflammation.
FETAL DEVELOPMENT | Environmental Pollutants and Thyroid Hormones during Pregnancy
Polychlorinated biphenyls (PCBs), chlorinated pesticides, and mercury can disrupt the endocrine system in animals and humans. Takser et al. (p. 1039) examined thyroid hormone levels during pregnancy and in cord blood in relation to blood concentrations of organochlorine compounds (OCs) and Hg. There was a significant negative correlation between maternal total triiodothyronine levels and three non-coplanar congeners, three pesticides, and inorganic Hg independently, without any other changes in thyroid status. Cord serum free thyroxin was negatively correlated with inorganic Hg. Results suggest that low levels of exposure to persistent environmental contaminants can interfere with thyroid status during pregnancy.
Also see Science Selections, p. A542
TOXICOGENOMICS | Gene Expression after Malathion Exposure
Malathion is a known endocrine disruptor widely used for insect control. Gwinn et al. (p. 1046) studied gene expression profiles of four normal human mammary epithelial cell lines in response to malathion. Clustering identified two aldo-keto reductases (AKR1C1 and AKR1C2) and an estrogen-responsive gene (EBBP) with increased expression after treatment in all four cell lines. Decreased expression of six RNA species was seen at various time points in all cell strains analyzed. Expression changes in these genes may yield biomarkers that provide insight into interindividual variation in malathion toxicity.
Environmental Medicine
CARDIOVASCULAR DISEASE | Air Pollution and Blood Pressure
Exposure to air pollution causes arterial vasoconstriction and alters autonomic balance. Urch et al. (p. 1052) compared blood pressure responses during 2-hr exposures to concentrated ambient fine particles (particulate matter < 2.5 µm; PM2.5) plus ozone (CAP+O3) with particle-free air (PFA) in normotensive, adults. A significant increase in diastolic blood pressure (DBP) was observed at 2 hr of CAP+O3 and there was a strong association between the 2-hr change in DBP and the concentration of the organic carbon fraction of PM2.5 but not with total PM2.5 mass. The magnitude of BP change is associated with the PM2.5 carbon content.
Children's Health
FETAL DEVELOPMENT | Prenatal Phthalate Exposure and Male AGD
Prenatal phthalate exposure impairs testicular function and shortens anogenital distance (AGD) in male rodents. Swan et al. (p. 1056) examined AGD and other genital measurements in relation to prenatal phthalate exposure in humans. An anogenital index (AGI) was defined as AGD divided by weight at examination and used to calculate the age-adjusted AGI by regression analysis. A summary phthalate score was used to quantify joint exposure to four phthalate metabolites. The age-adjusted AGI decreased significantly with increasing phthalate score and supports a hypothesis that prenatal phthalate exposure at environmental levels can adversely affect male reproductive development in humans.
Also see Science Selections, p. A542
FETAL DEVELOPMENT | The WTC Event, DNA Adducts, and Birth Outcomes
Polycyclic aromatic hydrocarbons (PAHs) are toxic pollutants released by the World Trade Center (WTC) fires and urban combustion sources. Benzo[a]pyrene (BaP)-DNA adducts as a PAH proxy, provide a measure of genetic damage possibly associated with adverse birth outcomes and cancer. Perera et al. (p. 1062) analyzed birth outcome together with BaP-DNA adducts in maternal and umbilical cord blood obtained at delivery from women who were pregnant on 11 September 2001 and enrolled at delivery at downtown Manhattan hospitals. A doubling of adducts among environmental tobacco smoke-exposed subjects corresponded to an estimated average reduction of 8% in birth weight and 3% in head circumference.
ASTHMA | Air Pollution Effects on Children with Asthma
Lewis et al. (p. 1068) examined relationships between lung function, ambient particulate matter, and ozone in a longitudinal cohort of primary-school-age children with asthma. Models considered effect modification by maintenance corticosteroid (CS) use and by the presence of upper respiratory infection (URI). Participants were predominantly African American, and > 75% were categorized as having persistent asthma. In both single-pollutant and two-pollutant models, many regressions demonstrated associations between higher exposure to ambient pollutants and poorer lung function among children using CSs but not among those not using CSs, and among children reporting URI symptoms but not among those who did not report URIs.
Mini-Monograph
EXPOSURE ASSESSMENT | The National Children's Study
Exposure assessment is evolving rapidly with the advancement of sophisticated methods for specific measurements in a variety of environmental and biologic matrices. Childhood development represents many critical windows where exposure to environmental contaminants may have significant health consequences later in life. This Mini-Monograph (p. 1076) provides a view of several exposure issues and notes various environmental agents and how best to assess exposure to them in the National Children's Study, a longitudinal epidemiologic study of children's health. Several criteria for the analytical methods are discussed, with particular emphasis on the need for long-term quality control and quality assurance measures.