Environews
NIEHS NEWS | Dynamics of Disparity
Diseases such as breast cancer, prostate cancer, and hypertension are burdens that affect millions of people. But some populations are more vulnerable than others--why? This question drives the research behind eight Centers for Population Health and Health Disparities throughout the United States. An update this month (p. A592) discusses research at these centers that seeks to shed light on factors that contribute to health disparities between different populations.
FOCUS | Planetary Overload
As the global population continues to increase, so does concern for the Earth's ability to support it. Although experts in the past predicted that the human population would eventually outstrip our planet's natural resources, through the help of technological advances and ingenuity we have been able to adapt and adjust. But with some projecting a near doubling of global population over the next 20-30 years, especially in the resource-poor developing world, can the Earth continue to meet our demands? This article (p. A598) discusses some of the ways population growth challenges the Earth's sustainability and looks at possible future scenarios.
SPHERES OF INFLUENCE | All's Not Well in Paradise
Known for their relaxing atmospheres and breathtaking scenery, small island nations are perceived by many to be simple oases of paradise. Beyond this idyllic view, however, are the everyday realities that these nations contend with: increasingly severe storm patterns, rising sea levels, and threats to economic stability, to name just a few. This article (p. A606) examines some of the strategies the leaders of these compact nations are employing to combat the threats to their citizens' way of life.
INNOVATIONS | Scanning for Disease Outbreaks
How helpful would it be to have early warning of where pockets of disease are emerging? For health authorities the advantage is clear: disease outbreaks could be contained before spreading too far into a given population. This article (p. A610) looks at a new model that uses space-time permutation scan statistics to predict patterns of disease outbreak in specific areas based on electronic medical records. Could this new method of evaluating data become a reliable tool to control the spread of disease?
Commentaries
RISK ASSESSMENT | NAS Review and Perchlorate RfD
The U.S. Environmental Protection Agency conducted a perchlorate risk assessment in 2002 that yielded a reference dose (RfD) based on both animal and human toxicology data. This assessment has been superceded by a recent National Academy of Sciences (NAS) review that derived a perchlorate RfD that is 20-fold greater. Ginsberg and Rice (p. 1117) raise concerns about the NAS approach to RfD development in three areas of toxicity assessment: the NAS no-observable adverse-effect level is actually associated with perchlorate-induced effects; consideration of uncertainties was insufficient; and the NAS considered the inhibition of iodine uptake to be a nonadverse effect.
TOXICOLOGY | Methylmercury in Laboratory Diets
During research on the neurodevelopmental effects of mercury vapor in rats, Weiss et al. (p. 1120) detected significant levels of mercury (30-60 ng/g) in the blood of nonexposed control subjects. Organic mercury was the dominant form, and laboratory chow was found to be the source of the contamination. The dietary levels were considered potentially biologically significant, even though some were below the limit of detection specified by the supplier. Such contamination may alter conclusions based on intentionally administered doses and interact with other agents that are the primary focus of the research.
REMEDIATION | Arsenic and Animal Waste Management
Changes in the poultry industry over the past 50 years have incidentally created a largely ignored environmental management crisis. Poultry concentrated animal feeding operations (CAFOs) produce far more waste than can be managed by land disposal within the regions where it is produced. The organic arsenicals used in poultry feed are converted to inorganic arsenicals in poultry waste, limiting the feasibility of waste management alternatives and increasing opportunities for population exposures. Nachman et al. (p. 1123) contend that removal of arsenic from animal feed is a critical step toward safe poultry waste management.
Review
CANCER REVIEW | Susceptibility from Early-Life Carcinogen Exposure
In cancer risk assessment, it is currently assumed that children and adults are equally susceptible to chemical exposure. Barton et al. (p. 1125) reviewed scientific literature to determine whether this was scientifically supported and identified > 50 chemicals that cause cancer after perinatal exposure. In general, early exposures to compounds with endocrine activity may produce different tumors after exposures at different ages. The analyses suggest increased susceptibility to cancer from early-life exposure, particularly for chemicals that act through a mutagenic mode of action.
