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Showing papers in "Environmental Health Perspectives in 2001"


Journal ArticleDOI
TL;DR: This review describes and discusses several approaches to selecting higher plants as candidates for drug development with the greatest possibility of success and identifies and discusses advantages and disadvantages of using plants as starting points for drugDevelopment, specifically those used in traditional medicine.
Abstract: In this review we describe and discuss several approaches to selecting higher plants as candidates for drug development with the greatest possibility of success. We emphasize the role of information derived from various systems of traditional medicine (ethnomedicine) and its utility for drug discovery purposes. We have identified 122 compounds of defined structure, obtained from only 94 species of plants, that are used globally as drugs and demonstrate that 80% of these have had an ethnomedical use identical or related to the current use of the active elements of the plant. We identify and discuss advantages and disadvantages of using plants as starting points for drug development, specifically those used in traditional medicine.

1,992 citations


Journal ArticleDOI
TL;DR: Based on the scientific knowledge of today and based on Nordic intake data, the possible consumer health risk from PBDEs appears limited, as a factor of over 10 separates the estimated present mean dietary intake from the suggested LOAEL value.
Abstract: Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in plastics (concentration, 5--30%) and in textile coatings. Commercial products consist predominantly of penta-, octa-, and decabromodiphenyl ether mixtures, and global PBDE production is about 40,000 tons per year. PBDEs are bioaccumulated and biomagnified in the environment, and comparatively high levels are often found in aquatic biotopes from different parts of the world. During the mid-1970--1980s there was a substantial increase in the PBDE levels with time in both sediments and aquatic biota, whereas the latest Swedish data (pike and guillemot egg) may indicate that levels are at steady state or are decreasing. However, exponentially increasing PBDE levels have been observed in mother's milk during 1972--1997. Based on levels in food from 1999, the dietary intake of PBDE in Sweden has been estimated to be 0.05 microg per day. Characteristic end points of animal toxicity are hepatotoxicity, embryotoxicity, and thyroid effects as well as maternal toxicity during gestation. Recently, behavioral effects have been observed in mice on administration of PBDEs during a critical period after birth. Based on the critical effects reported in available studies, we consider the lowest-observed-adverse-effect level (LOAEL) value of the PBDE group to be 1 mg/kg/day (primarily based on effects of pentaBDEs). In conclusion, with the scientific knowledge of today and based on Nordic intake data, the possible consumer health risk from PBDEs appears limited, as a factor of over 10(6) separates the estimated present mean dietary intake from the suggested LOAEL value. However, the presence of many and important data gaps, including those in carcinogenicity, reproduction, and developmental toxicity, as well as additional routes of exposure, make this conclusion only preliminary. Moreover, the time trend of PBDEs in human breast milk is alarming for the future.

1,091 citations


Journal ArticleDOI
TL;DR: It is concluded that the major contributing factor to death of the dialyses patients was intravenous exposure to microcystins, specificallymicrocystin-YR, -LR, and -AR.
Abstract: An outbreak of acute liver failure occurred at a dialysis center in Caruaru, Brazil (8 degrees 17' S, 35 degrees 58' W), 134 km from Recife, the state capital of Pernambuco. At the clinic, 116 (89%) of 131 patients experienced visual disturbances, nausea, and vomiting after routine hemodialysis treatment on 13-20 February 1996. Subsequently, 100 patients developed acute liver failure, and of these 76 died. As of December 1996, 52 of the deaths could be attributed to a common syndrome now called Caruaru syndrome. Examination of phytoplankton from the dialysis clinic's water source, analyses of the clinic's water treatment system, plus serum and liver tissue of clinic patients led to the identification of two groups of cyanobacterial toxins, the hepatotoxic cyclic peptide microcystins and the hepatotoxic alkaloid cylindrospermopsin. Comparison of victims' symptoms and pathology using animal studies of these two cyanotoxins leads us to conclude that the major contributing factor to death of the dialyses patients was intravenous exposure to microcystins, specifically microcystin-YR, -LR, and -AR. From liver concentrations and exposure volumes, it was estimated that 19.5 microg/L microcystin was in the water used for dialysis treatments. This is 19.5 times the level set as a guideline for safe drinking water supplies by the World Health Organization.

899 citations


Journal ArticleDOI
TL;DR: Better estimates of the confidence intervals due to the improved model of the relationship between annoyance and noise exposure are provided, which is easier to use for practical calculations than the model itself.
Abstract: We present a model of the distribution of noise annoyance with the mean varying as a function of the noise exposure. Day-night level (DNL) and day-evening-night level (DENL) were used as noise descriptors. Because the entire annoyace distribution has been modeled, any annoyance measure that summarizes this distribution can be calculated from the model. We fitted the model to data from noise annoyance studies for aircraft, road traffic, and railways separately. Polynomial approximations of relationships implied by the model for the combinations of the following exposure and annoyance measures are presented: DNL or DENL, and percentage "highly annoyed" (cutoff at 72 on a scale of 0-100), percentage "annoyed" (cutoff at 50 on a scale of 0-100), or percentage (at least) "a little annoyed" (cutoff at 28 on a scale of 0-100). These approximations are very good, and they are easier to use for practical calculations than the model itself, because the model involves a normal distribution. Our results are based on the same data set that was used earlier to establish relationships between DNL and percentage highly annoyed. In this paper we provide better estimates of the confidence intervals due to the improved model of the relationship between annoyance and noise exposure. Moreover, relationships using descriptors other than DNL and percentage highly annoyed, which are presented here, have not been established earlier on the basis of a large dataset.

