Environews
NIEHS NEWS | Centered on Breast Cancer
Researchers have long known of a link between early menarche and later development of breast cancer. Now investigators are considering early environmental exposures among young girls as possible triggers in the development of the disease later in life. This article (p. A132) describes study results presented at the third annual meeting of the NIEHS/National Cancer Institute–funded Breast Cancer and the Environment Centers, which are working to advance our knowledge of the basic biology of the mammary gland and its development as well as how environmental factors affect puberty in girls.
FOCUS | Secondhand Suspicions: Breast Cancer and Passive Smoking
Breast cancer is one of the leading causes of death in women, and finding causative links for its development is a top research priority. Studies have identified numerous mammary carcinogens in tobacco smoke, and some researchers believe that exposure to secondhand smoke could significantly raise a younger woman's risk of developing breast cancer. Other scientists say the current data, although suggestive, are insufficient to confirm such a link. This article (p. A136) discusses evidence presented on both sides of the debate.
SPHERES OF INFLUENCE | Environment: California Out in Front
Environmentalism has become a powerful force in California, where air pollution and the threat of water scarcity, among other problems, have spurred the creation of some of the strongest environmental laws ever passed. This article (p. A144) describes some of the proactive policies the Golden State has established to practice and encourage responsible environmental stewardship, and describes how these policies affect the rest of the nation.
INNOVATIONS | More Human, More Humane: A New Approach for Testing Airborne Toxicants
Much of today's human health research depends on data generated in animal models. Conventional tests of the toxicity of gases and vapors, in which laboratory animals are exposed to lethal or sublethal doses of chemicals, have been criticized as expensive, unethical, inhumane, time-consuming, and poorly predictive of effects that occur in people. Now a research team at the University of New South Wales in Australia is working on a more humane and possibly more accurate method of analysis. This article (p. A148) looks at the team's use of human cells grown on permeable membranes for more precise measurements of airborne chemical toxicity.
Commentaries
POPULATION HEALTH | Lead in Paint in South Africa
Surveys undertaken in South Africa have shown that a large proportion of children are exposed to lead from a variety of sources. Mathee et al. (p. 321) examined the role of lead-based paint in the blood lead distribution of South African children through a series of small-scale investigations. The authors recommend that the African public health community strengthen their efforts to prevent lead poisoning in African children through a holistic approach that includes the promulgation and enforcement of appropriate legislation, as well as research to identify further sources of exposure to lead.
RISK CHARACTERIZATION | Risks and Benefits of Seafood
Although fish and seafood provide important nutrients, they may also contain toxic contaminants such as methylmercury. Advisories against pollutants may therefore conflict with dietary recommendations. In resolving this conundrum, most epidemiologic studies provide little guidance because they address either nutrient benefits or mercury toxicity, not both. Budtz-Jørgensen et al. (p. 323) applied structural equation modeling to data from a prospective study of developmental methylmercury neurotoxicity in the Faroe Islands. The results suggest that adverse effects of methylmercury exposure from fish and seafood are likely to be underestimated by unadjusted results from observational studies, and the extent of this bias will be study dependent.
Review
EXPOSURE ASSESSMENT | Skin Exposure to Isocyanates
Isocyanates (di- and poly-), important chemicals used worldwide to produce polyurethane products, are a leading cause of occupational asthma. Respiratory exposures have been reduced through improved hygiene controls and the use of less-volatile isocyanates. However, isocyanate asthma continues to occur, often in settings with minimal inhalation exposure but opportunity for skin exposure. Bello et al. (p. 328) evaluated the potential role of skin exposure in the development of isocyanate asthma. Human isocyanate skin exposure appears to contribute to the development of isocyanate asthma in certain settings, presumably by inducing systemic sensitization.
Research
REPRODUCTIVE HEALTH | Serum Dioxin and Ovarian Function
Warner et al. (p. 336) examined the relationship between serum levels of2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and alterations in ovarian function and hormones in humans exposed to high levels of TCDD in Seveso, Italy, in 1976 (the Seveso Women's Health Study). The authors related TCDD levels measured in sera collected near the time of the explosion and ovarian function at follow-up. The study found no clear evidence that the 1976 TCDD exposure was associated with ovarian function 20 years later in women exposed to relatively high levels of TCDD.
