1,4-Dichlorobenzene (1,4-DCB) is a wide-spread environmental contaminant and well-described hepatotoxicant for rats and mice. The prolonged oral or inhalation exposure to 1,4-DCB is associated with an increased frequency of hepatic tumors in mice, but not in rats. Evidence is lacking of direct genotoxicity with 1,4-DCB or its metabolites, and no generally accepted mechanism has been found to account for the increased numbers of 1,4-DCB-induced hepatic tumors in mice. No information is available on the carcinogenic effects of 1,4-DCB in humans. Here we consider evidence that the biotransformation of 1,4-DCB to substituted hydroquinone species contributes to hepatic adenoma and carcinoma formation in mouse liver. This phenomenon has implications for human carcinogenesis.
Acrolein is a ubiquitous environmental pollutant that is known to cause respiratory tract injury and suppression of pulmonary host defense against infections in animal models. The mechanisms of acrolein-induced suppression of pulmonary host defense are not well understood. It has been generally believed that epithelial injury is responsible for the acrolein-caused decrease in resistance to infection. Emerging evidence suggests, however, that the alveolar macrophage is also a key target for acrolein-induced suppression of pulmonary host defense. It is likely that the combination of epithelial cell injury and inhibition of macrophage function may be responsible for acrolein-induced suppression of pulmonary host defense. To better assess the health risk of exposure to environmental levels of acrolein, more population-based studies are needed to monitor the levels of acrolein exposure and the adverse health effects associated with such exposures.
Wireless phones, i.e., mobile phones and cordless phones, emit radiofrequency electromagnetic fields (RF-EMF) when used. An increased risk of brain tumors is a major concern. The International Agency for Research on Cancer (IARC) at the World Health Organization (WHO) evaluated the carcinogenic effect to humans from RF-EMF in May 2011. It was concluded that RF-EMF is a group 2B, i.e., a "possible", human carcinogen. Bradford Hill gave a presidential address at the British Royal Society of Medicine in 1965 on the association or causation that provides a helpful framework for evaluation of the brain tumor risk from RF-EMF.
All nine issues on causation according to Hill were evaluated. Regarding wireless phones, only studies with long-term use were included. In addition, laboratory studies and data on the incidence of brain tumors were considered.
The criteria on strength, consistency, specificity, temporality, and biologic gradient for evidence of increased risk for glioma and acoustic neuroma were fulfilled. Additional evidence came from plausibility and analogy based on laboratory studies. Regarding coherence, several studies show increasing incidence of brain tumors, especially in the most exposed area. Support for the experiment came from antioxidants that can alleviate the generation of reactive oxygen species involved in biologic effects, although a direct mechanism for brain tumor carcinogenesis has not been shown. In addition, the finding of no increased risk for brain tumors in subjects using the mobile phone only in a car with an external antenna is supportive evidence. Hill did not consider all the needed nine viewpoints to be essential requirements.
Based on the Hill criteria, glioma and acoustic neuroma should be considered to be caused by RF-EMF emissions from wireless phones and regarded as carcinogenic to humans, classifying it as group 1 according to the IARC classification. Current guidelines for exposure need to be urgently revised.
An increasing percentage of smokers are quitting this unhealthy behavior during their life course. The aim of this study is to analyze which social factors play an important role regarding ex-smoking in Germany.
Data were derived from the 1995 German Microcensus, which is a representative survey for the population in Germany. Included in the analysis were 44,553 current smokers and 23,780 ex-smokers. The independent variables were education, occupational status, family status, unemployment/social welfare, household income, and community size. A two-stage statistical modeling procedure was used, initially to assess the most important effects of the independent variables on smoking cessation and secondly, to analyze the cumulative effects of the independent variables.
The most striking effects observed for smoking cessation were family status and education. For example, in males aged 30 to 49 years, the percentages of ex-smokers of all ever smokers were 44.7% for married males with high education compared with only 14.6% for males with low education. The corresponding percentages for females were 44.0% and 17.6%.
Such striking differences in the social polarization of smoking cessation in Germany demonstrate the importance of anti-smoking policies and new strategies that avoid a further increase in the social inequality of smoking behavior.
Rio de Janeiro, the second largest city in Brazil, is affected by severe pollution episodes and presents a high respiratory cancer incidence in comparison with the rest of the country. To monitor atmospheric pollution during the summer of 1998/1999 and to estimate the impact of organic pollution on public health, we determined the levels of two carcinogenic organic chemicals, benzo[a]pyrene and benzene, in four distinct sites throughout the city. A review of the levels recorded in other urban areas worldwide during the last ten years indicates that the benzo[a]pyrene (< or = 0.70 ng/m3) and benzene (< or = 11 micrograms/m3) concentrations found in Rio are relatively low. The highest levels were generally recorded in developing Asian countries, whereas the lowest values were found in North America. Unlike urban areas in temperate zones, pollution derived from domestic heating is minor in Rio de Janeiro, where most of the benzo[a]pyrene and benzene pollution originates from vehicular traffic. The quite distinct fuels used in light-duty vehicles in Brazil, combined with strong light incidence and increased rainfall during the summer, also contribute to diminish the levels of such pollutants.
Dichlorodiphenyltrichloroethane (DDT) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are complex organic compounds that are frequently found in the environment as a result of agricultural and industrial activities. Both compounds have substantial immune system and endocrine system disrupting activity, acting as estrogen agonists or antagonists (xenoestrogens). Research has demonstrated that exposure to xenoestrogens can result in body weight loss, developmental abnormalities, thymic atrophy, carcinogenesis, and tissue-specific hypoplastic and hyperplastic responses. Although several studies have reported significant adverse effects of these compounds on the endocrine system, very few investigations have focused on the specific mechanisms of action on the immune system. This paper reviews the cellular and molecular mechanisms of DDT- and TCDD-induced toxicity on the endocrine and immune systems, and explores their potential impact on the pathogenesis of immune disease.
