Environews
NIEHS NEWS | Ties that Bind
On the surface, chemical intolerance and addiction seem to be entirely different conditions, but emerging evidence suggests the two could be rooted in the same etiology. This article (p. A812) discusses a conference cosponsored by NIEHS and the National Institute on Alcohol Abuse and Alcoholism that opened the door for researchers to explore commonalities and potential collaborative efforts in addressing these two conditions.
FOCUS | Inflammation Rumination
Inflammation's purpose is protection, but this natural bodily defense against infection can sometimes endanger or even kill. Mounting evidence suggests that genetic factors influence a person's inflammatory response. This article (p. A816) examines some of the new gene-based theories that concentrate on emergency and critical care medicine to provide insight into this helpful but potentially hazardous physical reaction.
FOCUS | Environmental Assaults on Sight
Blindness and low vision affect millions worldwide, especially people in poorer developing countries. Although there are multiple causes of visual impairment, most cases are thought to be preventable with proper environmental safety and health care measures in place. This article (p. A822) takes a look at some of the environmental and genetic factors that can affect eyesight and discusses research and organizational efforts being instituted to ensure clearer vision for those most at risk.
SPHERES OF INFLUENCE | Chemical Accountability
With more research connecting chemical exposures to health risks, the need to monitor the production and use of chemicals is more important than ever. The Toxic Substances Control Act (TSCA) is the chief governmental regulation for providing a system of checks and balances for commercial and private chemical use. This article (p. A828) discusses a recent report released by the Government Accountability Office that analyzes how the Environmental Protection Agency is implementing TSCA and offers suggestions for change and improvement.
INNOVATIONS | The Next Generation of Succinate
Anytime a chemical can be produced safely and cheaply from renewable resources, it's a good thing. Add to that chemical the versatility to be used for a variety of applications, and you have the recipe for what's possibly the next best thing in green chemistry. What's this wonder substance? Some researchers believe it's succinate, a chemical used for a multitude of purposes that's currently derived from petrochemicals through expensive processes. This article (p. A832) looks at a new method that makes succinate more affordable and environmentally friendly by creating it from renewable starting materials.
Commentaries
ETHICS | The Tobacco Industry and Pesticide Regulations
Tobacco farming is heavily dependent on pesticides. Because pesticides involve human safety and health issues, they are regulated nationally and internationally, but little is known about how tobacco companies respond to regulatory pressures regarding pesticides. McDaniel et al. (p. 1659) analyzed internal tobacco industry documents to describe industry activities aimed at influencing pesticide regulations involving methoprene, the ethylene bisdithiocarbamates, and phosphine. Their results suggest that the tobacco industry has been able to exert influence over the pesticide regulatory process and that increased scrutiny of this process could aid in protecting the public interest.
HUMAN TOXICOLOGY | Human Dioxin Exposures Revisited
In epidemiologic studies, exposure assessments of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) assume a fixed elimination rate. Emond et al. (p. 1666) applied a physiologically based pharmacokinetic (PBPK) model using a body-burden-dependent elimination rate developed in rodents to describe the pharmacokinetics of TCDD in human exposures. This model suggests that previous exposure assessments may have significantly underestimated peak blood concentrations, resulting in exposure misclassifications. Application of this PBPK model may improve the exposure assessments in epidemiologic studies of TCDD.
Review
EXPOSURE ASSESSMENT | Biomarkers for Monitoring Lead Exposure
The primary biomarker for human lead exposure is Pb concentration in whole blood (BPb). Recent studies have reported the possibility of adverse health effects, including intellectual impairment in young children, at BPb levels < 10 µg/dL, suggesting that there may be no safe level of exposure. Barbosa et al. (p. 1669) review the limitations of Pb exposure biomarkers and the need to improve the accuracy of their measurement. The interpretation of BPb data must take into account both external and endogenous Pb exposure, past or recent exposure, and the significance of Pb determinations in human specimens including hair, nails, saliva, bone, blood (plasma, whole blood), urine, feces, and exfoliated teeth.
Research
ENVIRONMENTAL TOXICOLOGY | Environmental Toxicants and Reproduction in Sturgeon
Feist et al. (p. 1675) studied wild white sturgeon from the Columbia River (Oregon) for signs of reproductive endocrine disruption. Fish were sampled in the free-flowing portion of the river (area with reproductive success) and from three reservoirs behind hydroelectric dams (area with reduced reproductive success). Fish from the reservoir behind the oldest dam had the highest contaminant loads and incidence of gonadal abnormalities, as well as the lowest triglycerides, condition factor, gonad size, and plasma androgens. These data suggest that endocrine-disrupting chemicals may be accumulating behind dams over time.
