Showing papers in "Journal of Toxicology and Environmental Health in 2005"
TL;DR: Air pollution is associated with a broad spectrum of acute and chronic health effects, the nature of which may vary with the pollutant constituents, and particulate air pollution is consistently and independently related to the most serious effects, including lung cancer and other cardiopulmonary mortality.
Abstract: As part of the World Health Organization (WHO) Global Burden of Disease Comparative Risk Assessment, the burden of disease attributable to urban ambient air pollution was estimated in terms of deaths and disability-adjusted life years (DALYs). Air pollution is associated with a broad spectrum of acute and chronic health effects, the nature of which may vary with the pollutant constituents. Particulate air pollution is consistently and independently related to the most serious effects, including lung cancer and other cardiopulmonary mortality. The analyses on which this report is based estimate that ambient air pollution, in terms of fine particulate air pollution (PM(2.5)), causes about 3% of mortality from cardiopulmonary disease, about 5% of mortality from cancer of the trachea, bronchus, and lung, and about 1% of mortality from acute respiratory infections in children under 5 yr, worldwide. This amounts to about 0.8 million (1.2%) premature deaths and 6.4 million (0.5%) years of life lost (YLL). This burden occurs predominantly in developing countries; 65% in Asia alone. These estimates consider only the impact of air pollution on mortality (i.e., years of life lost) and not morbidity (i.e., years lived with disability), due to limitations in the epidemiologic database. If air pollution multiplies both incidence and mortality to the same extent (i.e., the same relative risk), then the DALYs for cardiopulmonary disease increase by 20% worldwide.
1,000 citations
TL;DR: Findings from updated analyses of data from 90 U.S. cities assembled for the National Morbidity, Mortality, and Air Pollution Study (NMMAPS) were unchanged and the effect of PM10 on respiratory and cardiovascular mortality combined was greater, but the pattern across models was similar.
Abstract: This article presents findings from updated analyses of data from 90 U.S. cities assembled for the National Morbidity, Mortality, and Air Pollution Study (NMMAPS). The data were analyzed with a generalized additive model (GAM) using the gamfunction in S-Plus (with default convergence criteria previously used and with more stringent criteria) and with a generalized linear model (GLM) with natural cubic splines. With the original method, the estimated effect of PM(10) (particulate matter 10 microm in mass median aerodynamic diameter) on total mortality from nonexternal causes was a 0.41% increase per 10-microg/m(3) increase in PM(10); with the more stringent criteria, the estimate was 0.27%; and with GLM, the effect was 0.21%. The effect of PM(10) on respiratory and cardiovascular mortality combined was greater, but the pattern across models was similar. The findings of the updated analysis with regard to spatial heterogeneity across the 90 cities were unchanged from the original analyses.
387 citations
TL;DR: Current ongoing analysis using the extended follow-up information will explore the role of ecologic, economic, and, demographic covariates in the particulate air pollution and mortality association, and whether critical instances in time of exposure to fine particles influence the risk of mortality from cardiopulmonary and lung cancer.
Abstract: This article provides an overview of previous analysis and reanalysis of the American Cancer Society (ACS) cohort, along with an indication of current ongoing analyses of the cohort with additional follow-up information through to 2000. Results of the first analysis conducted by Pope et al. (1995) showed that higher average sulfate levels were associated with increased mortality, particularly from cardiopulmonary disease. A reanalysis of the ACS cohort, undertaken by Krewski et al. (2000), found the original risk estimates for fine-particle and sulfate air pollution to be highly robust against alternative statistical techniques and spatial modeling approaches. A detailed investigation of covariate effects found a significant modifying effect of education with risk of mortality associated with fine particles declining with increasing educational attainment. Pope et al. (2002) subsequently reported results of a subsequent study using an additional 10 yr of follow-up of the ACS cohort. This updated analysis included gaseous copollutant and new fine-particle measurements, more comprehensive information on occupational exposures, dietary variables, and the most recent developments in statistical modeling integrating random effects and nonparametric spatial smoothing into the Cox proportional hazards model. Robust associations between ambient fine particulate air pollution and elevated risks of cardiopulmonary and lung cancer mortality were clearly evident, providing the strongest evidence to date that long-term exposure to fine particles is an important health risk. Current ongoing analysis using the extended follow-up information will explore the role of ecologic, economic, and, demographic covariates in the particulate air pollution and mortality association. This analysis will also provide insight into the role of spatial autocorrelation at multiple geographic scales, and whether critical instances in time of exposure to fine particles influence the risk of mortality from cardiopulmonary and lung cancer. Information on the influence of covariates at multiple scales and of critical exposure time windows can assist policymakers in establishing timelines for regulatory interventions that maximize population health benefits.
189 citations
TL;DR: In this paper, the authors quantified the process in primary mouse hepatocytes using the COMET assay in both the presence and absence of CYP450 inhibitors known to block acute CYN cytotoxicity.
