Showing papers in "Environmental Health Perspectives in 2002"

Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage.

Abstract: The objectives of this study were to determine whether differences in the size and composition of coarse (2.5-10 micro m), fine (< 2.5 microm), and ultrafine (< 0.1 microm) particulate matter (PM) are related to their uptake in macrophages and epithelial cells and their ability to induce oxidative stress. The premise for this study is the increasing awareness that various PM components induce pulmonary inflammation through the generation of oxidative stress. Coarse, fine, and ultrafine particles (UFPs) were collected by ambient particle concentrators in the Los Angeles basin in California and used to study their chemical composition in parallel with assays for generation of reactive oxygen species (ROS) and ability to induce oxidative stress in macrophages and epithelial cells. UFPs were most potent toward inducing cellular heme oxygenase-1 (HO-1) expression and depleting intracellular glutathione. HO-1 expression, a sensitive marker for oxidative stress, is directly correlated with the high organic carbon and polycyclic aromatic hydrocarbon (PAH) content of UFPs. The dithiothreitol (DTT) assay, a quantitative measure of in vitro ROS formation, was correlated with PAH content and HO-1 expression. UFPs also had the highest ROS activity in the DTT assay. Because the small size of UFPs allows better tissue penetration, we used electron microscopy to study subcellular localization. UFPs and, to a lesser extent, fine particles, localize in mitochondria, where they induce major structural damage. This may contribute to oxidative stress. Our studies demonstrate that the increased biological potency of UFPs is related to the content of redox cycling organic chemicals and their ability to damage mitochondria.

Cancer risk assessment, indicators, and guidelines for polycyclic aromatic hydrocarbons in the ambient air.

Abstract: Polycyclic aromatic hydrocarbons (PAHs) are formed during incomplete combustion. Domestic wood burning and road traffic are the major sources of PAHs in Sweden. In Stockholm, the sum of 14 different PAHs is 100-200 ng/m(3) at the street-level site, the most abundant being phenanthrene. Benzo[a]pyrene (B[a]P) varies between 1 and 2 ng/m(3). Exposure to PAH-containing substances increases the risk of cancer in humans. The carcinogenicity of PAHs is associated with the complexity of the molecule, i.e., increasing number of benzenoid rings, and with metabolic activation to reactive diol epoxide intermediates and their subsequent covalent binding to critical targets in DNA. B[a]P is the main indicator of carcinogenic PAHs. Fluoranthene is an important volatile PAH because it occurs at high concentrations in ambient air and because it is an experimental carcinogen in certain test systems. Thus, fluoranthene is suggested as a complementary indicator to B[a]P. The most carcinogenic PAH identified, dibenzo[a,l]pyrene, is also suggested as an indicator, although it occurs at very low concentrations. Quantitative cancer risk estimates of PAHs as air pollutants are very uncertain because of the lack of useful, good-quality data. According to the World Health Organization Air Quality Guidelines for Europe, the unit risk is 9 X 10(-5) per ng/m(3) of B[a]P as indicator of the total PAH content, namely, lifetime exposure to 0.1 ng/m(3) would theoretically lead to one extra cancer case in 100,000 exposed individuals. This concentration of 0.1 ng/m(3) of B[a]P is suggested as a health-based guideline. Because the carcinogenic potency of fluoranthene has been estimated to be approximately 20 times less than that of B[a]P, a tentative guideline value of 2 ng/m(3) is suggested for fluoranthene. Other significant PAHs are phenanthrene, methylated phenanthrenes/anthracenes and pyrene (high air concentrations), and large-molecule PAHs such as dibenz[a,h]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, and indeno[1,2,3-cd]pyrene (high carcinogenicity). Additional source-specific indicators are benzo[ghi]perylene for gasoline vehicles, retene for wood combustion, and dibenzothiophene and benzonaphthothiophene for sulfur-containing fuels.

How Sustainable Agriculture Can Address the Environmental and Human Health Harms of Industrial Agriculture

Abstract: The industrial agriculture system consumes fossil fuel, water, and topsoil at unsustainable rates. It contributes to numerous forms of environmental degradation, including air and water pollution, soil depletion, diminishing biodiversity, and fish die-offs. Meat production contributes disproportionately to these problems, in part because feeding grain to livestock to produce meat—instead of feeding it directly to humans—involves a large energy loss, making animal agriculture more resource intensive than other forms of food production. The proliferation of factory-style animal agriculture creates environmental and public health concerns, including pollution from the high concentration of animal wastes and the extensive use of antibiotics, which may compromise their effectiveness in medical use. At the consumption end, animal fat is implicated in many of the chronic degenerative diseases that afflict industrial and newly industrializing societies, particularly cardiovascular disease and some cancers. In terms of human health, both affluent and poor countries could benefit from policies that more equitably distribute high-protein foods. The pesticides used heavily in industrial agriculture are associated with elevated cancer risks for workers and consumers and are coming under greater scrutiny for their links to endocrine disruption and reproductive dysfunction. In this article we outline the environmental and human health problems associated with current food production practices and discuss how these systems could be made more sustainable. Key words: diet, environment, health, industrial agriculture, sustainability, sustainable agriculture. Environ Health Perspect 110:445‐456 (2002). [Online 20 March 2002] http://ehpnet1.niehs.nih.gov/docs/2002/110p445-456horrigan/abstract.html

The three modern faces of mercury.

