Environews
NIEHS NEWS | NTP Multigenerational Study of Environmental Estrogens
Endocrine disruption has garnered research interest at the NIEHS for close to three decades. Now the National Toxicology Program, in collaboration with the FDA's National Center for Toxicological Research, is set to release for institute peer review the first report from 10 years of multigenerational rodent model research on estrogenic compounds. This article (p. A348) takes a look at the origins and goals of the project, as well as the subject of the first report, the phytoestrogen genistein.
FOCUS | The Science of Soy: What Do We Really Know?
Soy is available in a variety of everyday consumables, from baby formula to meatless burgers to herbal supplements. But do we know enough about this widely used food? Although evidence exists to support its nutritive value, other research fails to link significant health benefits to consumption of soy-based foods, and some studies further suggest there is cause for concern regarding the effects of soy isoflavones on reproduction and development. This article (p. A352) takes a look at the role that soy and its constituents play in our diet, and the twists and turns in the research around this food.
SPHERES OF INFLUENCE | Human Experimentation: A Rule Gone Awry?
In a move aimed at better protecting human health, the U.S. EPA recently published the Protections for Subjects in Human Research rule. But the EPA has come under fire from human and environmental health advocates who say the rule contains dangerous loopholes that could allow pesticide companies to conduct dosing studies on vulnerable subjects such as children and pregnant women. This article (p. A360) looks at the main provisions of the rule, and also examines criticisms of its weaknesses.
INNOVATIONS | Plant vs. Pathogen: Enlisting Tobacco in the Fight against Anthrax
The threat of an anthrax-fueled bioterrorist attack is an ongoing concern for public health officials, and the current supply of vaccine falls drastically short of what would be needed to protect the entire civilian population in a widespread attack. Now researchers at the University of Central Florida are working on a way to grow the active ingredient in anthrax vaccine in genetically modified tobacco plants. If perfected, this method could produce large quantities of anthrax vaccine and perhaps others in a short amount of time. This article (p. A364) examines the production method that taps into the tobacco plant's potential as a life-saving agent.
Commentary
EXPOSURE ASSESSMENT | Maternal Daily Phthalate Exposures
A recent epidemiologic study showed certain phthalates to be significantly associated with reduced anogenital distance in human male infants, the first evidence of subtle developmental effects from prenatal exposure to phthalates. Marsee et al. (p. 805) used two previously published methods to estimate the daily phthalate exposures for the four phthalates whose urinary metabolites were significantly associated with developmental effects. The median and 95th percentile exposure estimates associated with reduced anogenital distance in the study population are substantially lower than current U.S. Environmental Protection Agency reference doses for these chemicals and could be informative to any updates of hazard and risk assessments for these chemicals.
Review
EXPOSURE ASSESSMENT | Origin and Health Impacts of Combustion Products
High-temperature, controlled incineration and thermal treatment of contaminated soils, sediments, and wastes at Superfund sites are often preferred methods for remediation of contaminated sites under the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 and related legislation. Although these methods may be executed safely, formation of toxic combustion or reaction by-products is still a cause of concern. Cormier et al. (p. 810) discuss the origin of different classes of pollutants, the nature of their association with combustion-generated particulate matter, and the mechanisms of their known and potential health impacts.
Research
CANCER | Leukemia, Lymphoma, and Myeloma in Uranium Miners
Rericha et al. (p. 818) investigated whether radon exposure is associated with increased incidence of leukemia, lymphoma, or multiple myeloma in uranium miners who are chronically exposed to low levels of radon and its progeny. The authors found no apparent association of radon with either non-Hodgkin lymphoma or multiple myeloma; however, incidence of all leukemias combined and chronic lymphocytic leukemia (CLL) alone were both positively associated with cumulative radon exposure. Therefore, CLL, not previously believed to be radiogenic, was linked to radon exposure in underground uranium miners.