795 citations


Journal ArticleDOI
TL;DR: The histories of three such diseases--malaria, yellow fever, and dengue--reveal that climate has rarely been the principal determinant of their prevalence or range; human activities and their impact on local ecology have generally been much more significant.
Abstract: Global atmospheric temperatures are presently in a warming phase that began 250--300 years ago. Speculations on the potential impact of continued warming on human health often focus on mosquito-borne diseases. Elementary models suggest that higher global temperatures will enhance their transmission rates and extend their geographic ranges. However, the histories of three such diseases--malaria, yellow fever, and dengue--reveal that climate has rarely been the principal determinant of their prevalence or range; human activities and their impact on local ecology have generally been much more significant. It is therefore inappropriate to use climate-based models to predict future prevalence.

778 citations


Journal ArticleDOI
TL;DR: The findings indicate that UV screens should be tested for endocrine activity, in view of possible long-term effects in humans and wildlife.
Abstract: Ultraviolet (UV) screens are increasingly used as a result of growing concern about UV radiation and skin cancer; they are also added to cosmetics and other products for light stability Recent data on bioaccumulation in wildlife and humans point to a need for in-depth analyses of systemic toxicology, in particular with respect to reproduction and ontogeny We examined six frequently used UVA and UVB screens for estrogenicity in vitro and in vivo In MCF-7 breast cancer cells, five out of six chemicals, that is, benzophenone-3 (Bp-3), homosalate (HMS), 4-methyl-benzylidene camphor (4-MBC), octyl-methoxycinnamate (OMC), and octyl-dimethyl-PABA (OD-PABA), increased cell proliferation with median effective concentrations (EC(50)) values between 156 and 373 microM, whereas butyl-methoxydibenzoylmethane (B-MDM) was inactive Further evidence for estrogenic activity was the induction of pS2 protein in MCF-7 cells and the blockade of the proliferative effect of 4-MBC by the estrogen antagonist ICI 182,780 In the uterotrophic assay using immature Long-Evans rats that received the chemicals for 4 days in powdered feed, uterine weight was dose-dependently increased by 4-MBC (ED(50 )309mg/kg/day), OMC (ED(50) 935 mg/kg/day), and weakly by Bp-3 (active at 1,525 mg/kg/day) Three compounds were inactive by the oral route in the doses tested Dermal application of 4-MBC to immature hairless (hr/hr) rats also increased uterine weight at concentrations of 5 and 75% in olive oil Our findings indicate that UV screens should be tested for endocrine activity, in view of possible long-term effects in humans and wildlife

759 citations


Journal ArticleDOI
TL;DR: Several pure PBDE congeners, but especially HO-PBDEs and brominated bisphenol A-analogs, are agonists of both ER alpha and ER beta receptors, thus stimulating ER-mediated luciferase induction in vitro and suggesting that in vivo metabolism of PBDEs may produce more potent pseudoestrogens.
Abstract: Polybrominated diphenyl ethers (PBDEs) are used in large quantities as additive flame retardants in plastics and textile materials. PBDEs are persistent compounds and have been detected in wildlife and in human adipose tissue and plasma samples. In this study, we investigated the (anti)estrogenic potencies of several PBDE congeners, three hydroxylated PBDEs (HO-PBDEs), and differently brominated bisphenol A compounds in three different cell line assays based on estrogen receptor (ER)-dependent luciferase reporter gene expression. In human T47D breast cancer cells stably transfected with an estrogen-responsive luciferase reporter gene construct (pEREtata-Luc), 11 PBDEs showed estrogenic potencies, with concentrations leading to 50% induction (EC(50)) varying from 2.5 to 7.3 microM. The luciferase induction of the most potent HO-PBDE [2-bromo-4-(2,4,6-tribromophenoxy)phenol] exceeded that of estradiol (E(2)), though at concentrations 50,000 times higher. As expected, brominated bisphenol A compounds with the lowest degree of bromination showed highest estrogenic potencies (EC(50) values of 0.5 microM for 3-monobromobisphenol A). In an ER alpha-specific, stably transfected human embryonic kidney cell line (293-ER alpha-Luc), the HO-PBDE 4-(2,4,6-tribromophenoxy)phenol was a highly potent estrogen with an EC(50) < 0.1 microM and a maximum 35- to 40-fold induction, which was similar to E(2). In an analogous ER beta-specific 293-ER betas-Luc cell line, the agonistic potency of the 4-(2,4,6-tribromophenoxy)phenol was much lower (maximum 50% induction compared to E(2)), but EC(50) values were comparable. These results indicate that several pure PBDE congeners, but especially HO-PBDEs and brominated bisphenol A-analogs, are agonists of both ER alpha and ER beta receptors, thus stimulating ER-mediated luciferase induction in vitro. These data also suggest that in vivo metabolism of PBDEs may produce more potent pseudoestrogens.

