Environews
NIEHS NEWS | Gene–Environment Studies: Who, How, When, and Where?
As research interest in gene–environment interaction continues to heat up, questions regarding well-defined parameters and funding sources for studies have also emerged. Many feel that one of the next logical steps in genetic research is the implementation of a large prospective cohort study to gather DNA data over the course of many years. But designing and executing such a large study would involve significant ethical, regulatory, scientific, and public health challenges. This article (p. A466) takes a look at some of these issues, as raised in a draft report from the DHHS Secretary's Advisory Committee on Genetics, Health, and Society.
FOCUS | The Apple Bites Back: Claiming Old Orchards for Residential Development
Former orchard lands offer an abundance of acreage for potential development, but this bounty might come with a caveat: pesticide residue in the soil. Some homeowners in new housing built on old orchard lands have inherited the legacy of the lead and arsenic pesticides administered during earlier periods of agricultural production. This article (p. A470) discusses potential health concerns associated with recycled orchards, and looks at various remediation methods being used to clean up the land.
SPHERES OF INFLUENCE | A Risky Environment for Investment
If natural disasters such as hurricanes, earthquakes, and tsunamis have taught us anything, it is that we are inexorably linked not only physically but also financially to the environment and to changing global climate patterns. As a proactive response to this complex relationship, the UN and other groups have created a number of programs in the last decade that interweave sustainability into virtually every segment of the market. This article (p. A478) describes the latest UN initiative, which focuses on incorporating environmental and social issues into the decision-making processes of pension funds and large institutional investors.
INNOVATIONS | Shiny Science: A New Substitute for Hexavalent Chromium
Hexavalent chromium has been used for a variety of industrial purposes throughout the years, including the electroplating process. But this compound is highly health-hazardous. Now researchers at the Massachusetts Institute of Technology have begun experimenting with an engineered nickel and tungsten nanostructure that offers the appearance and durability of hexvalent chromium without the known hazards. This article (p. A482) takes a look at the new alternative that could herald a brighter, cleaner future for chrome plating.
Commentaries
ENVIRONMENTAL TOXICOLOGY | Living Organisms, Biomarkers of the Evolutionary Process
For most of evolutionary history, scientific understanding of the environment and life forms is extremely limited. In this commentary, Herkovits (p. 1139) hypothesizes that ontogenetic features of living organisms can be considered biomarkers of coevolution between organisms and physicochemical agents during Earth's history. He provides a new vision of evolution based on correlations between metabolic features and stage-dependent susceptibility of organisms to physicochemical agents with well-known environmental signatures. Evoecotoxicology, as a multidisciplinary and transdisciplinary approach, can contribute to a better understanding of evolutionary history, including the phylogenetic significance of differences in susceptibility/resistance to physicochemical agents in various organisms.
BIOMONITORS | Biomonitoring and Biomarkers
Because biomonitoring can directly measure almost any chemical present in our bodies, the future role of classical exposure assessment may be marginalized. Although the concentration of chemicals in the environment will continue to be measured and related to exposure parameters, the prioritization of the national environmental agenda will be dictated by biomonitoring. Paustenbach and Galbraith (p. 1143) review benefits and challenges, along with select results from the Centers for Disease Control and Prevention's 2005 National Report on Human Exposure to Environmental Chemicals. The authors recommend that the data be carefully interpreted, with the goal of establishing baseline exposure information, rather than creating surrogates for conclusions about human health risk.
HEALTH DISPARITIES | Environment, Health Disparities, and Stress
The double jeopardy of exposure to environmental hazards combined with place-based stressors is associated with disparities in maternal and child health (MCH). Morello-Frosch and Shenassa (p. 1150) present evidence that individual-level and place-based psychosocial stressors may compromise host resistance such that environmental pollutants would have adverse health effects at relatively lower doses, thus partially explaining MCH disparities, particularly poor birth outcomes. The authors propose a conceptual framework for holistic approaches to future MCH research that elucidates the interplay of psychosocial stressors and environmental hazards in order to better explain drivers of MCH disparities.
Review
RISK ASSESSMENT | Digestion in Assessment of Protein Allergenicity
The food-allergy RISK ASSESSMENT for transgenic proteins expressed in crops is currently based on a weight-of-evidence approach that holistically considers multiple lines of evidence. This approach recognizes that no single test or property is known to distinguish allergens from nonallergens. The stability of a protein to digestion is currently used as one element in the RISK ASSESSMENT process. Herman et al. (p. 1154) review the literature on the use of the simulated gastric fluid assay to predict the allergenic status of proteins and suggest that more extensive kinetic studies with well-characterized reference proteins are required before the predictive value of this assay can be adequately judged.