The environmental contaminant 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) belongs to the category of highly toxic, persistent organic pollutants that accumulate in animal fat and plant tissues. Today, background TCDD levels in human fat are showing a decreasing trend. The food chain is the main source of exposure in the human population. TCDD regulates the expression of a wide range of drug-metabolizing enzymes and has an impact on a large number of biological systems. The most pronounced effects have occurred in occupational settings following the uncontrolled formation of TCDD after industrial accidents, as well as in rare intentional intoxications. Although the acute effects of TCDD exposure are well described in the literature, the long-term consequences have been underevaluated. The most well-known symptoms of severe acute intoxication are chloracne, porphyria, transient hepatotoxicity, and peripheral and central neurotoxicity. Because of the long-term persistence of TCDD in the human body, atherosclerosis, hypertension, diabetes, vascular ocular changes, and signs of neural system damage, including neuropsychological impairment, can be present several decades after massive exposure. Such chronic effects are nonspecific, multifactorial, and may be causally linked to TCDD only in heavily intoxicated subjects. This opinion is supported by the dose-dependent effect of TCDD found in exposed workers and by experimental animal studies.
Environmental contamination with 2,4,6-TNT (trinitrotoluene) represents a worldwide problem. Concern for carcinogenicity can be derived from chemically related compounds, especially the dinitrotoluenes. In the metabolism of TNT, the reductive routes are preponderant. The main urinary metabolites of TNT are 4-amino-2,6-dinitrotoluene and 2-amino-4,6-dinitrotoluene. In humans exposed to TNT, the formation of hemoglobin adducts of the amino-dinitrotoluenes is in general concordance with the ratio of urinary excretion. The variations in quantities of excreted metabolites among the different occupational cohorts studied are likely explained by the different routes of exposure to TNT, including dermal uptake. Most studies show that urinary excretion of the amino-dinitrotoluenes (4-amino-dinitrotoluene plus 2-amino-dinitrotoluene) in a range of 1 to 10 mg L(-1) (5-50 microM) are not uncommon--for instance in persons employed with the disposal of military waste. Trinitotoluene is mutagenic in Salmonella typhimurium strains TA98 and TA100, with and without exogenous metabolic activation. Mutagenic activity has been found in urine from workers who were occupationally exposed to TNT. An unpublished 2-year study was reported in 1984 by the IIT Research Institute, Chicago, IL. Fischer 344 rats were fed diets containing 0.4, 2.0, 10, or 50 mg/kg TNT per day. In the urinary bladder, hyperplasia (12 of 47 animals p < .01) and carcinoma (11 of 47 animals, p < .05) were observed at significant levels in high-dose (50 mg kg(-1)) females and in one or two females, respectively, at 10 mg kg(-1). Taking all the available evidence together, the appropriate precautions should be taken.
What do we currently know about the occupational and environmental causes of cancer? As of 2007, the International Agency for Research on Cancer (IARC) identified 415 known or suspected carcinogens. Cancer arises through an extremely complicated web of multiple causes, and we will likely never know the full range of agents or combinations of agents. We do know that preventing exposure to individual carcinogens prevents the disease. Declines in cancer rates-such as the drop in male lung cancer cases from the reduction in tobacco smoking or the drop in bladder cancer among cohorts of dye workers from the elimination of exposure to specific aromatic amines-provides evidence that preventing cancer is possible when we act on what we know. Although the overall age-adjusted cancer incidence rates in the United States among both men and women have declined in the last decade, the rates of several types of cancers are on the rise; some of which are linked to environmental and occupational exposures. This report chronicles the most recent epidemiologic evidence linking occupational and environmental exposures with cancer. Peer-reviewed scientific studies published from January 2005 to June 2007 were reviewed, supplementing our state-of-the-evidence report published in September 2005. Despite weaknesses in certain individual studies, we consider the evidence linking the increased risk of several types of cancer with specific exposures somewhat strengthened by recent publications, among them brain cancer from exposure to non-ionizing radiation, particularly radiofrequency fields emitted by mobile telephones; breast cancer from exposure to the pesticide dichlorodiphenyltrichloroethane (DDT) before puberty; leukemia from exposure to 1,3-butadiene; lung cancer from exposure to air pollution; non-Hodgkin's lymphoma (NHL) from exposure to pesticides and solvents; and prostate cancer from exposure to pesticides, polyaromatic hydrocarbons (PAHs), and metal working fluids or mineral oils. In addition to NHL and prostate cancer, early findings from the National Institutes of Health Agricultural Health Study suggest that several additional cancers may be linked to a variety of pesticides. Our report also briefly describes the toxicological evidence related to the carcinogenic effect of specific chemicals and mechanisms that are difficult to study in humans, namely exposures to bis-phenol A and epigenetic, trans-generational effects. To underscore the multi-factorial, multi-stage nature of cancer, we also present a technical description of cancer causation summarizing current knowledge in molecular biology. We argue for a new cancer prevention paradigm, one based on an understanding that cancer is ultimately caused by multiple interacting factors rather than a paradigm based on dubious attributable fractions. This new cancer prevention paradigm demands that we limit exposure to avoidable environmental and occupational carcinogens, in combination with additional important risk factors like diet and lifestyle. The research literature related to environmental and occupational causes of cancer is constantly growing, and future updates will be carried out in light of new biological understanding of the mechanisms and new methods for studying exposures in human populations. The current state of knowledge is sufficient to compel us to act on what we know. We repeat the call of ecologist Sandra Steingraber: "From the right to know and the duty to inquire flows the obligation to act."
Abstract To evaluate the possible impact that the BP Deepwater Horizon Gulf oil spill might have had on pollution levels in the State of Mississippi, the Mississippi Department of Environmental Quality (MDEQ), and the US Environmental Protection Agency (EPA) analyzed surface water and ambient air quality pollutant data taken from MDEQ and EPA monitoring sites on the Mississippi Gulf Coast. The data were compared with acute, chronic, and human health air and water quality standards to determine whether the pollutant levels occurring during the oil spill could cause ecological and/or human health effects. The water quality data indicated levels of nickel, vanadium, volatile organic compounds (VOCs), and semivolatile organic compounds analyzed remained below acute and chronic levels for both aquatic life and human health. The air quality sampling data showed that the levels of VOCs and polycyclic aromatic hydrocarbons associated with the oil spill were well below EPA chronic and human health screening levels. A comparison of the air quality monitoring data taken before and after the oil spill showed that the concentrations of ozone and fine particulate matter were elevated for brief periods but remained below actionable levels.
