Environews
NIEHS NEWS | The Feed Factor: Estrogenic Variability in Lab Animals Diets
Animal studies are a cornerstone of biomedical and environmental health research, and scientists need assurance that animals used in these studies are being cared for in ways that will not unknowingly influence experimental outcomes. Now some researchers are calling attention to the possible influence of dietary phytoestrogens present in animal feed. This article (p. A640) takes a look at how estrogenic activity varies across animal feeds and what should be done to minimize this outside influence, which was the subject of a recent meeting cosponsored by the NIEHS and the NIH Office of Dietary Supplements.
FOCUS | Fertile Grounds for Inquiry: Environmental Effects on Human Reproduction
Beneath the specter of overpopulation, which threatens to deplete available natural resources, is growing evidence of a decline in our overall biological fertility. While it is likely that modern lifestyle factors such as obesity and postponing having children have played a part in diminished fertility rates, other evidence suggests that exposures to environmental chemicals may also play a role. This article (p. A644) examines arguments for the culpability of these contaminants in the increasing occurrence of fertility decline.
SPHERES OF INFLUENCE | Setting a Baseline for Biomonitoring
Biomonitoring plays a key role in identifying, controlling, and preventing environmental health threats. Measuring human exposure to chemical contaminants helps inform public health policy as well as personal decisions regarding the use of these agents. But these measurements can't provide a complete picture when we don't know how the exposures are affecting our health. A new report released by a committee of the National Research Council, described in this article (p. A652), discusses the dilemma of having environmental exposure data on chemicals but lacking concrete information on the health implications.
INNOVATIONS | Fe-TAMLs: Catalysts for Cleanup
While most scientists agree that environmental exposure to hormones such as natural and synthetic estrogens can trigger negative health effects, consensus on what constitutes adverse exposure levels has yet to be reached. However, despite this uncertainty, most agree that these and other contaminants that find their way into our drinking water supplies should be tightly controlled. This article (p. A656) examines the Fe-TAML activator catalyst molecule, a promising contaminant reduction method developed by researchers at the Carnegie Mellon Institute for Green Oxidation Chemistry that could possibly become a valuable tool for wastewater cleanup.
Commentary
RISK ASSESSMENT | The Importance of Hormesis to Public Health
Hormesis is a specific type of nonmonotonic dose response whose occurrence has been documented across a broad range of biological models, diverse types of exposure, and a variety of outcomes. The effects that occur at various points along this curve can be interpreted as beneficial or detrimental, depending on the biological or ecologic context in which they occur. Hormesis appears to be a relatively common phenomenon that has not yet been incorporated into regulatory practice. Cook and Calabrese (p. 1631) explore some of its more obvious public health and risk assessment implications, with particular reference to issues raised recently in this journal by other authors.
Review
FETAL DEVELOPMENT | Nutrition Biomarkers, PM, and Perinatal Outcomes
Protecting the environmental health of mothers and infants remains a top global priority. The existing literature indicates that the effects of particulate matter (PM) on low birth weight, preterm delivery, and intrauterine growth retardation may arise through the cardiovascular mechanisms of oxidative stress, inflammation, coagulation, endothelial function, and hemodynamic responses. PM exposure studies relating mechanistic pathways to perinatal outcomes should consider the likelihood that biologic responses and adverse birth outcomes may be derived from both PM and non-PM sources (e.g., nutrition). Kannan et al. (p. 1636) present strategies for empirically testing the proposed model and developing future research efforts.
Research
ENDOCRINE SYSTEM | DBP, DEHP, and Decreased Serum Free Testosterone
Observations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled public concern about the potential for various chemicals to impair human fertility. Pan et al. (p. 1643) assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones, including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol. Urine and blood samples of male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) were examined. There was a modest and significant reduction of serum fT in workers with higher levels of urinary mono-n-butyl phthalate (MBP) and mono-2-ethylhexyl phthalate (MEHP) compared with unexposed workers.
