Environews
Digging Deeper in Bangladesh
Today, most people in Bangladesh get their drinking water from shallow tubewells that are naturally rich in arsenic, and exposure to the toxicant is a pressing public health concern. The NIEHS News (p. A374) takes a look at one approach proposed by researchers at Columbia University that involves installing community wells reaching deep into the region's uncontaminated aquifers.
Arsenic In-Depth
Arsenic has had various practical and medicinal purposes through history and into modern times. Today, however, it is probably best known as a critical public health threat to exposed populations worldwide. Perhaps worse, new findings suggest that other environmental exposures may act synergistically with arsenic to increase the risk of various diseases. One of two Focus articles this month (p. A378) discusses emerging information on the dangers of arsenic exposure.
India's Supreme Initiative
Rampant pollution has given India the dubious distinction of being a melting pot for hazardous waste. In response, India's Supreme Court has mounted an unprecedented campaign to hold industrial entities accountable for proper import, transport, and disposal of hazardous waste, as described in the Spheres of Influence (p. A394).
Leading the Way on Arsenic Removal
Naturally occurring arsenic is found in drinking water supplies all around the world, and efficient, economical methods for removing it from water are desperately needed. Many methods attempt to capitalize on the strong chemical bond between arsenic and iron to pull the former from water. This month's Innovations (p. A398) examines a new take on the iron-arsenic combination that promises safer, cheaper arsenic removal.
Reading the Tox Clues
A major goal of toxicogenomics research is to understand the biological processes underlying disease. This is the essence of biological inference--the highly iterative process of inferring cause-and-effect relationships from genomics data using computers and statistics. The second of this month's Focus articles (p. A388) discusses tools being used by teams of statisticians, bioinformaticists, and biologists to reach a better understanding of how data translate into disease.
Research
Arsenic-Induced Intracellular Calcium Changes
Arsenic and its methylated derivatives are known toxicants and carcinogens. In humans, inorganic arsenic is metabolically methylated to mono-, di-, and trimethylated forms, and recent findings suggest that this methylation represents a toxification pathway. Florea et al. (p. 659) review the relationship between induced disturbances of calcium homeostasis, genomic damage, and apoptotic cell death caused by arsenic and its organic derivatives.
Subject-Collected Dust Sampling
Studies of indoor allergen exposures are often limited by the cost and logistics of sending technicians to homes to collect dust. Arbes et al. (p. 665) evaluated the feasibility of having subjects collect their own dust samples using a dust-collection device and written instructions provided to them by mail. Results were compared with technician-collected samples. With some limitations, subject-collected dust sampling appears to be a valid and practical option for epidemiologic and clinical studies.
Air Pollution and Ventricular Arrhythmias
Epidemiologic studies demonstrate a consistent link between sudden cardiac deaths and particulate air pollution. Dockery et al. (p. 670) used implanted cardioverter defibrillator records of ventricular tachyarrhythmias to assess the role of air pollution as a trigger of these potentially life-threatening events. Results indicate statistically significant associations between air pollution and ventricular arrhythmias for episodes within 3 days of a previous arrhythmia. The associations of ventricular tachyarrhythmias with fine particle mass, carbon monoxide, nitrogen dioxide, and black carbon suggest a link with motor vehicle pollutants.
Bisphenol A Inhibits Hippocampal Synaptogenesis
Bisphenol A (BPA), an estrogenic chemical widely used in the manufacture of plastics and epoxy resins, leaches out of plastics, thereby potentially causing considerable human exposure. MacLusky et al. (p. 675) show that treatment of ovariectomized rats with BPA dose-dependently inhibits the estrogen-induced formation of dendritic spine synapses on pyramidal neurons in the hippocampus. The authors observed significant inhibitory effects at a dose below the current U.S. Environmental Protection Agency reference daily limit for human exposure. Environmental BPA exposure may interfere with the development and expression of normal sex differences in cognitive function.