A four-season, indoor air quality survey was conducted in Southern Louisiana to determine the indoor air levels of the pesticide chlorpyrifos. Gas chromatographic analysis of 213 air samples collected from 53 houses revealed levels of chlorpyrifos ranging from non-detected to 2.13 micrograms/m3. Using the Florida-Pinella exposure guideline (24-hr exposure to chlorpyrifos at 0.48 microgram/m3), it was noted that 14% of the samples exceeded this guideline. The exposure of occupants to the indoor air concentrations of the pesticide, however, were below either the irritation or the odor thresholds, and effects on acute and chronic health responses remains uncertain.
121 workers who were exposed to RFR (< 30 MHz) over one year were examined. They were divided into two groups: one group was exposed to high electric field intensity (> or = 100 V/m), another to low intensity (< 100 V/m) and both groups were compared to control subjects. No significant changes in the functioning of the autonomic nervous system and blood parameters (Hb, WBC and blood platelets) occurred in the exposed subjects of either group. Some changes in ECG (ST-T interval and abnormal heart rate) were observed in the group exposed to high intensity (> or = 100 V/m) radiation. 100 V/m is suggested as an exposure limit for RF (< 30 MHz) radiation.
Cytogenetic end-points used to estimate risk of genotoxic events in workers include the measurement of micronuclei (MN) in exfoliated cells, lymphocytes, and other tissues. Micronuclei are chromatin-containing bodies outside the cell nucleus resulting from contaminant-induced DNA damage. A review of 71 reports of human genotoxic responses to chemical or physical agents published between 1999 and 2001 revealed that 14% of such studies measured genotoxicity endpoints in specific target tissues relevant to the site of disease for the agent examined; 18% used endpoints in surrogate or non-target tissues but considered the relations between endpoints in surrogate and disease target tissues, and 68% measured genotoxicity endpoints in accessible tissues without reference to specific targets for disease. Methylenebis-(2-chloroaniline) (MOCA), used in polyurethane manufacture, is a suspected bladder carcinogen. Bitumen, used in road surfacing, contains skin and lung carcinogens. In this study, we aimed to compare genotoxicity in urothelial cells and in lymphocytes of workers exposed to these materials. Twelve men employed in polyurethane manufacture, twelve bitumen road layers, and eighteen hospital stores personnel (controls) were recruited and all provided blood and urine samples on the same day. Blood cultures were prepared using a cytochalasin B-block method. Exfoliated urothelial cells were collected from urine and stained for light microscopy. The number of MN in urothelial cells was higher in MOCA-exposed (14.27 +/- 0.56 MN/1000, 9.69 +/- 0.32 MN cells/1000) than in bitumen exposed workers (11.99 +/- 0.65 MN/1000, 8.66 +/- 0.46 MN cells/1000) or in control subjects (6.88 +/- 0.18 MN/1000, 5.17 +/- 0.11 MN cells/1000). Conversely, in lymphocytes, MN were higher in bitumen-exposed (16.24 +/- 0.63 MN/1000, 10.65 +/- 0.24 MN cells/1000) than in MOCA-exposed workers (13.25 +/- 0.48 MN/1000, 8.54 +/- 0.14 MN cells/1000) or in control subjects (9.24 +/- 0.29 MN/ 1000, 5.93 +/- 0.13 MN cells/1000). The results of this study suggest that genotoxins can cause different rates of micronuclei formation in different tissues. Thus, the sensitivity and relevance to cancer risk may be greater if the tissues selected for genotoxicity studies reflect the target tissue for the chemicals concerned.
MX (3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone), one of the byproducts formed during the chlorine disinfection process of drinking water, shows strong mutagenic activity for Salmonella strains in the Ames test. In several countries, the contribution of MX to the total mutagenicity of drinking water is estimated to range from 7% to 67%. To assess the risk of MX for human health, we summarized the toxicological properties of MX and estimated the tolerable daily intake (TDI) or tolerable concentration in drinking water. MX is genotoxic in cultured mammalian cells and causes in vivo DNA damage in several tissues. MX is carcinogenic for rodents in addition to possessing skin and gastric promotion activities. From these toxicological profiles of MX, we estimated the virtual safety dose (VSD) for genotoxic action as 5 ng/kg/d and the TDI for non-genotoxic action of MX as 40 ng/kg/d. We assumed a tolerable MX concentration of 150 ng/L in drinking water. Because of the uncertainty about human genotoxicity, however, and the lack of information on reproductive or developmental toxicity, the estimated tolerable dose level may be provisional.
The author examined the adrenal glands of rats that were kept in a workshop of an NPK fertilizer factory for 30 days and then for 60 days in the laboratory. Histochemical examination of the reticular zone revealed an increase in neutral lipids and triglycerides and a decrease in phospholipids. The nucleic acid content, predominantly RNA, was enhanced. Although the acid phosphatase activity was slightly lowered, both succinate dehydrogenase and monoamine oxidase activities were increased. The results indicate that exposure of rats to NPK fertilizer had a stimulating effect on the reticular zone of their adrenal glands.
Exposure to metals, particularly lead, remains a widespread issue that is associated with historical and current industrial practices. Whereas the toxic properties of metals are well described, exposure to metals per se is only one of many factors contributing to elevated blood metal concentrations and their consequent health effects in humans. The absorbed dose of metal is affected by geochemical, biochemical, and physiological parameters that influence the rate and extent of absorption. In children, the interplay among these factors can be of critical importance, especially when biochemical and physiological processes might not have matured to their normal adult status. Such immaturity represents an elevated risk to metal-exposed children because they might be more susceptible to enhanced absorption, especially via the oral route. This review brings together the more recent findings on the physiological mechanisms of metal absorption, especially lead, and examines several models that can be useful in assessing the potential for metal uptake in children.