Also see Science Selections, p. A660
REPRODUCTIVE HEALTH | TCDD Exposure and Risk of BPH
Operation Ranch Hand veterans were involved in spraying herbicides, including Agent Orange contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during the Vietnam War. It has been hypothesized that dioxins may be partially responsible for an increase of male reproductive tract disorders such as testicular cancer, cryptorchidism, and hypospadias. Gupta et al. (p. 1649) assess the effect of serum TCDD concentration on the risk of development of benign prostatic hyperplasia (BPH) and on serum testosterone levels. TCDD exposure, at general population levels, is associated with a decreasing risk of BPH at higher exposure levels. TCDD exposure is also negatively associated with serum testosterone levels.
METABOLISM | Xenobiotic Metabolizing Enzymes in Lung Tissue of Smokers
Cytochrome P450 monooxygenases (CYP) play an important role in the defense against inhaled toxicants, and expression of CYP enzymes may differ among various lung cells and tissue compartments. Thum et al. (p. 1655) found gene expression of pulmonary xenobiotic metabolizing enzymes and certain key transcription factors to be regulated in bronchoalveolar lavage cells and bronchial biopsies of smokers. The observed changes demonstrate tissue specificity in xenobiotic metabolism, with likely implications for the metabolic activation of procarcinogens to ultimate carcinogens of tobacco smoke.
CARDIOVASCULAR DISEASE | Cardiovascular Effects of Nickel in Ambient Air
Fine particulate matter (FPM) in ambient air causes premature mortality due to cardiac disease in susceptible populations. Lippmann et al. (p. 1662) exposeda mouse model of atherosclerosis (ApoE–/–) to either filtered air or concentrated FPM, and the FPM elemental composition was determined for each day. Associations between PM components and mortality for two population studies (National Mortality and Morbidity Air Pollution Study and Hong Kong) were also examined. Known biological mechanisms cannot account for the significant associations between nickel with the acute cardiac function changes in mice or with cardiovascular mortality in people at low ambient air concentrations; therefore, further research is needed.
REPRODUCTIVE HEALTH | Dioxins and Reproductive Parameters in Men
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and some related environmental contaminants are aryl hydrocarbon receptor (AhR) ligands that exert reproductive and developmental toxicity in laboratory animals. In humans, fertility-related effects are less documented. Dhooge et al. (p. 1670) investigated the relationship between dioxin-like biological activity in serum and parameters of reproductive status in men from the general population 5 months after a polychlorinated biphenyl and dioxin food-contamination episode in Belgium. The data suggest an interaction of dioxin-like compounds with the secretory function of the seminal vesicles or prostate, possibly indirectly through an effect on testosterone secretion, at levels not affecting spermatogenesis as such.
Also see Science Selections, p. A660
BIOMARKERS | Diabetogenic Action of Dioxin among Vietnam Veterans
One outcome positively associated with dioxin exposure in humans is type 2 diabetes. Fujiyoshi et al. (p. 1677) conducted a study in order to find the molecular biological evidence for the diabetogenic action of dioxin in adipose samples from Vietnam veterans. Adipose tissue samples were obtained both from veterans who were exposed to dioxin and from veterans with no record of exposure. The results show that the ratio of mRNA of glucose transporter 4 and nuclear transcription factor kappa B is a reliable marker for the diabetogenic action of dioxin, particularly at very low exposure levels that are not much higher than those found in the general public, implying a need to address current exposure levels.
EXPOSURE ASSESSMENT | Intervention to Reduce Residential Pesticide Use
Williams et al. (p. 1684) previously reported widespread insecticide exposure during pregnancy among inner-city women from New York City. They report on a pilot intervention using integrated pest management (IPM) to reduce pest infestations and residential insecticide exposures among pregnant New York City African-American and Latina women (25 intervention and 27 control homes). This is the first study to use biologic dosimeters of prenatal pesticide exposure for assessing effectiveness of IPM. These pilot data suggest that IPM is an effective strategy for reducing pest infestation levels and the internal dose of insecticides during pregnancy.
