Showing papers in "Environmental Health Perspectives in 2007"

Half-life of serum elimination of perfluorooctanesulfonate,perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers.

Abstract: Perfluorooctanesulfonate [PFOS; CF3(CF2)7SO3−] and its acid salts were derived from perfluorooctanesulfonyl fluoride [POSF; CF3(CF2)7SO2F]. Major product applications were developed using POSF through formation of N-alkylsulfonamides that were used in surfactants, paper and packaging treatments, and surface protectants (e.g., carpet, upholstery, textiles). Depending on the specific functional derivitization or polymerization, these POSF-based products may have degraded or metabolized, to an undetermined degree, to PFOS, a stable and persistent end product that has a widespread presence in the general population (Butenhoff et al. 2006) and wildlife (Houde et al. 2006). Salts of perfluorooctanoic acid, in particular ammonium perfluorooctanoate (APFO), have been used as surfactants and processing aids in the production of fluoropolymers and fluoro-elastomers. Industrial production of the salts of perfluorooctanoic acid occur through electrochemical fluorination and telomerization. Perfluorooctanoate [PFOA; CF3(CF2)6COO−], the dissociated carboxylate anion, has been measured in humans worldwide but generally at lower nanogram per milliliter concentrations than PFOS (Houde et al. 2006). In rats, PFOS and PFOA are not metabolized and enter into the enterohepatic circulation (Johnson et al. 1984; Kemper 2003; Kuslikis et al. 1992; Vanden Heuvel et al. 1991). Because of the stability of the carbon–fluorine bond and the high electronegativity of perfluorinated alkyl acids, metabolism would not be favored; thus, perfluorohexanesulfonate (PFHS) is also not expected to be metabolized. Based on the determination of volumes of distribution from single-dose intravenous studies in cynomolgus monkeys, the distributions of PFOS, PFHS, and PFOA are primarily extracellular (Butenhoff et al. 2004; Noker and Gorman 2003a, 2003b). Kerstner-Wood et al. (2003) found PFOS, PFHS, and PFOA to be highly bound in rat, monkey, and human plasma over a concentration range of 1–500 μg/mL. When incubated with human plasma protein fractions, all three compounds were highly bound (99.7 to > 99.9%) to albumin, and showed affinity for β-lipoproteins (95.6, 64.1, and 39.6% for PFOS, PFHS, and PFOA, respectively). Some binding to α - and γ -globulin fractions and minor interactions with transferrin (PFHS and PFOA) were also noted. PFOS and PFOA have been shown to compete for fatty acid binding sites on liver fatty acid binding protein, with PFOS giving the stronger response (Luebker et al. 2002). The elimination rates of PFOS and PFHS have been studied in male and female cynomolgus monkeys after intravenous dosing (Noker and Gorman 2003a, 2003b) and for PFOS after repeated oral dosing (Seacat et al. 2002). Noker and Gorman (2003a, 2003b) reported mean (± SD) terminal elimination half-lives, ranging from 88 to 146 days (132 ± 13 days for males and 110 ± 26 days for females) for PFOS and 49 to 200 days (141 ± 52 days for males and 87 ± 47 days for females) for PFHS, after intravenous dosing of three male and three female cynomolgus monkeys in separate experiments, with no significant difference between males and females or between the two compounds. Seacat et al. (2002) reported an approximate terminal elimination half-life of 200 days for PFOS in male and female cynomolgus monkeys during 1 year immediately following 6 months of daily oral dosing with either 0.15 or 0.75 mg/kg PFOS. Elimination rates in species other than the monkey have been determined for PFOS and PFOA. Within 89 days after a single intravenous dose of 14C-PFOS, 30% of the 14C was excreted in the urine and 12% in the feces of male rats (Johnson et al. 1979). For PFOA, significant interspecies differences have been observed (Hundley et al. 2006; Kudo and Kawashima 2003), and differential expression of organic anion transporters in renal proximal tubule cells have been suggested as an explanation for sex differences in the rat (Kudo et al. 2002) and low elimination rates in humans (Andersen et al. 2006). The purpose of the present study was to estimate the serum elimination half-life of PFOS, PFHS, and PFOA in humans through the long-term follow-up of retired fluoro-chemical production workers. Although these retirees were no longer occupationally exposed, their serum concentrations were expected to be considerably higher than those of the general population.

Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003-2004

Abstract: Of the more than 2,000 high-production volume chemicals that are manufactured in or imported into the United States in amounts of one million pounds or more per year (U.S. Environmental Protection Agency 2004), many are widely used in consumer products. Among these chemicals are bisphenol A [BPA; 2,2-bis(4-hydroxyphenyl)propane; CAS no. 80-05-7] and 4-tertiary-octylphenol [tOP; 4-(1,1,3,3-tetramethylbutyl)phenol; CAS no. 140-66-9]. BPA is used in the manufacture of polycarbonate plastic and epoxy resins, which can be used in impact-resistant safety equipment and baby bottles, as protective coatings inside metal food containers, and as composites and sealants in dentistry [Center for the Evaluation of Risks to Human Reproduction (CERHR) 2007; European Union 2003]. Exposure to BPA is thought to result primarily from ingestion of food containing BPA (Kang et al. 2006; Vandenberg et al. 2007). tOP is both a degradation product of and an intermediate in the manufacture of octylphenol ethoxylates, which are nonionic surfactants used in detergents, pesticide formulations, and other applications (Ying et al. 2002). Exposure to tOP may occur from contact with personal care products, detergents, water, and food containing tOP. Exposures to tOP can result in developmental and reproductive alterations in aquatic species (Segner et al. 2003) and in laboratory animals (Aydogan and Barlas 2006; Bian et al. 2006; Blake et al. 2004; Nagao et al. 2001; Willoughby et al. 2005). At high doses, BPA demonstrates estrogen-like effects on uterine and prostate organ weights in experimental animals. At doses below the putative lowest observed adverse effect level, exposure to BPA has reportedly resulted in decreased sperm production, increased prostate gland volume, altered development and tissue organization of the mammary gland, altered vaginal morphology and estrous cycles, disruption of sexual differentiation in the brain, and accelerated growth and puberty (Durando et al. 2007; Howdeshell et al. 1999; Kubo et al. 2003; Richter et al. 2007; Rubin et al. 2006; Schonfelder et al. 2002; Timms et al. 2005; vom Saal et al. 1998). At present, the interpretation of the evidence related to the low-dose effects of BPA is a subject of scientific debate (European Union 2003; Goodman et al. 2006; Gray et al. 2004; National Toxicology Program 2001; vom Saal and Hughes 2005). BPA and tOP are of concern to environmental public health because of the high potential for exposure of humans to these phenols and their demonstrated animal toxicity. Information about the concentrations of these compounds in the general population is important for understanding human exposure to BPA and tOP. The National Health and Nutrition Examination Survey (NHANES), conducted continuously since 1999 by the National Center for Health Statistics of the Centers for Disease Control and Prevention (CDC), is designed to measure the health and nutritional status of the civilian noninstitutionalized U.S. population ≥ 2 months of age (CDC 2003). The surveys include household interviews; collection of medical histories; standardized physical examinations; and collection of biologic specimens (e.g., blood and urine from participants ≥ 1 and ≥ 6 years of age, respectively) for clinical chemistry testing, nutritional indicators assessments, and assessment of exposure to environmental chemicals (CDC 2005, 2006). Previously, we analyzed 394 urine samples collected from adult participants of NHANES III, conducted during 1988–1994, to estimate urinary concentrations of total BPA (free plus conjugated species) in selected demographic groups (Calafat et al. 2005). We now report the first estimate of urinary concentrations of total BPA and tOP in NHANES 2003–2004 participants, a representative sample of the noninstitutionalized U.S. population ≥ 6 years of age.

Polyfluoroalkyl chemicals in the U.S. population: data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004 and comparisons with NHANES 1999-2000.

Abstract: BackgroundPolyfluoroalkyl chemicals (PFCs) have been used since the 1950s in numerous commercial applications. Exposure of the general U.S. population to PFCs is widespread. Since 2002, the manufac...

Lead exposure and cardiovascular disease--a systematic review.

Abstract: ObjectiveThis systematic review evaluates the evidence on the association between lead exposure and cardiovascular end points in human populations.MethodsWe reviewed all observational studies from ...

Household air pollution from coal and biomass fuels in China: measurements, health impacts, and interventions.

Abstract: Although some areas of China are becoming more urban, more than 60% of the population is still rural, most of which still uses biomass (mainly wood and crop residues) and coal fuels that produce substantial pollution in simple stoves. In 2003 approximately 80% of the energy consumed by rural households was in the form of biomass and almost 10% as coal. Furthermore, although most Chinese cities have plans to eliminate coal for households, many urban communities continue to rely on coal. The combustion of biomass and coal (collectively called “solid fuels”) is the dominant source of indoor air pollution (IAP) in the country and contributes significantly to the total burden of ill health. In the most recent global analysis of the health effects of major risk factors, the World Health Organization (WHO) estimated that solid fuels used in Chinese households cause approximately 420,000 premature deaths annually; this is 40% more than the approximately 300,000 premature deaths attributed to outdoor air pollution in Chinese cities with populations of more than 100,000 (Cohen et al. 2004; Smith et al. 2004). Household use of solid fuels is thus estimated to be the largest single environmental risk factor and ranks sixth among all risk factors examined for ill-health (Figure 1; Smith et al. 2005). These risk estimates, however, were based primarily on studies in other countries because, as discussed in this review, few epidemiologic studies have been conducted in China on biomass smoke compared with those conducted on coal smoke. Figure 1 Rough estimates of the burden of disease in China: the top 10 risk factors plus other selected risk factors [adapted from Smith et al. (2005)]. Note: Indoor smoke from solid fuels does not include smoke from other fuels or tobacco. Burden of disease is ... In the 1980s China conducted more IAP measurements focused on household combustion than all other developing countries combined. Indeed, by the early 1990s, the results of more than 100 published studies were combined into a WHO database (Sinton et al. 1996). In contrast, the Chinese environmental health community conducted few IAP measurements in the 1990s (Saksena et al. 2003), but epidemiologic studies of coal smoke, mainly on cancer end points, continued and have resulted in a large body of evidence. In particular, over 25 years a wide-ranging set of studies has been conducted on coal smoke exposures, toxicology, and health effects in one rural area—Xuanwei in Yunnan Province—with severe impacts. In this review we address the following questions in order to put Chinese household IAP from solid fuel use into perspective, nationally and internationally, and highlight research gaps: a) What toxic constituents have been found in the emissions of solid fuel combustion? b) What are the reported human exposure characteristics? c) What health effects have been documented? and d) What technologies exist or are possible for reducing this IAP exposure?

Concentrations of Urinary Phthalate Metabolites Are Associated with Increased Waist Circumference and Insulin Resistance in Adult U.S. Males

Abstract: BackgroundPhthalates impair rodent testicular function and have been associated with anti-androgenic effects in humans, including decreased testosterone levels. Low testosterone in adult human male...

Organophosphate Pesticide Exposure and Neurodevelopment in Young Mexican-American Children

Abstract: BackgroundOrganophosphate (OP) pesticides are widely used in agriculture and homes. Animal studies suggest that even moderate doses are neurodevelopmental toxicants, but there are few studies in hu...

Perfluorinated chemicals and fetal growth: a study within the Danish National Birth Cohort.

Abstract: Background Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are man-made, persistent organic pollutants widely spread throughout the environment and human populations. They have been found to interfere with fetal growth in some animal models, but whether a similar effect is seen in humans is uncertain.

Cord serum concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in relation to weight and size at birth.