HUMAN TOXICOLOGY | Folate, Homocysteine, and Arsenic in Bangladesh
Susceptibility to arsenic toxicity may be related to nutrition. Arsenic is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) via one-carbon metabolism that is dependent on folate. Gamble et al. (p. 1683) studied the relationships among folate, cobalamin, homocysteine, and arsenic metabolism in Bangladeshi adults. DMA in urine was positively associated with plasma folate and negatively associated with homocysteine (tHcys). MMA was negatively associated with folate and positively associated with tHcys; the percent inorganic arsenic was negatively associated with folate. These data suggest that factors involved in one-carbon metabolism influence arsenic methylation This may be particularly relevant in Bangladesh, where the prevalence of hyperhomocysteinemia is extremely high.
EXPOSURE ASSESSMENT | PBDEs among Urban Anglers
Polybrominated diphenyl ethers (PBDEs) are used worldwide as flame retardants. To determine whether fish consumption is a source of human PBDE exposure, Morland et al. (p. 1689) conducted a cross-sectional epidemiologic study of urban anglers on the lower Hudson River and Newark Bay (New York and New Jersey). Frequency of local fish consumption was assessed by questionnaire, and blood samples were analyzed for PBDEs. Anglers reporting consumption of local fish had higher, but nonstatistically significantly different, concentrations of PBDEs than anglers who did not eat local fish. These findings suggest that consumption of locally caught fish is not a major route of human exposure for this study population.
CARDIOVASCULAR DISEASE | Particulate Matter and Heart Rate Variability
It is unknown whether the associations between particulate matter (PM) and heart rate variability (HRV) differ by particle sizes with diameters between 0.3 µm and 1.0 µm (PM0.3-1.0), between 1.0 µm and 2.5 µm (PM1.0-2.5), and between 2.5 µm and 10 µm (PM2.5-10). Chuang et al. (p. 1693) measured electrocardiographics and PM exposures in patients with coronary heart disease and in patients with either prehypertension or hypertension. HRV was not associated with either PM1.0-2.5 or PM2.5-10. HRV reduction in susceptible population was associated with PM0.3-1.0 but was not associated with either PM1.0-2.5 or PM2.5-10.
CARCINOGENESIS | Leukotoxin Diol and Breast Cancer
Previous HPLC analysis of corncob bedding extracts characterized two components (peak I and peak II) that disrupted endocrine function in rats and stimulated breast and prostate cancer cell proliferation in vitro and in vivo. The active substances in peak I were identified as an isomeric mixture of tetrahydrofurandiols (THF-diols). Markaverich et al. (p. 1698) describe the purification and identification of the HPLC peak II component leukotoxin diol (LTX-diol). LTX-diol stimulated (p < 0.001) MCF-7 cell proliferation but did not compete for [3H]estradiol binding to the estrogen receptor or nuclear type II sites, even though oral administration of very low doses disrupted estrous cyclicity in female rats.
ENVIRONMENTAL TOXICOLOGY | Pathways for Drugs into the Aquatic Environment
A wide range of pharmaceuticals has been found in fresh and marine waters, and even in small quantities, some of these compounds have the potential to harm aquatic life. Although much of the research currently focuses on the removal of excreted pharmaceuticals during sewage treatment, disposal of unused pharmaceuticals via household waste should be investigated as a significant pathway. Bound and Voulvoulis (p. 1705) carried out a survey and interviewed members of 400 households. The resulting conceptual model demonstrated that disposal of unused pharmaceuticals, either by household waste or via the sink or toilet, may be a prominent route of aquatic contamination.
EXPOSURE ASSESSMENT | Spatial Analysis of Human Blood Organochlorine Levels
Gaffney et al. (p. 1712) investigated the geographic distribution of organochlorine levels in blood samples collected in 1974 from residents of a community with a potential organochlorine source using residents' street addresses coded in a geographic information system. The researchers found a significant inverse relationship between blood dieldrin levels and residential distance from the potential source. For every mile of distance from the source, participants' blood dieldrin levels decreased 1.6 ng/g, adjusting for age, sex, education level, smoking status, and drinking water source. DDE levels in the blood did not change significantly based on residential distance from the source.
