A survey among beachgoers was conducted to determine the swimming associated health effects experienced and its relationship with beach water exposure behaviour in Morib beach. For beach water exposure behaviour, the highest frequency of visit among the respondents was once a year (41.9%). For ways of water exposure, whole body exposure including head was the highest (38.5%). For duration of water exposure, 30.8% respondents prefer to be in water for about 30 min with low possibilities of accidental ingestion of beach water. A total of 30.8% of beachgoers in Morib beach were reported of having dermal symptoms. Bivariate analysis showed only water activity, water contact and accidental ingestion of beach water showed significant association with swimming associated health effects experienced by swimmers. This study output showed that epidemiological study can be used to identify swimming associated health effects in beach water exposed to faecal contamination.
Exposure to aflatoxins in the adult Malaysian diet was estimated by analysing aflatoxins in 236 food composites prepared as "ready for consumption". Dietary exposure to aflatoxin B1 (AFB1) ranged from 24.3 to 34.00 ng/kg b.w./day (lower to upper bound), with peanuts being the main contributor. Estimated liver cancer risk from this exposure was 0.61-0.85 cancers/100,000 population/year, contributing 12.4%-17.3% of the liver cancer cases. Excluding AFB1 occurrence data higher than 15 µg/kg reduced exposure by 65%-91% to 2.27-11.99 ng/kg b.w./day, reducing the cancer risk to 0.06-0.30 cancers/100,000 population/year (contributing 1.2%-6.1% liver cancer cases). Reducing further the ML of AFB1 from 15 to 5 µg/kg yielded 3%-7% greater drop in the exposure to 0.47-10.26 ng/kg b.w./day with an estimated risk of 0.01-0.26 cancers/100,000 population/year (0.2%-5.1% liver cancer cases attributed to dietary AFB1). These findings indicate that current MLs are adequate in protecting Malaysians' health.
This study aimed to determine the relationship between blood lead (BPb) concentrations and cognitive and physical development in school children. A total of 169 urban children and 100 industrial children of Malay ethnicity, in the age range of 6(1/2) to 8(1/2) years, were selected. BPb was determined using GF atomic absorption spectrophotometer. The mean cognitive score (102.55) of the children from the industrial area was significantly higher than that of the urban children (95.09; P < .001). However, no significant differences were found in the BPb levels between the 2 groups (industrial, 3.75 microg/dL; urban, 3.56 microg/dL). There was significant inverse correlation between BPb and cognitive scores for all children (P < .05). The cognitive scores for all children were influenced by BPb after adjustments (P < .05). The urban children had significantly better Weight for Height and Left Arm Circumference values than those from industrial area. There was no significant correlation between BPb and the anthropometric measurements. In conclusion, low BPb influenced the cognitive development, whereas physical development was not affected.
From the beginning of time, man has lived in a continuous state of interdependence with his environment. If the forces of nature are harnessed well, they are a source of great benefit to mankind, but when this balance is tipped, nature's backlash on man can be quite devastating. In recent times, we have seen many vivid examples of the magnitude of the destructive forces of nature, ranging from massive floods caused by typhoons such as Katrina and Rita, the hundreds of thousands of lives lost by the powerful tsunami and the destruction of the environment by the raging forest fires in Spain and California. Yet man has not learnt his lesson. Often greed, at times gross ignorance and more often than not, just indifference to the effects of his actions on the environment result in man upsetting his balance with the environment. In Malaysia, since 1990, the haze has become a predictable annual occurrence, varying only in its severity and duration. The cause being beyond our control, we are unable to prevent it from happening. However, it is within our means to be ready to take the necessary steps to minimize the effects of the haze on the health of Malaysians. In order to be able to give appropriate advice and to allay the anxiety of the general public, it is necessary to have a clear understanding about the various effects of haze on humans.