742 citations


Journal ArticleDOI
TL;DR: Pulmonary and systemic distribution of inhaled ultrafine elemental silver (EAg) particles was investigated on the basis of morphology and inductively coupled plasma mass spectrometry (ICP-MS) analysis, and it was shown that although instilled agglomerates of ultrafine EAg particles were retained in the lung, Ag was rapidly cleared from the lung after inhalation of ultra Fine silver particles, as well as after instillation of AgNO(3), and entered systemic pathways.
Abstract: The cardiovascular system is currently considered a target for particulate matter, especially for ultrafine particles. In addition to autonomic or cytokine mediated effects, the direct interaction of inhaled materials with the target tissue must be examined to understand the underlying mechanisms. In the first approach, pulmonary and systemic distribution of inhaled ultrafine elemental silver (EAg) particles was investigated on the basis of morphology and inductively coupled plasma mass spectrometry (ICP-MS) analysis. Rats were exposed for 6 hr at a concentration of 133 microg EAg m(3) (3 x 10(6) cm(3), 15 nm modal diameter) and were sacrificed on days 0, 1, 4, and 7. ICP-MS analysis showed that 1.7 microg Ag was found in the lungs immediately after the end of exposure. Amounts of Ag in the lungs decreased rapidly with time, and by day 7 only 4% of the initial burden remained. In the blood, significant amounts of Ag were detected on day 0 and thereafter decreased rapidly. In the liver, kidney, spleen, brain, and heart, low concentrations of Ag were observed. Nasal cavities, especially the posterior portion, and lung-associated lymph nodes showed relatively high concentrations of Ag. For comparison, rats received by intratracheal instillation either 150 microL aqueous solution of 7 microg silver nitrate (AgNO(3) (4.4 microg Ag) or 150 microL aqueous suspension of 50 microg agglomerated ultrafine EAg particles. A portion of the agglomerates remained undissolved in the alveolar macrophages and in the septum for at least 7 days. In contrast, rapid clearance of instilled water-soluble AgNO(3) from the lung was observed. These findings show that although instilled agglomerates of ultrafine EAg particles were retained in the lung, Ag was rapidly cleared from the lung after inhalation of ultrafine EAg particles, as well as after instillation of AgNO(3), and entered systemic pathways.

684 citations


Journal ArticleDOI
TL;DR: This present review considers the likely interactions between the ultrafine particles the acute phase response and cardiovascular disease in populations exposed to air pollution episodes.
Abstract: Well-documented air pollution episodes throughout recent history have led to deaths among individuals with cardiovascular and respiratory disease. Although the components of air pollution that cause the adverse health effects in these individuals are unknown, a small proportion by mass but a large proportion by number of the ambient air particles are ultrafine, i.e., less than 100 nm in diameter. This ultrafine component of particulate matter with a mass median aerodynamic diameter less than 10 microm (PM(10) may mediate some of the adverse health effects reported in epidemiologic studies and for which there is toxicologic evidence to support this contention. The exact mechanism by which ultrafine particles have adverse effects is unknown, but these particles have recently been shown to enhance calcium influx on contact with macrophages. Oxidative stress is also to be anticipated at the huge particle surface; this can be augmented by oxidants generated by recruited inflammatory leukocytes. Atheromatous plaques form in the coronary arteries and are major causes of morbidity and death associated epidemiologically with particulate air pollution. In populations exposed to air pollution episodes, blood viscosity, fibrinogen, and C-reactive protein (CRP) were higher. More recently, increases in heart rate in response to rising air pollution have been described and are most marked in individuals who have high blood viscosity. In our study of elderly individuals, there were significant rises in CRP, an index of inflammation. In this present review, we consider the likely interactions between the ultrafine particles the acute phase response and cardiovascular disease.

639 citations


Journal ArticleDOI
TL;DR: It is argued that a shift to more precautionary policies creates opportunities and challenges for scientists to think differently about the ways they conduct studies and communicate results.
Abstract: Environmental scientists play a key role in society's responses to environmental problems, and many of the studies they perform are intended ultimately to affect policy. The precautionary principle, proposed as a new guideline in environmental decision making, has four central components: taking preventive action in the face of uncertainty; shifting the burden of proof to the proponents of an activity; exploring a wide range of alternatives to possibly harmful actions; and increasing public participation in decision making. In this paper we examine the implications of the precautionary principle for environmental scientists, whose work often involves studying highly complex, poorly understood systems, while at the same time facing conflicting pressures from those who seek to balance economic growth and environmental protection. In this complicated and contested terrain, it is useful to examine the methodologies of science and to consider ways that, without compromising integrity and objectivity, research can be more or less helpful to those who would act with precaution. We argue that a shift to more precautionary policies creates opportunities and challenges for scientists to think differently about the ways they conduct studies and communicate results. There is a complicated feedback relation between the discoveries of science and the setting of policy. While maintaining their objectivity and focus on understanding the world, environmental scientists should be aware of the policy uses of their work and of their social responsibility to do science that protects human health and the environment. The precautionary principle highlights this tight, challenging linkage between science and policy.

597 citations


Journal ArticleDOI
TL;DR: Data indicate an increased sensitivity to BPA during the perinatal period and suggest the need for careful evaluation of the current levels of exposure to this compound.
Abstract: The nonsteroidal estrogenic compound bisphenol A (BPA) is a monomer used in the manufacture of polycarbonate plastics and resins. BPA may be ingested by humans as it reportedly leaches from the lining of tin cans into foods, from dental sealants into saliva, and from polycarbonate bottles into their contents. Because BPA is weakly estrogenic--approximately 10,000-fold less potent than 17beta-estradiol--current environmental exposure levels have been considered orders of magnitude below the dose required for adverse effects on health. Herein we demonstrate measurable effects on the offspring of Sprague-Dawley female rats that were exposed, via their drinking water, to approximately 0.1 mg BPA/kg body weight (bw)/day (low dose) or 1.2 mg BPA/kg bw/day (high dose) from day 6 of pregnancy through the period of lactation. Offspring exposed to BPA exhibited an increase in body weight that was apparent soon after birth and continued into adulthood. In addition, female offspring exposed perinatally to the high dose of BPA exhibited altered patterns of estrous cyclicity and decreased levels of plasma luteinizing hormone (LH) in adulthood. Administration of neither the doses of BPA that caused effects during perinatal exposure nor a 10-fold higher dose was able to evoke a uterotropic response in ovariectomized postpubertal females. These data indicate an increased sensitivity to BPA during the perinatal period and suggest the need for careful evaluation of the current levels of exposure to this compound.