CARDIOVASCULAR DISEASE | PM10 Modifies Temperature Effect
A number of studies have shown that both temperature and air pollution are associated with health outcomes. In assessing air pollution effects, temperature is usually considered a confounder. Few studies are available on whether or not air pollution modifies the temperature–disease relationship. Ren et al. (p. 1690) used three parallel Poisson generalized additive models to examine whether particulate matter < 10 µm in aerodynamic diameter (PM10) modified the effects of minimum temperature on cardiorespiratory morbidity and mortality. Enhanced adverse temperature effects were found at higher levels of PM10, but no clear evidence emerged for interactive effects on respiratory and cardiovascular emergency visits.
NANOTECHNOLOGY | Distribution of Nanoparticles in Medaka
Because the environmental fate of manufactured nanoparticles is considered an emerging environmental concern, Kashiwada (p. 1697) used water-suspended fluorescent nanoparticles (solid latex solution) to investigate the distribution of nanoparticles in the eggs and bodies of see-through medaka (Oryzias latipes). Nanoparticles were detected in the chorion, yolk, and gallbladder during embryonic development and in gills, intestines, brain, testis, liver, and blood of adult medaka. The bioavailability and toxicity of nanoparticles depend on environmental factors and multiple physicochemical properties. Further studies on the toxic effects of nanoparticles used in commercial products, and their environmental relevance, are necessary to define the risks and benefit of nanomaterial applications.
NEURODEVELOPMENT | Genotoxicants Induce Neuronal Molecular Signatures
Exposure of the brain to environmental agents during critical periods of neuronal development is considered a key factor underlying many neurologic disorders. Kisby et al. (p. 1703) examined the influence of genotoxicants on cerebellar function during early development by measuring global gene expression changes. Global gene expression was measured in immature cerebellar neurons (i.e., granule cells) after treatment with two distinct alkylating agents, methylazoxymethanol (MAM) and nitrogen mustard (HN2). Results indicate that individual genotoxicants induce distinct gene expression signatures and may explain the variable response of the developing brain to different types of environmental genotoxicants.
Also see Science Selections, p. A661
Environmental Medicine
CIRCULATORY DISEASE | Anemia and Fire Extinguisher Gas
Although there are ample data on the respiratory effects of exposure to fire extinguisher gas, the potential hematologic effects have not been fully documented. Lo et al. (p. 1713) examined the possible etiologic agent(s) for a decrease in red blood cells among community residents in Taipei, Taiwan, after they were exposed to leakage of mixed fire extinguishants containing bromotrifluoromethane (CF3Br, Halon 1301), bromochlorodifluoromethane (CF2BrCl, Halon 1211), and dichlorodifluoromethane (CF2Cl2, CFC-12). The acute transient hematologic effects observed were associated with the incident of leakage of mixed fire extinguisher gases and were most likely caused by a small amount of pyrolytic products, probably phosgene.
CARDIOVASCULAR DISEASE | Low-Level Lead, Metabolic Syndrome, and HRV
Altered heart rate variability (HRV), a marker of poor cardiac autonomic function, is associated with sudden cardiac death and heart failure. Park et al. (p. 1718) examined the association of low-level lead exposure measured in bone by K-X-ray fluorescence with alterations in HRV, and whether metabolic syndrome (MetS) or its individual components modify those associations. The results suggest that elderly men with MetS were more susceptible to autonomic dysfunction in association with chronic lead exposure as measured in patella. The modification by MetS is consistent with a role for oxidative stress in lead toxicity on the cardiovascular system.