Abstract: Polyfluoroalkyl compounds (PFCs) comprise a class of man-made, fluorinated organic compounds that have been used in a variety of consumer and industrial applications. Although these have been produced for many years, only recently have reports surfaced suggesting widespread exposure in wildlife and humans (Butenhoff et al. 2006; Calafat et al. 2007; Giesy and Kannan 2001; Houde et al. 2006; Kannan et al. 2004). Two of the most widely detected and studied compounds in this class are perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). PFOS and related compounds (polyfluorinated sulfonamides) are surfactants used in applications ranging from oil and water repellents for fabrics, apparel, carpets, and paper coatings to specialty chemical applications such as insecticides and fire fighting foams (3M Company 1999). PFOA and its salts are used as chemical intermediates and processing aids in the production of fluoropolymers and fluoroelastomers. Both PFOS and PFOA have shown the potential for developmental toxicity in animal studies. PFOS has been shown, in rats and mice, to induce developmental and reproductive effects, such as reduced birth weight, decreased gestational length, structural defects, developmental delays, and increased neonatal mortality (Fuentes et al. 2006; Grasty et al. 2003; Lau et al. 2003; Luebker et al. 2005a, 2005b; Thibodeaux et al. 2003). Recent studies have also reported developmental toxicity from PFOA in rodents, including pregnancy loss, reduced fetal weight, reduced postnatal survival, and delays in postnatal growth and development in offspring (Butenhoff et al. 2004; Lau et al. 2004, 2006). However, such studies of PFOS and PFOA have been conducted using doses that produce serum concentrations much higher than general population human exposures. There are limited epidemiologic data on the potential impacts of PFC exposure on fetal growth and development. However, one recent occupational study found no association between employment in jobs with high exposure to PFOS before the end of pregnancy and maternally reported birth weight (Grice et al. 2007). PFOS and PFOA have also been shown to cause reductions in serum cholesterol and/or triglycerides in several animal species (Haughom and Spydevold 1992; Seacat et al. 2002, 2003; Thibodeaux et al. 2003). Conversely, a few cross-sectional occupational studies conducted among fluorochemical production employees have reported positive relationships between PFOS and/or PFOA concentrations and serum lipid levels (Gilliland and Mandel 1996; Olsen et al. 1999, 2003). The fetus is likely to be sensitive to the availability of cholesterol and triglycerides, which support cellular growth, differentiation, and adipose accumulation (Woollett 2001). Disruptions to normal fetal growth and development have been associated with effects across the lifespan, including adverse neonatal and childhood outcomes (Hofman et al. 1997; Kramer et al. 1990) and metabolic diseases in adulthood (Barker 2006). In a previous report, we documented factors associated with cord serum concentrations of PFOS and PFOA in a population of newborn deliveries known as the Baltimore THREE study (Apelberg et al. 2007). In this study, we examined the relationship between these concentrations and gestational age, birth weight, and measures of birth size, including head circumference, length, and ponderal index (a measure of body mass at birth).

Ten years of mixing cocktails: a review of combination effects of endocrine-disrupting chemicals.

Abstract: In the last 10 years, good evidence has become available to show that the combined effects of endocrine disruptors (EDs) belonging to the same category (eg, estrogenic, antiandrogenic, or thyroid-disrupting agents) can be predicted by using dose addition This is true for a variety of end points representing a wide range of organizational levels and biological complexity Combinations of EDs are able to produce significant effect, even when each chemical is present at low doses that individually do not induce observable effects However, comparatively little is known about mixtures composed of chemicals from different classes of EDs Nevertheless, I argue that the accumulated evidence seriously undermines continuation with the customary chemical-by-chemical approach to risk assessment for EDs Instead, we should seriously consider group-wise regulation of classes of EDs Great care should be taken to define such classes by using suitable similarity criteria Criteria should focus on common effects, rather than common mechanisms In this review I also highlight research needs and identify the lack of information about exposure scenarios as a knowledge gap that seriously hampers progress with ED risk assessment Future research should focus on investigating the effects of combinations of EDs from different categories, with considerable emphasis on elucidating mechanisms This strategy may lead to better-defined criteria for grouping EDs for regulatory purposes Also, steps should be taken to develop dedicated mixtures exposure assessment for EDs

Spatial and Temporal Variation in PM2.5 Chemical Composition in the United States for Health Effects Studies

Abstract: BackgroundAlthough numerous studies have demonstrated links between particulate matter (PM) and adverse health effects, the chemical components of the PM mixture that cause injury are unknown.Objec...

Elevated Blood Lead Levels of Children in Guiyu, an Electronic Waste Recycling Town in China

Abstract: BackgroundElectronic waste (e-waste) recycling has remained primitive in Guiyu, China, and thus may contribute to the elevation of blood lead levels (BLLs) in children living in the local environme...

Urinary Concentrations of Triclosan in the U.S. Population: 2003–2004

Abstract: Background Triclosan is a synthetic chemical with broad antimicrobial activity that has been used extensively in consumer products, including personal care products, textiles, and plastic kitchenware.

Risk Factors for Acute Leukemia in Children: A Review

Abstract: Although overall incidence is rare, leukemia is the most common type of childhood cancer. It accounts for 30% of all cancers diagnosed in children younger than 15 years. Within this population, acute lymphocytic leukemia (ALL) occurs approximately five times more frequently than acute myelogenous leukemia (AML) and accounts for approximately 78% of all childhood leukemia diagnoses. Epidemiologic studies of acute leukemias in children have examined possible risk factors, including genetic, infectious, and environmental, in an attempt to determine etiology. Only one environmental risk factor (ionizing radiation) has been significantly linked to ALL or AML. Most environmental risk factors have been found to be weakly and inconsistently associated with either form of acute childhood leukemia. Our review focuses on the demographics of childhood leukemia and the risk factors that have been associated with the development of childhood ALL or AML. The environmental risk factors discussed include ionizing radiation, non-ionizing radiation, hydrocarbons, pesticides, alcohol use, cigarette smoking, and illicit drug use. Knowledge of these particular risk factors can be used to support measures to reduce potentially harmful exposures and decrease the risk of disease. We also review genetic and infectious risk factors and other variables, including maternal reproductive history and birth characteristics.