Abstract Benzene is a widespread, naturally occurring substance of environmental concern as systemic exposure in humans is proven to be carcinogenic. Dermal exposure is a common and significant route of systemic entry and percutaneous absorption is critical in exposure risk assessment. This article reviews the scientific principles, methodologies, and research behind the multiple steps of the percutaneous absorption of benzene in animals and man and the application of this information to optimize exposure risk assessments. A focus on occupational exposures to benzene is made with an exploration of the limitations of current preventative measures and hazard assessments. Finally, recommendations for future research to fill existing knowledge gaps are made.
Abstract A wide range of water problems faces nations and individuals around the world. These problems include international and regional disputes over water, water scarcity and contamination, unsustainable use of groundwater, ecological degradation, and the threat of climate change. At the heart of the world's water problems, however, is the failure to provide even the most basic water services for billions of people and the devastating human health problems associated with that failure. In 2000, the World Health Organization reported about regularly monitoring access to water and sanitation of 89% of the world's population, in which about 1.1 billion people lacked access to "improved water supply" and more than 2.4 billion lacked access to "improved sanitation" The development of water and basic sanitation services in Indonesia does not indicate any significant progress in the last two decades. The prevalence of water-borne diseases tends to increase yearly, which poses a risk for a population of over a million people. Therefore, it is not realistic to achieve the Millennium Development Goals target by 2015. Redefining approaches like providing integrated programs and action in water and sanitation services must be a priority to protect human health in Indonesia.
Mercury is a largely uncontrollable heavy metal contaminant in that it is globally ubiquitous, and environmentally persistent. The element has the potential for global mobilization following liberation from environmental stores, which can occur as a consequence of either anthropogenic activities or natural processes. Furthermore, organic forms like methylmercury accumulate in biological tissues with an exceptionally long biological half-life, facilitating the magnification of this toxin along trophic food chains. Bioaccumulation is particularly evident in aquatic environments, in which long-lived piscivorous fishes and marine mammals are reported with a mercury burden one-million times that of the surrounding water body, typically attaining mercury burdens exceeding 1 microg g(-1). Mercury levels in other seafood, however, are typically reported in the range of 0.1 to 0.2 microg g(-1) and usually less then 0.5 microg g(-1). The primary source of human exposure to environmental mercury is through seafood consumption. The dangers associated with the consumption of large amounts of methylmercury accumulated in seafood are well recognized from past poisoning incidents, in which fish with mercury burdens in the range of 9 to 24 microg g(-1) were consumed. Nevertheless, the toxicological consequence of chronic low-level mercury exposure from habitual seafood consumption is an area of contention. This review discusses the mechanisms of mercury accumulation and distribution in fish tissues and the toxicological consequences of mercury exposure from seafood consumption with regard to international safety guidelines.
The menstrual cycle is an important indicator of underlying hormonal function. Although menstrual cycle variability (sometimes referred to as 'regularity') is associated with a variety of demographic, behavioral, occupational, and environmental factors, as well as with several chronic diseases, few studies have examined its association with fecundity. We investigated whether a woman's menstrual cycle variability was associated with the likelihood of her achieving pregnancy. In this prospective study, we analyzed 3,536 menstrual cycles from 401 women (aged 19-41) recruited from 1990-1994. The women provided daily diaries recording menstrual bleeding, intercourse, and birth control use. Urine samples were assayed for human chorionic gonadotropin to identify early pregnancies during each menstrual cycle. Each woman's menstrual cycle variability was defined by the standard deviation of her cycle lengths during followup. The median follow-up was eight cycles. The outcome was her per-cycle probability of pregnancy. We found that women with high menstrual cycle variability had a reduced (51% lower) per cycle probability of pregnancy (fecundity ratio: 0.49; 95% confidence interval: 0.31, 0.77) compared with women with minimal variability. This relationship was independent of a woman's age and her mean cycle length. Thus, researchers and clinicians using menstrual cycle characteristics as indicators of endocrine or reproductive health should include measures of cycle variability in addition to the more commonly examined cycle length.
Despite the success of childhood vaccination in industrialized countries, diphtheria, tetanus, pertussis (whooping cough), and poliomyelitis (polio) still affect adults and adolescents whose immunity has waned. The resurgence in the 1990s of diphtheria in the area of the former Soviet Union and its subsequent control with immunization campaigns, demonstrates the value of continued adult vaccination. Tetanus cannot be eradicated from the soil reservoir, necessitating routine primary vaccination and regular booster doses to maintain protective immunity. Although Europe has been certified endogenous polio-free since June 2002, polio imported from endemic areas continues to pose a serious threat for vulnerable populations. Booster polio vaccination is required in adolescence and adulthood. Pertussis among adults and adolescents is underestimated, representing a considerable health burden. The consequences can be more serious as this pool of susceptible adolescents and adults is a major source of pertussis transmission to newborns not yet protected by vaccination. The now available acellular pertussis-based combination vaccine covering diphtheria, tetanus, polio, and pertussis, suitable for adults and adolescents, provides the ideal tool for implementing booster immunization programs. Strong recommendations for adolescent and adult boosters are needed to overcome the continued threat of these diseases.
The purpose of this paper is to present information gathered regarding, in general, the physical characteristics, and, in particular, the possible toxic nature of polyacrilamides. A short discussion of the properties and toxicity of the acrylamide monomer is also included.
The United States government, specifically the Food and Drug Administration and the Environmental Protection Agency, already regulates several uses of polyacrylamide; criteria and standards have been established based on numerous toxicological studies of both polyacrylamide and acrylamide. These studies are reviewed and summarized.
The regulations generally restrict both the amount of residual acrylamide monomer in the polyacrylamide and the amount of polymer that may be used in the specified application. By imposing this type of restriction, a maximum limit on the amount of acrylamide in contact with food or drinking water can be indirectly achieved.