Abstract: The three modern "faces" of mercury are our perceptions of risk from the exposure of billions of people to methyl mercury in fish, mercury vapor from amalgam tooth fillings, and ethyl mercury in the form of thimerosal added as an antiseptic to widely used vaccines. In this article I review human exposure to and the toxicology of each of these three species of mercury. Mechanisms of action are discussed where possible. Key gaps in our current knowledge are identified from the points of view both of risk assessment and of mechanisms of action.

Parent bisphenol A accumulation in the human maternal-fetal-placental unit.

Abstract: Bisphenol A (BPA), an endocrine disruptor, is employed in the manufacture of a wide range of consumer products. The suggestion that BPA, at amounts to which we are exposed, alters the reproductive organs of developing rodents has caused concern. At present, no information exists concerning the exposure of human pregnant women and their fetuses to BPA. We therefore investigated blood samples from mothers (n = 37) between weeks 32 and 41 of gestation. Afer the births, we also analyzed placental tissue and umbilical cord blood from the same subjects. We developed a novel chemical derivatization-gas chromatography/mass spectrometry method to analyze parent BPA at concentrations < 1 micro g/mL in plasma and tissues. Concentrations of BPA ranged from 0.3 to 18.9 ng/mL (median = 3.1 ng/mL) in maternal plasma, from 0.2 to 9.2 ng/mL (median = 2.3 ng/mL) in fetal plasma, and from 1.0 to 104.9 ng/g (median = 12.7 ng/g) in placental tissue. BPA blood concentrations were higher in male than in female fetuses. Here we demonstrate parent BPA in pregnant women and their fetuses. Exposure levels of parent BPA were found within a range typical of those used in recent animal studies and were shown to be toxic to reproductive organs of male and female offspring. We suggest that the range of BPA concentrations we measured may be related to sex differences in metabolization of parent BPA or variable maternal use of consumer products leaching BPA.

Estimating the burden of disease from water, sanitation, and hygiene at a global level

Abstract: We estimated the disease burden from water, sanitation, and hygiene at the global level taking into account various disease outcomes, principally diarrheal diseases. The disability-adjusted life year (DALY) combines the burden from death and disability in a single index and permits the comparison of the burden from water, sanitation, and hygiene with the burden from other risk factors or diseases. We divided the world's population into typical exposure scenarios for 14 geographical regions. We then matched these scenarios with relative risk information obtained mainly from intervention studies. We estimated the disease burden from water, sanitation, and hygiene to be 4.0% of all deaths and 5.7% of the total disease burden (in DALYs) occurring worldwide, taking into account diarrheal diseases, schistosomiasis, trachoma, ascariasis, trichuriasis, and hookworm disease. Because we based these estimates mainly on intervention studies, this burden is largely preventable. Other water- and sanitation-related diseases remain to be evaluated. This preliminary estimation of the global disease burden caused by water, sanitation, and hygiene provides a basic model that could be further refined for national or regional assessments. This significant and avoidable burden suggests that it should be a priority for public health policy.

Atrazine-induced hermaphroditism at 0.1 ppb in American leopard frogs (Rana pipiens): Laboratory and field evidence

Abstract: Atrazine is the most commonly used herbicide in the United States and probably the world. Atrazine contamination is widespread and can be present in excess of 1.0 ppb even in precipitation and in areas where it is not used. In the current study, we showed that atrazine exposure (> or = to 0.1 ppb) resulted in retarded gonadal development (gonadal dysgenesis) and testicular oogenesis (hermaphroditism) in leopard frogs (Rana pipiens). Slower developing males even experienced oocyte growth (vitellogenesis). Furthermore, we observed gonadal dysgenesis and hermaphroditism in animals collected from atrazine-contaminated sites across the United States. These coordinated laboratory and field studies revealed the potential biological impact of atrazine contamination in the environment. Combined with reported similar effects in Xenopus laevis, the current data raise concern about the effects of atrazine on amphibians in general and the potential role of atrazine and other endocrine-disrupting pesticides in amphibian declines.