Research
CANCER | Arsenic-Induced Androgen Independence
Benbrahim-Tallaa et al. (p. 1134) used a nontumorigenic arsenic-transformed human prostate epithelial cell line to determine whether arsenic affects prostate tumor progression to androgen independence. Control and chronic arsenic-exposed human prostate epithelial cells (CAsE-PE) were maintained in a complete medium or in steroid-depleted medium. Arsenic-transformed cells showed a more rapid proliferation rate in complete medium than control cells, and they also showed sustained proliferation in steroid-depleted medium. Control and CAsE-PE cells had similar levels of androgen receptor, but androgens were less effective in stimulating cell proliferation and gene expression in CAsE-PE cells. Thus, arsenic-induced malignant transformation is associated with acquired androgen independence in human prostate cells.
Also see Science Selections, p. A614
RESPIRATORY DISEASE | PM2.5 and Public Health
Johnson and Graham (p. 1140) identified the magnitude of general and susceptible populations within the northeastern United States that would benefit from compliance with alternative U.S. Environmental Protection Agency (EPA) annual and 24-hr mass-based standards for particulate matter ≤ 2.5 µm in aerodynamic diameter (PM2.5). Results indicate that only 16% of the general population lives in counties that do not meet the existing annual/24-hr PM2.5 standard. The PM2.5 standards recommended by California and Canada would protect 84-100% of the Northeast population, and standards within the current range recommended by the U.S. EPA would protect 29-100% of that population.
RISK ASSESSMENT | Moving Total Mortality and Particulate Matter
Time-series studies of mortality and particulate matter (PM) conducted in cities where ambient PM measurements are available only every few days are restricted to using a single day's PM as the measure of PM exposure. However, current evidence suggests that the effects of PM on mortality are spread over multiple days. Roberts (p. 1148) introduces a new model for estimating mortality effects of PM when only every-sixth-day PM data are available. The moving total model uses information in the daily mortality time series to infer information that would otherwise be lost; it also produces estimates that are more precise and accurate than those in the standard model.
RISK CHARACTERIZATION | Diet and Arsenic Methylation
The primary metabolic pathway of ingested inorganic arsenic (InAs) is methylation to monomethyl arsenic (MMA) and dimethyl arsenic (DMA); people who excrete high proportions of MMA may be more susceptible to arsenic-caused cancer. Steinmaus et al. (p. 1153) assessed the effect of diet on arsenic metabolism. Subjects in the lower quartile of protein intake excreted a higher proportion of MMA and a lower proportion of DMA than did subjects in the upper quartile of protein intake. The findings are consistent with the theory that people with diets deficient in protein and other nutrients are more susceptible to arsenic-caused cancer.
ENDOCRINE | OP Exposure Alters Pituitary Hormone Levels
Organophosphorous pesticides (OPs) are suspected of altering reproductive function by reducing brain acetylcholinesterase activity and monoamine levels. In a longitudinal study, Recio et al. (p. 1160) evaluate the association between OP exposure and serum levels of pituitary and sex hormones in Mexican agriculture workers. More than 80% of the participants had at least one OP metabolite in their urine samples. A high proportion of individuals had follicle-stimulating hormone (FSH) concentrations outside the range of normality. These data, together with results from animal studies, suggest that OP exposure disrupts the hypothalamic-pituitary endocrine function and indicate that FSH and (leutinizing) hormone are most affected.
TOXICOGENOMICS | A Bead-Based High-Throughput Gene Expression Assay
Microarrays have led to the discovery of genes involved in particular biochemical processes; the next step is to focus on the response of a subset of relevant genes. Naciff et al. (p. 1164) have developed a sensitive, high-throughput gene expression assay for this purpose based on the Luminex xMAP system. Carefully selected oligonucleotides are covalently linked to fluorescently coded microspheres, then hybridized to biotinylated cRNA followed by amplification of the signal. This assay offers increased throughput with decreased costs compared with existing microarray technologies, with the trade-off being in the total number of transcripts that can be analyzed.