Abstract: Cylindrospermopsin (CYN) is a cyanobacterial toxin found in drinking-water sources world wide. It was the likely cause of human poisonings in Australia and possibly Brazil. Although CYN itself is a potent protein synthesis inhibitor, its acute toxicity appears to be mediated by cytochrome p-450 (CYP450)-generated metabolites. CYN also induces genotoxic effects both in vitro and in vivo, and preliminary evidence suggests that tumors are generated by oral exposure to CYN. To understand the role of CYP450-activated CYN metabolites on in vitro genotoxicity, this study quantified the process in primary mouse hepatocytes using the COMET assay in both the presence and absence of CYP450 inhibitors known to block acute CYN cytotoxicity. CYN was cytotoxic at concentrations above 0.1 μM(EC50 = 0.5 μM) but produced significant increases in Comet tail length, area, and tail moment at 0.05 μM and above; hence genotoxicity is unlikely to be secondary to metabolic disruption due to toxicity. The CYP450 inhibitors omepraz...
186 citations
TL;DR: This article examines the use of interpolation methods and dynamic modeling techniques, including modeling of time–activity patterns for air pollution epidemiology, and raises the questions of which exposure metrics should be used and what level of spatial and temporal accuracy is required to meet the needs of environmental epidemiology.
Abstract: Geographical information systems (GIS) offer potentially powerful tools for exposure assessment in support of both air pollution epidemiology and air quality policy. To date, however, most epidemiological applications have relied on relatively simple techniques, such as buffering and distance functions. In part, this reflects the often limited understanding of the underlying exposure pathways or etiology and the nonspecific nature of the hypotheses being examined. In part, also, it reflects lack of awareness or suspicion of the more advanced capabilities for exposure modeling available in GIS. This article outlines and illustrates some of these techniques. After an initial consideration of "traditional" location-based methods, it examines the use of interpolation methods and dynamic modeling techniques, including modeling of time-activity patterns. It then discusses some of the implications of these different approaches for air pollution epidemiology, and raises the questions of which exposure metrics should be used and what level of spatial and temporal accuracy is required to meet the needs of environmental epidemiology.
166 citations
TL;DR: The estrogenic effects of three classes of substances included in cosmetic formulations—parabens, ultraviolet (UV) screens, and musk fragrances—were studied and eight of the 15 substances tested showed specific estrogenic activity with the following degree of potency on ERα.
Abstract: In this work, the estrogenic effects of three classes of substances included in cosmetic formulations-parabens, ultraviolet (UV) screens, and musk fragrances-were studied. Their estrogenic activity was measured with the use of three reporter cell lines: HELN, HELN ERalpha, and HELN ERbeta. These three cell lines allowed for the measurement of estrogenic activity toward estrogen receptors alpha and beta (ERalpha and ERbeta, while taking nonspecific interactions into account. Eight of the 15 substances tested showed specific estrogenic activity with the following degree of potency on ERalpha butylparaben > propylparaben > homosalate = octyl-dimethyl-PABA = 4-methyl-benzylidenecamphor = octyl-methoxycinnamate > ethylparaben = galaxolide. Among these active substances, parabens activated ERalpha and ERbeta similarly, UV screens activated ERalpha moderately and had almost no effect on ERbeta, and fragrances did not activate ERbeta. Methylparaben, ethylparaben, musk moskene, celestolide, and cashmeran did not activate estrogenic responses up to 10(-5) M. Musk ketone and benzophenone-3 were not considered estrogenic at 10(-5) M.
153 citations
TL;DR: Before urinary DAP concentrations can be reliably used in exposure and risk assessment, the proportion of the concentration attributable to environmental DAP exposure, particularly through the diet, must be ascertained.
Abstract: This study was designed to determine whether dialkylphosphates (DAPs) are present in fresh fruit juices, as a result of organophosphorus (OP) pesticides degradation. Fresh conventional and organic fruit (apple and orange) juices were purchased from local grocery stores. DAPs were found in both conventional and organic juices, and the original levels were higher, for both apple and orange juices, in conventional than in organic juices. Additional DAPs were found in OP pesticide fortified juices after 72 h of storage at 4°C, suggesting a degradation of OP pesticides in juices. Overall, 12% and 36.2% of fortified azinphosmethyl, a dimethyl OP pesticide, and the combination of fortified diazinon and chlorpyrifos, both diethyl OP pesticides, were degraded to dimethyl and diethyl DAPs, respectively. Although the exact mechanism of the degradation is unknown, hydrolysis is likely the cause of OP pesticide degradation in juice. The presence of DAPs in fresh fruit juices clouds the validity of using urinary DAP me...
129 citations
TL;DR: The congener profiles observed in this study varied considerably, however these congener profile differ from the pattern seen in U.S. human milk, human blood and in food, where PBDEs 47 and 99 predominate.