Polycyclic aromatic hydrocarbons (PAHs) are primarily formed as a result of thermal treatment of food, especially barbecuing or grilling. Contamination by PAHs is due to generation by direct pyrolysis of food nutrients and deposition from smoke produced through incomplete combustion of thermal agents. PAHs are ubiquitous compounds, well-known to be carcinogenic, which can reach the food in different ways. As an important human exposure pathway of contaminants, dietary intake of PAHs is of increasing concern for assessing cancer risk in the human body. In addition, the risks associated with consumption of barbecued meat may increase if consumers use cooking practices that enhance the concentrations of contaminants and their bioaccessibility. Since total PAHs always overestimate the actual amount that is available for absorption by the body, bioaccessibility of PAHs is to be preferred. Bioaccessibility of PAHs in food is the fraction of PAHs mobilized from food matrices during gastrointestinal digestion. An in vitro human digestion model was chosen for assessing the bioaccessibility of PAHs in food as it offers a simple, rapid, low cost alternative to human and animal studies; providing insights which may not be achievable in in vivo studies. Thus, this review aimed not only to provide an overview of general aspects of PAHs such as the formation, carcinogenicity, sources, occurrence, and factors affecting PAH concentrations, but also to enhance understanding of bioaccessibility assessment using an in vitro digestion model.
Carbon nanotubes (CNTs) are an important class of nanomaterials, which have numerous novel properties that make them useful in technology and industry. Generally, there are two types of CNTs: single-walled nanotubes (SWNTs) and multi-walled nanotubes. SWNTs, in particular, possess unique electrical, mechanical, and thermal properties, allowing for a wide range of applications in various fields, including the electronic, computer, aerospace, and biomedical industries. However, the use of SWNTs has come under scrutiny, not only due to their peculiar nanotoxicological profile, but also due to the forecasted increase in SWNT production in the near future. As such, the risk of human exposure is likely to be increased substantially. Yet, our understanding of the toxicological risk of SWNTs in human biology remains limited. This review seeks to examine representative data on the nanotoxicity of SWNTs by first considering how SWNTs are absorbed, distributed, accumulated and excreted in a biological system, and how SWNTs induce organ-specific toxicity in the body. The contradictory findings of numerous studies with regards to the potential hazards of SWNT exposure are discussed in this review. The possible mechanisms and molecular pathways associated with SWNT nanotoxicity in target organs and specific cell types are presented. We hope that this review will stimulate further research into the fundamental aspects of CNTs, especially the biological interactions which arise due to the unique intrinsic characteristics of CNTs.
Children are the vulnerable group in the agricultural community due to their early exposure to pesticides through the dynamic interplay between genetic predisposition, environment, and host-related factors. This study aims to identify the possible association between the depression in blood cholinesterase level and genotoxic effect among farm children. The results of micronuclei assay and comet assay showed that the reduced blood cholinesterase level from organophosphate pesticide exposure is significantly associated with an increase in chromosome breakage and DNA strand breaks. These genotoxicity end points suggest that farm children's cells experience early DNA damage that may lead to uncontrolled cell proliferation during their adulthood. Thus, farm children who grow up near pesticide-treated farmland have a higher probability of developing cancer than children with minimal or zero exposure to pesticides.
Forecasting higher than expected numbers of health events provides potentially valuable insights in its own right, and may contribute to health services management and syndromic surveillance. This study investigates the use of quantile regression to predict higher than expected respiratory deaths. Data taken from 70,830 deaths occurring in New York were used. Temporal, weather and air quality measures were fitted using quantile regression at the 90th-percentile with half the data (in-sample). Four QR models were fitted: an unconditional model predicting the 90th-percentile of deaths (Model 1), a seasonal/temporal (Model 2), a seasonal, temporal plus lags of weather and air quality (Model 3), and a seasonal, temporal model with 7-day moving averages of weather and air quality. Models were cross-validated with the out of sample data. Performance was measured as proportionate reduction in weighted sum of absolute deviations by a conditional, over unconditional models; i.e., the coefficient of determination (R1). The coefficient of determination showed an improvement over the unconditional model between 0.16 and 0.19. The greatest improvement in predictive and forecasting accuracy of daily mortality was associated with the inclusion of seasonal and temporal predictors (Model 2). No gains were made in the predictive models with the addition of weather and air quality predictors (Models 3 and 4). However, forecasting models that included weather and air quality predictors performed slightly better than the seasonal and temporal model alone (i.e., Model 3 > Model 4 > Model 2) This study provided a new approach to predict higher than expected numbers of respiratory related-deaths. The approach, while promising, has limitations and should be treated at this stage as a proof of concept.