OH-PCBs Inhibit Sulfonation of 3-OH-BaP
Sulfonation is a major phase II biotransformation reaction. Wang et al. (p. 680) report that several polychlorobiphenylols (OH-PCBs) inhibited the sulfonation of 3-hydroxybenzo[a]pyrene (3-OH-BaP) by human liver cytosol and some cDNA-expressed sulfotransferases. The inhibition mechanism was noncompetitive, and suggested that OH-PCBs competed with 3-OH-BaP at an inhibitory site on the enzyme. Findings demonstrate an interaction between potentially toxic hydroxylated metabolites of PCBs and polycyclic aromatic hydrocarbons, which could result in reduced clearance of toxicants by sulfonation.
Climate and Coccidioidomycosis
Although broad links between climatic factors and coccidioidomycosis have been established, the identification of simple and robust relationships remained elusive. Using an adaptive data-oriented method for estimating date of exposure, Comrie (p. 688) analyzed hypotheses linking climate and dust to fungal growth and dispersion, and evaluated their respective roles for Pima County, Arizona. Results confirm a strong bimodal disease seasonality. Precipitation during the normally arid foresummer 1.5-2 years before the season of exposure is the dominant predictor of the disease in all seasons.
Disparities in Air Toxics Cancer Risk in Maryland
Apelberg et al. (p. 693) linked risk estimates from the U.S. Environmental Protection Agency's National Air Toxics Assessment to racial and socioeconomic characteristics in Maryland to evaluate disparities in estimated cancer risk from exposure to air toxics. Census tracts in the highest quartile defined by the fraction of African-American residents were three times more likely to be high-risk than those in the lowest quartile. Risk decreased as the proportion of whites increased. Census tracts in the lowest quartile of socioeconomic position, as measured by various indicators, were 10-100 times more likely to be high-risk than those in the highest quartile.
Perinatal Vz Exposure Alters Sex Differentiation
Colbert et al. (p. 700) examined the effects of rat prenatal exposure to the antiandrogenic fungicide vinclozolin (Vz) on the development of two sex-differentiated behaviors that are organized by the perinatal actions of androgens. Play behavior of juvenile offspring was examined on postnatal day (PND) 22 and again on PND34. A 12-mg/kg Vz dose significantly increased play behavior in the male offspring on PND34 compared with controls. Adult male offspring showed a significant reduction of erections at all dose levels. Perinatal Vz disrupts the development of androgen-mediated behavior at exposure levels that do not produce obvious structural changes.
ATR Alters Function in Monoamine Systems
Catecholaminergic systems such as the two major long-length dopaminergic tracts of the central nervous system play key roles in mediating critical behavioral functions. Rodriguez et al. (p. 708) examined the hypothesis that atrazine (ATR) would adversely affect brain dopaminergic systems in rats. Results indicate that ATR can produce neurotoxicity in dopaminergic systems that are critical to the mediation of movement as well as cognition and executive function.
Effects of Roundup on Human Cells and Aromatase
Roundup is a glyphosate-based herbicide used worldwide. Richard et al. (p. 716) show that glyphosate is toxic to human placental JEG3 cells within 18 hr at concentrations lower than those found with agricultural use. The effect increases with concentration and time or in the presence of Roundup adjuvants. The glyphosate-based herbicide disrupts aromatase activity, but the effects of glyphosate are facilitated by the Roundup formulation in microsomes or in cell culture. Roundup adjuvants may enhance glyphosate bioavailability and/or bioaccumulation. (Also see Science Selections, p. A403)
Prediction of Estrogenic Mixture Effects in Fish
Brian et al. (p. 721) investigated the combined effects of a multicomponent mixture of five estrogenic chemicals using vitellogenin induction in male fathead minnows as an end point. Concentration-response curves were developed for each chemical individually. The chemicals were then combined at equipotent concentrations and the mixture tested using fixed-ratio design. The results demonstrate that estrogenic chemicals have the capacity to act together in an additive manner and that combined effects can be predicted by concentration addition.