Abstract: Polybrominated diphenyl ethers (PBDEs), a type of brominated flame retardant chemically and toxicologically similar to polychlorinated biphenyls (PCBs), are a class of emerging environmental and human contaminants. They have recently been detected in U.S. milk, blood, and food at the highest levels in the world. This pilot study was undertaken with the aim of determining levels of PBDE in the U.S. indoor environment, to assess the potential exposure to PBDEs from computer surfaces and carpets. Food of animal origin is the usual source of polychlorinated dibenzo-p-dioxin (PCDD), polychlorinated dibenzofurans (PCDF), and PCBs in humans, but there may also be environmental sources for intake of PBDEs. It was also our aim to characterize the PBDE congener profile in these indoor environmental samples. Four computer wipe samples and 9 domestic vacuum-sweeping samples were analyzed for 13 PBDE congeners, PBDEs 17 (2,2',4), 28 (2,4,4'?), 47 (2,2',4,4'?), 66 (2,3',4,4'?), 77 (3,3',4,4'?), 85 (2,2',3,4,4'?), 99 (2,2'4,4',5), 100 (2,2',4,4',6), 138 (2,2',3,4,4',5'?), 153 (2,2',4,4',5,5'?), 154 (2,2',4,4',5,6'?), 183 (2,2',3,4,4',5',6), and 209 (2,2',3,3',4,4',5,5',6,6'?). All samples tested positive for PBDEs. PBDE 209 was the dominant congener in all 4 computer wipe samples and in 7 out of the 9 vacuum dust samples. The congener profiles observed in this study varied considerably, a finding that has been observed previously. However these congener profiles differ from the pattern seen in U.S. human milk, human blood and in food, where PBDEs 47 and 99 predominate.
126 citations
TL;DR: DNA hypomethylation at the promoter region of the estrogen receptor α (ERα) gene was investigated by methylation-specific polymerase chain reaction (MSP) and suggested that an altered ER mRNA expression by BBP might be related to aberrant DNA methylation in the promoter.
Abstract: The phthalates are ubiquitous industrial plasticizers and include agents such as di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and butyl benzyl phthalate (BBP), which are classified as endocrine disruptors because of their anti-androgenic or pro-estrogenic effects. A recent study suggested that DBP produced the hypomethylation of c-myc protooncogene in mouse liver to activate c-myc. In the present study, DNA hypomethylation at the promoter region of the estrogen receptor α (ERα) gene was investigated by methylation-specific polymerase chain reaction (MSP) in a human breast cancer (MCF7) and in a normal (MCF10A) cell line after DBP treatment. Yeast-based estrogen receptor transcription assays showed that hERα gene expression was induced by BBP but not DBP. Moreover, MCF7 cells treated with BBP or DBP at 10−5M led to the demethylation of ERα promoter-associated CpG islands. These data suggest that an altered ER mRNA expression by BBP might be related to aberrant DNA methylation in the promoter...
107 citations
TL;DR: Findings suggest that paraquat may induce the pathogenesis of dopaminergic neurons through oxidative stress, and verify the hypothesis that paraQuat produces oxidative stress-mediated toxicity in SH-SY5Y cells.
Abstract: Paraquat (PQ) is a cationic nonselective bipyridyl herbicide widely used to control weeds and grasses in agriculture. Epidemiologic studies indicate that exposure to pesticides can be a risk factor in the incidence of Parkinson's disease (PD). A strong correlation has been reported between exposure to paraquat and PD incidence in Canada, Taiwan, and the United States. This correlation is supported by animal studies showing that paraquat produces toxicity in dopaminergic neurons of the rat and mouse brain. However, it is unclear how paraquat triggers toxicity in dopaminergic neurons. Based on the prooxidant properties of paraquat, it was hypothesized that paraquat may induce oxidative stress-mediated toxicity in dopaminergic neurons. To explore this possibility, dopaminergic SH-SY5Y cells were treated with paraquat, and several biomarkers of oxidativestress were measured. First, a specific dopamine transporter inhibitor GBR12909 significantly protected SY5Y cells against the toxicity of paraquat, indicating that paraquat exerts its toxicity by a mechanism involving the dopamine transporter (DAT). Second, paraquat increased intracellular levels of reactive oxygen species (ROS), but decreased the levels of glutathione. Third, paraquat inhibited glutathione peroxidase activity, but did not affect glutathione reductase activity. On the other hand, paraquat increased GST activity by 24 h, after which GST activity returned to the control value at 48 h. Fourth, paraquat dissipated mitochondrial transmembrane potential (MTP). Fifth, paraquat produced increases of malondialdehyde (MDA) and protein carbonyls, as well as DNA fragmentation, indicating oxidative damage to major cellular components. Sixth, paraquat increased the protein level of heme oxygenase-1 (HO-1). Taken together, these findings verify our hypothesis that paraquat produces oxidative stress-mediated toxicity in SH-SY5Y cells. Thus, current findings suggest that paraquat may induce the pathogenesis of dopaminergic neurons through oxidative stress.
105 citations
TL;DR: It is demonstrated that OC exposure significantly influences specific lymphocyte proliferation responses and part of the cell-mediated immunity, which also is associated with impaired ability to produce antibodies.