ENVIRONMENTAL TOXICOLOGY | Biomarkers Signal Contaminant Effects
Fish that live in contaminated environments accumulate toxic chemicals in their tissues. Biomarkers are needed to identify the resulting health effects, particularly focusing on early changes at a subcellular level. Malins et al. (p. 823) used a suite of complementary biomarkers to signal contaminant-induced changes in the DNA structure and cellular physiology of the livers and gills of English sole from two different sites. Various spectroscopy and chromatography methods were used to identify potentially deleterious alterations in DNA. The biomarkers described are highly promising for identifying contaminant-induced stresses in fish populations from polluted and reference sites and also for monitoring the progress of remedial actions.
BONE/CARTILAGE | Cadmium Exposure and Bone Effects in Humans
High cadmium exposure is known to cause bone damage, but the association between low-level cadmium exposure and osteoporosis remains to be clarified. Using a population-based women's health survey in an area of southern Sweden with no known historical cadmium contamination, Åkesson et al. (p. 830) investigated cadmium-related effects on bone in 820 women. The results suggest negative effects of low-level cadmium exposure on bone, possibly exerted via increased bone resorption, which seemed to be intensified after menopause. Based on the prevalence of osteoporosis and the low level of exposure, the observed effects, although slight, should be considered as early signals of potentially more adverse health effects.
Also see Science Selections, p. A369
HUMAN TOXICOLOGY | Human OGG1 Expression and Chronic Arsenic Exposure
Arsenic, a human carcinogen, induces oxidative damage to DNA. Bayingnormen (Ba Men) residents in Inner Mongolia are chronically exposed to As via drinking water. Mo et al. (p. 835) investigated oxidative stress and As exposure by determining gene expression of OGG1, which codes for 8-oxoguanine DNA glycosylase, which is involved in removing 8-oxoguanine in As-exposed individuals. OGG1 expression was strongly associated with water As concentrations. The researchers found no significant differences in the As-induced OGG1 expression due to sex, smoking, or age, even though the oldest group showed the strongest OGG1 response. OGG1 expression may be useful as a biomarker for assessing oxidative stress from As exposure.
TOXICOLOGY | TCE Alters Heart Development and Function
It is controversial whether trichloroethylene (TCE) is a cardiac teratogen. Drake et al. (p. 842) exposed chick embryos to 0, 0.4, 8, or 400 ppb TCE/egg during the period of cardiac valvuloseptal morphogenesis (2–3.3 days' incubation). Their results confirm that TCE disrupts cardiac development of the chick embryo and identify valvuloseptal development as a period of sensitivity. This is the first report that trichloroacetic acid is a cardioteratogen for the chick and the first report that TCE exposure depresses cardiac function. Notably, these effects were observed at a TCE exposure (8 ppb) only slightly higher than the U.S. Environmental Protection Agency maximum containment level for drinking water (5 ppb).
RISK ASSESSMENT | Residential Mercury Spills from Gas Regulators
Many older homes are equipped with mercury-containing gas regulators that reduce the pressure of natural gas in the mains to the low pressure used in home gas piping. Removal of these regulators can result in elemental mercury spills inside the home. Mercury contamination was discovered in 1,363 Chicago-area homes after removal of gas regulators. Hryhorczuk et al. (p. 848) present theresults of urine bioassays and indoor mercury air measurements for 171 homes. Gas companies, their contractors, and residents should be aware of these risks and should take appropriate actions to prevent these spills and to remediate those that occur.
Also see Science Selections, p. A368
POPULATION HEALTH | Trends in U.S. Secondhand Smoke Exposure
Pirkle et al. (p. 853) describe the exposure of nonsmokers in the U.S. population to secondhand smoke (SHS) using serum cotinine concentrations measured over a period of 14 years. The study consisted of a series of National Health and Nutrition Examination Surveys that measured serum cotinine as an index of SHS exposure of participants. Study participants were individuals representative of the U.S. civilian, noninstitutionalized population. Results document a substantial decline of approximately 70% in serum cotinine concentrations in nonsmokers. The findings suggest that recent public health efforts to reduce exposures have had an important effect, although children and non-Hispanic black nonsmokers still show relatively higher levels of serum cotinine.