Tungsten Alloy-Induced Rhabdomyosarcomas
Concern about potential health and environmental effects of depleted uranium and lead has resulted in many countries using tungsten alloy (WA) to replace these metals in munitions. Kalinich et al. (p. 729) implanted rats with 4 (low dose) or 20 (high dose) pellets of WA. The high-dose WA-implanted rats developed extremely aggressive tumors surrounding the pellets within 4-5 months after implantation. The low-dose WA-implanted rats and nickel-implanted rats developed tumors, but at a slower rate. Rats implanted with tantalum, an inert control metal, did not develop tumors. Results point out the need for further studies of tungsten and tungsten-based alloys. (Also see Science Selections, p. A403)
Ozone and Peak Expiratory Flow Rates
Chan and Wu (p. 735) measured peak expiratory flow rates (PEFRs) in mail carriers twice daily for 6 weeks in 2001. The daily exposure of each mail carrier to ozone, particulate matter < 10 µm in aerodynamic diameter, and nitrogen dioxide was estimated by one air monitoring station in the center of the mail carrier's delivery area. Linear mixed-effects models were used to estimate the association between air pollution exposures and PEFR after adjusting for sex, age, disease status, temperature, and humidity. Reduction of acute lung function was found to occur in mail carriers exposed to ozone concentrations below current air quality standards and occupational exposure limits.
WTC-Related Exposures among Pregnant Women
Wolff et al. (p. 739) characterized environmental exposures among women who were pregnant and were at or near the World Trade Center (WTC) on or soon after 11 September 2001. Exposures were assessed by estimating time spent in zones around the WTC and by developing an exposure index (EI) based on plume reconstruction modeling. Daily EIs were highest immediately after 11 September and became lower but variable over the next 4 weeks. The authors report intense bystander exposure after the WTC collapse and provide information about nonoccupational exposures among a vulnerable population of pregnant women.
Effects of Pb Exposure on Skeletal Repair
Individuals with past lead exposure develop increased blood Pb levels during periods of high bone turnover or resorption. Pb affects osteoblasts, osteoclasts, and chondrocytes and is associated with osteoporosis, but effects on skeletal repair have not been studied. Carmouche et al. (p. 749) exposed C57/B6 mice to various concentrations of Pb acetate in their drinking water to achieve environmentally relevant blood Pb levels. Results indicate that Pb exposure delays fracture healing at environmentally relevant doses and induces fibrous nonunions at higher doses by inhibiting the progression of endochondral ossification.
Hazardous Waste Sites and Coronary Heart Disease
Sergeev and Carpenter (p. 756) determined the ZIP codes of areas containing or abutting each of the approximately 900 hazardous waste sites in New York and identified the major contaminants in each. The authors assessed effects of residence in each ZIP code on coronary heart disease (CHD) and acute myocardial infarction (AMI) hospital discharge rates using a negative binomial model, adjusting for age, sex, race, income, and health insurance coverage. Patients living in ZIP codes contaminated with persistent organic pollutants had a significant elevation in discharge rates for CHD and AMI compared with those living in clean ZIP codes.
Environmental Medicine
Chronic Sequelae of Acute Pesticide Poisoning
Roldán-Tapia et al. (p. 762) describe two cases of accidental cholinesterase inhibitor (carbamate) poisoning. The medical diagnosis in both cases was overcholinergic syndrome. After the patients had recovered from acute intoxication, they were subjected to extensive neuropsychological evaluation 3 and 12 months after the event. The assessments point to cognitive deficits in attention, memory, perceptual, and motor domains 3 months after intoxication. One year later these sequelae remained, even though the brain magnetic resonance imaging and computed tomography scans were interpreted as within normal limits.