GENE POLYMORPHISM | Urinary Arsenic Methylation, GSTs, and Skin Lesions
McCarty et al. (p. 341) investigated whether primary and secondary arsenic methylation ratios were associated with skin lesions and whether polymorphisms in the glutathione S-transferase (GST) genes GSTT1, GSTP1, and GSTM1 modify these relationships. A case–control study of 600 cases and 600 controls, frequency matched on age and sex, was conducted in Pabna, Bangladesh, in 2001–2002. Individual well water, urine, and blood samples were collected. The findings suggest that increasing primary methylation ratios are associated with an increase in risk of arsenic-related skin lesions. The interaction between GSTT1 wildtypeand secondary methylation ratio modifies the risk of skin lesions among arsenic-exposed individuals.
CARCINOGENESIS | Impact of Arsenicals on Selenoprotein Synthesis
Evidence suggests that an increase in oxidative stress in cells treated with arsenicals represents the molecular mechanism behind arsenic-induced carcinogenesis. Selenocysteine is necessary for the activity of enzymes with a role in defense against reactive oxygen species. To determine whether changes in selenoprotein synthesis may be an underlying mechanism behind arsenic-induced carcinogenesis, Ganyc et al. (p. 346) analyzed the new synthesis of selenoproteins within cells after exposure to inorganic or methylated arsenicals. The impact of the trivalent arsenicals arsenite and monomethylarsonous acid on selenoprotein synthesis may represent a potential molecular mechanism for the higher rates of cancer observed in populations exposed to high levels of arsenic.
RISK CHARACTERIZATION | Immunogenicity of Low Doses of LT-B
Transgenic maize that produces the nontoxic B subunit of the Escherichia coli heat-labile toxin (LT-B) in seed has proven to be an effective oral immunogen in mice. Currently, there is considerable concern over accidental consumption of this transgenic maize by humans and domestic animals. Beyer et al. (p. 354) determined the highest dose of LT-B orally administered to mice that does not result in a measurable immune response. The results demonstrate that LT-B derived from transgenic maize is immunogenic at nanogram levels when orally administered to mice.
REMEDIATION | Evaluation of Perchlorate PRG
Perchlorate is a common contaminant of drinking water and food. It competes with iodide for uptake into the thyroid, thus interfering with thyroid hormone production. The U.S. Environmental Protection Agency set a groundwater preliminary remediation goal (PRG) of 24.5 µg/L to prevent exposure to pregnant women that would affect the fetus. However, the PRG does not take into account additional exposure possible in nursing infants or the relative source contribution (RSC), a factor that allows for the possibility that not all exposure comes from water. Ginsberg et al. (p. 361) assessed whether the PRG protects infants from exposures from breast-feeding and evaluated the perchlorate RSC.
BIOMONITORS | Biomonitoring of 2,4-D
Alexander et al. (p. 370) estimated exposure and systemic dose of 2,4-dichlorophenoxyacetic acid (2,4-D) in farm family members following an application of 2,4-D on their farms. Farm families were recruited from licensed applicators in Minnesota and South Carolina. Exposure profiles were characterized with 24-hr urine 2,4-D concentrations, which then were related to potential predictors of exposure. Multivariate models identified glove use, repairing equipment, and number of acres treated as predictors of exposure in the applicators. The authors observed considerable heterogeneity of 2,4-D exposure among farm family members, which was primarily attributable to level of contact with the application process.
NANOTECHNOLOGY | Single-Wall Carbon Nanotubes and Cardiovascular Effects
Engineered nanosized materials, such as single-wall carbon nanotubes (SWCNTs), are becoming technologically important in different industries. The unique physical characteristics and the pulmonary toxicity of SWCNTs raise concerns that respiratory exposure to these materials may be associated with cardiovascular adverse effects. Li et al. (p. 377) evaluated aortic mitochondrial alterations using oxidative stress assays, including quantitative polymerase chain reaction of mitochondrial DNA and plaque formation by morphometric analysis in mice exposed to SWCNTs. The findings are of sufficient significance to warrant further studies to evaluate the systemic effects of SWCNTs under workplace or environmental exposure paradigms.