Mechanisms of Phthalate Ester Toxicity in the Female Reproductive System

Abstract: Phthalates are high-production-volume synthetic chemicals with ubiquitous human exposures because of their use in plastics and other common consumer products. Recent epidemiologic evidence suggests that women have a unique exposure profile to phthalates, which raises concern about the potential health hazards posed by such exposures. Research in our laboratory examines how phthalates interact with the female reproductive system in animal models to provide insights into the potential health effects of these chemicals in women. Here we review our work and the work of others studying these mechanisms and propose a model for the ovarian action of di-(2-ethylhexyl) phthalate (DEHP). In vivo, DEHP (2 g/kg) causes decreased serum estradiol levels, prolonged estrous cycles, and no ovulations in adult, cycling rats. In vitro, monoethylhexyl phthalate (MEHP; the active metabolite of DEHP) decreases granulosa cell aromatase RNA message and protein levels in a dose-dependent manner. MEHP is unique among the phthalates in its suppression of aromatase and in its ability to activate peroxisome proliferator-activated receptors (PPARs). We hypothesize that MEHP activates the PPARs to suppress aromatase in the granulosa cell. MEHP-, PPAR alpha-, and PPAR gamma-specific ligands all similarly decreased estradiol production and RNA message levels of aromatase in vitro. Our model shows that MEHP acts on the granulosa cell by decreasing cAMP stimulated by follicle stimulating hormone and by activating the PPARs, which leads to decreased aromatase transcription. Thus, the environmental contaminant DEHP, through its metabolite MEHP, acts through a receptor-mediated signaling pathway to suppress estradiol production in the ovary, leading to anovulation.

The Effect of Weather on Respiratory and Cardiovascular Deaths in 12 U.S. Cities

Abstract: We carried out time-series analyses in 12 U.S. cities to estimate both the acute effects and the lagged influence of weather on respiratory and cardiovascular disease (CVD) deaths. We fit generalized additive Poisson regressions for each city using nonparametric smooth functions to control for long time trend, season, and barometric pressure. We also controlled for day of the week. We estimated the effect and the lag structure of both temperature and humidity based on a distributed lag model. In cold cities, both high and low temperatures were associated with increased CVD deaths. In general, the effect of cold temperatures persisted for days, whereas the effect of high temperatures was restricted to the day of the death or the day before. For myocardial infarctions (MI), the effect of hot days was twice as large as the cold-day effect, whereas for all CVD deaths the hot-day effect was five times smaller than the cold-day effect. The effect of hot days included some harvesting, because we observed a deficit of deaths a few days later, which we did not observe for the cold-day effect. In hot cities, neither hot nor cold temperatures had much effect on CVD or pneumonia deaths. However, for MI and chronic obstructive pulmonary disease deaths, we observed lagged effects of hot temperatures (lags 4-6 and lags 3 and 4, respectively). We saw no clear pattern for the effect of humidity. In hierarchical models, greater variance of summer and winter temperature was associated with larger effects for hot and cold days, respectively, on respiratory deaths.

Dichlorodiphenyltrichloroethane (DDT): ubiquity, persistence, and risks.

Abstract: Due to uncontrolled use for several decades, dichlorodiphenyltrichloroethane (DDT), probably the best known and most useful insecticide in the world, has damaged wildlife and might have negative effects on human health. This review gives a brief history of the use of DDT in various countries and presents the results of epidemiologic and experimental studies of carcinogenesis. Even though its use has been prohibited in most countries for ecologic considerations, mainly because of its negative impact on wildlife, it is still used in some developing countries for essential public health purposes, and it is still produced for export in at least three countries. Due to its stability and its capacity to accumulate in adipose tissue, it is found in human tissues, and there is now not a single living organism on the planet that does not contain DDT. The possible contribution of DDT to increasing the risks for cancers at various sites and its possible role as an endocrine disruptor deserve further investigation. Although there is convincing experimental evidence for the carcinogenicity of DDT and of its main metabolites DDE and DDD, epidemiologic studies have provided contrasting or inconclusive, although prevailingly negative, results. The presence and persistence of DDT and its metabolites worldwide are still problems of great relevance to public health. Efficient pesticides that do not have the negative properties of DDT, together with the development of alternative methods to fight malaria, should be sought with the goal of completely banning DDT.

Environmental pollutants and disease in American children: estimates of morbidity, mortality, and costs for lead poisoning, asthma, cancer, and developmental disabilities.

Abstract: In this study, we aimed to estimate the contribution of environmental pollutants to the incidence, prevalence, mortality, and costs of pediatric disease in American children. We examined four categories of illness: lead poisoning, asthma, cancer, and neurobehavioral disorders. To estimate the proportion of each attributable to toxins in the environment, we used an environmentally attributable fraction (EAF) model. EAFs for lead poisoning, asthma, and cancer were developed by panels of experts through a Delphi process, whereas that for neurobehavioral disorders was based on data from the National Academy of Sciences. We define environmental pollutants as toxic chemicals of human origin in air, food, water, and communities. To develop estimates of costs, we relied on data from the U.S. Environmental Protection Agency, Centers for Disease Control and Prevention, National Center for Health Statistics, the Bureau of Labor Statistics, the Health Care Financing Agency, and the Practice Management Information Corporation. EAFs were judged to be 100% for lead poisoning, 30% for asthma (range, 10-35%), 5% for cancer (range, 2-10%), and 10% for neurobehavioral disorders (range, 5-20%). Total annual costs are estimated to be $54.9 billion (range $48.8-64.8 billion): $43.4 billion for lead poisoning, $2.0 billion for asthma, $0.3 billion for childhood cancer, and $9.2 billion for neurobehavioral disorders. This sum amounts to 2.8 percent of total U.S. health care costs. This estimate is likely low because it considers only four categories of illness, incorporates conservative assumptions, ignores costs of pain and suffering, and does not include late complications for which etiologic associations are poorly quantified. The costs of pediatric environmental disease are high, in contrast with the limited resources directed to research, tracking, and prevention.