Acrylamide is a highly water soluble vinyl monomer formed from the hydration of acrylonitrile. The major commercial use of acrylamide is the formation of polymers. In the environment acrylamide has a high mobility in soil, may travel great distances in ground-water, is biodegradable, and is not absorbed by sediments or affected by water treatment. It is absorbed by all routes of animal exposure. The main metabolite is N-acetyl-S-(3-amino-3-oxypropyl)-cysteine and is excreted predominantly in the urine. Acrylamide produces an ascending central/peripheral axonopathy in man and animals. The major histological findings are swelling of axons and/or decrease in number of large diameter axons. Acrylamide axonopathy is reversible with time, but full recovery depends upon the severity of the intoxication. All reported cases of acrylamide toxicity have been attributed to handling the monomer. Polyacrylamide is non-toxic. Specific clinical features of acrylamide intoxication are more conclusive than electrophysiological, histological or biochemical laboratory tests for diagnosis. Acrylamide can be detected by titration, colorimetry, high performance chromatography, gas chromatography and polarography in air, water, biological fluids, tissues and polyacrylamides. Present research on the effects of acrylamide focuses on developmental and reproductive effects, genotoxicity and carcinogenicity.
This review considers a paradigm shift on microwave electromagnetic field (EMF) action from only thermal effects to action via voltage-gated calcium channel (VGCC) activation. Microwave/lower frequency EMFs were shown in two dozen studies to act via VGCC activation because all effects studied were blocked by calcium channel blockers. This mode of action was further supported by hundreds of studies showing microwave changes in calcium fluxes and intracellular calcium [Ca2+]i signaling. The biophysical properties of VGCCs/similar channels make them particularly sensitive to low intensity, non-thermal EMF exposures. Non-thermal studies have shown that in most cases pulsed fields are more active than are non-pulsed fields and that exposures within certain intensity windows have much large biological effects than do either lower or higher intensity exposures; these are both consistent with a VGCC role but inconsistent with only a heating/thermal role. Downstream effects of VGCC activation include calcium signaling, elevated nitric oxide (NO), NO signaling, peroxynitrite, free radical formation, and oxidative stress. Downstream effects explain repeatedly reported biological responses to non-thermal exposures: oxidative stress; single and double strand breaks in cellular DNA; cancer; male and female infertility; lowered melatonin/sleep disruption; cardiac changes including tachycardia, arrhythmia, and sudden cardiac death; diverse neuropsychiatric effects including depression; and therapeutic effects. Non-VGCC non-thermal mechanisms may occur, but none have been shown to have effects in mammals. Biologically relevant safety standards can be developed through studies of cell lines/cell cultures with high levels of different VGCCs, measuring their responses to different EMF exposures. The 2014 Canadian Report by a panel of experts only recognizes thermal effects regarding safety standards for non-ionizing radiation exposures. Its position is therefore contradicted by each of the observations above. The Report is assessed here in several ways including through Karl Popper's assessment of strength of evidence. Popper argues that the strongest type of evidence is evidence that falsifies a theory; second strongest is a test of "risky prediction"; the weakest confirms a prediction that the theory could be correct but in no way rules out alternative theories. All of the evidence supporting the Report's conclusion that only thermal effects need be considered are of the weakest type, confirming prediction but not ruling out alternatives. In contrast, there are thousands of studies apparently falsifying their position. The Report argues that there are no biophysically viable mechanisms for non-thermal effects (shown to be false, see above). It claims that there are many "inconsistencies" in the literature causing them to throw out large numbers of studies; however, the one area where it apparently documents this claim, that of genotoxicity, shows no inconsistencies; rather it shows that various cell types, fields and end points produce different responses, as should be expected. The Report claims that cataract formation is produced by thermal effects but ignores studies falsifying this claim and also studies showing [Ca2+]i and VGCC roles. It is time for a paradigm shift away from only thermal effects toward VGCC activation and consequent downstream effects.
Environmental health has a significant role to play in all stages of disaster management, from planning through to recovery. The conceptualizetion of the environmental health role by environmental health practitioners and other disciplines involved with disaster management is the focus of this review. To provide context for this discussion, we present an overview of disasters and disaster management and the public health and environmental health impact of disasters. The literature indicates that the role of environmental health in disaster management is not clearly conceptualized, and the following barriers have been identified: the continued emergence of environmental health as a professional discipline, ambiguity about environmental health functions in disasters, limited representation in disaster planning, low visibility profile of the profession, positioning of environmental health within public health, power and politics within agencies that result in a narrow assignment of the environmental health role, and a top-down approach to disaster management. The Australian experience indicates that if environmental health practitioners can overcome such barriers and increase their involvement in disaster management, then this achievement will raise the profile of the profession and renegotiate the environmental health role in disaster management. Ultimately, this success will also improve our capacity to manage disaster situations, and the higher profile, greater recognition, and representation of environmental health that is gained will then be able to flow into normal day-to-day activities.
This review relates to possible explanations of the often-observed findings that exposure to certain air pollutants or their mixture results in an increased rate of acute respiratory diseases. Epidemiological investigations have shown that exposure to manganese (MnO2) concentrations only 10 to 50 times higher than the normal urban concentrations of 0.01 to 0.03 microgram/m3 air might have an adverse health effect on respiratory organs. The assumption that one possible mechanism of action could be that manganese at such exposure levels disturbs certain protective functions in the lung--thus making the organism more susceptible to infections--is supported by toxicological studies. In vitro studies have demonstrated the cytotoxic action of manganese, including the inhibition of activities of alveolar macrophages. Animal experiments showed a decrease in resistance toward respiratory infections that were caused by simultaneous exposure to MnO2 and pathogenic bacteria. In cases of combined exposure to gaseous upper respiratory tract irritants and suspended particles, the involvement of adsorption of gaseous compounds on solid particles as carriers has been suggested. The assumption is that through such a mechanism, water-soluble gaseous irritants can be transported deep into air passages, which such irritants normally do not reach. As the adsorption is reversible, the gaseous compounds can later be released from the particles, inducing a local irritating effect in the small airways and alveoli.
The effects of magnetic fields on biological membranes in general and on the red blood cell membrane in particular have been studied intensively in the last two decades. A variety of methods for evaluation of magnetic field action on the structure and function of biological membranes has been used. It has been suggested /1/ that the cell membrane can be considered as one of the primary targets affected by magnetic field exposure.