Hypersensitivity Pneumonitis
Beckett et al. (p. 767) present the case of a previously healthy man who worked as a machine operator in an automotive factory. Medical evaluation showed abnormal pulmonary function tests, and lung biopsy showed hypersensitivity pneumonitis. His illness was traced to the work environment. He was removed from exposure to metalworking fluids, but symptoms reoccurred upon later reexposure. Further permanent decrement in his lung function occurred. Investigation of his workplace showed that metalworking fluids (cutting oils) grew Mycobacterium chelonae. His lung function remained stable after complete removal from exposure.
Bladder Cancer in an MBOCA-Exposed Worker
A 52-year-old male chemical worker was admitted to the hospital with a history of paroxysmal microscopic hematuria for about 2 years and nocturia with gross hematuria (~ 5 times/night) for 2 months. Intravenous urogram imaging showed a bladder mass, and cystoscopic biopsy revealed invasive transitional cell carcinoma with marked necrosis. The patient had worked for 14 years in a company that produced the curing agent 4,4´-methylenebis(2-chloroaniline) (MBOCA). This case finding by Liu et al. (p. 771) supports the conclusion that MBOCA is a potential human carcinogen. Safe use of skin-protective equipment and respirators is required to prevent MBOCA exposure in workers.
Children's Health
CYT19 Genetic Association with Arsenic Metabolism in Children
Meza et al. (p. 775) report the results of a screen for genetic association with urinary arsenic metabolite levels in three arsenic metabolism candidate genes, PNP, GSTO, and CYT19, among arsenic-exposed subjects from the Yaqui Valley in Sonora, Mexico. Initial phenotypes included the ratio of urinary inorganic arsenic(III) to inorganic arsenic(V) and the ratio of urinary dimethylarsenic(V) to monomethylarsenic(V). The data indicate a strong developmentally regulated genetic association between CYT19 and arsenic metabolism with importance for both arsenic pharmacogenetics and arsenic toxicology. (Also see Science Selections, p. A404)
Toxicokinetics of Deltamethrin in Children
Ortiz-Pérez et al. (p. 782) explored the levels of deltamethrin in soil samples and obtained relevant toxicokinetic data of deltamethrin in exposed children. After spraying, indoor levels of deltamethrin in soil samples were higher than outdoor levels. Using the comet assay, the authors found no evidence of DNA damage in children before or 24 hr after indoor spraying of deltamethrin. They also found no relationship between soil concentrations of deltamethrin and urinary levels of the metabolites. (Also see Science Selections, p. A402)
Solvents and Childhood Leukemia
Infante-Rivard et al. (p. 787) conducted a population-based case-control study of childhood acute lymphoblastic leukemia cases and controls, matched on age and sex. Maternal occupational and home exposure to solvents was estimated. Risk did not increase with increasing exposure, except for alkanes, where a significant trend was observed. Home exposure was not associated with increased risk. The study shows that maternal exposure to solvents in the workplace does not seem to play a major role in childhood leukemia.
Soil Lead, Blood Lead, and Climate in Three U.S. Cities
Laidlaw et al. (p. 793) investigated the temporal relationship between pediatric blood lead (BPb), weather, soil moisture, and dust in Indianapolis, Indiana; Syracuse, New York; and New Orleans, Louisiana. Average monthly child BPb levels were regressed against several independent variables. A conceptual model suggests that when temperature is high and evapotranspiration maximized, soil moisture decreases and soil dust is deposited. Thus, seasonal variation of children's Pb exposure is probably caused by inhalation and ingestion of Pb brought about by the effect of weather on soils and fluctuation in Pb loading.
Toxicogenomics
Gene Expression Profiling of Benzene Exposure
Benzene, an industrial chemical and component of gasoline, is an established cause of leukemia. Forrest et al. (p. 801) examined the effect of benzene exposure on peripheral blood mononuclear cell gene expression in a population of workers with well-characterized occupational exposures using microarrays and real-time polymerase chain reaction. Results indicate that altered expressions of CXCL16, ZNF331, JUN, and PF4 are potential biomarkers of benzene exposure.