Rapid increases in the steady-state concentration of reactive oxygen species in the lungs and heart after particulate air pollution inhalation.

Abstract: In vitro studies suggest that reactive oxygen species contribute to the cardiopulmonary toxicity of particulate air pollution. To evaluate the ability of particulate air pollution to promote oxidative stress and tissue damage in vivo, we studied a rat model of short-term exposure to concentrated ambient particles (CAPs). We exposed adult Sprague-Dawley rats to either CAPs aerosols (group 1; average CAPs mass concentration, 300 +/- 60 micro g/m3) or filtered air (sham controls) for periods of 1-5 hr. Rats breathing CAPs aerosols for 5 hr showed significant oxidative stress, determined as in situ chemiluminescence in the lung [group 1, 41 +/- 4; sham, 24 +/- 1 counts per second (cps)/cm2] and heart (group 1, 45 +/- 4; sham, 24 +/- 2 cps/cm2) but not liver (group 1, 10 +/- 3; sham, 13 +/- 3 cps/cm2). Increases in oxidant levels were also triggered by highly toxic residual oil fly ash particles (lung chemiluminescence, 90 +/- 10 cps/cm2; heart chemiluminescence, 50 +/- 3 cps/cm2) but not by particle-free air or by inert carbon black aerosols (control particles). Increases in chemiluminescence showed strong associations with the CAPs content of iron, manganese, copper, and zinc in the lung and with Fe, aluminum, silicon, and titanium in the heart. The oxidant stress imposed by 5-hr exposure to CAPs was associated with slight but significant increases in the lung and heart water content (approximately 5% in both tissues, p < 0.05) and with increased serum levels of lactate dehydrogenase (approximately 80%), indicating mild damage to both tissues. Strikingly, CAPs inhalation also led to tissue-specific increases in the activities of the antioxidant enzymes superoxide dismutase and catalase, suggesting that episodes of increased particulate air pollution not only have potential for oxidant injurious effects but may also trigger adaptive responses.

Community-based participatory research as a tool to advance environmental health sciences.

Abstract: The past two decades have witnessed a rapid proliferation of community-based participatory research (CBPR) projects. CBPR methodology presents an alternative to traditional population-based biomedical research practices by encouraging active and equal partnerships between community members and academic investigators. The National Institute of Environmental Health Sciences (NIEHS), the premier biomedical research facility for environmental health, is a leader in promoting the use of CBPR in instances where community-university partnerships serve to advance our understanding of environmentally related disease. In this article, the authors highlight six key principles of CBPR and describe how these principles are met within specific NIEHS-supported research investigations. These projects demonstrate that community-based participatory research can be an effective tool to enhance our knowledge of the causes and mechanisms of disorders having an environmental etiology, reduce adverse health outcomes through innovative intervention strategies and policy change, and address the environmental health concerns of community residents.

The association between noise exposure and blood pressure and ischemic heart disease: a meta-analysis.

Abstract: It has been suggested that noise exposure is associated with blood pressure changes and ischemic heart disease risk, but epidemiologic evidence is still limited. Furthermore, most reviews investigating these relations were not carried out in a systematic way, which makes them more prone to bias. We conducted a meta-analysis of 43 epidemiologic studies published between 1970 and 1999 that investigate the relation between noise exposure (both occupational and community) and blood pressure and/or ischemic heart disease (International Classification of Diseases, Ninth Revision, codes 410-414). We studied a wide range of effects, from blood pressure changes to a myocardial infarction. With respect to the association between noise exposure and blood pressure, small blood pressure differences were evident. Our meta-analysis showed a significant association for both occupational noise exposure and air traffic noise exposure and hypertension: We estimated relative risks per 5 dB(A) noise increase of 1.14 (1.01-1.29) and 1.26 (1.14-1.39), respectively. Air traffic noise exposure was positively associated with the consultation of a general practitioner or specialist, the use of cardiovascular medicines, and angina pectoris. In cross-sectional studies, road traffic noise exposure increases the risk of myocardial infarction and total ischemic heart disease. Although we can conclude that noise exposure can contribute to the prevalence of cardiovascular disease, the evidence for a relation between noise exposure and ischemic heart disease is still inconclusive because of the limitations in exposure characterization, adjustment for important confounders, and the occurrence of publication bias.