Endocrine-disrupting potential of bisphenol A, bisphenol A dimethacrylate, 4-n-nonylphenol, and 4-n-octylphenol in vitro: new data and a brief review.

Abstract: BackgroundAn array of environmental compounds is known to possess endocrine disruption (ED) potentials. Bisphenol A (BPA) and bisphenol A dimethacrylate (BPA-DM) are monomers used to a high extent ...

DDT and Breast Cancer in Young Women: New Data on the Significance of Age at Exposure

Abstract: Background Previous studies of DDT and breast cancer assessed exposure later in life when the breast may not have been vulnerable, after most DDT had been eliminated, and after DDT had been banned.

Blood Lead Concentrations < 10 μg/dL and Child Intelligence at 6 Years of Age

Abstract: Cohort studies of children during the 1980s in North America, Europe, and Australia documented that blood lead concentrations of at least 10 μg/dL are inversely associated with cognitive test scores in children (Needleman and Gatsonis 1990; Pocock et al. 1994; Schwartz 1994). These findings led to the 1991 revision of the Centers for Disease Control and Prevention’s (CDC) definition of an elevated blood lead concentration, which was lowered from 25 to 10 μg/dL (CDC 1991). Accumulating evidence since 1991 suggests that children’s intellectual ability is adversely affected at blood lead concentrations < 10 μg/dL (Bellinger and Needleman 2003; Canfield et al. 2003a, 2004; Chiodo et al. 2004; Lanphear et al. 2000, 2005; Schnaas et al. 2006; Schwartz 1994; Surkan et al. 2007; Tellez-Rojo et al. 2006). To examine some of this evidence in detail, a working group (Weitzman et al. 2004) was convened by the CDC, and the fifth revision of the CDC’s Preventing Lead Poisoning in Young Children was issued in 2005 (CDC 2005b). The working group concluded that the “overall weight of evidence supports an inverse association between blood lead levels < 10 μg/dL and the cognitive function of children,” with the caveat that the available data were limited by the small number of “directly relevant cohort studies”—studies that include multiple measures of lead exposure throughout early life and key covariate information to reduce the potential for residual confounding (CDC 2005b). Despite the conclusions reached by the working group, the CDC definition of an elevated blood lead level was not lowered at that time (CDC 2005b). This report, based on a prospective study that includes eight measures of children’s blood lead concentrations from 6 months to 6 years of age and that includes measures of key potential confounders in the lead–IQ relation, meets the criteria for a study that is directly relevant to assess questions of possible cognitive effects of lead exposure at blood lead concentrations < 10 μg/dL.

Nanosize titanium dioxide stimulates reactive oxygen species in brain microglia and damages neurons in vitro.

Abstract: BackgroundTitanium dioxide is a widely used nanomaterial whose photo-reactivity suggests that it could damage biological targets (e.g., brain) through oxidative stress (OS).ObjectivesBrain cultures...

Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley.

Abstract: “Autism” refers to a set of neurodevelopmental disorders that are characterized by impaired social interaction, restricted communication, and repetitive, stereotypic behaviors. The number of children reported as having autism spectrum disorders (ASD) has risen dramatically since the early 1990s. In the United States, some of this increase is attributable to changes in diagnosis and reporting, although this pattern is not uniform across all states (Shattuck 2005). Symptoms of classic autism do not typically become evident until early childhood, but current evidence is consistent with a pathogenic process originating during fetal development (Arndt et al. 2005; Hertz-Picciotto et al. 2006; Kemper and Bauman 1998; Nelson et al. 2001). Many of the hypotheses regarding ASD pathogenesis involve a functional deficit caused by alterations to specific brain structures occurring in utero during defined temporal windows of vulnerability (Polleux and Lauder 2004). The lesions in question might result from genetic factors, environmental insults, or a combination of the two. A variety of lesions could give rise to a “final common pathway” to autism; ASD as currently defined may well include multiple disorders that have not yet been successfully differentiated. A large number of widely used agricultural pesticides have known neurologic effects (Weiss et al. 2004), raising the possibility that gestational exposure to these compounds could play an etiologic role in ASD and related neurodevelopmental disorders. Most compounds are prone to “drift,” and detectable levels in air samples are often measurable at locations beyond the site of application for extended periods afterwards (Kegley et al. 2003; Lee et al. 2002). Elevated levels of agricultural pesticides in household dust and their metabolites in urine have been associated with residential proximity to treated fields (Loewenherz et al. 1997; Lu et al. 2000; Simcox et al. 1995). Studies of pediatric diseases and their associations with residential proximity or parental occupational exposure to pesticides have been accumulating, most notably for cancer (Birnbaum and Fenton 2002; Daniels et al. 1997; Feychting et al. 2001; Flower et al. 2004; Linet et al. 2003; Meinert et al. 2000; Olshan et al. 2000; Reynolds et al. 2002; Robison et al. 1995; Shannon 1998; Zahm and Devesa 1995) and, more recently, neurodevelopmental delay (Grandjean et al. 2005). Many environmental toxicants are conveyed transplacentally, and the blood–brain barrier remains relatively permeable to many of these compounds until well into the first year of life (Andersen et al. 2000). In general, experimental and epidemiologic evidence regarding pesticides and pediatric neurodevelopment is strikingly lacking, despite considerable knowledge about pesticide toxicity (particularly neurotoxicity) (Kamel and Hoppin 2004; Weiss et al. 2004). We evaluated a series of hypotheses regarding an association between in utero residential “exposure” to specific agricultural pesticides (that is, maternal residence in close proximity to sites of application) and the development of ASD by linking existing databases using a retrospective case–control design. This study was conducted as part of a demonstration project of the utility of environmental public health tracking, an initiative funded by the Centers for Disease Control and Prevention (McGeehin et al. 2004) to generate clues for further etiologic study.