Also see Science Selections, p. A370
GENE REGULATION | Induction of Grp78 Expression by Cadmium
To reveal the effects of cadmium exposure on the endoplasmic reticulum (ER) stress response, Liu et al. (p. 859) examined the expression and function of 78-kDa glucose-regulated protein (Grp78), an ER-resident molecular chaperone, in LLC-PK1 cells. Compared with other heavy-metal compounds, CdCl2 could increase the levels of Grp78, activating transcription factor 4 (ATF4), and the phosphorylated form of eIF2
more markedly without definite cellular damage. The silencing of Grp78 expression using short-interference RNA enhanced CdCl2-induced cellular damage. These results show that cadmium induces the expression of Grp78 probably via phosphorylation of eIF2 and resultant translation of ATF4. The ER stress response plays a role in protection against cadmium cytotoxicity in this renal epithelial cell.
CLIMATE CHANGE | Spring Onset and CO2 Influence Ragweed Pollen
Increasing atmospheric carbon dioxide is responsible for climate changes that are having widespread effects on biological systems. One of the clearest changes is earlier onset of spring and lengthening of the growing season. Rogers et al. (p. 865) designed their study to examine the interactive effects of timing of dormancy release of seeds with low and high atmospheric CO2 on biomass, reproduction, and phenology in ragweed plants, which produce highly allergenic pollen. At high CO2 levels, plants showed greater biomass and reproductive effort compared with those in ambient CO2 but only for later cohorts. Overall, ragweed pollen production can be expected to increase significantly under predicted future climate conditions.
RESPIRATORY DISEASE | PM, Stress, and Asthma
Exposure to ambient particulate matter (PM) is linked to respiratory diseases, but the mechanism by which PM produces these diseases is not clear. Sirivelu et al. (p. 870) hypothesize that PM could act on the brain directly to stimulate the stress axis and predispose individuals to disease. This study was designed to determine if exposure to PM can affect brain areas involved in the regulation of neuroendocrine functions, especially the stress axis, and to study whether the presence of preexisting allergic airway disease aggravates the stress response. Results indicate that exposure to concentrated ambient particles can activate the stress axis, which could play a role in aggravating allergic airway disease.
IMMUNOLOGY | Periplanetaamericana Arginine Kinase is a Major Allergen
Although Periplaneta americana is the predominant cockroach species and a major source of indoor allergens in Thailand, data on the nature and molecular characteristics of its allergenic components are rare. Sookrung et al. (p. 875) conducted a study to identify and characterize the P. americana allergenic protein. They used a random heptapeptide phage display library and a monoclonal antibody (MAb) specific to the P. americana component previously shown to be an allergenic molecule to identify the MAb-bound mimotope and its phylogenic distribution. The results reveal that P. americana arginine kinase is a pan-insect protein and a major allergen for CR-allergic Thai patients.
RISK ASSESSMENT | Drinking Water Level for Perchlorate
Ting et al. (p. 881) evaluated animal and human toxicity data for perchlorate and identified reduction of thyroidal iodide uptake as the critical end point in the development of a health-protective drinking water level [also known as the public health goal (PHG)] for the chemical. The California Department of Health Services will use the PHG, together with other considerations such as economic impact and engineering feasibility, to develop a California maximum contaminant level for perchlorate. The authors consider the PHG to be adequately protective of sensitive subpopulations, including pregnant women, fetuses, infants, and people with hypothyroidism.
CANCER | Pollution and Tumor-Associated Protein Levels
van Larebeke et al. (p. 887) measured tumor-associated proteins (TAPs) and pollutants in blood, serum, and urine of 200 nonsmoking women living in a rural municipality in Flanders and two industrial suburbs of Antwerp, Belgium. For 5 of the 12 TAPs assessed in this study, the authors observed significant differences in serum levels among residents of the three municipalities after adjusting for personal and lifestyle parameters. Although levels of internal exposure to pollutants were homogeneous in Flanders, significantly higher levels of TAPs were found only in the industrial suburbs. This study provides some evidence that levels of internal exposure such as those present in Flanders, in particular concerning lead, are indeed associated with biologic effects.