Abstract: Previous studies have reported alarmingly high levels of organochlorines (OCs), particularly polychlorinated biphenyls (PCBs), in free-ranging polar bears (Ursus maritimus). In this study plasma concentration of PCBs ranged from 14.8 to 200 ng/g wet weight. The aim of the study was to investigate associations between OCs and lymphocyte proliferation after in vitro stimulation with different mitogens and antigens. In 1998 and 1999, 26 and 30 free-ranging polar bears from Svalbard and Churchill, Canada, respectively, were recaptured 32-40 d following immunization with inactivated tetanus toxoid and hemocyanin from keyhole limpets (KLH) to sensitize lymphocytes. At recapture, blood was sampled for determination of plasma levels of PCBs and organochlorine pesticides (OCPs) and lymphocyte proliferation after in vitro stimulation with specific mitogens--phytohemagglutinin (PHA), pokeweed mitogen (PWM), concanavalin A (Con A), lipopolysaccharide (LPS), and purified protein derivative of Mycobacterium avium subsp. paratuberculosis (PPD)--and antigens: tetanus toxoid and KLH. The combinations of sum(PCBs) (sum of 12 individual PCB congeners), sum(OCPs) (sum of 6 OCPs), and their interactions contributed up to 15% of the variations in the lymphocyte responses. By using multiple regression analyses, followed by classical mathematic function analyses, thresholds for immunomodulation were estimated. Depending on the lymphocyte proliferation response studied, the estimated thresholds for significant immunomodulation were within the concentration ranges 32-89 ng/g wet weight (ww) and 7.8-14 ng/g ww for sum(PCBs) and sum(OCPs), respectively. Thus, this study demonstrated that OC exposure significantly influences specific lymphocyte proliferation responses and part of the cell-mediated immunity, which also is associated with impaired ability to produce antibodies (Lie et al., 2004).
TL;DR: Data show that chemical composition, form, durability, and cell toxicity indicate balangeroite as a potentially harmful fibrous mineral that needs to be examined by further chemical and cellular tests.
Abstract: In the Italian western Alps, asbestos mineralization (both chrysotile and tremolite amphibole) takes place from serpentinites, together with other less common asbestiform minerals not regulated by the current legislation. In the context of a study on the evaluation of the asbestos risk in this area, the possible role played by the associated asbestiform minerals in the overall toxicity of the airborne fraction has been examined. The first mineral investigated was balangeroite [(Mg,Fe2+,Fe3+,Mn2+)42Si16O54(OH)36], an iron-rich asbestiform contaminant of chrysotile from the Balangero mine (Piedmont), which crystallizes as rigid and brittle fibers. In order to prepare a sample in a form appropriate for chemical and cellular tests, the fibers were separated from the rock and comminuted without damage to their crystalline structure and surface state (as confirmed by X-ray diffraction [XRD] and ultraviolet–visible [UV-Vis] spectroscopy). The first properties examined were durability in simulated body fluids (Ga...
TL;DR: The effects of dust storms on CVD were prominent 1 d after the event (3.65% increase) and it may be worthwhile to focus more on the potential adverse effects of ADS events in the future.
Abstract: In spring, windblown dust storms originating in the deserts of Mongolia and China make their way to Taipei city. These occurrences are known as Asian dust storm (ADS) events. The objective of this study was to assess the possible effects of ADS on the hospital cardiovascular disease (CVD) admissions of residents in Taipei, Taiwan, during the period from 1996 to 2001. Fifty-four dust storm episodes, which were classified as index days, were identified. Daily CVD admissions on index days were compared with admissions on comparison days. Two comparison days were selected for each index day, 7 d before the index day and 7 d after the index day. The effects of dust storms on CVD were prominent 1 d after the event (3.65% increase). However, the association was not statistically significant. Nonetheless, it may be worthwhile to focus more on the potential adverse effects of ADS events in the future.
TL;DR: The relationship between freshwater fish consumption and mercury was significant in all biological media and the high-consumption group had much higher mercury levels in blood, hair, blood, urine, and urine than the low-cons consumption group, which implies that the typical blood–hair ratio of 1:250 is valid also for exposure to low amounts of methylmercury.
Abstract: Human exposure to methylmercury occurs mainly via consumption of fish. The aim of the study was to investigate the influence of freshwater fish consumption on mercury levels in hair, blood, urine, and end-exhaled air. Twenty subjects without dental amalgam fillings were recruited from sport-fishing societies. They ranged in age from 61 to 87 yr. Six individuals ate freshwater fish at least once a week and were categorized as high consumers. Eight individuals were classified as medium consumers and ate freshwater fish at least once a month but less than once a week. Six individuals were categorized as low consumers and had not eaten freshwater fish in the past 3 mo. Among the high consumers, median concentrations of mercury were 8.6 μg/L in blood, 2.4 μg/g in hair, 10 pg/L in end-exhaled air, and 1.1 μg/g creatinine in urine. The relationship between freshwater fish consumption and mercury was significant in all biological media. The high-consumption group had much higher mercury levels in blood (9-fold), ...
TL;DR: How each concept encompasses many lower level issues such as meteorological dispersion of pollutants, time–space activity patterns, and population distributions of susceptible individuals in time and space is discussed.
Abstract: This article addresses the question of how to incorporate spatial processes into the assessment of chronic health effects from air pollution exposure. An analytic framework is developed around three related concepts: (1) the geography of susceptibility; (2) the geography of exposure; and (3) points of intersection between these two, termed the geography of risk. The article discusses how each concept encompasses many lower level issues such as meteorological dispersion of pollutants, time-space activity patterns, and population distributions of susceptible individuals in time and space. A key premise is that researchers should target studies with high degrees of overlap between geographies of exposure and susceptibility. Instances where the overlap remains incomplete, or systematically biased, usually produce attenuated or unreliable risk estimates, and some of this discordance may find expression in spatially autocorrelated residuals.