Journal ArticleDOI
TL;DR: Overall death rates are higher in winter than in summer, and it is possible that milder winters could reduce deaths in winter months, however, the relationship between winter weather and mortality is difficult to interpret.
Abstract: Heat and heat waves are projected to increase in severity and frequency with increasing global mean temperatures. Studies in urban areas show an association between increases in mortality and increases in heat, measured by maximum or minimum temperature, heat index, and sometimes, other weather conditions. Health effects associated with exposure to extreme and prolonged heat appear to be related to environmental temperatures above those to which the population is accustomed. Models of weather-mortality relationships indicate that populations in northeastern and midwestern U.S. cities are likely to experience the greatest number of illnesses and deaths in response to changes in summer temperature. Physiologic and behavioral adaptations may reduce morbidity and mortality. Within heat-sensitive regions, urban populations are the most vulnerable to adverse heat-related health outcomes. The elderly, young children, the poor, and people who are bedridden or are on certain medications are at particular risk. Heat-related illnesses and deaths are largely preventable through behavioral adaptations, including the use of air conditioning and increased fluid intake. Overall death rates are higher in winter than in summer, and it is possible that milder winters could reduce deaths in winter months. However, the relationship between winter weather and mortality is difficult to interpret. Other adaptation measures include heat emergency plans, warning systems, and illness management plans. Research is needed to identify critical weather parameters, the associations between heat and nonfatal illnesses, the evaluation of implemented heat response plans, and the effectiveness of urban design in reducing heat retention.

Journal ArticleDOI
TL;DR: It is shown that neonatal exposure to PBDE 99 and PBDE 47 can cause permanent aberrations in spontaneous behavior, evident in 2- and 4-month-old animals, and changes were dose-response related.
Abstract: Brominated flame retardants are a novel group of global environmental contaminants. Within this group the polybrominated diphenyl ethers (PBDE) constitute one class of many that are found in electr...

Journal ArticleDOI
TL;DR: The findings that the fumonisins cause field outbreaks of mycotoxicoses in animals, are carcinogenic in rats, and disrupt sphingolipid metabolism have resulted in much worldwide interest in these compounds during the first 10 years after the discovery of the fUMonisins in 1988.
Abstract: This article describes the events leading to the discovery of the fumonisins in South Africa in 1988 and highlights the first 10 years (1988-1998) of fumonisin research. The predominant fungus isol...

Journal ArticleDOI
TL;DR: The tremendous growth in international travel increases the risk of importation of vector-borne diseases, some of which can be transmitted locally under suitable circumstances at the right time of the year, and it is unlikely that these diseases will cause major epidemics in the United States if the public health infrastructure is maintained and improved.
Abstract: Diseases such as plague, typhus, malaria, yellow fever, and dengue fever, transmitted between humans by blood-feeding arthropods, were once common in the United States. Many of these diseases are no longer present, mainly because of changes in land use, agricultural methods, residential patterns, human behavior, and vector control. However, diseases that may be transmitted to humans from wild birds or mammals (zoonoses) continue to circulate in nature in many parts of the country. Most vector-borne diseases exhibit a distinct seasonal pattern, which clearly suggests that they are weather sensitive. Rainfall, temperature, and other weather variables affect in many ways both the vectors and the pathogens they transmit. For example, high temperatures can increase or reduce survival rate, depending on the vector, its behavior, ecology, and many other factors. Thus, the probability of transmission may or may not be increased by higher temperatures. The tremendous growth in international travel increases the risk of importation of vector-borne diseases, some of which can be transmitted locally under suitable circumstances at the right time of the year. But demographic and sociologic factors also play a critical role in determining disease incidence, and it is unlikely that these diseases will cause major epidemics in the United States if the public health infrastructure is maintained and improved. Key words: dengue fever, encephalitis, global warming, hantavirus, leptospirosis, Lyme disease, malaria, plague, vectorborne diseases. — Environ Health Perspect 109(suppl 2):223‐233 (2001). http://ehpnet1.niehs.nih.gov/docs/2001/suppl-2/223-233gubler/abstract.html

Journal ArticleDOI
TL;DR: A V-like relationship between mortality and temperature is found, with an optimum temperature value of 16.5 degrees C for total mortality, cardiovascular mortality, respiratory mortality, and mortality among those [Greater and equal to] 65 year of age, and the elderly were most effected by extreme heat.
Abstract: We conducted the study described in this paper to investigate the impact of ambient temperature on mortality in the Netherlands during 1979-1997, the impact of heat waves and cold spells on mortality in particular, and the possibility of any heat wave- or cold spell-induced forward displacement of mortality. We found a V-like relationship between mortality and temperature, with an optimum temperature value (e.g., average temperature with lowest mortality rate) of 16.5 degrees C for total mortality, cardiovascular mortality, respiratory mortality, and mortality among those [Greater and equal to] 65 year of age. For mortality due to malignant neoplasms and mortality in the youngest age group, the optimum temperatures were 15.5 degrees C and 14.5 degrees C, respectively. For temperatures above the optimum, mortality increased by 0.47, 1.86, 12.82, and 2.72% for malignant neoplasms, cardiovascular disease, respiratory diseases, and total mortality, respectively, for each degree Celsius increase above the optimum in the preceding month. For temperatures below the optimum, mortality increased 0.22, 1.69, 5.15, and 1.37%, respectively, for each degree Celsius decrease below the optimum in the preceding month. Mortality increased significantly during all of the heat waves studied, and the elderly were most effected by extreme heat. The heat waves led to increases in mortality due to all of the selected causes, especially respiratory mortality. Average total excess mortality during the heat waves studied was 12.1%, or 39.8 deaths/day. The average excess mortality during the cold spells was 12.8% or 46.6 deaths/day, which was mostly attributable to the increase in cardiovascular mortality and mortality among the elderly. The results concerning the forward displacement of deaths due to heat waves were not conclusive. We found no cold-induced forward displacement of deaths.