Hypertension and exposure to noise near airports: the HYENA study.

Abstract: BackgroundAn increasing number of people are exposed to aircraft and road traffic noise. Hypertension is an important risk factor for cardiovascular disease, and even a small contribution in risk f...

Direct Evidence Revealing Structural Elements Essential for the High Binding Ability of Bisphenol A to Human Estrogen-Related Receptor-γ

Abstract: Background Various lines of evidence have shown that bisphenol A [BPA; HO-C6H4-C(CH3)2-C6H4-OH] acts as an endocrine disruptor when present in very low doses We have recently demonstrated that BPA binds strongly to human estrogen-related receptor-γ (ERR-γ ) in a binding assay using [3H]4-hydroxytamoxifen ([3H]4-OHT) We also demonstrated that BPA inhibits the deactivation activity of 4-OHT

Ambient Air Pollution and Low Birth Weight in Connecticut and Massachusetts

Abstract: Low birth weight is an important predictor of children’s health and is associated with higher risk of infant and childhood mortality (McCormick 1985), coronary heart disease (Vos et al. 2006), and other health problems (Ashdown-Lambert 2005). For example, in a cohort of 10,803 singleton births, Lawlor et al. (2005a) found an inverse relationship between birth weight and coronary heart disease and stroke. Identified risk factors for low birth weight include mother’s age (Khoshnood et al. 2005), prenatal care (Shi et al. 2004), maternal smoking and educational status (Kleinman and Madans 1985), race (Alexander et al. 2003), and socioeconomic factors (Valero de Bernabe et al. 2004). Several studies examined whether maternal exposure to air pollution adversely impacts birth outcomes, such as low birth weight, preterm delivery, intrauterine growth restriction, and postneonatal infant mortality (Glinianaia et al. 2004; Maisonet et al. 2004; Sram et al. 2005; Woodruff et al. 2006). Results regarding the relationship between air pollution and birth weight are inconclusive, with some studies identifying associations where others did not, and the suite of adverse pollutants and exposure periods differing by study. For instance, higher levels of carbon monoxide were associated with low birth weight in southern California; six Northeastern U.S. cities; Sao Paulo, Brazil; Sydney, Australia; and Seoul, South Korea (Gouveia et al. 2004; Ha et al. 2001; Maisonet et al. 2001; Mannes et al. 2005; Ritz et al. 2000; Salam et al. 2005; Wilhelm and Ritz 2003, 2005). However no association was identified in studies based in the Czech Republic, Taiwan, Nevada, and California (Bobak 2000; Chen et al. 2002; Lin et al. 2004; Parker et al. 2005). Particulate matter (PM) with an aerodynamic diameter < 10 μm (PM10) was linked with low birth weight in Sao Paulo, Southern California, Taiwan, the Czech republic, and Seoul (Dejmek et al. 1999; Gouveia et al. 2004; Ha et al. 2001; Wilhelm and Ritz 2005; Yang et al. 2003), with no such evidence provided by other work in Taiwan and six U.S. cities (Lin et al. 2004; Maisonet et al. 2001) and limited evidence in Nova Scotia, Canada (Dugandzic et al. 2006). Three recent reviews summarized scientific evidence regarding the association between air pollution and birth weight. One review concluded that the effects of air pollution on low birth weight are not fully apparent and that current scientific knowledge is limited (Maisonet et al. 2004). Another determined that PM has either a small effect on fetal growth or no effect, and recommended further research (Glinianaia et al. 2004). The most recent review concluded that existing literature supports a causal link between air pollution and birth weight, although additional research is needed to confirm the effect, investigate the exposure window of importance, and distinguish which pollutants cause harm (Sram et al. 2005). The seemingly conflicting evidence may result from inadequate control for confounders, variation in populations and pollution characteristics, or differences in study design such as modeling structure, exposure time frame, and sample size. Residential mobility may differ by study population, resulting in varying levels of exposure misclassification. Effect estimates for PM and mortality and hospital admissions show spatial and temporal heterogeneity, which may be related to dissimilar chemical composition. In particular, the risk of cardiovascular admissions for the elderly from PM with an aerodynamic diameter < 2.5 μm (PM2.5) is higher in the eastern United States, including the Northeast region (Dominici et al. 2006), and mortality effects of PM10 are strongest in the northeastern United States (Peng et al. 2005). Variation in PM composition may partially explain differing results from studies of PM and low birth weight. Many study areas for air pollution and birth weight research are outside the United States, such as those areas listed above as well as Lithuania (Maroziene and Grazuleviciene 2002), Zimbabwe (Mishra et al. 2004), Canada (Liu et al. 2003), Croatia (Mohorovic 2004), Poland (Jedrychowski et al. 2004), and China (Wang et al. 1997). Of the U.S.-based studies, most focused on Southern California (Basu et al. 2004; Parker et al. 2005; Ritz and Yu 1999; Salam et al. 2005; Wilhelm and Ritz 2003, 2005). Only one study investigated the northeastern United States, using births from six cities over a 3-year period, and found adverse effects of CO and sulfur dioxide, but not PM10 (Maisonet et al. 2001). To the best of our knowledge, no previous study explored the impacts of nitrogen dioxide or fine PM (PM2.5) on birth weight in the northeastern United States. In this research we investigated the effects of air pollution on birth weight in Connecticut and Massachusetts over a 4-year period for SO2, NO2, CO, PM10, and PM2.5 and explored effects by gestational and trimester exposure and by race.

Reviewing the environmental and human health knowledge base of carbon nanotubes.