In this review, our aim was to examine the influence of geographic variations on asthma prevalence and morbidity among adults, which is important for improving our understanding, identifying the burden, and for developing and implementing interventions aimed at reducing asthma morbidity. Asthma is a complex inflammatory disease of multifactorial origin, and is influenced by both environmental and genetic factors. The disparities in asthma prevalence and morbidity among the world's geographic locations are more likely to be associated with environmental exposures than genetic differences. In writing this article, we found that the indoor factors most consistently associated with asthma and asthma-related symptoms in adults included fuel combustion, mold growth, and environmental tobacco smoke in both urban and rural areas. Asthma and asthma-related symptoms occurred more frequently in urban than in rural areas, and that difference correlated with environmental risk exposures, SES, and healthcare access. Environmental risk factors to which urban adults were more frequently exposed than rural adults were dust mites,high levels of vehicle emissions, and a westernized lifestyle.Exposure to indoor biological contaminants in the urban environment is common.The main risk factors for developing asthma in urban areas are atopy and allergy to house dust mites, followed by allergens from animal dander. House dust mite exposure may potentially explain differences in diagnosis of asthma prevalence and morbidity among adults in urban vs. rural areas. In addition, the prevalence of asthma morbidity increases with urbanization. High levels of vehicle emissions,Western lifestyles and degree of urbanization itself, may affect outdoor and thereby indoor air quality. In urban areas, biomass fuels have been widely replaced by cleaner energy sources at home, such as gas and electricity, but in most developing countries, coal is still a major source of fuel for cooking and heating, particularly in winter. Moreover, exposure to ETS is common at home or at work in urban areas.There is evidence that asthma prevalence and morbidity is less common in rural than in urban areas. The possible reasons are that rural residents are exposed early in life to stables and to farm milk production, and such exposures are protective against developing asthma morbidity. Even so, asthma morbidity is disproportionately high among poor inner-city residents and in rural populations. A higher proportion of adult residents of nonmetropolitan areas were characterized as follows:aged 55 years or older, no previous college admission, low household income, no health insurance coverage, and could not see a doctor due to healthcare service availability, etc. In rural areas, biomass fuels meet more than 70% of the rural energy needs. Progress in adopting modern energy sources in rural areas has been slow. The most direct health impact comes from household energy use among the poor, who depend almost entirely on burning biomass fuels in simple cooking devices that are placed in inadequately ventilated spaces. Prospective studies are needed to assess the long-term effects of biomass smoke on lung health among adults in rural areas.Geographic differences in asthma susceptibility exist around the world. The reason for the differences in asthma prevalence in rural and urban areas may be due to the fact that populations have different lifestyles and cultures, as well as different environmental exposures and different genetic backgrounds. Identifying geographic disparities in asthma hospitalizations is critical to implementing prevention strategies,reducing morbidity, and improving healthcare financing for clinical asthma treatment. Although evidence shows that differences in the prevalence of asthma do exist between urban and rural dwellers in many parts of the world, including in developed countries, data are inadequate to evaluate the extent to which different pollutant exposures contribute to asthma morbidity and severity of asthma between urban and rural areas.
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.
Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis.