Journal ArticleDOI
TL;DR: These epidemiologic studies provide early guidance to possible pathways of particulate air pollution health effects, which can only be addressed fully in toxicologic and physiologic studies.
Abstract: Scientific and policy interests in the health effects of particulate air pollution have increased dramatically in the past decade in response to numerous epidemiologic reports of increased daily mortality associated with episodes of particulate air pollution (1,2). In a recent comprehensive analysis of daily mortality and particulate air pollution in 90 U.S. cities, Samet and colleagues (3‐5) confirmed that these associations were real, robust, and not confounded by weather; furthermore, these particle effects were independent of the effects of other co-pollutants. Analyses by cause of death generally find larger relative risks for respiratory deaths. For example, in a combined analysis across six eastern U.S. cities, each 10-µg/m3 increase in fine particle mass [particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5)] was associated with an increase in total mortality of 1.7%, compared to an increase of 3.3% in chronic obstructive pulmonary disease deaths and 4.0% in pneumonia deaths (6). Increased relative risks are also generally reported for cardiovascular deaths (1). In the combined six-city analysis, PM 2.5 was associated with a 2.1% increase in ischemic heart disease deaths. Respiratory deaths (chronic obstructive pulmonary disease, pneumonia, influenza) accounted for only 8.5% of all deaths in the United States in 1997, while cardiovascular deaths (heart, cerebrovascular, and arterial diseases) accounted for 39.5% (7). Thus, while the relative effects of particulate air pollution are larger for respiratory than for cardiovascular deaths, the numbers of deaths attributable to particulate air pollution are much larger for cardiovascular than for respiratory causes. Understanding the mechanisms by which these particle exposures produce sudden cardiac events is important not only scientifically but also in risk assessment and in setting public policy. Epidemiology cannot show causation, but innovative study designs do provide insights into possible causal pathways. Several years ago several colleagues and I investigated possible mechanisms by which particles deposited in the lungs might produce an immediate, fatal cardiac event. We hypothesized that particle exposures might interfere with oxygen transport and that the resultant hypoxemia might trigger cardiac arrhythmias. To test this hypoxemia hypothesis, we recruited two panels of elderly subjects living in Utah Valley, Utah (18). One panel consisted of emeritus faculty from Brigham Young University and their spouses living in Orem and Provo. The other panel consisted of residents in an assisted living facility in Orem. Members of the first panel measured their oxygen saturation twice daily (on arising and before retiring) with a pulse oximeter. Pulse rate, oxygen saturation, date, and time were automatically recorded. Residents of the retirement community had the same measurements

Journal ArticleDOI
TL;DR: About 12,000 excess deaths occurred from December 1952 through February 1953 because of acute and persisting effects of the 1952 London smog, which was 5-19 times above current regulatory standards and guidelines and approximate current levels in some rapidly developing regions.
Abstract: This article develops and assesses novel indicators of respiratory and other morbidity and mortality following London's lethal smog in the winter of 1952. Public health insurance claims, hospital admission rates for cardiac and respiratory disease, pneumonia cases, mortality records, influenza reports, temperature, and air pollutant concentrations are analyzed for December-February 1952-1953 and compared with those for the previous year or years. Mortality rates for the smog episode from December 1952 to February 1953 were 50-300% higher than the previous year. Claims that the smog only elevated health risks during and immediately following the peak fog 5-9 December 1952 and that an influenza epidemic accounted fully for persisting mortality increases in the first 2 months of 1953 are rejected. We estimate about 12,000 excess deaths occurred from December 1952 through February 1953 because of acute and persisting effects of the 1952 London smog. Pollution levels during the London smog were 5-19 times above current regulatory standards and guidelines and approximate current levels in some rapidly developing regions. Ambient pollution in many regions poses serious risks to public health.

Journal ArticleDOI
TL;DR: All these processes--the effects of fumonisins on sphingolipid metabolism, the pathways altered by perturbation of sphingosine metabolism, and the complex cellular behaviors regulated by sphingoipids--must be borne in mind when evaluating the pathologic effects of FUMonisins.
Abstract: Sphingolipids have important roles in membrane and lipoprotein structure and in cell regulation as second messengers for growth factors, differentiation factors, cytokines, and a growing list of ag...

Journal ArticleDOI
TL;DR: Transgenic plants have been engineered to rapidly detoxify and transform such xenobiotic chemicals, which could be used in phytoremediation applications if issues of cost and public acceptability are overcome.
Abstract: Phytoremediation is the use of plants to remedy contaminated soils, sediments, and/or groundwater. Sorption and uptake are governed by physicochemical properties of the compounds, and moderately hydrophobic chemicals (logarithm octanol--water coefficients = 1.0--3.5) are most likely to be bioavailable to rooted, vascular plants. Some hydrophilic compounds, such as methyl-tert-butylether and 1,4-dioxane, may also be taken up by plants via hydrogen bonding with transpiration water. Organic chemicals that pass through membranes and are translocated to stem and leaf tissues may be converted (e.g., oxidized by cytochrome P450s), conjugated by glutathione or amino acids, and compartmentalized in plant tissues as bound residue. The relationship between metabolism of organic xenobiotics and toxicity to plant tissues is not well understood. A series of chlorinated ethenes is more toxic to hybrid poplar trees (Populus deltoides x nigra, DN-34) than are the corresponding chlorinated ethanes. Toxicity correlates best with the number of chlorine atoms in each homologous series. Transgenic plants have been engineered to rapidly detoxify and transform such xenobiotic chemicals. These could be used in phytoremediation applications if issues of cost and public acceptability are overcome.