TL;DR: The data suggest that Koreans (women and children) were exposed to significant levels of phthalate, which should be reduced to as low a level as technologically feasible to protect Koreans from the exposure to toxic phthalates.
Abstract: Some phthalates, such as di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP), and their metabolites are suspected of producing teratogenic and endocrino-disrupting effects. In this study, urinary levels of phthalates (DEHP, DBP, diethyl phthalate (DEP), butylbenzyl phthalate BBP), and monoethylhexyl phthalate (MEHP, a major metabolite of DEHP) were measured by high performance liquid chromatography (HPLC) in human populations (women [hospital visitors], n = 150, and children, n = 150). Daily exposure level of DEHP in children was estimated to be 12.4 µg/kg body weight/d (male 9.9 µg/kg body weight/d, female 17.8 µg/kg body weight/d), but, in women was estimated to be 41.7 µg/kg body weight/d, which exceeded the tolerable daily intake (TDI, 37 µg/kg body weight/day) level established by the European Union (EU) Scientific Committee for Toxicity, Ecotoxicity, and the Environment (SCTEE) based on reproductive toxicity. Based on these data, hazard indices (HIs) were calculated to be 1.12 (41.7/37 TDI...
TL;DR: These analyses support the approach of assuming twofold greater inhalation dose in children than adults, although there are cases in which this differential can be greater and others where it can be less.
Abstract: Young children have a greater ventilation rate per body weight or pulmonary surface area as compared to adults. The implications of this difference for inhalation dosimetry and children’s risk assessment were evaluated in runs of the U.S. Environmental Protection Agency (U.S. EPA) 1994 reference concentration (RfC) methodology and the ICRP 1994 inhalation dosimetry model. Dosimetry estimates were made for 3-mo-old children and adults for particles and Category 1 and 2 reactive gases in the following respiratory-tract regions: extrathoracic (ET), tracheobronchial (BB), bronchioles (bb), and pulmonary (PU). Systemic dosimetry estimates were made for nonreactive (Category 3) gases. Results suggest similar ET dosimetry for children and adults for all types of inhaled materials. BB dosimetry was also similar across age groups except that the dosimetry of ultrafine particles in this region was twofold greater in 3-mo-old children than in adults. In contrast, the bb region generally showed higher dosimetry of pa...
TL;DR: Losses of POPs were significantly and linearly correlated with the losses of lipid during cooking, suggesting removal of lipids is the critical factor for POPs reduction in cooked fish.
Abstract: Recent studies have raised concern over the presence of high levels of persistent organic pollutants (POPs) in farmed fish relative to wild specimens of the same species, particularly salmon. Although cooking is known to reduce the burden of POPs in fish, the mechanisms of loss/degradation are not clearly understood. This study investigated the loss of POPs, including polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), p,p'-DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and its related metabolites (sum noted as DDTs), and chlordane congeners, from salmon (Salmo salar) steaks when subjected to baking, boiling, frying, or microwave cooking. Ranges in the raw flesh were 25.1-62.9 ng/g wet weight (ww) for PCBs, 2.5-7.6 ng/g ww for PBDEs, 2.4-5.3 ng/g ww for chlordanes, and 17.5-43.8 ng/g ww for DDTs. Analysis of raw steaks from along the fish body revealed a significant variation of POP concentrations along the fish body, with higher concentrations at the head end than the tail, with a peak in the central section. After cooking, levels of POPs decreased in salmon steak with an average loss of 26 +/- 15% relative to the initial POP load in the raw steak. The removal of the skin from the cooked salmon steak resulted in a further average loss of 9 +/- 3%. The loss of POPs did not differ significantly between cooking methods. Losses of POPs were significantly and linearly correlated with the losses of lipid during cooking, suggesting removal of lipids is the critical factor for POPs reduction in cooked fish. Cooking of raw fish contaminated with POPs can therefore be expected to reduce the consumption exposure risk to human health.
TL;DR: The immune system was suppressed by oral MA exposure, and splenic NK activity in exposed mice was significantly enhanced.
Abstract: The abuse of methamphetamine (MA) is an increasingly growing problem globally and produces serious side effects. In the present study, the immunomodulating effects of MA were examined on the immune system after MA (5 mg/kg body weight) was administered daily orally for 14 d. The immune system was evaluated by the antibody response to sheep red blood cells (SRBC; plaque assay and serum immunoglobulin [Ig] G), natural killer (NK) activity, lymphocyte subpopulations in the spleen and thymus, and concanavalin A (Con A)- and lipopolysaccharide (LPS)-stimulated lymphocyte proliferation using splenocytes. Body weight, spleen weight, and thymus weight generally decreased in MA-treated mice. MA treatment induced an increase in the percentage of CD4+ cells with simultaneous decrease in the percentages of CD8+ and double-positive CD4+CD8+ in thymus. MA inhibited the IgM plaque-forming cell number, and lowered the level of IgG, the proliferation of mitogen-stimulated B and T cells, and the growth of granulocyte–macro...
TL;DR: Results indicate that alcohol and its metabolite acetaldehyde induce fetal developmental abnormalities by disrupting cellular differentiation and growth and demonstrate that some antioxidants can partially protect against the alcohol-induced embryonic developmental toxicity.