Research
EXPOSURE ASSESSMENT | MCIOP, MOINP, and MHINP are DINP Biomarkers
Diisononyl phthalate (DINP) causes antiandrogenic effects on developing male rodent fetuses. Traditionally, human exposure to DINP has been assessed using monoisononyl phthalate (MINP), the hydrolytic metabolite of DINP, as a biomarker. However, MINP is only a minor urinary metabolite of DINP. Oxidative metabolites, including mono(carboxyisooctyl) phthalate (MCIOP), mono(oxoisononyl) phthalate (MOINP), and mono(hydroxyisononyl) phthalate (MHINP), are the major urinary metabolites in DINP-treated rats. Silva et al. (p. 1158) measured urinary concentrations of MINP, MCIOP, MOINP, and MHINP in 129 adult human volunteers with no known exposure to DINP. The results suggest that the oxidative metabolites are better biomarkers of DINP exposure than is MINP.
EXPOSURE ASSESSMENT | Relative Bioavailability of Lead
Casteel et al. (p. 1162) summarize the results of a series of studies that measured the relative bioavailability (RBA) of lead in a variety of soil and soil-like test materials. Reference material (Pb acetate) or Pb-contaminated soils were administered orally to juvenile swine. The variability in RBA between different samples highlights the importance of reliable RBA data to help improve RISK ASSESSMENTs. Although the RBA value for a sample depends on the relative amounts of the different chemical and physical forms of Pb present, data are not yet adequate to allow reliable quantitative predictions of RBA from chemical speciation data alone.
TOXICOLOGY | Translocation of Inhaled Mn Oxides to the CNS
Studies in monkeys with intranasally instilled gold ultrafine particles (UFPs) and in rats with inhaled carbon UFPs suggested that solid UFPs deposited in the nose travel along the olfactory nerve to the olfactory bulb. To determine if olfactory translocation occurs for other solid metal UFPs and assess potential health effects, Elder et al. (p. 1172) exposed rats to manganese oxide UFPs. The authors conclude that the olfactory neuronal pathway is efficient for translocating inhaled Mn oxide as solid UFPs to the central nervous system (CNS) and that this can result in inflammatory changes. In spite of differences between humans and rodents, this pathway may be relevant in humans.
Also see Science Selections, p. A486
EXPOSURE ASSESSMENT | PBDEs and PCBs in Human Serum and Breast Milk
Blood and/or breast milk have been used to assess human exposure to various environmental contaminants. Inoue et al. (p. 1179) measured levels of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) in Japanese women, analyzing the effects of lifestyle and dietary habits on these levels, and developed a quantitative structure–activity relationship (QSAR) with which to predict the ratio of serum concentration to breast milk concentration. QSAR analysis revealed that the calculated octanol/water partition and the number of hydrogen-bond acceptors were significant descriptors. During the first weeks of lactation, the predicted partitioning of PBDE and PCB congeners from serum to milk agreed with the observed values.
HUMAN TOXICOLOGY | Blood Lead Micronutrient Relationships
Gulson et al. (p. 1186) evaluated the association of dietary intakes of selected micronutrients and blood lead (PbB) concentrations in female adults and in children. Using longitudinal monitoring, daily intakes of calcium, magnesium, sodium, potassium, barium, strontium, phosphorus, zinc, iron (limited data), and copper were measured from 6-day duplicate diets and PbB concentrations. In contrast to most previous studies, this study found no statistically significant relationships between PbB concentrations and micronutrient intake. In adults and older children with low PbB concentrations and minimal exposure to Pb, micronutrient supplementation is probably unnecessary.
DNA REPAIR | Arsenic Decreases DNA Repair
The mechanism(s) by which arsenic exposure contributes to human cancer risk is unknown; however, several indirect co-carcinogenesis mechanisms have been proposed. Many studies support the role of As in altering one or more DNA repair processes. Andrew et al. (p. 1193) used individual-level exposure data and biologic samples to investigate the effects of As exposure on nucleotide excision repair, focusing on the excision repair cross-complement 1 (ERCC1) component. In support of the in vivo data, As exposure decreased ERCC1 mRNA expression and enhanced levels of DNA damage after a 2-acetoxyacetylaminofluorene challenge in cell culture. The data provides further evidence to support the ability of As to inhibit the DNA repair mechanisms.