Mechanistic data must be incorporated into the assessment of the human risks of chemical carcinogens, for trichloroethylene in particular. The total weight of evidence compiled from data on the genotoxicity of trichloroethylene indicates that systemic mutagenic activity is not expressed in vivo. New epidemiologic data on trichloroethylene generated in Denmark showed a steady decline of occupational exposure to trichloroethylene since 1947, but with occasions of high exposures before 1980. Earlier exposures were related to a slight increase in risk of non-Hodgkin's lymphoma, renal carcinoma, and esophageal carcinoma. Such confounders as coexposure to other industrial solvents (non-Hodgkin's lymphoma) and alcohol drinking (esophageal cancer) must be discussed. In Germany, a new consecutive case-control study on kidney cancer confirmed that the risk of renal cell cancer is significantly elevated in persons reporting long-term (several years) exposure to trichloroethylene. The results of all these studies indicate that low exposure (not higher than the current Occupational Exposure Limits) is not associated with increased risk of malignancy. In the kidney, trichloroethylene can act as a complete carcinogen at the stages of both tumor induction and tumor promotion/progresssion in a in a dose-dependent manner. Different types of kidney cancer can be triggered by different genes. Clear-cell renal carcinoma, preferentially induced by trichloroethylene, is linked with the homozygous inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. In highly exposed subjects, the local genotoxic effect of trichloroethylene results from bioactivation pathways leading to renal VHL gene damage and renal cell carcinomas. The view that renal cell cancer development after long-term (several years) and high (with prenarcotic episodes) occupational exposure to trichloroethylene is due to chronic damage of the proximal tubule of the kidney as a key step argues for the existence of a practical threshold. Prolonged and unusually high-dose exposure to trichloroethylene is deemed a strong risk factor for the development of renal cell cancer. The findings of experimental, mechanistic, and epidemiologic studies lead to the conclusion that trichloroethylene can be considered a human carcinogen for which a practical threshold appears likely and below which no relevant carcinogenic effect is to be expected.
The toxicity of chemicals of environmental concern to the immune system has been primarily evaluated in animals and, to a lesser extent, in humans. In particular, the effects of various pollutants on B-cell, T-cell, natural killer cells, and monocyte-macrophage cells have been the focus of several reports, but polymorphonuclear neutrophils have largely been neglected. Recent data indicate that neutrophils are important targets for such chemicals, suggesting a potential role of these products in the development of the inflammatory process. The bulk of this review will focus on the role of certain environmental pollutants on human neutrophil cell physiology.
Soil health can be defined as the continued capacity of a specific kind of soil to function as a vital living system, within natural or managed ecosystem boundaries, to sustain plant and animal productivity, to maintain or enhance the quality of air and water environments, and to support human health and habitation. Because of the conflicting pressures increasingly applied to the soil, it is clear that relevant indicators are urgently needed to assess and monitor soil health. Biological indicators of soil health offer certain advantages over physicochemical methods. Among the various biological indicators that have been proposed to monitor soil health, soil enzyme activities have great potential to provide a unique integrative biological assessment of soils and the possibility of assessing the health of the soil biota. Besides, soil enzyme activities provide an easy, relatively rapid, and low cost procedure to monitor soil health. Nevertheless, soil enzyme activities also present some limitations and must always be considered in conjunction with other biological and physicochemicals measurements if we are to diagnose soil health correctly.
Copper is an essential element for all living beings. Exposure to copper results almost exclusively from the ingestion of food and water. Generally, potable water contains low levels of copper, but high concentrations of this mineral have been found in water from private wells or when water or beverages with low pH have been conducted through copper piping. Some authors have associated acute gastrointestinal symptoms (diarrhea, abdominal pain, nausea, and vomiting) with elevated levels of copper in water or beverages, but without excluding other confounding factors that could produce such symptoms. Recently, various controlled studies have demonstrated that a concentration of 2 mg Cu/L of potable water does not produce an increase in gastrointestinal symptoms in infants, and that in women, only concentrations greater than 3 mg Cu/L increase the number of episodes of nausea, vomiting, and abdominal pain, but not diarrhea. This critical analysis of scientific publications verifies the WHO provisional level for copper in drinking water (2 mg/L) as safe for human health.
The use of aerometric network data has been criticized before on the grounds that it might give an unreliable picture of population exposure. However, the extensive data obtained from networks is still being used for studies of health effects of air pollution. This study uses a rigorous approach in analyzing these data to test their suitability for studies of acute health effects of air pollution. New York City, with one of the most extensive aerometric networks, consisting of 40 air pollution monitoring stations, is taken as an example. Three years of hourly SO2 readings and bi-hourly readings of smokeshade have been analyzed. The use of one aerometric station to represent the daily exposure of the population of New York City as has been done in previous studies is shown to be invalid. The use of individual monitoring stations of the New York City aerometric network to represent the day-to-day exposure to SO2 and smokeshade of the populations surrounding these monitoring stations is examined, with results showing that further work will be necessary before such an approach is justified.
The origin of acute lymphoblastic leukemia (ALL), the most common pediatric cancer, can be explained by a combination of genetic factors and environmental exposure. The environmental toxicants to which an individual is exposed are biotransformed and eliminated from the body after metabolic conversion mediated by Phase I and Phase II xenobiotic-metabolizing enzymes. Phase I enzymes catalyze hydroxylation, reduction and oxidation reactions of xenobiotics (carcinogens/drugs), often converting them into more active or toxic compounds. Phase II enzymes catalyze conjugation reactions (glucuronidation, acetylation, methylation), thereby converting the metabolites into non-reactive, water-soluble products that are eliminated from the organism. The genetic polymorphism underlying the variation in enzyme activity can modify susceptibility to diverse adult cancers, probably by influencing the activation and removal of toxicants or drugs. Here we present an overview of the role of genetic variants of certain Phase I and Phase II enzymes in the development of childhood ALL, a good model for such studies because of its short latency period. The genetic contribution to the development of ALL is examined by association studies that analyze the loci of Phase I enzymes (cytochrome P-450, myeloperoxidase) and Phase II enzymes (quinone-oxidoreductase, glutathione-S-transferase, N-acetyltransferase). The loci of the enzyme variants CYPlA1, CYP2E1, NQO1, GSTM1, GSTP1, NAT2 are associated with disease development, and evidence of gene-gene interactions has emerged as well. Despite the improvements in treatment, resistant cases of ALL remain a leading cause of cancer-related death in children. Although the underlying mechanism of drug resistance is not well understood, differences in the capacity of ALL patients to process drugs and environmental carcinogens could play a role by modifying the risk of recurrent malignancy, as well as the response to therapy. Therefore, polymorphic genes encoding carcinogen- and drug-metabolizing enzymes may not only increase the risk of ALL but also influence the risk of relapse in patients. We found that the prognosis of patients with CYPlA1 and NQO1 variants was worse than that of patients who lack these variants. We conclude that genotyping ALL patients for functional polymorphisms of candidate genes can become an important tool in predicting disease outcome.