Abstract: Alcohol drinking during pregnancy results in abnormal fetal development, including fetal alcohol syndrome (FAS) in humans and experimental animals. FAS is characterized by two major effects, including central nervous system (CNS) dysfunction and multiple anomalies recognizable mainly as a typical face. However, the mechanisms of alcohol-induced embryotoxicity have not been clearly demonstrated. The aim of the present study was to investigate the possible mechanisms underlying ethanol-induced FAS in the developing embryo. First, ethanol-induced developmental abnormalities were investigated in vitro. Postimplantation embryos at gestation day (GD) 9.5 were cultured for 48 h and observed for morphological changes. Ethanol-mediated changes in proteins regulated apoptosis (p53 and bcl-2), antioxidant (vitamin E and catalase) activities, generation of reactive oxygen species (ROS), and oxidative DNA damage shown as 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured in embryonic midbrain cells. Alcohol or acetaldehyde significantly induced cytotoxicity in cultured rat embryonic midbrain cells. The levels of p53, bcl-2, and 8-OHdG were concomitantly changed by alcohol and acetaldehyde treatment in midbrain cells. Injured cells induced by ROS were increased by alcohol or acetaldehyde treatment in midbrain cells. Cotreatment with alcohol or acetaldehyde and catalase decreased cytotoxicity in midbrain cells. In postimplantation embryo culture, alcohol or acetaldehyde-treated embryos showed retardation of embryonic growth and development in a concentration-dependent manner. These results indicate that alcohol and its metabolite acetaldehyde induce fetal developmental abnormalities by disrupting cellular differentiation and growth. Data demonstrate that some antioxidants can partially protect against the alcohol-induced embryonic developmental toxicity.
TL;DR: This conclusion supports the policy position of the U.S. Environmental Protection Agency that there should be no growth of Bacillus anthracis spores from all postremediation environmental samples, for the cleanup of a site to be judged effective and for that site to been considered safe for reoccupancy.
Abstract: Since the 2001 attacks in which Bacillus anthracisspores were mailed to various media offices and two U.S. Senators, considerable interest has focused on developing estimates of the risk of contracting inhalational anthrax from exposure to such spores. Credible risk estimates would have significant utility in establishing future cleanup goals for contaminated sites. To perform a meaningful risk assessment, one needs sufficient data to identify the hazards, conduct dose-response assessment, and assess exposure. This report reviews the existing data on mortality produced by Bacillus anthracisspores in laboratory animals and humans. In particular, it focuses on the 11 cases of inhalational anthrax resulting from the 2001 attacks and their impact on hazard identification activities. It also addresses factors that may contribute to increased risk among exposed populations and the sources of uncertainty in dose response analysis. The article examines the state of the science for assessing exposure levels to Bacillus anthracis spores and concludes that significant challenges exist to performing robust assessments of risk. This conclusion supports the policy position of the U.S. Environmental Protection Agency (EPA) that there should be no growth of Bacillus anthracis spores from all postremediation environmental samples, for the cleanup of a site to be judged effective and for that site to be considered safe for reoccupancy. This has been the ultimate criterion for efficacy of cleanups performed in response to the 2001 anthrax attacks.
TL;DR: Blood levels of polychlorinated biphenyls, PCBs, and DDE were quantified in free-ranging seals, and an inverse relationship between red blood cell count and PBDEs was found in seals, which may serve as sentinel indications of contaminant-induced alterations in harbor seals of SFB.
Abstract: An expanding body of research indicates that exposure to contaminants may impact marine mammal health, thus possibly contributing to population declines. The harbor seal population of the San Francisco Bay (SFB), California, has suffered habitat loss and degradation, including decades of environmental contamination. To explore the possibility of contaminant-induced health alterations in this population, blood levels of polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), and polybrominated diphenyl ethers (PBDEs) were quantified in free-ranging seals; relationships between contaminant exposure and several key hematological parameters were examined; and PCB levels in the present study were compared with levels determined in SFB seals a decade earlier. PCB residues in harbor seal blood decreased during the past decade, but remained at levels great enough that adverse reproductive and immunological effects might be expected. Main results included a positive association between leukocyte ...
TL;DR: The results suggested that the NADPH oxidase, MnSOD, and e-NOS polymorphisms, but not catalase, might play a role in the development of arsenic-related hypertension, especially in subjects with high triglyceride levels.