Combining xenoestrogens at levels below individual no-observed-effect concentrations dramatically enhances steroid hormone action.

Abstract: The low potency of many man-made estrogenic chemicals, so-called xenoestrogens, has been used to suggest that risks arising from exposure to individual chemicals are negligible. Another argument used to dismiss concerns of health effects is that endogenous steroidal estrogens are too potent for xenoestrogens to contribute significantly to estrogenic effects. Using a yeast reporter gene assay with the human estrogen receptoralpha, we tested these ideas experimentally by assessing the ability of a combination of 11 xenoestrogens to affect the actions of 17ss-estradiol. Significantly, each xenoestrogen was present at a level well below its no-observed-effect concentration (NOEC). To derive accurate descriptions of low effects, we recorded concentration-response relationships for each xenoestrogen and for 17ss-estradiol. We used these data to predict entire concentration-response curves of mixtures of xenoestrogens with 17ss-estradiol, assuming additive combination effects. Over a large range of concentrations, the experimentally observed responses decisively confirmed the model predictions. The combined additive effect of the 11 xenoestrogens led to a dramatic enhancement of the hormone's action, even when each single agent was present below its NOEC. Our results show that not even sub-NOEC levels of xenoestrogens can be considered to be without effect on potent steroidal estrogens when they act in concert with a large number of similarly acting chemicals. It remains to be seen to what degree these effects can be neutralized by environmental chemicals with antiestrogenic activity. Nevertheless, potential human and wildlife responses induced by additive combination effects of xenoestrogens deserve serious consideration.

Characterization of the dust/smoke aerosol that settled east of the World Trade Center (WTC) in lower Manhattan after the collapse of the WTC 11 September 2001.

Abstract: The explosion and collapse of the World Trade Center (WTC) was a catastrophic event that produced an aerosol plume impacting many workers, residents, and commuters during the first few days after 11 September 2001. Three bulk samples of the total settled dust and smoke were collected at weather-protected locations east of the WTC on 16 and 17 September 2001; these samples are representative of the generated material that settled immediately after the explosion and fire and the concurrent collapse of the two structures. We analyzed each sample, not differentiated by particle size, for inorganic and organic composition. In the inorganic analyses, we identified metals, radionuclides, ionic species, asbestos, and inorganic species. In the organic analyses, we identified polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls, polychlorinated dibenzodioxins, polychlorinated dibenzofurans, pesticides, phthalate esters, brominated diphenyl ethers, and other hydrocarbons. Each sample had a basic pH. Asbestos levels ranged from 0.8% to 3.0% of the mass, the PAHs were > 0.1% of the mass, and lead ranged from 101 to 625 microg/g. The content and distribution of material was indicative of a complex mixture of building debris and combustion products in the resulting plume. These three samples were composed primarily of construction materials, soot, paint (leaded and unleaded), and glass fibers (mineral wool and fiberglass). Levels of hydrocarbons indicated unburned or partially burned jet fuel, plastic, cellulose, and other materials that were ignited by the fire. In morphologic analyses we found that a majority of the mass was fibrous and composed of many types of fibers (e.g., mineral wool, fiberglass, asbestos, wood, paper, and cotton). The particles were separated into size classifications by gravimetric and aerodynamic methods. Material 53 microm in diameter. The results obtained from these samples can be used to understand the contact and types of exposures to this unprecedented complex mixture experienced by the surviving residents, commuters, and rescue workers directly affected by the plume from 11 to 12 September and the evaluations of any acute or long-term health effects from resuspendable dust and smoke to the residents, commuters, and local workers, as well as from the materials released after 11 September until the fires were extinguished. Further, these results support the need to have the interior of residences, buildings, and their respective HVAC systems professionally cleaned to reduce long-term residential risks before rehabitation.

Cancer and developmental exposure to endocrine disruptors.

Abstract: Developing organisms have increased susceptibility to cancer if they are exposed to environmental toxicants during rapid growth and differentiation. Human studies have demonstrated clear increases in cancer after prenatal exposure to ionizing radiation, and there is suggestive evidence that brain tumors and leukemia are associated with parental exposures to chemicals. Animal experiments have demonstrated increased tumor formation induced by prenatal or neonatal exposure to a variety of chemicals, including direct-acting carcinogens and drugs. Recently, natural estrogens have been classified as known human carcinogens. Prenatal exposure to natural and synthetic estrogens is associated with increases in breast and vaginal tumors in humans as well as uterine tumors in animals. Synthetic halogenated chemicals increase liver tumors after early life-stage exposure. Recently, a prototypical endocrine-disrupting compound, 2,3,7,8-tetrachlorodibenzo-p-dioxin, has been shown to be a developmental toxicant of the mammary gland in rodents. Dioxin alters multiple endocrine systems, and its effects on the developing breast involve delayed proliferation and differentiation of the mammary gland, as well as an elongation of the window of sensitivity to potential carcinogens. Implications of these new findings suggest that causes of endocrine-related cancers or susceptibility to cancer may be a result of developmental exposures rather than exposures existing at or near the time of tumor detection.