The aim of this work is to review current knowledge relating the established cancer hallmark, sustained cell proliferation to the existence of chemicals present as low dose mixtures in the environment. Normal cell proliferation is under tight control, i.e. cells respond to a signal to proliferate, and although most cells continue to proliferate into adult life, the multiplication ceases once the stimulatory signal disappears or if the cells are exposed to growth inhibitory signals. Under such circumstances, normal cells remain quiescent until they are stimulated to resume further proliferation. In contrast, tumour cells are unable to halt proliferation, either when subjected to growth inhibitory signals or in the absence of growth stimulatory signals. Environmental chemicals with carcinogenic potential may cause sustained cell proliferation by interfering with some cell proliferation control mechanisms committing cells to an indefinite proliferative span.
Environmental contributions to cancer development are widely accepted, but only a fraction of all pertinent exposures have probably been identified. Traditional toxicological approaches to the problem have largely focused on the effects of individual agents at singular endpoints. As such, they have incompletely addressed both the pro-carcinogenic contributions of environmentally relevant low-dose chemical mixtures and the fact that exposures can influence multiple cancer-associated endpoints over varying timescales. Of these endpoints, dysregulated metabolism is one of the most common and recognizable features of cancer, but its specific roles in exposure-associated cancer development remain poorly understood. Most studies have focused on discrete aspects of cancer metabolism and have incompletely considered both its dynamic integrated nature and the complex controlling influences of substrate availability, external trophic signals and environmental conditions. Emerging high throughput approaches to environmental risk assessment also do not directly address the metabolic causes or consequences of changes in gene expression. As such, there is a compelling need to establish common or complementary frameworks for further exploration that experimentally and conceptually consider the gestalt of cancer metabolism and its causal relationships to both carcinogenesis and the development of other cancer hallmarks. A literature review to identify environmentally relevant exposures unambiguously linked to both cancer development and dysregulated metabolism suggests major gaps in our understanding of exposure-associated carcinogenesis and metabolic reprogramming. Although limited evidence exists to support primary causal roles for metabolism in carcinogenesis, the universality of altered cancer metabolism underscores its fundamental biological importance, and multiple pleiomorphic, even dichotomous, roles for metabolism in promoting, antagonizing or otherwise enabling the development and selection of cancer are suggested.
As part of the Halifax Project, this review brings attention to the potential effects of environmental chemicals on important molecular and cellular regulators of the cancer hallmark of evading growth suppression. Specifically, we review the mechanisms by which cancer cells escape the growth-inhibitory signals of p53, retinoblastoma protein, transforming growth factor-beta, gap junctions and contact inhibition. We discuss the effects of selected environmental chemicals on these mechanisms of growth inhibition and cross-reference the effects of these chemicals in other classical cancer hallmarks.
Carcinogenesis is thought to be a multistep process, with clonal evolution playing a central role in the process. Clonal evolution involves the repeated 'selection and succession' of rare variant cells that acquire a growth advantage over the remaining cell population through the acquisition of 'driver mutations' enabling a selective advantage in a particular micro-environment. Clonal selection is the driving force behind tumorigenesis and possesses three basic requirements: (i) effective competitive proliferation of the variant clone when compared with its neighboring cells, (ii) acquisition of an indefinite capacity for self-renewal, and (iii) establishment of sufficiently high levels of genetic and epigenetic variability to permit the emergence of rare variants. However, several questions regarding the process of clonal evolution remain. Which cellular processes initiate carcinogenesis in the first place? To what extent are environmental carcinogens responsible for the initiation of clonal evolution? What are the roles of genotoxic and non-genotoxic carcinogens in carcinogenesis? What are the underlying mechanisms responsible for chemical carcinogen-induced cellular immortality? Here, we explore the possible mechanisms of cellular immortalization, the contribution of immortalization to tumorigenesis and the mechanisms by which chemical carcinogens may contribute to these processes.
The purpose of this review is to stimulate new ideas regarding low-dose environmental mixtures and carcinogens and their potential to promote invasion and metastasis. Whereas a number of chapters in this review are devoted to the role of low-dose environmental mixtures and carcinogens in the promotion of invasion and metastasis in specific tumors such as breast and prostate, the overarching theme is the role of low-dose carcinogens in the progression of cancer stem cells. It is becoming clearer that cancer stem cells in a tumor are the ones that assume invasive properties and colonize distant organs. Therefore, low-dose contaminants that trigger epithelial-mesenchymal transition, for example, in these cells are of particular interest in this review. This we hope will lead to the collaboration between scientists who have dedicated their professional life to the study of carcinogens and those whose interests are exclusively in the arena of tissue invasion and metastasis.