EXPOSURE ASSESSMENT | Microwaves Affect 53BP1 and -H2AX Foci
The data on biologic effects of nonthermal microwaves (MWs) from mobile telephones are diverse. Markovà et al. (p. 1172) investigated effects of MWs of the Global System for Mobile Communication (GSM) at different carrier frequencies on human lymphocytes from healthy persons and from persons reporting hypersensitivity to electromagnetic fields. Experiments measured changes in chromatin, tumor suppressor p53-binding protein 1 (53BP1), and phosphorylated histone H2AX (-H2AX). Depending on carrier frequency, MWs from GSM mobile telephones affected chromatin conformation and 53BP1/-H2AX foci similar to heat shock. The same response was observed in lymphocytes from hypersensitive and healthy subjects.
MIXTURES | Study of Environmental Sensitivities
Joffres et al. (p. 1178) explored the length of the adaptation period to obtain stable readings, evaluate responses to substances, and measure levels and types of symptomatic and physiologic reactions to low-level exposures among individuals with and without reported chemical sensitivities. Subjects with chemical sensitivities (cases) took longer to adapt to baseline protocols than did controls. After adaptation, cases displayed statistically significant responses in tonic electrodermal response to test substances compared with controls and compared with the control substance. This study shows the importance of using an adaptation period in testing individuals with reported chemical sensitivities.
EXPOSURE ASSESSMENT | Organophosphate Use and Outdoor Air Concentrations
Harnly et al. (p. 1184) used multivariate linear regression analysis to examine the temporal and spatial associations between agricultural use and measured air concentrations of chlorpyrifos, chlorpyrifos oxon, diazinon, and malathion. Agricultural use within a 3-mile radius on the monitoring day and use on the 2-4 prior days were significantly associated with air concentrations for all analytes except malathion; chlorpyrifos oxon showed the strongest association. Recent cellular, animal, and human evidence of toxicity, particularly in newborns, supports the public health concern. Agricultural applications of organophosphates and their oxon products are a probable source of exposures of public health concern.
RISK CHARACTERIZATION | Dose-Response Curve for Lead-Health Effects
Economic evaluation of the health benefits of lead reduction usually assumes a linear dose-response function. Rothenberg and Rothenberg (p. 1190) reanalyzed a pooled data set combining data from seven lead studies examining blood lead effect on IQ (intelligence quotient) of 7-year-old children. Results indicate that a log-linear lead-IQ relationship was a significantly better fit than was a linear-linear relationship for IQ. Substitution of the log-linear lead-IQ effect in a previously published health benefits model found that the economic savings due to U.S. population lead decrease between 1976 and 1999 was 2.2 times (US$319 billion) that calculated using a linear-linear dose-response function (US$149 billion). In addition, the limit of 10 µg/dL for children fails to protect against most damage and economic cost.
ANALYTICAL CHEMISTRY | An Innovative Method for Measuring Arsenic
Limited resources and the magnitude of measuring arsenic in Bangladesh's approximately 10 million tube wells have led to the use of low-cost field kits that measure As to a relatively high 50 µg/L standard rather than the more protective 10 µg/L World Health Organization guideline. Frisbie et al. (p. 1196) developed an inexpensive and sensitive laboratory method for measuring As and compare it with the silver diethyldithiocarbamate [AgSCSN(CH2CH3)2] and graphite furnace atomic absorption spectroscopy (GFAAS) methods. Their method is more accurate, precise, and environmentally safe than the AgSCSN(CH2CH3)2 method, and it is more accurate and affordable than GFAAS.