Abstract: The association of 4 genetic polymorphisms, NAD(P)H oxidase, manganese superoxide dismutase (MnSOD), catalase, and endothelial nitric oxide synthase (e-NOS), was assessed with arsenic-related hypertension risk among 79 hypertensive cases and 213 controls in an arseniasis-hyperendemic area of Taiwan. Overall, MnSOD polymorphism significantly increased the risk of hypertension regardless of arsenic exposure. NADPH oxidase and eNOS polymorphisms were significantly associated with hypertension risk in the high arsenic expo- sure group; however, catalase polymorphism was not associated with hypertension. Groups were further stratified by triglyceride levels to evaluate whether the cumulative arsenic expo- sure combined the three polymorphisms together. The adjusted adds ratios (ORs) of at least two risk factors of the cumulative arsenic exposure and MnSOD, NADPH oxidase, and eNOS three-polymorphism combination versus any one risk factor of them were 0.8 (95% CI 0.3-2.3) for individuals with low triglyceride levels ( 110 mg/dl), respectively. These results suggested that the NADPH oxidase, MnSOD, and e-NOS polymorphisms, but not catalase, might play a role in the development of arsenic-related hypertension, especially in subjects with high triglyceride levels. This study was supported by grants NSC-86-2314-B-038-038, NSC-87-2314-B-038-029, NSC-88- 2314-B-038-112, NSC-88-2318-B-038-002-M51, NSC-89-2320-B-038-013, NSC-89-2318-B-038-M51, NSC-89-2314-B-038-049, NSC-90-2320-B-038-021, NSC-90-2320-B-002-197, NSC-90-2320-B-038-021, NSC-91-3112-B-038-001, NSC-92-2320-B-002-156, NSC-92-3112-B-038-001, and NSC-92-2321-B-038- 004 from the National Science Council of the ROC.
TL;DR: Daily intake of As, DDTs, heptachlor, and PCBs in seafood exceeded the conservative cancer benchmark concentrations set by the U.S. Environmental Protection Agency (EPA), suggesting that a significant number of people are potentially at risk in Singapore over a lifetime from seafood consumption.
Abstract: In this study, the levels of several heavy metals and persistent organic pollutants (POPs) were measured in the edible portions of 20 different seafood types consumed in Singapore (2 < n < 12). The mean heavy metal concentrations among the seafood types ranged from below detection limits (BLD) to 14.2 μg/g wet weight (ww) for As (shark), to 0.50 μg/g ww for Cd (kunning), to 25.5 μg/g ww for Cu (gray prawn), to 0.58 μg/g ww for Hg (eel), and to 1.21 μg/g ww for Pb (salmon). Chlordane, polychlorinated biphenyls (PCBs), and p, p′-DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and its related metabolites (sum noted as DDTs) were the main POPs found among the seafood types, with highest concentrations in salmon fillets and green mussels. Polybrominated diphenyl ether (PBDE) concentrations in salmon fillets (2.75 ng/g ww) were one order of magnitude lower than the highest concentration of PCBs (28.5 ng/g ww). The mean daily intake of contaminants from seafood was calculated for the general population of Si...
TL;DR: Data indicated that prenatal exposure to PCBs and PCDFs may have implications for boys’ sex hormone homeostasis at puberty, and further studies are needed to identify the congeners of PCBs/PCDFs responsible for disruption of the endocrine system.
Abstract: Polychlorinated biphenyls (PCBs) and dibenzofurans (PCDFs) are persistent environmental pollutants shown to adversely interact with several functions of the endocrine system. In 1978-1979, over 2000 Taiwanese people ingested rice oil accidentally contaminated with PCBs and PCDFs. This is one of the major toxic exposure episodes that occurred globally and was later called Yucheng (oil disease in Chinese). The children born to exposed Yucheng women were therefore exposed in utero to high doses of PCBs/PCDFs. In 1995, 60 Yucheng and 61 control boys participated in physical examination, and serum hormones were measured by radioimmunoassay (RIA). Age, body weight, body height, Tanner status, testicular size, serum luteinizing hormone (LH), prolactin (PRL), thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) levels were not statistically different between Yucheng and control boys in the subgroups of before and at the age of puberty. However, the serum estradiol (E2) levels were significant higher in Yucheng boys at the age of puberty. Yucheng and control boys were further divided into two subgroups, those before (age or = 13 yr). There was a decrease of serum testosterone (TT) levels and increase of serum follicle-stimulating hormone (FSH) levels in Yucheng boys at the age of puberty as compared with controls. There was a significant decrease of the square root of TT/E2 and TT/FSH; however, the square root of E2/FSH was increased in Yucheng boys at the age of puberty as compared with controls. Data indicated that prenatal exposure to PCBs and PCDFs may have implications for boys' sex hormone homeostasis at puberty. Further studies are needed to identify the congeners of PCBs/PCDFs responsible for disruption of the endocrine system, as well as the mechanisms of such disruption.
TL;DR: Tocopherol seems to be a potential useful biomarker for exposure to PBDEs in bird species, and levels of retinol, retinyl palmitate, and α-tocopherol were measured in the liver of the newly hatched chicks and levels correlated negatively to the exposure toPBDE-99.
Abstract: Polybrominated diphenyl ethers (PBDEs) used to prevent fire are found in several products, such as textiles, electronics, and building materials. They are lipophilic and persistent substances, and their toxicological endpoints resemble those of polychlorinated bipenyls (PCBs). One of the most abundant congeners of PBDEs in wildlife is the 2,2',4,4',5-pentabromodiphenyl ether (PBDE-99). To study the effect of PBDE-99 on vitamin status in birds and evaluate the possible application of vitamins as biomarkers for use in monitoring of wildlife, eggs of domestic duck (Anas platyrhynchos) were exposed by yolk sac injection to environmental realistic doses of this congener (0.1, 1, or 10 ng/g ww). Levels of retinol (vitamin A), retinyl palmitate, and a-tocopherol (vitamin E) were measured in the liver of the newly hatched chicks, and levels of retinol and tocopherol were also measured in plasma. Liver tocopherol levels correlated negatively to the exposure to PBDE-99. This is an indication that exposure to PBDE-99 reduces levels of tocopherol in liver. Thus, tocopherol seems to be a potential useful biomarker for exposure to PBDEs in bird species.