Abstract: Carbon nanotubes (CNTs) are considered one of the most promising materials in nanotechnology, with attractive properties for many technologic applications. The different synthesis, purification, and postprocessing methods produce CNTs with different physical characteristics, which can be applied in different fields ranging from composite materials, medical applications, and electronics to energy storage. The widespread projected use of CNTs makes it important to understand their potential harmful effects. In this environmental health review we observed a remarkable range of results of some of the toxicology studies. The comparability should be improved by further standardization and introduction of reference materials. However, at present the findings of this review suggest several key points: a) there are different types of CNTs, and therefore they cannot be considered a uniform group of substances; and b) in environmental compartments, CNTs can be bioavailable to organisms. The properties of CNTs suggest a possible accumulation along the food chain and high persistence. In organisms the absorption, distribution, metabolism, excretion, and toxicity of CNTs depend on the inherent physical and chemical characteristics such as CNT functionalization, coating, length, and agglomeration state that are influenced by the external environmental conditions during CNT production, use, and disposal stages. Characterized exposure scenarios could therefore be useful when conducting toxicologic studies. However, CNTs produce a toxic response upon reaching the lungs in sufficient quantity; this reaction is produced in a time-and dose-dependent manner. The identification of possible risks to human health and environment is a prerequisite for a successful introduction of CNTs in future applications.

Flame retardants in placenta and breast milk and cryptorchidism in newborn boys.

Abstract: Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants, and the general population is exposed through products such as upholstery, building materials, insulation, electronic equipment, and contaminated food. PBDEs are added to polymers without being chemically bound and can leach into the environment, where they settle with air particles and sludge. They are persistent, and some—BDE-47, BDE-99, and BDE-153—can accumulate in lipid-rich tissues (Agency for Toxic Substances and Disease Registry 2004; Sjodin et al. 2003). Concentrations of PBDE in human European breast milk samples are generally low compared with those in the United States, and considered to be well below the estimated lowest observed adverse effect level (LOAEL) of 1 mg/kg/day (Darnerud et al. 2001). Two technical mixtures, penta- and octa-mixtures of PBDEs, have been banned from use in Europe since 2003 (Darnerud et al. 2001), and Swedish studies indicated a decrease in breast milk levels since the middle of the 1990s (Meironyte et al.1999; Sjodin et al. 2003). However, annual production rates of some PBDEs are still considerable in some areas (Alaee et al. 2006; Betts 2002; Law et al. 2006). Animal studies show that some PBDEs exhibit endocrine-disrupting activity, which has been studied predominantly for thyroid hormone transport and metabolism (Legler and Brouwer 2003), but data on adverse effects on reproductive outcome after gestational exposure are also emerging (Lilienthal et al. 2006). The prevalence of cryptorchidism in newborn boys appears to have increased in some areas, such as Great Britain and Denmark, over the past decades, and its current prevalence is considerably higher in Denmark than in Finland (Anonymous 1986; Boisen et al. 2004). Although the reason for this is as yet unknown, the rapid increase in prevalence suggests that environmental factors are involved (Sharpe 2006; Skakkebaek et al. 2001). Adverse effects of fetal exposure to environmental chemicals on testicular descent and hormonal function may be detectable during the short physiologic activation of the pituitary–gonadal axis at approximately 3 months of age (Andersson et al. 1998; Main et al. 2000, 2006b; Suomi et al. 2006). In this study we aimed to evaluate the association between exposure to 14 PBDEs (BDEs 28, 47, 66, 71, 75, 77, 85, 99, 100,119, 138, 153, 154, 183) in newborn boys and the position and function of the testes.

Water arsenic exposure and intellectual function in 6-year-old children in Araihazar, Bangladesh

Abstract: We recently reported an adverse association between drinking water arsenic and cognitive function in 10-year-old children living in Bangladesh (Wasserman et al. 2004), where approximately 30–40 million people (British Geological Survey and Bangladesh Department of Public Health Engineering 2001) are chronically exposed to naturally elevated levels of arsenic in groundwater pumped from approximately half the total of approximately 10 million tube wells in the country. That finding supplements reports of neurologic sequelae of acute and chronic exposure in adults (Bolla-Wilson and Bleecker 1987; Morton and Caron 2003; Morton and Dunnette 1994; Pershagen et al. 1981; Schoolmeester and White 1980). Two other studies have examined children’s intellectual function, in a small sample of children from a Mexican lead smelter area (Calderon et al. 2001) and from Taiwanese children in regions with and without elevated As in well water (Tsai et al. 2003). Both reported negative associations with As exposure, although the domains of vulnerable intellectual function differed across investigations. In a related investigation (Wasserman et al. 2006), we recently observed poorer intellectual functioning, primarily in visual motor skills, in 10-year-olds from a region in Bangladesh where household well water concentrations were variable in manganese but extremely low in As. These findings were consistent with other investigations of motor function in children exposed to high levels of Mn (e.g., Takser et al. 2003). We sought to expand these findings on children’s intellectual function to a younger age group, drawing once again on children of adults participating in our prospective study of the health effects of As in Araihazar, Bangladesh. Wells in the study site, a 25-km2 region located approximately 30 km east of Dhaka, are characterized by a wide range of As concentrations in drinking water, with 75% exceeding the World Health Organization (WHO) As standard of 10 μg/L, and 53% exceeding the Bangladesh standard of 50 μg/L (van Geen et al. 2003a). We report here the results of a cross-sectional investigation of intellectual function in 301 6-year-old children.

Phthalate diesters and their metabolites in human breast milk, blood or serum, and urine as biomarkers of exposure in vulnerable populations.