TOXICOGENOMICS | Acute Ozone-Induced Gene Expression in Rat Lung
Ozone, an oxidant gas, can directly induce lung injury. Initial molecular events of the acute O3 response would be useful in developing biomarkers of exposure or response. Nadadur et al. (p. 1717) exposed rats to toxic concentrations of O3 (2 and 5 ppm) for 2 hr and assesed the molecular changes in lung tissue using a rat cDNA expression array containing 588 characterized genes. Although the specific gene interactions remain unclear, the data indicate a dose-dependent direct and immediate induction of gene expression that may be separate from those genes involved in inflammation after acute O3 exposure.
CARDIOVASCULAR DISEASE | Fatal CHD Association with Ambient Particles
Chen et al. (p. 1723) studied the effect of long-term ambient particulate matter (PM) on risk of fatal coronary heart disease (CHD) in white adults followed for 22 years. Monthly concentrations of ambient air pollutants were obtained [PM < 10 µm (PM10), ozone, sulfur dioxide, nitrogen dioxide, PM < 2.5 µm (PM2.5)] and interpolated to ZIP codes. In females, the relative risk (RR) for fatal CHD with each 10-µg/m3 increase in PM2.5 was 1.42 in the single-pollutant model and 2.00 in the two-pollutant model with PM2.5 and O3. Corresponding RRs for a 10-µg/m3 increase in PM10-2.5 and PM10 were 1.62 and 1.45, respectively, in all females and 1.85 and 1.52 in postmenopausal females. Fatal CHD was positively associated with all three PM fractions in females but not in males.
Also see Science Selections, p. A836
NEURODEGENERATIVE DISEASE | Peripheral Nerve Fibers and Chronic Lead Exposure
Bleecker et al. (p. 1730) investigated lead exposure and its interaction with ergonomic stressors on peripheral nerve function among smelter workers. They measured blood and bone lead levels, derived working-lifetime integrated blood lead (IBL) and working-lifetime weighted-average blood lead from historical records, and created metrics that cumulated exposure only above increasing blood lead levels ranging from 20 to 60 µg/dL (IBL20-IBL60). Current perception threshold (CPT) was used to assess large myelinated (CPT2000), small myelinated (CPT250), and unmyelinated (CPT5) sensory nerve fibers. As the criterion blood lead level increased from IBL20 through IBL60, so did the percentage of CPT2000 variance. Chronic blood lead exposure is associated with impairment of large and small myelinated sensory nerve fibers; the effect is enhanced at the highest doses by ergonomic stressors.
Also see Science Selections, p. A838
EXPOSURE ASSESSMENT | Exposure to Arsenic in Soil
Tsuji et al. (p. 1735) conducted a biomonitoring study in which children younger than 7 years of age were compared with older participants in response to community concerns about arsenic in soil from a pesticide-manufacturing plant. Urine samples were analyzed for total arsenic and arsenic species related to ingestion of inorganic arsenic. Speciated urinary arsenic levels were similar between children and older participants and consistent with unexposed populations. Correlations between speciated urinary arsenic and arsenic in soil or house dust were not significant for children. Similarly, questionnaire responses indicating soil exposure were not associated with increased urinary arsenic levels.
RESPIRATORY DISEASE | Fractional Exhaled Nitric Oxide and Black Carbon
Jansen et al. (p. 1741) measured fractional exhaled nitric oxide (FENO), spirometry, blood pressure, blood oxygen saturation (SaO2), and pulse rate in older subjects with asthma or chronic obstructive pulmonary disease. PM10 and PM2.5 (particulate matter ≤ 10 µm or ≤ 2.5 µm, respectively) were collected at an outdoor site, outside and inside the subjects' homes, and from personal PM10 filters. For subjects with asthma, a 10 µg/m3 increase in 24-hr average outdoor PM10 and PM2.5was associated with a 5.9 and 4.2 ppb increase in FENO, respectively. Increases in outdoor, indoor, and personal black carbon (BC) were also associated with increases in FENO. No association was found between PM or BC and changes in spirometry, blood pressure, pulse rate, or SaO2 .