TL;DR: The results are cause for concern as they suggest an AhR-independent pathway through which non-coplanar PCBs modulate phagocytosis, the immune system's first line of defense, possibly increasing the risk to developing infectious disease.
Abstract: Organochlorine (OC) contaminants, notably polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are ubiquitous in all ecosystems and found in the tissues of humans and wildlife. Although the immunotoxicity of coplanar, dioxinlike PCBs is well documented, the adverse effects exerted by non-coplanar, non-dioxinlike PCBs have received little attention. Direct causal relationship between PCB and dioxin exposure and the observed detrimental effects on the immune system has yet to be fully established in humans. The immunomodulatory potential of toxic coplanar PCB 169 and TCDD and abundant non-coplanar PCBs 138, 153, and 180 on human leukocyte phagocytosis, an important innate immune function that initiates the clearance of pathogens, was tested upon in vitro exposure. Mixture and concentration-response experiments demonstrated a suppression of phagocytosis by non-coplanar PCBs suggesting a previously unrecognized aryl hydrocarbon receptor (AhR)-independent pathway. Regression analysis revealed that reduction of phagocytosis was mostly explained by the non-coplanar congeners. The effects on phagocytosis could not be accurately predicted by either the currently used toxic equivalence (TEQ) approach or the mouse model, thus undermining the use of the traditional models in the risk assessment for OC mixtures containing non-coplanar congeners. Our results are cause for concern as they suggest an AhR-independent pathway through which non-coplanar PCBs modulate phagocytosis, the immune system's first line of defense, possibly increasing the risk to developing infectious disease.
TL;DR: The application of stress appeared to increase brain uranium clearance, as initial tissue levels were similar in stressed and unstressed rats.
Abstract: Long-term exposure to depleted uranium (DU) has been shown to increase brain uranium and alter hippocampal function; however, little is known about the short-term kinetics of DU in the brain. To address this issue, temporal and regional distribution of brain uranium was investigated in male Sprague-Dawley rats treated with a single intraperitoneal injection of 1 mg uranium/kg as uranyl acetate. Due to the inherent stress of combat and the potential for stress to alter blood-brain barrier permeability, the impact of forced swim stress on brain uranium distribution was also examined in this model. Uranium in serum, hippocampus, striatum, cerebellum, and frontal cortex was quantified by inductively coupled plasma-mass spectrometry (ICP-MS) at 8 h, 24 h, 7 d, and 30 d after exposure. Uranium entered the brain rapidly and was initially concentrated in hippocampus and striatum. While multiple phases of uranium clearance were observed, overall clearance was relatively slow and the uranium content of hippocampus, cerebellum, and cortex remained elevated for more than 7 d after a single exposure. Prior exposure to stress significantly reduced hippocampal and cerebellar uranium 24 h post-exposure and tended to reduce uranium in all brain regions 7 d after exposure. The application of stress appeared to increase brain uranium clearance, as initial tissue levels were similar in stressed and unstressed rats.
TL;DR: In this article, the relationship between alcohol dependence and oxidative status was examined among 28 patients with alcohol dependence, and biochemical parameters and antioxidants status were measured among 28 healthy persons without drinking problem were recruited as the control subjects.
Abstract: The aim of this study is to examine the relationship between alcohol dependence and oxidative status. The biochemical parameters and antioxidants status were measured among 28 patients with alcohol dependence. Nineteen healthy persons without drinking problem were recruited as the control subjects. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (γ-GT), and levels of cholesterol, triglyceride (TG), and uric acid were significantly increased in the specimen of patients compared with control. Serum malondialdehyde (MDA) levels of the patients were found to be significantly increased compared with controls and decreased after abstinence. Superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were, respectively, 86% and 37% lower in alcoholic patients. After 14 d of abstinence, SOD activity was significantly reduced by 85%, CAT by 52%, and GPX by 54%, whereas no change was found in activity of glutathione reductase (GR). The duratio...
TL;DR: A no-threshold, multipollutant AQI was developed, based on the relationship of CO, NO2, O3, SO2 and PM2.5 with mortality in Canadian cities in a daily time-series study, and results did not appear to be sensitive to an alternative choice of risk coefficients based on a worldwide meta-analysis.
Abstract: The example of the development of an alternative air quality index (AQI) is used to illustrate issues related to quantifying the public health burden attributable to air pollution. These issues include: (1) appropriately representing the weight of evidence; (2) extrapolation of risk measures over time and space; (3) attribution of health effects to air pollution versus other risk factors and to individual pollutants versus the rest of the mix; (4) application of complementary approaches from health economics; and (5) effective risk communication. A no-threshold, multipollutant AQI was developed, based on the relationship of CO, NO2, O3, SO2 and PM2.5 with mortality in Canadian cities in a daily time-series study. Risk coefficients were applied to daily air pollution concentrations to calculate multipollutant percent excess mortality, and results were scaled to a 0 to 10 range. The observed distribution of values was used to characterize days as low, medium, high, or extreme risk. Considerable day-to-day v...