Also see Science Selections, p. A152
EXPOSURE ASSESSMENT | Variability in Indoor-Air Insecticide Levels
Residential insecticide use is widespread in the United States, but few data are available on the persistence and variability in levels in the indoor environment. Whyatt et al. (p. 383) assessed within- and between-home variability in indoor-air insecticides over the final 2 months of pregnancy among a cohort of African-American and Dominican women from New York City. Sixty-one percent of the women reported using pest control during the air samplings. Results showed that the insecticides were persistent in the home over the 2-month period, with little variability in air concentrations, and that the insecticides contributed to chronic maternal inhalation exposures during pregnancy.
ENDOCRINE SYSTEM | In Vitro and in Vivo Effects of DBP/MBP
Certain phthalates can impair Leydig cell distribution and steroidogenesis in the fetal rat in utero, but it is unknown whether similar effects might occur in the human. Hallmark et al. (p. 390) investigated the effects of di(n-butyl) phthalate (DBP) and its metabolite monobutyl phthalate (MBP) on testosterone production and Leydig cell aggregation (LCA) in fetal testis explants from rats and humans, and compared the results with in vivo findings for DBP-exposed rats. The findings suggest that MBP and DBP suppress steroidogenesis by fetal-type Leydig cells in primates as in rodents, Future in vivo studies in the fetal marmoset may offer the best direct approach to evaluating effects relevant to the human.
Also see Science Selections, p. A153
TOXICOLOGY | Inhalation Studies of 2- to 5-nm TiO2 Nanoparticles
Nanotechnology offers great promise in many industrial applications. However, little is known about the health effects of manufactured nanoparticles, the building blocks of nanomaterials. Titanium dioxide (TiO2) nanoparticles with a primary size of 2–5 nm represent some of the smallest manufactured nanoparticles. Grassian et al. (p. 397) assess the toxicity of these nanoparticles using a murine model of lung inflammation and injury. Mice subacutely exposed to 2- to 5-nm TiO2 nanoparticles showed a significant but moderate inflammatory response among animals at 0, 1, or 2 weeks after exposure, but this response resolved by 3 weeks after exposure.
CARDIOVASCULAR DISEASE | Nanoparticle-Induced Inflammation in Endothelium
The mechanisms governing the correlation between exposure to ultrafine particles and the increased incidence of cardiovascular disease remain unknown. Ultrafine particles appear to cross the pulmonary epithelial barrier into the bloodstream, raising the possibility of direct contact with the vascular endothelium; endothelial inflammation is critical for the development of cardiovascular pathology. To test their hypothesis that direct exposure of human aortic endothelial cells (HAECs) to ultrafine particles induces an inflammatory response and that this response depends on particle composition, Gojova et al. (p. 403) exposed HAECS to nanoparticles and measured mRNA and protein levels of three inflammatory markers. The results demonstrate that inflammation in HAECs following acute exposure to metal oxide nanoparticles depends on particle composition.
RISK CHARACTERIZATION | Estimating Risk from Ambient Acrolein
Estimated ambient concentrations of acrolein, a hazardous air pollutant, are greater than the U.S. Environmental Protection Agency (EPA) reference concentration, making it a concern for human health. However, there is no method for assessing the extent of risk under the U.S. EPA noncancer risk assessment framework. Woodruff et al. (p. 410) estimated excess risks from ambient concentrations of acrolein based on dose–response modeling of a study in rats with a relationship between acrolein and the residual volume/total lung capacity ratio and specific compliance markers for altered lung function. Their analysis demonstrates a method for estimating health risks for noncancer effects and suggests that acrolein could be associated with decreased respiratory function in the United States.
RISK CHARACTERIZATION | Cellular-Telephone Base-Antenna Health Effects
Radiofrequency (RF) waves have long been used for different types of information exchange via the airwaves. Increasingly larger numbers of people rely on mobile telephone technology; health concerns about the associated RF exposure have been raised, particularly since the mobile phone handset operates in close proximity to the human body and also because large numbers of base station antennas are required to provide widespread availability of service to large populations. Valberg et al. (p. 416) state thatcurrent scientific data are consistent with the conclusion that public exposures to permissible RF levels from mobile telephony and base stations are not likely to adversely affect human health.
