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.
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.
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 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.
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.
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.