INFECTIOUS DISEASE | Methods for Estimating Microbial Risks in Drinking Water
Risk assessments and intervention trials have been used by the U.S. Environmental Protection Agency to estimate drinking water health risks, but both methods are seldom used concurrently. Eisenberg et al. (p. 1199) simultaneously collected illness data and exposure data, providing a unique opportunity to compare direct risk estimates of waterborne disease from the intervention trial with indirect estimates from a RISK ASSESSMENT. Trials provide direct risk estimates, and the upper confidence limit estimates, even if not statistically significant, are informative about possible upper estimates of likely risk. These differences suggest that conclusions about waterborne disease risk may be strengthened by the joint use of these two approaches.
PROSTATE CANCER | Occupational Phorate Exposure and Cancer Incidence
Mahajan et al. (p. 1205) recently reported a link between use of the organophosphate pesticide phorate and the risk of prostate cancer among applicators with a family history of prostate cancer in the Agricultural Health Study (AHS). Although prostate cancer risk was not significantly related to phorate use overall or among those without a family history, the risk tended to increase among applicators with a family history of prostate cancer. The results suggest a gene–environment interaction between family history and phorate exposure in the incidence of prostate cancer, but other explanations are also possible.
RESPIRATORY DISEASE | VOCs and Pulmonary Function in NHANES III
Volatile organic compounds (VOCs) have been associated with respiratory symptoms, but few studies address objective respiratory end points such as pulmonary function. Blood levels of VOCs may be more indicative of personal exposures than are air concentrations, but no studies have addressed their relationship with respiratory outcomes. Elliott et al. (p. 1210) examined whether concentrations of 11 VOCs that were commonly identified in blood from a sample of the U.S. population were associated with pulmonary function. After adjustment for smoking, only 1,4-dichlorobenzene, a component in products such as air fresheners, toilet bowl deodorants, and mothballs, was associated with reduced pulmonary function.
CARDIOVASCULAR DISEASE | Coarse Particles and Heart Rate Variability
Alterations in cardiac autonomic control, assessed by changes in heart rate variability (HRV), provide one plausible mechanistic explanation for consistent associations between exposure to airborne particulate matter (PM) and increased risks of cardiovascular mortality. Decreased HRV has been linked with exposures to PM10 (PM ≤ 10 µm in aerodynamic diameter) and with fine particles originating primarily from combustion sources. Lipsett et al. (p. 1215) measured several HRV variables in nonsmoking older adults with coronary artery disease residing in California. The magnitude of the associations was comparable with those observed in several other studies of PM. Elevated levels of ambient PM10–2.5 may adversely affect HRV in older subjects with coronary artery disease.
BIOMARKERS | Satratoxin G Adducts as Biomarkers for Stachybotrys
Despite the growing body of evidence showing adverse health effects from inhalation exposure to the trichothecene-producing mold Stachybotrys chartarum, controversy remains. Currently, there are no reliable assays suitable for clinical diagnosis of exposure. Yike et al. (p. 1221) hypothesized that satratoxin G (SG)–albumin adducts may serve as biomarkers of exposure to this fungus. Mass spectrometry analysis found that as many as 10 toxin molecules can be bound in vitro to one albumin molecule. The data documents the occurrence of SG–albumin adducts in both in vitro experiments and in vivo human and animal exposures and may therefore serve as a reliable dosimeter biomarker for detection of exposure to S. chartarum.
CARDIOVASCULAR DISEASE | Ozone and Daily Mortality
The relationship between ambient ozone and mortality remains controversial. Because of the changes in types of air pollution from conventional coal combustion to the mixed coal combustion/motor vehicle emissions in China's large cities, Zhang et al. (p. 1227) conducted a time-series study to investigate the relationship between ozone and daily mortality in Shanghai using 4 years of daily data. O3 pollution has stronger health effects in the cold than in the warm season in Shanghai. The analyses strengthens the rationale for further limiting levels of O3 pollution in outdoor air in the city.
CARDIOVASCULAR DISEASE | Pb Is Associated with Decreased Serum PON1 Activity
Lead exposure causes cardiac and vascular damage in animals; however, There is considerable debate regarding the causal relationship between lead exposure and cardiovascular dysfunction in humans. Previous studies have shown that, in vitro, lead and several other metal ions are able to inhibit the activity of PON1, an enzyme capable of hydrolyzing oxidized lipids and thus protecting against atherosclerosis. Li et al. (p. 1233) conducted a cross-sectional study of workers from a lead battery manufactory and lead recycling plant to determine if lead exposure affects serum PON1 activity. Their results suggest that the decrease in serum PON1 activity due to lead exposure may render individuals more susceptible to atherosclerosis, particularly subjects who are homozygous for the R192 allele.