Abstract: BACKGROUND: Phthalates may pose a risk for perinatal developmental effects. An important question relates to the choice of suitable biological matrices for assessing exposure during this period. OBJECTIVES: This study was designed to measure the concentrations of phthalate diesters or their metabolites in breast milk, blood or serum, and urine and to evaluate their suitability for assessing perinatal exposure to phthalates. METHODS: In 2001, 2-3 weeks after delivery, 42 Swedish primipara provided breast milk, blood, and urine samples at home. Special care was taken to minimize contamination with phthalates (e.g., use of a special breast milk pump, heat treatment of glassware and needles, addition of phosphoric acid). RESULTS: Phthalate diesters and metabolites in milk and blood or serum, if detected, were present at concentrations close to the limit of detection. By contrast, most phthalate metabolites were detectable in urine at concentrations comparable to those from the general population in the United States and in Germany. No correlations existed between urine concentrations and those found in milk or blood/serum for single phthalate metabolites. Our data are at odds with a previous study documenting frequent detection and comparatively high concentrations of phthalate metabolites in Finnish and Danish mothers' milk. CONCLUSIONS: Concentrations of phthalate metabolites in urine are more informative than those in milk or serum. Furthermore, collection of milk or blood may be associated with discomfort and potential technical problems such as contamination (unless oxidative metabolites are measured). Although urine is a suitable matrix for health-related phthalate monitoring, urinary concentrations in nursing mothers cannot be used to estimate exposure to phthalates through milk ingestion by breast-fed infants.

Arsenic and fluoride exposure in drinking water: children's IQ and growth in Shanyin county, Shanxi province, China.

Abstract: Exposure to arsenic (As) in drinking water has been associated with a decline in intellectual function in children. This association has been established recently on the basis of a cross-sectional study of 201 ten-year-old children in Bangladesh (Wasserman et al. 2004). The authors point out the absence of research on the effects of As on children’s intellectual function. They attribute the lack of data to poorly described dosimetry in reported studies on the neurologic consequences of acute and chronic exposures in adults. Only two other studies, one in Mexico (Calderon et al. 2001) and the other in Taiwan (Tsai et al. 2003), have established tentative adverse associations between As exposure and children’s intellectual function although both studies evaluated only a small number of subjects (n < 100). Significant impairments of height, body weight, brain, and intelligence were reported in children poisoned by milk powder containing As in Japan when compared with that of the control group of the same age 16 years after the poisoning event (Wang 1997). In the 1980s in China, it became known that arsenicosis was occurring in individuals drinking groundwater containing As (Wang and Huang 1994). Shanxi province, where our study was conducted, has been recognized as an area with significant exposure in terms of both As concentration (up to 4,440 μg/L) and population (Sun 2004). Individuals with arsenicosis were first correctly diagnosed by a team of Chinese endemic disease experts during a survey in 1994 in Shanxi. Groundwater As data that accumulated over the years point to two sedimentary basins, Datong (1,350 km2) and Jinzhong (800 km2), where tube well water drawn from depths between 20 and 50 m often contains As concentrations > 50 μg/L, which is the Chinese drinking water standard (GB 5749-85; Ministry of Health 2007). Groundwater from these basins also contains elevated concentrations of fluoride (up to 10 mg/L) but not always together with elevated concentrations of As. The population residing in Datong and Jinzhong basins is 932,086, although only 60% of the total population (569,685) was exposed to high-As concentrations in groundwater because of the heterogeneity of groundwater As distribution. To date, 3,998 individuals with arsenicosis, including children, have been identified, with most living in rural areas. Here, we report the results of an ecologic study on the intelligence and growth in 720 children between 8 and 12 years of age from Shanxi province, China. Subjects were drawn from control (n = 196), high-fluoride (n = 253), medium-As (n = 91), and high-As (n = 180) groups. Our study expands the existing but very limited literature base on the effect of As on the intellectual function of children, and reports a measurable reduction of IQ (intelligence quotient) scores due to As exposure. We initially included fluoride in our investigation because of the high concentrations of fluoride contained in some of the groundwater wells in our study area. To the best of our knowledge, there is no literature published in English that shows fluoride exposure has an effect on the intellectual function of children, although literature published in Chinese points to significant impairment of children’s intellectual function (Li et al. 2004; Liu et al. 2000; Yu et al. 1998), and growth (Qian et al. 1989; Xu and Huo 2000), based on studies of children with fluorosis.

Meeting report: The role of environmental lighting and circadian disruption in cancer and other diseases

Abstract: Light, including artificial light, has a range of effects on human physiology and behavior and can therefore alter human physiology when inappropriately timed. One example of potential lightinduced disruption is the effect of light on circadian organization, including the production of several hormone rhythms. Changes in light‐dark exposure (e.g., by nonday occupation or transmeridian travel) shift the timing of the circadian system such that internal rhythms can become desynchronized from both the external environment and internally with each other, impairing our ability to sleep and wake at the appropriate times and compromising physiologic and metabolic processes. Light can also have direct acute effects on neuroendocrine systems, for example, in suppressing melatonin synthesis or elevating cortisol production that may have untoward long-term consequences. For these reasons, the National Institute of Environmental Health Sciences convened a workshop of a diverse group of scientists to consider how best to conduct research on possible connections between lighting and health. According to the participants in the workshop, there are three broad areas of research effort that need to be addressed. First are the basic biophysical and molecular genetic mechanisms for phototransduction for circadian, neuroendocrine, and neurobehavioral regulation. Second are the possible physiologic consequences of disrupting these circadian regulatory processes such as on hormone production, particularly melatonin, and normal and neoplastic tissue growth dynamics. Third are effects of light-induced physiologic disruption on disease occurrence and prognosis, and how prevention and treatment could be improved by application of this knowledge.

Recommendations for Medical Management of Adult Lead Exposure

Abstract: Research conducted in recent years has increased public health concern about the toxicity of lead at low dose and has supported a reappraisal of the levels of lead exposure that may be safely tolerated in the workplace. In this article, which appears as part of a mini-monograph on adult lead exposure, we summarize a body of published literature that establishes the potential for hypertension, effects on renal function, cognitive dysfunction, and adverse female reproductive outcome in adults with whole-blood lead concentrations 5 μg/dL. Chelation may have an adjunctive role in the medical management of highly exposed adults with symptomatic lead intoxication but is not recommended for asymptomatic individuals with low blood lead concentrations.