CANCER | IARC Monographs on Formaldehyde and Glycol Ethers
Cogliano et al. (p. 1205) provide an overview of a working group that met to develop IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans (IARC Monographs) on formaldehyde, 2-butoxyethanol, and 1-tert-butoxy-2-propanol. The working group concluded that formaldehyde is carcinogenic to humans, based on sufficient evidence in humans and in experimental animals. In the epidemiologic studies, there was sufficient evidence that formaldehyde causes nasopharyngeal cancer, "strong but not sufficient" evidence of leukemia, and limited evidence of sinonasal cancer. The working group concluded that 2-butoxyethanol and 1-tert-butoxy-2-propanol are not classifiable as carcinogenic to humans.
Environmental Medicine
CANCER | ALAD Polymorphism and Risk of Adult Brain Tumors
Inhibition of -aminolevulinic acid dehydratase (ALAD) is a potential risk factor for brain tumors, particularly meningioma. Rajaraman et al. (p. 1209) examine whether the ALAD G177C polymorphism (codominant alleles ALAD1 and 2) is associated with risk of intracranial tumors of the brain and nervous system in a brain tumor case-control study. One or more copies of the ALAD2 allele was associated with increased risk for meningioma, with a stronger association in males than in females. No increased risk associated with the ALAD2 variant was observed for glioma or acoustic neuroma.
Also see Science Selections, p. A616
Children's Health
FETAL DEVELOPMENT | Air Pollution and Adverse Birth Outcomes
Wilhelm and Ritz (p. 1212) extended previous analyses of term low-birth-weight (LBW) and preterm birth 1994-2000, speculating that previous effects of carbon monoxide, particulate matter < 10 µm diameter (PM10), and traffic density were attributable to toxicants sorbed to exhaust particles. Varying residential distances from monitoring stations were examined for risk estimate affects because attenuation may result from local pollutant heterogeneity. The new results for 1994-2000 generally confirm previous observations for the period 1989-1993, again linking CO and particle exposures to term LBW and preterm birth. In addition, they confirm suspicions about the need to address local heterogeneity for these pollutants in Los Angeles.
Also see Science Selections, p. A615
EXPOSURE ASSESSMENT | DEHP-Containing Medical Products and Urinary MEHP
Medical devices containing di(2-ethylhexyl) phthalate (DEHP) are used extensively in neonatal intensive care units (NICUs). Green et al. (p. 1222) studied exposure to DEHP-containing medical devices in relation to urinary levels of mono(2-ethylhexyl) phthalate (MEHP), a metabolite of DEHP. The infants' exposures to DEHP were classified as low, medium, and high based on the extent of medical products used. Urinary MEHP levels increased monotonically with DEHP exposure. After adjustment for institution and sex, urinary MEHP levels of infants in the high exposure group were 5.1 times those of infants in the low exposure group.
Also see Science Selections, p. A614
MUTAGENESIS | Baseline Micronuclei Frequency in Children
Neri et al. (p. 1226) provide estimates of the baseline frequency of micronuclei (MN) in children by conducting a meta-analysis of MN frequency reported by field studies in children and a pooled analysis of individual data. Overall means of 4.48 and 5.70 MN per 1,000 binucleated cells were estimated by the meta-analysis and pooled analysis, respectively. A clear effect of age was detected, with significantly lower frequency values in newborns and no influence of sex.
Mini-Monograph
NEURODEGENERATIVE DISEASE | Neurodegeneration and Environmental Risks
The population of the United States is aging, and the number of Americans afflicted with neurodegenerative diseases is continuing to increase. Because the pathogenesis of many of these diseases remains unknown, we must consider that environmental factors may play a causal role. This Mini-Monograph (p. 1230) provides an overview of the epidemiologic evidence for environmental etiologies for neurodegenerative diseases such as Alzheimer disease, Parkinson disease, parkinsonian syndromes (multiple system atrophy and progressive supranuclear palsy), and amyotrophic lateral sclerosis. Epidemiologic evidence for an association between neurodegenerative diseases and exposure to environmental agents is not conclusive, but there are indications that there may be causal links; therefore, the need for more research is obvious.