RISK ASSESSMENT | Human Hepatocytes in TCE Risk Assessment
Trichloroethylene (TCE), a suspected carcinogen and groundwater contaminant, is metabolized by aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH) to form chloral hydrate and trichloroacetate, respectively. ALDH and ADH are polymorphic in humans. These polymorphisms may yield subpopulations with greater than expected trichloroacetate formation with associated risk of liver tumors after TCE exposure. Bronley-DeLancey et al. (p. 1237) studied the feasibility of using commercially available, human hepatocytes to determine the kinetics of chloral hydrate metabolism and ALDH/ADH genotype. The data support the use of cryopreserved human hepatocytes to generate metabolic and genomic information for incorporation into TCE cancer risk assessment models.
AUTOIMMUNE DISEASE | Asbestos Exposure and Autoimmune Disease
To explore the potential association between asbestos exposure and risk of autoimmune disease, Noonan et al. (p. 1243) conducted a case–control study among a cohort of current and former residents of Libby, Montana, a community with historical occupational and environmental exposure to asbestos-contaminated vermiculite. Cases were defined as those who reported having one of three systemic autoimmune diseases (SAIDs): systemic lupus erythematosus, scleroderma, or rheumatoid arthritis. The preliminary findings support the hypothesis that asbestos exposure is associated with autoimmune disease. Refined measurements of asbestos exposure and SAID status among this cohort will help to further clarify the relationship between these variables.
RISK ASSESSMENT | The Agricultural Health Study: Cyanazine and Cancer Incidence
Cyanazine is a common pesticide used frequently in the United States during the 1980s and 1990s. Animal and human studies have suggested that triazines may be carcinogenic, but results have been mixed. Lynch et al. (p. 1248) evaluated cancer incidence in cyanazine-exposed pesticide applicators among the 57,311 licensed pesticide applicators in the Agricultural Health Study (AHS). A total of 20,824 cancer-free AHS applicators reported ever using cyanazine at enrollment. No clear, consistent associations between cyanazine exposure and any cancer analyzed were found. The small numbers of of female applicators and certain cancer types limit the conclusions with regard to ovarian, breast, and some other cancers.
TOXICOLOGY | Role of Nitric Oxide in DEP-Mediated Lung Toxicity
Diesel exhaust particles (DEPs) activate oxidant generation by alveolar macrophages, alter xenobiotic metabolic pathways, and modify the balance of pro-antiinflammatory cytokines. Zhao et al. (p. 1253) investigated the role of nitric oxide in DEP-mediated and DEP organic extract (DEPE)-mediated inflammatory responses and evaluated the interaction of inducible NO synthase (iNOS) and cytochrome P450-1A1 (CYP1A1). Both DEPs and DEPEs induced CYP1A1 expression. The results show that NO plays a major role in DEPE-induced lung inflammation and CYP-dependent mutagen activation but a lesser role in particulate-induced inflammatory damage.
TOXICOLOGY | OECD Validation of Rat Hershberger Assay
Owens et al. (p. 1259) report that the Organization for Economic Cooperation and Development (OECD) has completed phase 1 of the Hershberger validation intended to identify in vivo activity of suspected androgens and antiandrogens. Seventeen laboratories participated, and results were collated and evaluated by the OECD with the support of an international committee of experts. The results indicate that the OECD Hershberger protocol is robust, reproducible, and transferable across laboratories. The protocols have now been refined, and the next phase of the OECD validation program will test the protocol with selected doses of weak androgen agonists, androgen antagonists, a 5-reductase inhibitor, and chemicals having no androgenic activity.
SKIN | Di-(2-ethylhexyl) Phthalate Aggravates Atopic Dermatitis
Di-(2-ethylhexyl) phthalate (DEHP) has been widely used in polyvinyl chloride products and has become ubiquitous in developed countries. DEHP reportedly displays an adjuvant effect on immunoglobulin production; however, an association between DEHP and the aggravation of atopic dermatitis has not been elucidated. Takano et al. (p. 1266) investigated the effects of DEHP on atopic dermatitis-like skin lesions induced by mite allergen in NC/Nga mice. The results indicate that DEHP enhances atopic dermatitis-like skin lesions at hundred-fold lower levels than the no observed adverse effect level determined on histologic changes in the liver of rodents.