United Nations Convention to Combat Desertification.

Abstract: The Web sites Information for Public and Media page provides links to information such as secretariat press releases educational information kits for classroom use books posters images and the Down to Earth newsletter. Many of the materials are available in French Spanish. Russian Arabic Chinese and/or German. Multilingual fact sheets have been developed on topics including the causes and consequences of desertification partnership agreements between aid donors and affected states and how desertificatjon is fought in certain regions. (excerpt)

The health impacts of exposure to indoor air pollution from solid fuels in developing countries: knowledge, gaps, and data needs.

Abstract: Globally, almost 3 billion people rely on biomass (wood, charcoal, crop residues, and dung) and coal as their primary source of domestic energy. Exposure to indoor air pollution (IAP) from the combustion of solid fuels is an important cause of morbidity and mortality in developing countries. In this paper, we review the current knowledge on the relationship between IAP exposure and disease and on interventions for reducing exposure and disease. We take an environmental health perspective and consider the details of both exposure and health effects that are needed for successful intervention strategies. We also identify knowledge gaps and detailed research questions that are essential in successful design and dissemination of preventive measures and policies. In addition to specific research recommendations, we conclude that given the interaction of housing, household energy, and day-to-day household activities in determining exposure to indoor smoke, research and development of effective interventions can benefit tremendously from integration of methods and analysis tools from a range of disciplines in the physical, social, and health sciences.

Health effects assessment for environmental perchlorate contamination: the dose response for inhibition of thyroidal radioiodine uptake in humans.

Abstract: Application of a sensitive new detection method has revealed widespread perchlorate contamination of groundwater in the southwestern United States, typically at 0.005-0.020 mg/L (5-20 ppb). Perchlorate is a competitive inhibitor of the process by which iodide is actively transported from the bloodstream into the thyroid. This inhibitory action of perchlorate is the basis of its pharmaceutical use (in the treatment of hyperthyroidism) as well as its potential toxicity. To establish the dose response in humans for perchlorate inhibition of thyroidal iodide uptake and any short-term effects on thyroid hormones, we gave perchlorate in drinking water at 0.007, 0.02, 0.1, or 0.5 mg/kg-day to 37 male and female volunteers for 14 days. In 24 subjects we performed 8- and 24-hr measurements of thyroidal (123)I uptake (RAIU) before exposure, on exposure days 2 (E2) and 14 (E14), and 15 days postexposure (P15). In another 13 subjects we omitted both E2 studies and the 8-hr P15 study. We observed a strong correlation between the 8- and 24-hr RAIU over all dose groups and measurement days. We found no difference between E2 and E14 in the inhibition of RAIU produced by a given perchlorate dose. We also found no sex difference. On both E2 and E14, the dose response was a negative linear function of the logarithm of dose. Based on the dose response for inhibition of the 8- and 24-hr RAIU on E14 in all subjects, we derived estimates of the true no-effect level: 5.2 and 6.4 micro g/kg-day, respectively. Given default body weight and exposure assumptions, these doses would be ingested by an adult if the drinking-water supply contained perchlorate at concentrations of approximately 180 and 220 micro g/L (ppb), respectively. On P15, RAIU was not significantly different from baseline. In 24 subjects we measured serum levels of thyroxine (total and free), triiodothyronine, and thyrotropin in blood sampled 16 times throughout the study. Only the 0.5 mg/kg-day dose group showed any effect on serum hormones: a slight downward trend in thyrotropin levels in morning blood draws during perchlorate exposure, with recovery by P15.

Renal effects of uranium in drinking water.

Abstract: Animal studies and small studies in humans have shown that uranium is nephrotoxic. However, more information about its renal effects in humans following chronic exposure through drinking water is required. We measured uranium concentrations in drinking water and urine in 325 persons who had used drilled wells for drinking water. We measured urine and serum concentrations of calcium, phosphate, glucose, albumin, creatinine, and beta-2-microglobulin to evaluate possible renal effects. The median uranium concentration in drinking water was 28 microg/L (interquartile range 6-135, max. 1,920 microg/L) and in urine 13 ng/mmol creatinine (2-75), resulting in the median daily uranium intake of 39 microg (7-224). Uranium concentration in urine was statistically significantly associated with increased fractional excretion of calcium and phosphate. Increase of uranium in urine by 1 microg/mmol creatinine increased fractional excretion of calcium by 1.5% [95% confidence interval (CI), 0.6-2.3], phosphate by 13% (1.4-25), and glucose excretion by 0.7 micromol/min (-0.4-1.8). Uranium concentrations in drinking water and daily intake of uranium were statistically significantly associated with calcium fractional excretion, but not with phosphate or glucose excretion. Uranium exposure was not associated with creatinine clearance or urinary albumin, which reflect glomerular function. In conclusion, uranium exposure is weakly associated with altered proximal tubulus function without a clear threshold, which suggests that even low uranium concentrations in drinking water can cause nephrotoxic effects. Despite chronic intake of water with high uranium concentration, we observed no effect on glomerular function. The clinical and public health relevance of the findings are not easily established, but our results suggest that the safe concentration of uranium in drinking water may be within the range of the proposed guideline values of 2-30 microg/L.