TOXICOGENOMICS | Gene Profiling for Vanadium and Zinc
Gene expression profiling may discriminate vanadium from zinc in human bronchial epithelial cells. Using hierarchical clustering analysis, Li et al. (p. 1747) showed that 12 genes discriminated V from Zn and consisted of two clusters. Cluster 1 genes (ZBTB1, PML, ZNF44, SIX1, BCL6, ZNF450) were down-regulated by V and involved in gene transcription, whereas cluster 2 genes (IL8, IL1A, PTGS2, DTR, TNFAIP3, CXCL3) were up-regulated and linked to inflammatory response and cell proliferation. Metallothionein 1 genes (MT1F, MT1G, MT1K ) were up-regulated by Zn only. The novel genes and pathways identified may aid understanding the pathogenesis of health effects caused by environmental V and Zn exposure.
EXPOSURE ASSESSMENT | Aflatoxin Contamination of Market Maize, Kenya 2004
In April 2004, one of the largest aflatoxicosis outbreaks occurred in rural Kenya. Aflatoxin-contaminated homegrown maize was the source of the outbreak, but the extent of contamination and status of commercial maize were unknown. Lewis et al. (p. 1763) surveyed the extent of contamination and the relationship between market maize aflatoxin and the aflatoxicosis outbreak. Contaminated homegrown maize bought from local farms entered the distribution system, resulting in widespread aflatoxin contamination of market maize. Contaminated market maize, purchased by farmers after their homegrown supplies are exhausted, may represent a source of continued exposure to aflatoxin. Efforts to interrupt aflatoxin exposure must take into account the role of the market system in food distribution.
ENVIRONMENTAL TOXICOLOGY | AhR-Independent Toxicity of Petrogenic PAHs
Studies after the Exxon Valdez oil spill demonstrated that fish embryos exposed to low levels of polycyclic aromatic hydrocarbons (PAHs) in weathered crude oil develop a syndrome of edema and craniofacial and body axis defects. Using zebrafish embryos, Incardona et al. (p. 1755) show that the weathered crude oil syndrome is distinct from the well-characterized AhR-dependent effects of dioxin toxicity. Blocking AhR pathway components with antisense morpholino oligonucleotides demonstrated that the key developmental defects induced by weathered crude oil exposure are mediated by low-molecular-weight tricyclic PAHs through AhR-independent disruption of cardiovascular function and morphogenesis.
EXPOSURE ASSESSMENT | Source Apportionment of Particle Health Effects
Although the association between exposure to PM2.5 (ambient fine particulate matter with aerodynamic diameter < 2.5 µm) and human mortality is well established, the most responsible particle types and sources are not yet certain. Thurston et al. (p. 1768) evaluated the consistency of the various source apportionment methods in assessing source contributions to daily PM2.5 mass-mortality associations. Analyses indicated that source types were a significant predictor of relative risk, whereas apportionment group differences were not. These results provide supportive evidence that existing PM2.5 source apportionment methods can be used to derive reliable insights into the source components that contribute to PM2.5 health effects.
Environmental Medicine
RESPIRATORY DISEASE | Acute Effects of a Fungal Volatile Compound
Methylfuran (3-MF) is a common fungal volatile product that contributes to airway disease. Wålinder et al. (p. 1775) assessed acute effects via chamber exposure to 3-MF (1 mg/m3). Volunteers provided symptom reports, ocular electromyography, measurement of eye tear film break-up time, vital staining of the eye, nasal lavage, acoustic rhinometry, transfer tests, and dynamic spirometry. No subjective ratings were significantly increased during exposure. Blinking frequency and the lavage biomarkers myeloperoxidase and lysozyme were significantly increased, and forced vital capacity was significantly decreased during exposure to 3-MF compared with air control. Acute effects in the eyes, nose, and airways were detected and might be the result of 3-MF.
HUMAN TOXICOLOGY | Acute Aflatoxicosis in Kenya
An aflatoxicosis outbreak in 2004 in eastern Kenya resulted in many deaths. Azziz-Baumgartner et al. (p. 1779) conducted a case-control study of risk factors for maize contamination and quantitated biomarkers associated with aflatoxicosis. Maize was analyzed for total aflatoxins, and serum was analyzed for aflatoxin B1-lysine albumin adducts and hepatitis B surface antigen. Regression and survival analyses were used to explore the relationship between aflatoxins, maize consumption, hepatitis B surface antigen, and case status. Homegrown maize kernels from case households had higher concentrations of aflatoxins than did kernels from control households; case patients stored wet maize inside their homes rather than in granaries more often than did controls. Serum adduct concentrations were associated with time from jaundice to death.