EXPOSURE ASSESSMENT | Proximity to Crops and Agricultural Herbicides
Rural residents can be exposed to agricultural pesticides through the proximity of their homes to crop fields. To determine whether crop maps are useful for predicting levels of crop herbicides in carpet dust samples from residences, Ward et al. (p. 893) collected vacuum cleaner dust from homes of participants in a case–control study of non-Hodgkin lymphoma in Iowa and measured 14 herbicides with high use on corn and soybeans. Detections and concentrations were highest in homes with an active farmer. The results indicate that crop maps may be useful for estimating levels of herbicides in homes from nearby crop fields.
GENE EXPRESSION | PCBs and the Wnt7a Pathway in the Reproductive Tract
Polychlorinated biphenyls (PCBs) are proposed to have a weak estrogenic activity and therefore pose a risk as potential environmental endocrine disruptors to perinatal development of the female reproductive tract. Ma and Sassoon (p. 898) injected neonatal mice with a commercial PCB mixture (Aroclor 1254) or with low levels of diethylstilbestrol (DES) and measured effects of exposure on Wnt7a expression and uterine morphology. Neonatal PCB or low-level DES exposure resulted in the down-regulation of Wnt7a expression. These data reveal that weak estrogens such as PCBs act through a Wnt7a-dependent pathway and suggest that Wnt7a regulation is a sensitive biomarker for testing weak estrogenic candidate compounds.
Also see Science Selections, p. A368
Children's Health
FETAL DEVELOPMENT | Air Pollutants and Preterm Delivery
investigated the relationship between preterm delivery (PTD) and exposure to air pollutants in Incheon, Republic of Korea, using spatial and temporal modeling to better infer individual exposures. The results indicate a significant association between air pollution and PTD during the third trimester of pregnancy. The study showed that, during pregnancy, relatively low concentrations of air pollution under current air quality standards may contribute to an increased risk of PTD. The authors discuss a biologic mechanism involving increased prostaglandin levels that are triggered by inflammatory mediators during exposure periods.
RESPIRATORY DISEASE | Ozone and Infant Respiratory Symptoms
Recent studies indicate that the U.S. Environmental Protection Agency (EPA) ozone standards may not protect sensitive individuals. Triche et al. (p. 911) examined respiratory effects of O3 in infants who may be vulnerable, particularly if they are children of asthmatic mothers. Repeated measures logistic regression models were run separately for wheeze, difficulty breathing, and cough for 691 infants. Maximum 8-hr O3 and peak 1-hr O3 were associated with difficulty breathing, but not wheeze, in infants of asthmatic mothers; O3 was not associated with cough. At levels of O3 exposure near or below current U.S. EPA standards, infants are at increased risk of respiratory symptoms, particularly infants whose mothers have physician-diagnosed asthma.
EXPOSURE ASSESSMENT | Childhood Lead Exposure in the Middle East
In the Middle East, the major sources of lead exposure have been leaded gasoline, lead-contaminated flour from traditional stone mills, local exposures from small battery plants and smelters, and kohl (blue color) in cosmetics. Safi et al. (p. 917) measured blood lead levels (BLL) in children in Israel, Jordan, and the Palestinian Authority. High levels in Gaza were all among children living near a battery factory. The findings, taken together with data on time trends in lead emissions and in BLL in children in previous years, indicate the benefits from phasing out leaded gasoline but state the case for further reductions and investigation of hot spots.
Mini-Monograph
RISK CHARACTERIZATION | Farmworker Exposure to Pesticides
A major goal of studying farmworkers is to better understand how their work environment, including exposure to pesticides, affects their health. Although a number of health conditions have been associated with pesticide exposure, clear linkages have yet to be made between exposure and health effects, except in cases of acute pesticide exposure. The articles included in this mini-monograph (p. 923) discuss some of the important challenges in terms of environmental exposure assessment, biomonitoring, predictors of exposure, and health outcomes of exposure. There are also important issues associated with definition and size of the farmworker populations, problems in communication and access, and the organization of agricultural work.