Cadmium in Blood and Urine-Impact of Sex, Age, Dietary Intake, Iron Status, and Former Smoking-Association of Renal Effects

Abstract: We studied determinants of cadmium status and kidney function in nonsmoking men and women living on farms in southern Sweden. Median blood Cd (BCd) was 1.8 nmol/L (range, 0.38-18) and median urinar...

The prevalence of lead-based paint hazards in U.S. housing.

Abstract: In this study we estimated the number of housing units in the United States with lead-based paint and lead-based paint hazards. We included measurements of lead in intact and deteriorated paint, interior dust, and bare soil. A nationally representative, random sample of 831 housing units was evaluated in a survey between 1998 and 2000; the units and their occupants did not differ significantly from nationwide characteristics. Results indicate that 38 million housing units had lead-based paint, down from the 1990 estimate of 64 million. Twenty-four million had significant lead-based paint hazards. Of those with hazards, 1.2 million units housed low-income families (< 30,000 US dollars/year) with children under 6 years of age. Although 17% of government-supported, low-income housing had hazards, 35% of all low-income housing had hazards. For households with incomes greater than or equal to 30,000 US dollars/year, 19% had hazards. Fourteen percent of all houses had significantly deteriorated lead-based paint, and 16% and 7%, respectively, had dust lead and soil lead levels above current standards of the U.S. Department of Housing and Urban Development and the U.S. Environmental Protection Agency. The prevalence of lead-based paint and hazards increases with age of housing, but most painted surfaces, even in older housing, do not have lead-based paint. Between 2% and 25% of painted building components were coated with lead-based paint. Housing in the Northeast and Midwest had about twice the prevalence of hazards compared with housing in the South and West. The greatest risk occurs in older units with lead-based paint hazards that either will be or are currently occupied by families with children under 6 years of age and are low-income and/or are undergoing renovation or maintenance that disturbs lead-based paint. This study also confirms projections made in 2000 by the President's Task Force on Environmental Health Risks and Safety Risks to Children of the number of houses with lead-based paint hazards. Public- and private-sector resources should be directed to units posing the greatest risk if future lead poisoning is to be prevented.

The concentration-response relation between PM(2.5) and daily deaths.

Abstract: Particulate air pollution at commonly occurring concentrations is associated with daily deaths. Recent attention has focused on the shape of the concentration-response curve, particularly at low doses. Several recent articles have reported that particulate matter with aerodynamic diameter < or = 10 microm (PM(10)) was associated with daily deaths with no evidence of a threshold. These reports have used smoothing or spline methods in individual cities and pooled the results across multiple cities to obtain estimates that are more robust. To date, fine particulate matter (aerodynamic diameter Less than or equal to 2.5 microm; PM(2.5)), a component of PM(10), has not been examined in this regard. We examined this association in a hierarchical model in six U.S. cities. In the first stage, we fit log-linear models including smooth functions of PM(2.5) in each city, controlling for season, weather, and day of the week. These smooth functions allowed for nonlinearities in the city-specific associations. We combined the estimated curves across cities using a hierarchical model that allows for heterogeneity. We found an essentially linear relationship down to 2 microg/m(3). The same approach was applied to examine the concentration response to traffic particles, controlling for particles from other sources. Once again, the association showed no sign of a threshold. The magnitude of the association suggests that controlling fine particle pollution would result in thousands of fewer early deaths per year.

Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts.

Abstract: Inhaled ultrafine titanium dioxide (UF-TiO2) particles cause pronounced pulmonary inflammation, in contrast to fine TiO2. Previous studies provide evidence for the production of reactive oxygen species by alveolar macrophages, after overloading with UF-TiO2 particles and cytotoxicity of UF-TiO2 in rat lung alveolar macrophages. UF-TiO2 also causes pulmonary fibrosis and lung tumors in rats. UF-TiO2 particles are photogenotoxic, but in general, information on the genotoxicity of UF-TiO2 is still limited. We studied the potential of UF-TiO2 (particle size less than or equal to 20 nm) and fine TiO2 (particle size > 200 nm) to induce chromosomal changes, which can be monitored by the formation of micronuclei (MN) in Syrian hamster embryo (SHE) cells. We also analyzed UF-TiO2-treated cells for apoptosis induction. The MN assay revealed a significant increase in MN induction (p less than or equal to 0.05) in SHE cells after treatment with UF-TiO2 (1.0 micro g/cm2) for 12 hr (mean, 24.5 MN/1,000 cells), 24 hr (mean, 31.13 MN/1,000 cells), 48 hr (mean, 30.8 MN/1,000 cells), 66 hr (mean, 31.2 MN/1,000 cells), and 72 hr (mean, 31.3 MN/1,000 cells). Bisbenzimide staining of the fixed cells revealed typical apoptotic structures (apoptotic bodies), and the apoptosis-specific "DNA ladder pattern" resulting from internucleosomal cleavage was identified by gel electrophoresis. Furthermore, transmission electron microscopy of the exposed cells revealed the typical chromatin compaction of apoptosis.