NEUROBEHAVIORAL DISEASE | UMTS Exposure, Well-Being, and Cognitive Performance
Regel et al. (p. 1270) investigated the influence of a Universal Mobile Telecommunications System (UMTS) base station-like signal on well-being and cognitive performance in subjects with and without self-reported sensitivity to radio-frequency electromagnetic fields. In both groups, well-being and perceived field strength were not associated with actual exposure levels. No consistent condition-induced changes in cognitive performance were observed except for two marginal effects. In contrast to a recent Dutch study, a short-term effect of UMTS base station-like exposure on well-being could not be confirmed. The reported effects on brain functioning were marginal and may have occurred by chance.
TOXICOLOGY | U.S. EPA Endocrine-Disrupting Chemicals Program Review
At the request of the U.S. Environmental Protection Agency (EPA) Office of Research and Development, a subcommittee of the Board of Scientific Counselors Executive Committee conducted an independent and open peer review of the Endocrine Disrupting Chemicals (EDC) Research Program of the U.S. EPA. The subcommittee was charged with reviewing the design, relevance, progress, scientific leadership, and resources of the program. Harding et al. (p. 1276) report thatthe subcommittee found that the long-term goals and science questions in the EDC program are appropriate and represent an understandable and solid framework for setting research priorities, representing a combination of problem-driven and core research.
Environmental Medicine
NEURODEGENERATIVE DISEASE | Toluene, Noise, and Hearing Loss
Chang et al. (p. 1283) investigated the risk of hearing loss among workers exposed to both toluene and noise at an adhesive materials manufacturing plant. The prevalence of hearing loss of ≥ 25 dB in the toluene plus noise group was much greater than that in the noise-only group and in administrative clerks. Multivariate logistic regression analysis showed that the toluene plus noise group had an estimated risk for hearing loss ≥ 25 dB, 10.9 times higher than that of the noise-only group. The results suggest that toluene exacerbates hearing loss in a noisy environment, with the main impact on the lower frequencies.
Also see Science Selections, p. A487
Children's Health
NEURODEVELOPMENT | Prenatal Exposure to Air Pollution and Cognition
Perera et al. (p. 1287) evaluated the role of prenatal exposure to urban pollutants, including polycyclic aromatic hydrocarbons (PAHs), environmental tobacco smoke, and pesticides, in the pathogenesis of neurobehavioral disorders in a prospective cohort study of nonsmoking African-American and Dominican mothers and children in New York City. High prenatal exposure to PAHs was associated with lower mental development index at 3 years of age; there were no differences in effect sizes by ethnicity. PAHs at levels recently encountered in New York City air may adversely affect children's cognitive development, with implications for school performance.
Also see Science Selections, p. A487
RESPIRATORY DISEASE | Childhood Arsenic Exposure and Early Mortality
Arsenic in drinking water is an established cause of lung cancer, and preliminary evidence suggests that ingested arsenic may also cause nonmalignant lung disease. Antofagasta, the second largest city in Chile, had a distinct period of very high arsenic exposure that began in 1958 and lasted until 1971, when an arsenic removal plant was installed. Smith et al. (p. 1293) compared mortality rates in Antofagasta with those of the rest of Chile. The findings suggest that exposure to arsenic in drinking water during early childhood or in utero has pronounced pulmonary effects, greatly increasing subsequent mortality in young adults from both malignant and nonmalignant lung disease.
Also see Science Selections, p. A486
FETAL DEVELOPMENT | PAH–DNA Adducts in Cord Blood and Development
Polycyclic aromatic hydrocarbons (PAHs) are toxic pollutants released by fossil fuel combustion. PAH–DNA adducts, or benzo[a]pyrene adducts as their proxy, provide a chemical-specific measure of individual biologically effective doses that have been associated with increased risk of cancer and adverse birth outcomes. Tang et al. (p. 1297) examined the relationship between prenatal PAH exposure and fetal and child growth and development in Tongliang, China, where a seasonally operated coal-fired power plant was the major pollution source. The findings suggest that exposure to elevated levels of PAHs is associated with reduced fetal and child growth.
INFECTIOUS DISEASE | Infections and PCBs in Inuit Children
Dallaire et al. (p. 1301) assess whether environmental prenatal exposure to polychlorinated biphenyls (PCBs) is associated with incidence of acute respiratory infections in preschool Inuit children. The associations between PCB-153 concentration in umbilical cord plasma and the incidence rates of acute otitis media (AOM) and of upper and lower respiratory tract infections (URTIs and LRTIs, respectively) were evaluated. The incidence rates of AOM and LRTIs were positively associated with prenatal exposure to PCBs. There was no association between prenatal PCB exposure and incidence rate of URTIs or hospitalization. Prenatal exposure to PCBs could be responsible for a significant portion of respiratory infections in children of this population.