Journal ArticleDOI
Joel Schwartz1
TL;DR: PM(10), but not gaseous air pollutants, is associated with blood markers of cardiovascular risk, and this may explain epidemiologic associations with early deaths, providing considerable biologic plausibility to the mortality studies.
Abstract: Recent studies have linked air pollution to tens of thousands of premature cardiovascular deaths per year. The mechanisms of such associations remain unclear. In this study we examine the association between blood markers of cardiovascular risk and air pollution in a national sample of the U.S. population. Air pollution concentrations were merged to subjects in the Third National Health and Nutrition Examination Survey (NHANES III) in the United States, and the association with fibrinogen levels and counts of platelets and white blood cells were examined. The subjects in NHANES III are a representative sample of the U.S. population. Regressions controlled for age, race, sex, body mass index, current smoking, and number of cigarettes per day. The complex survey design was dealt with using mixed models with a random sampling site effect. In single-pollutant models, PM(10) (particulate matter with a mass median aerodynamic diameter less than 10 microm) was associated with all three outcomes (p< 0.05): Sulfur dioxide (SO(2)) was significantly associated only with white cell counts, nitrogen dioxide (NO(2)) with platelet counts and fibrinogen, and ozone with none of the outcomes. In two-pollutant models, PM(10) remained a significant predictor of white cell counts controlling for SO(2) but not vice versa. PM(10) was marginally significant in a model for platelet counts with NO(2), and the sign of the NO(2) coefficient was reversed. These results were stable with control for indoor exposures (wood stoves, environmental tobacco smoke, gas stoves, fireplaces), dietary risk factors (saturated fat, alcohol, caffeine intake, n-3 fatty acids), and serum cholesterol. The magnitude of the effects are modest [e.g., 13 microg/dL fibrinogen for an interquartile range (IQR) change in PM(subscript)10(/subscript), 95% confidence interval (CI) 4.6-22.1 mg/dL]. However, the odds ratio of being in the top 10% of fibrinogen for the same IQR change was 1.77 (95% CI 1.26-2.49). These effects provide considerable biologic plausibility to the mortality studies. PM(10), but not gaseous air pollutants, is associated with blood markers of cardiovascular risk, and this may explain epidemiologic associations with early deaths.

Journal ArticleDOI
TL;DR: Adverse pregnancy outcomes in terms of spontaneous abortion, stillbirth, and preterm birth rates were significantly higher in the exposed group than those in the nonexposed group (p=0.008, p = 0.046, and p =0.018, respectively).
Abstract: We studied a group of women of reproductive age (15-49 years) who were chronically exposed to arsenic through drinking water to identify the pregnancy outcomes in terms of live birth, stillbirth, spontaneous abortion, and preterm birth. We compared pregnancy outcomes of exposed respondents with pregnancy outcomes of women of reproductive age (15-49 years) who were not exposed to arsenic-contaminated water. In a cross-sectional study, we matched the women in both exposed and nonexposed groups for age, socioeconomic status, education, and age at marriage. The total sample size was 192, with 96 women in each group (i.e., exposed and nonexposed). Of the respondents in the exposed group, 98% had been drinking water containing [Greater and equal to] 0.10 mg/L arsenic and 43.8% had been drinking arsenic-contaminated water for 5-10 years. Skin manifestation due to chronic arsenic exposure was present in 22.9% of the respondents. Adverse pregnancy outcomes in terms of spontaneous abortion, stillbirth, and preterm birth rates were significantly higher in the exposed group than those in the nonexposed group (p = 0.008, p = 0.046, and p = 0.018, respectively).

Journal ArticleDOI
TL;DR: In this paper, the authors consider the potential health effects of climate variability in combination with other stresses such as overfishing, introduced species, and rise in sea level, and recommend incorporating a range of future scenarios of improvement plans for current deficiencies in the public health infrastructure to achieve more realistic risk assessments.
Abstract: Exposure to waterborne and foodborne pathogens can occur via drinking water (associated with fecal contamination), seafood (due to natural microbial hazards, toxins, or wastewater disposal) or fresh produce (irrigated or processed with contaminated water). Weather influences the transport and dissemination of these microbial agents via rainfall and runoff and the survival and/or growth through such factors as temperature. Federal and state laws and regulatory programs protect much of the U.S. population from waterborne disease; however, if climate variability increases, current and future deficiencies in areas such as watershed protection, infrastructure, and storm drainage systems will probably increase the risk of contamination events. Knowledge about transport processes and the fate of microbial pollutants associated with rainfall and snowmelt is key to predicting risks from a change in weather variability. Although recent studies identified links between climate variability and occurrence of microbial agents in water, the relationships need further quantification in the context of other stresses. In the marine environment as well, there are few studies that adequately address the potential health effects of climate variability in combination with other stresses such as overfishing, introduced species, and rise in sea level. Advances in monitoring are necessary to enhance early-warning and prevention capabilities. Application of existing technologies, such as molecular fingerprinting to track contaminant sources or satellite remote sensing to detect coastal algal blooms, could be expanded. This assessment recommends incorporating a range of future scenarios of improvement plans for current deficiencies in the public health infrastructure to achieve more realistic risk assessments.

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TL;DR: This review discusses how exposure to different forms of DDT with varying estrogenicities may have affected the results of studies on DDT, DDE, and breast cancer risk and addresses the emerging research on whether serum levels of the persistent organochlorine insecticide dieldrin are related to Breast cancer risk in Danish and American women.
Abstract: Established risk factors for breast cancer explain breast cancer risk only partially. Hence, there has been interest in evaluating what role environmental chemicals, especially those with evidence of being hormonally active agents, play in breast cancer risk. Organochlorine pesticides have received the most attention because of their persistence in the environment, ability to concentrate up the food chain, continued detection in the food supply and breast milk, and ability to be stored in the adipose tissue of animals and humans. Although several early descriptive studies and a cohort study identified a strong positive association with breast cancer risk and adipose or blood levels of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) and/or its metabolite dichlorodiphenyldichloroethylene (DDE), most of the more recent case--control and nested case--control studies have not supported this association. In this review I discuss these findings and explore how exposure to different forms of DDT with varying estrogenicities may have affected the results of these studies. I also address how other factors influence the interpretation of the studies on DDT, DDE, and breast cancer risk. These include the effect of analytic methods, dietary factors, menopausal status, use of different types of control populations, lactation history, estrogen receptor status, ethnic/racial subgroups, breast tumor characteristics, and polymorphisms. I also discuss the emerging research on whether serum levels of the persistent organochlorine insecticide dieldrin are related to breast cancer risk in Danish and American women. Further research needs are also identified.