A new methodology is proposed for the identification of environmental events of health significance. Health indices measured on a daily basis at various location in a single geographical area are collected over time. First, the daily variations are examined to determine whether they reflect purely random variations or whether there are days on which there are extreme variations not plausibly explicable as random events. After such days are identified, the question of whether they occur only at a single location within the larger geographical area at one time, or whether the occur simultaneously at more than one location is investigated. Tests of statistical significance for both temporal and spatial clustering are propose. The methodology is applied to daily hospital emergency room visits for various respiratory complaints to several New York City hospitals situated in two geographically separated districts which however have population of similar socio-economic and ethnic composition.
Acute organophosphate (OP) poisoning is a major health issue in developing countries. Organophosphate insecticides inhibit cholinesterase (ChE) enzymatic activity, thereby eliciting cholinergic signs and symptoms. Victims of OP poisoning require immediate hospital emergency room (ER) treatment to prevent a fatal outcome. We present an epidemiologic review of acute OP poisoning in hospital ER patients. Areas of interest include countries with acute OP poisoning, nature of exposure, gender and age of patients, clinical cholinergic features, ChE activity, and health outcome, including recovery rate, case fatality rate, and post-ER complications. The review comprises case reports, hospital surveys, and clinical studies on acute OP poisoning. More studies were conducted in developed than in developing countries. Suicidal and occupational OP poisoning in agricultural workers was prevalent in developing countries, whereas accidental OP poisoning was prevalent in developed countries. Healthcare workers in the ER were also affected by OP poisoning. Both males and females were affected. Children accounted for 35% of the OP-poisoned victims. Patients presented with a classic cholinergic syndrome and serum ChE depresssion, with a recovery rate above 90%. Neurologic impairment was the most frequent complication. Preventing environmental OP exposure and increasing the awareness of pesticide toxicity would reduce acute OP poisoning and protect human health.
This review presents current information on the adaptive changes of the liver in the metabolism of toxicants. Many lipid soluble foreign compounds given chronically to mammals stimulate their own metabolism and the metabolism of other compounds by increasing the activity of enzymes in liver microsomes. Enzyme induction seems to be an adaptive phenomenon, that influences the toxicity of foreign compounds as well as the metabolism of normal body constituents. The evidence available from studies with experimental animals strongly indicates that some of the environmental pollutants are concerned with this phenomenon. As the general population is always exposed to a variety of such inducers, biochemical, physiological or toxicological alterations may be taking place in man's body. However, the question remains whether these biochemical responses are toxic side effects of the foreign compound or perhaps represent beneficial adaptations designed to restore a homeostasis that was upset by administration of the compound. Unsettled, also, is the question whether or not the capacity for adaptive reactions is limited and should be spared as much as possible. (70 references).
The aim of the investigation was to study the effect of high ambient temperature (HAT) on the adjustment to fast rotating 12-h shifts by following the time-of-day variations of certain circadian and stress indicators. We investigated 12 male HAT operators and 21 individuals working in normal ambient temperature (NAT) in a thermoelectric power plant. The shift system of both groups comprised an 8-day cycle of 2 shifts per day (day shift: 0700 to 1900; night shift: 1900 to 0700), with 2 successive days of the same shift followed by 2 days off. We followed variations in oral temperature, 11-oxycorticoids, as well as catecholamines adrenaline and noradrenaline excretion at 4-h intervals during 2 day and 2 night shifts. Our data show daily oriented circadian rhythms of operators working on fast rotating 12-h shifts in conditions of HAT and NAT. Reduced general activation was observed in the second half of the prolonged 12-h night shifts, more pronounced in HAT operators. The stress indicators investigated here showed a stress reaction in HAT operators at the beginning of the first day shift. Both prolonged 12-h shifts and high ambient temperature impose extra demands and may have an impact on the performance and work safety of the operators.
Phthalate exposure is ubiquitous and may affect child and adolescent health through both in utero exposure and direct exposure during childhood. Variability in exposure within women is not well documented. We analyzed 90 first-morning urine samples collected by ten reproductive-age women for phthalate metabolites and creatinine. Monoethyl [122 ng/mL (geometric mean concentration = 139 microg/g creatinine)], monobutyl [85.4 ng/mL (97.0 microg/g creatinine)], monobenzyl [37.2 ng/mL (42.2 microg/g creatinine)], and mono-2-ethylhexyl phthalate [9.4 ng/mL (10.7 microg/g creatinine)] were detected in most (94.4%) samples. The concentrations ranged from 23.8-1090 ng/mL, 43-437 ng/mL, 12.4-186 ng/mL, and 1.3-31.1 ng/mL, respectively. We observed considerable variation in phthalate concentrations by day for individual women. The intraclass correlation coefficient, indicating the proportion of variance explained by differences between subjects, ranged from 0.40 (monobutyl) to 0.68 (monoethyl). Monobenzyl and monoethyl phthalates showed higher levels on weekends as compared with weekdays (p = .01 for both). We found no significant difference between monoester levels from different menstrual cycles. Phthalate concentrations vary considerably for an individual and may require multiple samples for accurate assessment
Increasing attention has been paid to whether low frequency non-ionizing radiation causes human cancers. In an ongoing case-control study of primary malignant brain cancer in adults, we examined the risk associated with common household appliances. Subjects were questioned about their use of personal computers, electric heaters, electric hair dryers, electric razors, and other appliances. No risk of brain cancer was observed with regular use of any of these items. Although magnetic field exposures were not measured, this study does not implicate the use of electric appliances in adult astroglial cancers.