The role of biomethylation in toxicity and carcinogenicity of arsenic: a research update.

Abstract: Recent research of the metabolism and biological effects of arsenic has profoundly changed our understanding of the role of metabolism in modulation of toxicity and carcinogenicity of this metalloi...

Understanding the human health effects of chemical mixtures.

Abstract: Most research on the effects of chemicals on biologic systems is conducted on one chemical at a time. However, in the real world people are exposed to mixtures, not single chemicals. Although various substances may have totally independent actions, in many cases two substances may act at the same site in ways that can be either additive or nonadditive. Many even more complex interactions may occur if two chemicals act at different but related targets. In the extreme case there may be synergistic effects, in which case the effects of two substances together are greater than the sum of either effect alone. In reality, most persons are exposed to many chemicals, not just one or two, and therefore the effects of a chemical mixture are extremely complex and may differ for each mixture depending on the chemical composition. This complexity is a major reason why mixtures have not been well studied. In this review we attempt to illustrate some of the principles and approaches that can be used to study effects of mixtures. By the nature of the state of the science, this discussion is more a presentation of what we do not know than of what we do know about mixtures. We approach the study of mixtures at three levels, using specific examples. First, we discuss several human diseases in relation to a variety of environmental agents believed to influence the development and progression of the disease. We present results of selected cellular and animal studies in which simple mixtures have been investigated. Finally, we discuss some of the effects of mixtures at a molecular level.

A model of the development of the brain as a construct of the thyroid system.

Abstract: Thyroid hormone is essential for normal brain development. However, little is known about the molecular and cellular mechanisms that mediate thyroid hormone action on the developing brain or the developmental events selectively affected. Consequently, although a large number of environmental chemicals interfere with the thyroid system, there are few neurodevelopmental end points to recruit for toxicological studies. Therefore, my goal here is to review what is known about the relative timing of normal brain construction and thyroid system development, with special focus on the period of in utero development in humans and the comparable developmental period in laboratory rats. These data are presented as a timeline to aid in the identification of thyroid-sensitive end points in brain development and to highlight important data gaps. I discuss the known influence of certain synthetic chemicals on the thyroid system and include a brief review of the effects of developmental exposure to chemicals on thyroid system function. The relationship between the thyroid hormone and retinoic acid systems, as well as the thyroid hormone sensitivity of the developing cochlea, is also discussed.

Personal PM2.5 exposure and markers of oxidative stress in blood.

Abstract: Ambient particulate air pollution assessed as outdoor concentrations of particulate matter less than or equal to 2.5 micro m in diameter (PM(2.5)) in urban background has been associated with cardiovascular diseases at the population level. However, the significance of individual exposure and the involved mechanisms remain uncertain. We measured personal PM(2.5) and carbon black exposure in 50 students four times in 1 year and analyzed blood samples for markers of protein and lipid oxidation, for red blood cell (RBC) and platelet counts, and for concentrations of hemoglobin and fibrinogen. We analyzed protein oxidation in terms of gamma-glutamyl semialdehyde in hemoglobin (HBGGS) and 2-aminoadipic semialdehyde in hemoglobin (HBAAS) and plasma proteins (PLAAS), and lipid peroxidation was measured as malondialdehyde (MDA) in plasma. Median exposures were 16.1 micro g/m(3) for personal PM(2.5) exposure, 9.2 micro g/m(3) for background PM(2.5) concentration, and 8.1 X 10(-6)/m for personal carbon black exposure. Personal carbon black exposure and PLAAS concentration were positively associated (p < 0.01), whereas an association between personal PM(2.5) exposure and PLAAS was only of borderline significance (p = 0.061). A 3.7% increase in MDA concentrations per 10 micro g/m(3) increase in personal PM(2.5) exposure was found for women (p < 0.05), whereas there was no significant relationship for the men. Similarly, positive associations between personal PM(2.5)exposure and both RBC and hemoglobin concentrations were found only in women (p < 0.01). There were no significant relationships between background PM(2.5) concentration and any of the biomarkers. This suggests that exposure to particles in moderate concentrations can induce oxidative stress and increase RBCs in peripheral blood. Personal exposure appears more closely related to these biomarkers potentially related to cardiovascular disease than is ambient PM(2.5) background concentrations.