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TL;DR: This first estimation of the exposure-response relationship for the high-exposure levels characteristic of developing countries has immediate and important consequences for international public health policies, energy and combustion research, and technology transfer efforts that affect more than 2 billion people worldwide.
Abstract: Acute respiratory infections (ARI) are the leading cause of burden of disease worldwide and have been causally linked with exposure to pollutants from domestic biomass fuels in developing countries. We used longitudinal health data coupled with detailed monitoring and estimation of personal exposure from more than 2 years of field measurements in rural Kenya to estimate the exposure-response relationship for particulates < 10 microm diameter (PM(10)) generated from biomass combustion. Acute respiratory infections and acute lower respiratory infections are concave, increasing functions of average daily exposure to PM(10), with the rate of increase declining for exposures above approximately 1,000-2,000 microg/m(3). This first estimation of the exposure-response relationship for the high-exposure levels characteristic of developing countries has immediate and important consequences for international public health policies, energy and combustion research, and technology transfer efforts that affect more than 2 billion people worldwide.

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TL;DR: Examining the average annual rates of diarrhea in adults, as well as temperature and water availability from 1986 to 1994 for 18 Pacific Island countries, suggests that global climate change is likely to exacerbate diarrheal illness in many Pacific Island states.
Abstract: Freshwater resources are a high-priority issue in the Pacific region. Water shortage is a serious problem in many small island states, and many depend heavily on rainwater as the source of their water. Lack of safe water supplies is an important factor in diarrheal illness. There have been no previous studies looking specifically at the relationship between climate variability and diarrhea in the Pacific region. We carried out two related studies to explore the potential relationship between climate variability and the incidence of diarrhea in the Pacific Islands. In the first study, we examined the average annual rates of diarrhea in adults, as well as temperature and water availability from 1986 to 1994 for 18 Pacific Island countries. There was a positive association between annual average temperature and the rate of diarrhea reports, and a negative association between water availability and diarrhea rates. In the second study, we examined diarrhea notifications in Fiji in relation to estimates of temperature and rainfall, using Poisson regression analysis of monthly data for 1978-1998. There were positive associations between diarrhea reports and temperature and between diarrhea reports and extremes of rainfall. These results are consistent with previous research and suggest that global climate change is likely to exacerbate diarrheal illness in many Pacific Island countries.

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TL;DR: Outdoor ambient air pollutant exposures in communities are relevant to the acute exacerbation and possibly the onset of asthma, but the complexity of pollutant mixtures and etiologic heterogeneity of asthma has made it difficult to identify causal components in those mixtures.
Abstract: Outdoor ambient air pollutant exposures in communities are relevant to the acute exacerbation and possibly the onset of asthma. However, the complexity of pollutant mixtures and etiologic heterogeneity of asthma has made it difficult to identify causal components in those mixtures. Occupational exposures associated with asthma may yield clues to causal components in ambient air pollution because such exposures are often identifiable as single-chemical agents (e.g., metal compounds). However, translating occupational to community exposure-response relationships is limited. Of the air toxics found to cause occupational asthma, only formaldehyde has been frequently investigated in epidemiologic studies of allergic respiratory responses to indoor air, where general consistency can be shown despite lower ambient exposures. The specific volatile organic compounds (VOCs) identified in association with occupational asthma are generally not the same as those in studies showing respiratory effects of VOC mixtures on nonoccupational adult and pediatric asthma. In addition, experimental evidence indicates that airborne polycyclic aromatic hydrocarbon (PAH) exposures linked to diesel exhaust particles (DEPs) have proinflammatory effects on airways, but there is insufficient supporting evidence from the occupational literature of effects of DEPs on asthma or lung function. In contrast, nonoccupational epidemiologic studies have frequently shown associations between allergic responses or asthma with exposures to ambient air pollutant mixtures with PAH components, including black smoke, high home or school traffic density (particularly truck traffic), and environmental tobacco smoke. Other particle-phase and gaseous co-pollutants are likely causal in these associations as well. Epidemiologic research on the relationship of both asthma onset and exacerbation to air pollution is needed to disentangle effects of air toxics from monitored criteria air pollutants such as particle mass. Community studies should focus on air toxics expected to have adverse respiratory effects based on biological mechanisms, particularly irritant and immunological pathways to asthma onset and exacerbation.