Environmental Medicine
RESPIRATORY DISEASE | Chemically Induced Airway Symptoms
In asthma and allergy clinics, to see patients often present with upper and lower airway symptoms that are induced by chemicals and scents and not explained by allergic or asthmatic reactions. These patients often have increased cough sensitivity to inhaled capsaicin; this sensitivity is known to reflect the airway sensory reactivity. Ternesten-Hasséus et al. (p. 425) evaluated the duration of symptoms and measure health-related quality of life (HRQL) in patients with chemically induced airway symptoms. Upper and lower airway symptoms induced by chemicals and scents represent an entity of chronic diseases with persistent symptoms, a reduced HRQL, and unchanged sensory hyperreactivity.
Children's Health
RESPIRATORY DISEASE | Particle and Metal Effects on Lungs
The contribution of the metal components of particulate pollutants to acute respiratory effects has not been adequately evaluated. Also, little is known about the effects of genetic polymorphisms of xenobiotic metabolism on pulmonary function. In a study of 43 schoolchildren, Hong et al. (p. 430) assessed lung function decrement associated with metal components in particulate pollutants and determined genetic polymorphisms of glutathione S-transferase (GST) M1 and T1. The results demonstrated that particulate pollutants and metals such as manganese and lead in the particles are associated with a decrement of peak expiratory flow rate. These effects were robust even with consideration of genetic polymorphisms of GSTM1 and GSTT1.
Also see Science Selections, p. A153
NEURODEVELOPMENT | Psychomotor Effects of Prenatal p,p´-DDE Exposure
Evidence suggests that p,p´-dichlorodiphenyldichloroethene (DDE), the principal metabolite of dichlorodiphenyltrichloroethane (DDT), affects neurodevelopment in infants. Torres-Sánchez et al. (p. 435) assessed the prenatal DDE exposure window and its effect on the psychomotor development index and the mental development index during the first year of life. The first trimester of pregnancy appeared to be a critical window of in utero exposure to DDE, and psychomotor development is a target of this compound. Residues of DDT metabolites may present a risk of developmental delay for years after termination of DDT use.
Also see Science Selections, p. A152
NEUROBEHAVIORAL DISEASE | Amalgam and Neuropsychological Function
To determine whether children's exposure to mercury vapor from dental amalgams produces neurotoxicity, Bellinger et al. (p. 440) compared the neuropsychological function of children, without prior exposure to dental amalgam, whose caries were repaired using either dental amalgam or mercury-free composite materials. Although the mean urinary mercury concentration was greater among children in the amalgam group than in the composite group, few significant differences were found between the test scores of children in the two groups. The differences found were inconsistent in direction. Analyses using two cumulative exposure indices, surface years of amalgam and urinary mercury concentration, produced similar results.
NEURODEVELOPMENT | HCB and Children's Behavior
Hexachlorobenzene (HCB) is an organochlorine chemical that has been used in agriculture and industrial processes. Although behavioral impairment after HCB exposure has been described in animal models, little information is available in humans. Ribas-Fitó et al. (p. 447) studied the association of prenatal exposure to HCB with the social behavior of preschool-age children in two birth cohorts in Ribera d'Ebre and Menorca, Spain. Prenatal exposure to current concentrations of HCB in Spain is associated with a decrease in the behavioral competence of preschoolers-age children. These results should be considered when evaluating the potential neurotoxicologic effects of HCB.
Mini-Monograph
ENVIRONMENTAL MEDICINE | Adult Lead Exposure
The Mini-Monograph (p. 451) summarizes recent thinking on lead biomarkers and their relevance to epidemiologic research, provides guidance to clinicians and public health professionals, and reviews two key lead-related outcomes, namely, cardiovascular disease and cognitive function. The current lead standards are woefully out of date, given the growing evidence of the health effects of lead at levels of exposure previously thought to be safe.