We examined the association between the somatotype and its main components (endomorphy, mesomorphy and ectomorphy), and the prevalence of several chronic diseases. The data were obtained from a cross-sectional survey designed to assess somatotype and morbidity with special reference to most often diagnosed diseases. The study population comprised 524 men and 250 women. The subjects underwent laboratory tests and clinical and anthropometric examinations. Of all examined workers, 94.8% fell into the five somatotype categories; of these, 394 were endomorphic mesomorphs. The most common somatotype was endomorphic mesomorph for men and mesomorph-endomorph for women. In five disease groups, prevalence was significantly related to a somatotype. Mesomorphic endomorphs most frequently suffered from digestive system diseases (40.6%, p < 0.05), neuroses (30.1%, p < 0.05), and radiculitis lumbosacralis (15.4%). The prevalence of arterial hypertension in mesomorph-endomorphs (37.1%), endomorphic mesomorphs (35.5%), and mesomorphic endomorphs (34.3%) was equal. In both genders, those with the highest endomorphy and mesomorphy and the lowest ectomorphy, grouped by cluster analysis, were those who suffered most frequently from arterial hypertension and liver disease. The authors conclude that the somatotype having a dominant mesomorphy and marked endomorphy constitutes a risk factor as a particular predisposition toward certain diseases and requires body weight control.
In this review we summarize the work conducted over the past decade that has advanced our knowledge of pulmonary diseases associated with exposure to beryllium that has provided a molecular-based understanding of the chemistry, immunopathology, and immunogenetics of beryllium toxicity. Beryllium is a strong and lightweight metal that generates and reflects neutrons, resists corrosion, is transparent to X-rays, and conducts electricity. Beryllium is one of the most toxic elements on the periodic table, eliciting in susceptible humans (a) an allergic immune response known as beryllium sensitization (BeS); (b) acute beryllium disease, an acutely toxic, pneumonitis-like lung condition resulting from exposure to high beryllium concentrations that are rarely seen in modern industry; and (c) chronic beryllium disease (CBD) following either high or very low levels of exposure. Because of its exceptional strength, stability, and heat-absorbing capability, beryllium is used in many important technologies in the modern world. In the early 1940s, beryllium was recognized as posing an occupational hazard in manufacturing and production settings. Although acute beryllium disease is now rare, beryllium is an insidious poison with a latent toxicity and the risk of developing CBD persists. Chronic beryllium disease-a systemic granulomatous lung disorder caused by a specific delayed immune response to beryllium within a few months to several decades after exposure-has been called the "unrecognized epidemic". Although not a disease in itself, BeS, the innate immune response to beryllium identified by an abnormal beryllium lymphocyte proliferation test result, is a population-based predictor of CBD. Genetic susceptibility to CBD is associated with alleles of the major histocompatibility gene, human leukocyte antigen DP (HLA-DP) containing glutamic acid at the 69th position of the beta chain (HLA-DPbeta-E69). Other genes are likely to be involved in the disease process, and research on this issue is in progress. The current Occupational Safety & Health Administration permissible exposure limit of 2 microg/m3 has failed to protect workers from BeS/CBD. As a safe exposure limit that will not lead to BeS or CBD has not yet been determined, the realization that the risk of CBD persists has led to a renaissance in research on the effects of the metal on human health. Current data support further reductions in exposure levels to help minimize the incidence of CBD. Steps that would directly impact both the power of epidemiologic studies and the cost of surveillance would be to develop and validate improved screening and diagnostic tests, and to identify more genetic factors that affect either sensitization or disease process. The major focus of this review is the recent research on the cellular and molecular basis of beryllium sensitization and disease, using a multidisciplinary approach of bioinorganic chemistry and immunology. First we present a historical background of beryllium exposure and disease, followed by occurrence of beryllium in the environment, toxicokinetics, biological effects, beryllium lung disease, and other human health effects.
Abstract Organophosphate (OP) compounds are the most widely used pesticides with more than 100 OP compounds in use around the world. The high-intensity use of OP pesticides contributes to morbidity and mortality in farmworkers and their families through acute or chronic pesticides-related illnesses. Many factors contributing to adverse health effects have been investigated by researchers to determine pathways of OP-pesticide exposure among farmers in developed and developing countries. Factors like wind/agricultural pesticide drift, mixing and spraying pesticides, use of personal protective equipment (PPE), knowledge, perceptions, washing hands, taking a shower, wearing contaminated clothes, eating, drinking, smoking, and hot weather are common in both groups of countries. Factors including low socioeconomic status areas, workplace conditions, duration of exposure, pesticide safety training, frequency of applying pesticides, spraying against the wind, and reuse of pesticide containers for storage are specific contributors in developing countries, whereas housing conditions, social contextual factors, and mechanical equipment were specific pathways in developed countries. This paper compares existing research in environmental and behavioural exposure modifying factors and biological monitoring between developing and developed countries. The main objective of this review is to explore the current depth of understanding of exposure pathways and factors increasing the risk of exposure potentially leading to adverse health effects specific to each group of countries.
Epidemiologic studies and case reports have shown that chronic exposure to selenium compounds is associated with several adverse health effects in humans. An early toxic effect of selenium is on endocrine function, particularly on the synthesis of thyroid hormones following dietary exposure of around 300 micrograms Se/d, and on the metabolism of growth hormone and insulin-like growth factor-1. Other adverse effects of selenium exposure can be the impairment of natural killer cells activity and at higher levels, hepatotoxicity and gastrointestinal disturbances. Dermatologic effects, such as nail and hair loss and dermatitis, occur after exposure to high levels of environmental selenium. Assessing the toxicity and morbidity after long-term exposure to environmental selenium is difficult: neurotoxicity, particularly the degeneration of motor neurons leading to increased risk of amyotrophic lateral sclerosis, might occur after chronic exposure to both organic and inorganic selenium compounds. The results of laboratory investigations and cohort studies suggest that selenium species exhibit a bivalent effect in cancer, either increasing or decreasing risk. Current environmental selenium exposure limits appear to be inadequate for averting adverse health effects.
Among air pollutants, sulfur dioxide has been found to be very injurious. The present article deals with the adverse effects of sulfur dioxide gas on metals, metal alloys, buildings and plants, animals and human beings.