The Association between Phthalates in Dust and Allergic Diseases among Bulgarian Children

Abstract: In the developed parts of the world, people spend ≥ 90% of their life indoors (Brasche and Bischof 2005), which implies that indoor environmental conditions are important for people’s health. Indoors, pollutants in dust and air are often generated from sources such as environmental tobacco smoke, building materials, furniture, cleaning and hygienic products, air fresheners, computers, printers, cooking and other indoor activities, and from people themselves. Over the last few decades, asthma and allergies have increased all over the world [Asher et al. 2006; ISAAC (International Study of Asthma and Allergy in Childhood) Steering Committee 1998; World Health Organization 2003]. The causes of the increase in asthma and allergies are still unknown. Genetic changes are not believed to be important because the time interval (30–50 years) for the increase in allergies is far too short. Instead, environmental changes are suspected as possible causes. Several hypotheses have been put forward. Much interest has been focused on the so called “hygiene hypothesis”—that a lack of microbial exposure during critical periods in infancy increases the risk of allergies (Strachan 1989). However, it seems likely that this hypothesis may not be the sole cause, and that other hypotheses are required (Platts-Mills et al. 2005). One such hypothesis is that the increase in allergies is attributable to new adjuvant factors: exposure to environmental pollutants such as endocrine disruptors (e.g., phthalate esters) which may act as modulators of the immune system and induce an allergic response (Chalubinski and Kowalski 2006). One of the main sources for phthalate esters indoors is the plasticized polyvinyl chloride (PVC) materials (Bornehag et al. 2005a) that are used in floor and wall covering materials, shower curtains, adhesives, synthetic leather, toys, cosmetics, and many other consumer products. Phthalates are constantly being emitted to the air and indoor dust because they are not chemically bound to the PVC structure (Wormuth et al. 2006). The presence of phthalates in indoor dust (Becker et al. 2004; Bornehag et al. 2004; Butte et al. 2001; Clausen et al. 2003; Fromme et al. 2004; Kersten and Reich 2003; Oie et al. 1997; Pohner et al. 1997; Rudel et al. 2003) and in indoor air (Adibi et al. 2003; Fromme et al. 2004; Rudel et al. 2003) is well documented. In the literature, the predominant phthalate described in indoor dust is di(2-ethylhexyl) phthalate (DEHP), typically observed in a concentration range of 0.01–10 mg/g dust, followed by butyl benzyl phthalate (BBzP) in concentrations up to 1.3 mg/g dust. The phthalate concentration in indoor air is usually lower than the concentration in dust, and the predominant phthalates are diethyl phthalate (DEP) and di-n-butyl phthalate (DnBP) in the concentration range of 0.05–5 μg/m3. Human exposure to phthalates has been studied mainly by monitoring concentrations of metabolites in body fluids such as urine or blood (Adibi et al. 2003; Becker et al. 2004; Blount et al. 2000; Calafat et al. 2004; Green et al. 2005; Koch et al. 2003, 2005). The results have shown that people are exposed to multiple phthalates and that children often are more exposed than adults (Calafat et al. 2004; Green et al. 2005; Koch et al. 2005). There is some epidemiologic evidence for an association between the concentration of phthalates in indoor dust and/or the occurrence indoors of plasticized products such as PVC and allergic symptoms in the airways (e.g., asthma), nose, and skin. Jaakkola et al. (1999) found that the total area of PVC surface materials in homes was associated with the development of bronchial obstruction in small children in Norway. In a study from Finland (Jaakkola et al. 2000), lower respiratory tract symptoms in children such as persistent wheezing, cough, and phlegm were associated with the presence of plastic wall materials, whereas upper respiratory tract symptoms were not. Also, the relative risk estimated for pneumonia, bronchitis, and otitis media among children was slightly increased in the presence of plastic wall materials (Jaakkola et al. 2000). In a population-based incident case–control study among adults (21–63 years of age), Jaakkola et al. (2006) found that the risk of asthma was significantly related to the presence of plastic wall materials at work. In the first phase of the Swedish DBH (Dampness in Buildings and Health) study it was found that PVC as flooring material in combination with moisture problems in the floors was associated with asthma among children 1–6 years of age (Bornehag et al. 2005b). Furthermore, in the second phase of the DBH study a strong dose–response relationship was found between asthma among children and DEHP concentration in indoor dust and between eczema and rhinitis and BBzP (Bornehag et al. 2004). Oie et al. (1997) provided evidence that inhalation exposure to DEHP as aerosols adsorbed to particulate matter is even more important than vapor phase exposure. They discussed possible mechanisms for respiratory effects by inhalation exposure and concluded that deposition of DEHP in the lungs may increase the risk of inflammation in the airways, a characteristic feature of asthma. The results from toxicologic studies are conflicting. Lee et al. (2004) reported that DEHP and di-isononyl phthalate (DINP) enhance allergic responses by enhancement of interleukin (IL)-4 production in CD4+ T cells via stimulation of NF-AT (nuclear factor of activated T cells)–binding activity. Glue et al. (2005) investigated the effect of phthalates to modulate the release of histamine from isolated basophils. None of the phthalates tested was found to induce histamine release per se, but higher histamine release was observed when the cells were first treated with phthalates and then exposed to an allergen. Recently, Larsen et al. (2007) reported that long-term inhalation of DEHP together with an allergen resulted in allergy sensitization only in concentrations of 13 mg/m3. These authors concluded that DEHP, at realistic concentrations, does not cause adjuvant effects nor allergic lung inflammation in humans. In a recent review, Nielsen et al. (2007) concluded that results from animal and epidemiologic studies are discordant. This study (The ALLHOME study) was initiated in Bulgaria in 2004. The overall aim of the study was to map housing conditions and indoor exposures in Bulgaria and to investigate the role of such factors for allergies and asthma among small children (Naydenov 2007; Naydenov et al. 2005). Our main aim in the present article is to investigate associations between persistent allergic symptoms in preschool Bulgarian children and the concentrations of different phthalate esters in dust collected from the children’s bedrooms.