Also see Science Selections, p. A837
HUMAN TOXICOLOGY | Dimethylamine Borane Intoxication
Dimethylamine borane (DMAB) is used in nonelectric plating of semiconductors. Tsan et al. (p. 1784) report four cases of work-related exposure to DMAB. Three patients who decontaminated immediately and consumed water had dizziness, nausea, and diarrhea later. The fourth patient did not decontaminate at once and suffered more severe symptoms, including dizziness, nausea, limb numbness, slurred speech, irritable mood, and ataxia; lower leg weakness and drop foot were found bilaterally. A nerve conduction study revealed polyneuropathy with motor-predominant axonal degeneration. DMAB induces acute cortical and cerebellar injuries and delayed peripheral neuropathy. Early decontamination with copious water is currently the best treatment.
Children's Health
RESPIRATORY DISEASE | DDE and Asthma in Children
Although the prevalence of asthma increases with increasing levels of dichlorodiphenyldichloroethylene (DDE), the effect of early-life exposure is unknown. Sunyer et al. (p. 1787) assessed the association between prenatal DDE and other organochlorine compounds, and atopy and asthma during infancy. Prenatal exposure to organochlorine compounds was measured in cord serum, and asthma was defined on the basis of wheezing at 4 years of age, persistent wheezing, or doctor-diagnosed asthma. Wheezing at 4 years of age increased with DDE concentration. The association was not modified by specific IgE sensitization and occurred with the same strength among nonatopic subjects and those with persistent wheezing or diagnosed asthma.
Also see Science Selections, p. A836
ASTHMA | Short-Term PM Exposures and FeNO
Mar et al. (p. 1791) evaluated associations between short-term (hourly) exposures to PM2.5 (particulate matter with aerodynamic diameters < 2.5 µm) and the fractional concentration of nitric oxide in exhaled breath (FeNO) in children with asthma participating in an intensive panel study in Seattle, Washington. FeNO was associated with hourly averages of PM2.5 up to 10-12 hr after exposure. The results provide new information concerning the lag structure between PM2.5 exposure and a respiratory health outcome in children with asthma.
EXPOSURE ASSESSMENT | Housing Quality for Latina Women and Their Children
Health burdens associated with poor quality housing and indoor pest infestations are likely to affect young children. Bradman et al. (p. 1795) conducted environmental assessments in 644 homes of pregnant Latina women and their children living in the Salinas Valley (California). Pesticides were stored or used in 51% of the households, in part to control roach and rodent infestations. The data indicate that adverse housing conditions are common in this community and increase the likelihood of pest infestations and home pesticide use. Interventions are needed to improve housing and promote children's health and safety in this population.
EXPOSURE ASSESSMENT | Pesticide Exposures of Pregnant Women
Little is known about pesticide exposures of pregnant women. Bradman et al. (p. 1802) measured six dialkyl phosphate (DAP) urinary metabolites of organophosphate (OP) pesticides in pregnant, low-income women living in an agricultural area. Of the women, 28% were employed as farmworkers during pregnancy, and 81% had at least one household member who worked in agriculture. Total DAP metabolite levels were higher after delivery than during pregnancy, and both prenatal and postpartum metabolite levels were higher in these women of childbearing age than in the general U.S. population. Higher DAP metabolite levels in the immediate postpartum period may have implications for estimating dose during pregnancy and for exposure during lactation.
FETAL DEVELOPMENT | Late-Pregnancy Exposures to DBPs
Growth-related birth outcomes are associated with exposure to high concentrations of disinfection by-products (DBPs), including trihalomethane (THM) and haloacetic acid (HAA). Hinckley et al. (p. 1808) conducted a retrospective cohort study to examine the effects of exposure to THMs and HAAs during the third trimester and during individual weeks and months of late gestation on the risks for term low birth weight, intrauterine growth retardation, and very preterm and preterm births. Results suggest a critical window of exposure with respect to fetal development during weeks 33-40 for the effects of dibromoacetic acid and during weeks 37-40 for the effects of dichloroacetic acid.
Mini-Monograph
ENVIRONMENTAL JUSTICE | Evolving Partnerships in Community
In recent years a significant number of articles have been published on the benefits and challenges of community-based participatory research (CBPR). The monograph (p. 1814) provides an overview of three projects and highlights their commonalities and differences in developing community-university partnerships. Although the studies were not required to use CBPR strategies in their work, they did engage community members in a participatory manner. The outcomes indicate the importance of nonprescriptive frameworks for conducting community-based participatory research that focuses on more equitable power relationships to address health disparities to help alleviate environmental health problems.