RESPIRATORY DISEASE | Effects of Glass Fiber–Reinforced Plastic
The inhalation of glass dusts mixed in resin, generally known as glass fiber–reinforced plastic (GRP), represents a little-studied occupational hazard. The few studies performed have highlighted nonspecific lung disorders in animals and in humans. Abbate et al. (p. 1725) evaluated the alteration of the respiratory system and the pathogenic mechanisms causing the changes in a group of working men employed in different GRP processing operations and exposed to production dusts. Inhalation of GRP, independent of environmental concentration, causes alterations of the cellular and humoral components of pulmonary interstitium; these alterations are identified microscopically as acute alveolitis.
Children's Health
NEURODEVELOPMENT | Fetal Lead Exposure and Infant Mental Development
The impact of prenatal lead exposure on neurodevelopment remains unclear in terms of consistency, the trimester of greatest vulnerability, and the best method for estimating fetal lead exposure. Hu et al. (p. 1730) studied the impact of prenatal lead exposure on neurodevelopment using repeated measures of fetal dose as reflected by maternal whole blood and plasma lead levels. Lead was measured during each trimester in women from Mexico City. Fetal lead exposure had an adverse effect on neurodevelopment, with an effect that may be most pronounced during the first trimester and best captured by measuring lead in either maternal plasma or whole blood.
Also see Science Selections, p. A661
RESPIRATORY DISEASE | Air Pollution and FeNO in Asthmatic Children
There are associations between pediatric asthma outcomes and airborne particulate matter (PM). The importance of particle components remains to be determined. Delfino et al. (p. 1736) followed a panel of 45 schoolchildren with persistent asthma living in Southern California. Subjects were monitored over 10 days with offline fractional exhaled nitric oxide (FeNO), a biomarker of airway inflammation. Personal active sampler exposures included continuous PM2.5, 24-hr PM2.5 elemental and organic carbon, and 24-hr nitrogen dioxide. PM associations with airway inflammation in asthmatics may be missed using ambient particle mass, which may not sufficiently represent causal pollutant components from fossil fuel combustion.
FETAL DEVELOPMENT | Prenatal PAH Exposure and Fetal Growth
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitously distributed human mutagens and carcinogens. Lack of adequate air monitoring data has limited understanding of the effects of airborne PAHs on fetal growth. Choi et al. (p. 1744) examined the association between prenatal exposure to airborne PAHs and birth weight, birth length, and birth head circumference in Krakow, Poland, and New York City. The results confirm the adverse reproductive effect of relatively low PAH concentrations in two populations and suggest increased susceptibility of New York City African Americans. Fetal growth impairment has been linked to child developmental and health problems. Thus, substantial health benefits would result from global reduction of PAH emissions.
RESPIRATORY DISEASE | Air Pollution, Social Status, and Respiratory Illness
Current levels of ambient air pollution are associated with morbidity and mortality in the general population. To determine the influence of gaseous air pollutants on neonatal respiratory morbidity, Dales et al. (p. 1751) tested the association between daily respiratory hospitalizations and daily concentrations of ambient air pollution gases (ozone, carbon monoxide, sulfur dioxide, and nitrogen dioxide). Daily time-series analyses were employed, and results were adjusted for day of the week, temperature, barometric pressure, and relative humidity. The results suggest that neonates experience adverse effects of air pollution at current levels, and that accounts for a significant proportion of hospitalizations in this subgroup.
Mini-Monograph
BIOMONITORING | Biomonitoring Data and Risk Assessment
Biomonitoring uses analytic methods that permit the accurate measurement of low levels of environmental chemicals in human tissues. In 2004, various agencies cosponsored the International Biomonitoring Workshop, which explored the processes and information needed for placing biomonitoring data into perspective for risk assessment purposes, with special emphasis on integrating biomarker measurements of exposure, internal dose, and potential health outcome. The monograph (p. 1755) gives specific examples of biomonitor use, summarizes lessons learned, identifies data gaps, outlines research needs, and offers guidance for designing and conducting biomonitoring studies, as well as interpreting biomonitoring data in the context of risk assessment and risk management.