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TL;DR: The results demonstrate that the male reproductive system is far more sensitive to DEHP early in development than when animals are exposed as juveniles or adults, and suggest that DEHP acts partly by mechanisms distinct from those of other antiandrogens.
Abstract: Several members of the phthalate ester family have antiandrogenic properties, yet little is known about how exposure to these ubiquitous environmental contaminants early in development may affect sexual development. We conducted experiments to determine effects of in utero and lactational exposure to the most prevalent phthalate ester, di(2-ethylhexyl) phthalate (DEHP), on male reproductive system development and sexual behavior. Sprague-Dawley rats were dosed with corn oil or DEHP (0, 375, 750, or 1,500 mg/kg/day, per os) from gestation day 3 through postnatal day (PND) 21. Dose-related effects on male offspring included reduced anogenital distance, areola and nipple retention, undescended testes, and permanently incomplete preputial separation. Testis, epididymis, glans penis, ventral prostate, dorsolateral prostate, anterior prostate, and seminal vesicle weights were reduced at PND 21, 63, and/or 105-112. Additional dose-related effects included a high incidence of anterior prostate agenesis, a lower incidence of partial or complete ventral prostate agenesis, occasional dorsolateral prostate and seminal vesicle agenesis, reduced sperm counts, and testicular, epididymal, and penile malformations. Many DEHP-exposed males were sexually inactive in the presence of receptive control females, but sexual inactivity did not correlate with abnormal male reproductive organs. These results suggest that in utero and lactational DEHP exposure also inhibited sexually dimorphic central nervous system development. No major abnormalities were found in any of eight control litters, but DEHP caused severe male reproductive system toxicity in five of eight litters at 375 mg/kg/day, seven of eight litters at 750 mg/kg/day, and five of five litters at 1,500 mg/kg/day. These results demonstrate that the male reproductive system is far more sensitive to DEHP early in development than when animals are exposed as juveniles or adults. The effects of DEHP on male reproductive organs and sexual behaviors and the lack of significant effects on time to vaginal opening and first estrus in their littermates demonstrate that DEHP (and/or its metabolites) affects development of the male reproductive system primarily by acting as an antiandrogen. The pattern of effects of in utero and lactational DEHP exposure differed from patterns caused by other phthalate esters, and the preponderance of anterior prostate agenesis appears to be unique among all chemicals. These results suggest that DEHP acts partly by mechanisms distinct from those of other antiandrogens.

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TL;DR: Evidence shows an association of amyotrophic lateral sclerosis with occupational EMF exposure although confounding is a potential explanation and further studies need to be designed to test specific hypotheses such as aspects of selection bias or exposure.
Abstract: Exposures to extremely low-frequency electric and magnetic fields (EMF) emanating from the generation, transmission, and use of electricity are a ubiquitous part of modern life. Concern about potential adverse health effects was initially brought to prominence by an epidemiologic report two decades ago from Denver on childhood cancer. We reviewed the now voluminous epidemiologic literature on EMF and risks of chronic disease and conclude the following: a) The quality of epidemiologic studies on this topic has improved over time and several of the recent studies on childhood leukemia and on cancer associated with occupational exposure are close to the limit of what can realistically be achieved in terms of size of study and methodological rigor. b) Exposure assessment is a particular difficulty of EMF epidemiology, in several respects: i) The exposure is imperceptible, ubiquitous, has multiple sources, and can vary greatly over time and short distances. ii) The exposure period of relevance is before the date at which measurements can realistically be obtained and of unknown duration and induction period. iii) The appropriate exposure metric is not known and there are no biological data from which to impute it. c) In the absence of experimental evidence and given the methodological uncertainties in the epidemiologic literature, there is no chronic disease for which an etiological relation to EMF can be regarded as established. d) There has been a large body of high quality data for childhood cancer, and also for adult leukemia and brain tumor in relation to occupational exposure. Among all the outcomes evaluated in epidemiologic studies of EMF, childhood leukemia in relation to postnatal exposures above 0.4 microT is the one for which there is most evidence of an association. The relative risk has been estimated at 2.0 (95% confidence limit: 1.27-3.13) in a large pooled analysis. This is unlikely to be due to chance but, may be, in part, due to bias. This is difficult to interpret in the absence of a known mechanism or reproducible experimental support. In the large pooled analysis only 0.8% of all children were exposed above 0.4 microT. Further studies need to be designed to test specific hypotheses such as aspects of selection bias or exposure. On the basis of epidemiologic findings, evidence shows an association of amyotrophic lateral sclerosis with occupational EMF exposure although confounding is a potential explanation. Breast cancer, cardiovascular disease, and suicide and depression remain unresolved.

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TL;DR: In this paper, climate change may affect exposures to air pollutants by affecting weather, anthropogenic emissions, and biogenic emissions and by changing the distribution and types of airborne allergens, but the specific types of change (i.e., local, regional, or global), the direction of change in a particular location, and the magnitude of change that may be attributable to climate change are a matter of speculation, based on extrapolating present understanding to future scenarios.
Abstract: Climate change may affect exposures to air pollutants by affecting weather, anthropogenic emissions, and biogenic emissions and by changing the distribution and types of airborne allergens. Local temperature, precipitation, clouds, atmospheric water vapor, wind speed, and wind direction influence atmospheric chemical processes, and interactions occur between local and global-scale environments. If the climate becomes warmer and more variable, air quality is likely to be affected. However, the specific types of change (i.e., local, regional, or global), the direction of change in a particular location (i.e., positive or negative), and the magnitude of change in air quality that may be attributable to climate change are a matter of speculation, based on extrapolating present understanding to future scenarios. There is already extensive evidence on the health effects of air pollution. Ground-level ozone can exacerbate chronic respiratory diseases and cause short-term reductions in lung function. Exposure to particulate matter can aggravate chronic respiratory and cardiovascular diseases, alter host defenses, damage lung tissue, lead to premature death, and possibly contribute to cancer. Health effects of exposures to carbon monoxide, sulfur dioxide, and nitrogen dioxide can include reduced work capacity, aggravation of existing cardiovascular diseases, effects on pulmonary function, respiratory illnesses, lung irritation, and alterations in the lung's defense systems. Adaptations to climate change should include ensuring responsiveness of air quality protection programs to changing pollution levels. Research needs include basic atmospheric science work on the association between weather and air pollutants; improving air pollution models and their linkage with climate change scenarios; and closing gaps in the understanding of exposure patterns and health effects.