Cell death is a process of dying within biological cells that are ceasing to function. This process is essential in regulating organism development, tissue homeostasis, and to eliminate cells in the body that are irreparably damaged. In general, dysfunction in normal cellular death is tightly linked to cancer progression. Specifically, the up-regulation of pro-survival factors, including oncogenic factors and antiapoptotic signaling pathways, and the down-regulation of pro-apoptotic factors, including tumor suppressive factors, confers resistance to cell death in tumor cells, which supports the emergence of a fully immortalized cellular phenotype. This review considers the potential relevance of ubiquitous environmental chemical exposures that have been shown to disrupt key pathways and mechanisms associated with this sort of dysfunction. Specifically, bisphenol A, chlorothalonil, dibutyl phthalate, dichlorvos, lindane, linuron, methoxychlor and oxyfluorfen are discussed as prototypical chemical disruptors; as their effects relate to resistance to cell death, as constituents within environmental mixtures and as potential contributors to environmental carcinogenesis.
Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be considered. Disruptive chemicals may also contribute to multiple stages of tumor development through effects on the tumor microenvironment. In turn, the tumor microenvironment consists of a complex interaction among blood vessels that feed the tumor, the extracellular matrix that provides structural and biochemical support, signaling molecules that send messages and soluble factors such as cytokines. The tumor microenvironment also consists of many host cellular effectors including multipotent stromal cells/mesenchymal stem cells, fibroblasts, endothelial cell precursors, antigen-presenting cells, lymphocytes and innate immune cells. Carcinogens can influence the tumor microenvironment through effects on epithelial cells, the most common origin of cancer, as well as on stromal cells, extracellular matrix components and immune cells. Here, we review how environmental exposures can perturb the tumor microenvironment. We suggest a role for disrupting chemicals such as nickel chloride, Bisphenol A, butyltins, methylmercury and paraquat as well as more traditional carcinogens, such as radiation, and pharmaceuticals, such as diabetes medications, in the disruption of the tumor microenvironment. Further studies interrogating the role of chemicals and their mixtures in dose-dependent effects on the tumor microenvironment could have important general mechanistic implications for the etiology and prevention of tumorigenesis.
One of the important 'hallmarks' of cancer is angiogenesis, which is the process of formation of new blood vessels that are necessary for tumor expansion, invasion and metastasis. Under normal physiological conditions, angiogenesis is well balanced and controlled by endogenous proangiogenic factors and antiangiogenic factors. However, factors produced by cancer cells, cancer stem cells and other cell types in the tumor stroma can disrupt the balance so that the tumor microenvironment favors tumor angiogenesis. These factors include vascular endothelial growth factor, endothelial tissue factor and other membrane bound receptors that mediate multiple intracellular signaling pathways that contribute to tumor angiogenesis. Though environmental exposures to certain chemicals have been found to initiate and promote tumor development, the role of these exposures (particularly to low doses of multiple substances), is largely unknown in relation to tumor angiogenesis. This review summarizes the evidence of the role of environmental chemical bioactivity and exposure in tumor angiogenesis and carcinogenesis. We identify a number of ubiquitous (prototypical) chemicals with disruptive potential that may warrant further investigation given their selectivity for high-throughput screening assay targets associated with proangiogenic pathways. We also consider the cross-hallmark relationships of a number of important angiogenic pathway targets with other cancer hallmarks and we make recommendations for future research. Understanding of the role of low-dose exposure of chemicals with disruptive potential could help us refine our approach to cancer risk assessment, and may ultimately aid in preventing cancer by reducing or eliminating exposures to synergistic mixtures of chemicals with carcinogenic potential.