Cancer Holistic Treatment

Do I Have Cancer

This ebook from medical practitioner and family doctor Dr. Parajuli gives you all of the signs and symptoms that you need to know in order to catch cancer in the very early stages and protect yourself from it. You don't have to worry about if you have cancer anymore, and better yet you don't have to spend thousands of dollars to make sure of that either! All it takes is a bit of knowledge and you are on your way! This book also teaches about other aspects of cancer patients, such as how to live with different kinds of cancer, how to prepare yourself mentally to accept this reality if it IS a reality for you, and how to deal with doctors and insurance companies. This book is easy to read and in PDF format, so you don't have to worry at all about reading it. Make it easy on yourself! Read more here...

Do I Have Cancer Overview

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This is one of the best e-books I have read on this field. The writing style was simple and engaging. Content included was worth reading spending my precious time.

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Repair capacity and cancer risk

The reduced capacity phenotypes exists at an incidence of at least 10 , it would be expected that at least 1 of the individuals in the population will exhibit a reduced capacity in two repair pathways. Such individuals, with reduced capacity to repair both bleomycin and BPDE induced damage, are observed. These individuals exhibit a higher risk (OR > 30) of developing lung cancer77 and hepatocellular carcinoma90 than individuals with a reduced capacity in only one pathway (OR 5-7). Thus, the evidence supports the conclusion that DNA repair capacity is a highly heritable trait that is related to individual cancer risk.

Summary of genetic variation and cancer risk

Genetic variation as exemplified by cancer susceptibility alleles is a key element in determining an individual's risk of cancer even in the absence of the highly penetrant variant alleles observed in cancer families. Cancer susceptibility alleles, although increasing risk only a few fold, exist at polymorphic frequency and have the potential to have a major impact on the population incidence of cancer.72 This impact is in contrast to the generally rare cancer alleles, which have a major impact on risk for the affected individual but only limted impact of the population incidence. Note the use of the term alleles rather than genes. This reflects the growing realization that different variants, with different degrees of negative impact on normal protein expression or function, exist in these genes. That is, cancer alleles and susceptibility alleles are likely to exist at the same locus. Note also that the normal function of these cancer genes is to prevent cancer and that it is the...

Cigarette smoke carcinogens

Tobacco smoke and its condensate contain a complex mixture of over 3800 compounds of these 50 have been identified as being either animal or human carcinogens.9 Of the several carcinogens present in cigarette smoke, polycyclic aromatic hydrocarbons (PAHs) (e.g., benzo a pyrene or B a P) and the tobacco-specific nitrosamines (e.g., or NNK) appear to play a major role in inducing lung cancer.10 Other classes of chemicals such as aza-arenes, aromatic amines (e.g., 4-ami-nobiphenyl or 4-ABP), heterocyclic aromatic amines, aldehydes, miscellaneous organic compounds (e.g., 1,3-butadiene), and inorganic compounds (e.g., Ni, Cr) are also known to be carcinogenic.9,10 In addition, tobacco smoke contains volatile compounds (e.g., benzene) and radioelements (e.g., polo-nium-210) that may also play a role in its carcinogenicity.10 Cigarette smoke also contains free radicals capable of inducing oxidative DNA damage. For example, the tar phase contains stable free radicals, such as catechols,...

Metabolic activation of cigarette smoke carcinogens and DNA adduct formation

Several of the chemical carcinogens present in cigarette smoke are inactive per se and require metabolic activation (e.g., PAH). Biotransformation of these chemical carcinogens results in the formation of reactive electrophilic intermediates, which covalently bind to nucleophilic sites in DNA forming carcinogen DNA adducts.13 In a human lung, several of the PAH carcinogens are predominantly activated by cytochrome P4501A1 (CYP1A1) enzyme to their ultimate carcinogenic metabolites, such as diol epoxides which bind covalently to DNA forming bulky aromatic DNA adducts.14 For example, the major metabolic pathway of B a P involves its conversion to benzo a pyrene 7,8-diol-9,10-epoxide (BPDE) via B a P-7,8-diol by CYP1A1, CYP3A4, and epoxide hydrolase in a two-step reaction. BPDE is an ultimate carcinogenic Similarly, several reactive metabolites generated through metabolic activation of PAHs, N-nitrosamines and aromatic amines are capable of forming bulky DNA adducts.15 In addition to the...

Role of smokingrelated DNA adducts in lung cancer

DNA adducts represent the biologically effective dose, defined as the amount of carcinogen bound to DNA in either target tissue or a surrogate tissue taking into account the individual differences in absorption and metabolism of a carcinogen to its DNA reactive intermediate(s), detoxification of the reactive intermediates, and repair of DNA damage. DNA adduct formation is generally accepted as one of the key events in tumor initiation during chemical carcinogenesis.19 The biological potential of a given DNA adduct depends on its mutagenic potential, ability to be repaired, location within a target gene, and the nature of the target gene.20 For example, formation of BPDE-dG adducts in mutational hot spots of the p53 tumor suppressor gene in lung cancer patients substantiates the association between tobacco carcinogen-induced DNA damage and lung cancer.21 Total DNA adduct levels, and in some cases specific adducts, have been correlated with in vitro muta tions,2223 chromosomal...

DNA adducts as intermediate biomarkers of lung cancer A Tobacco carcinogeninduced bulky DNA adducts

The presence of smoking-related DNA adducts was first established in human placenta,39 and the lung and larynx of smokers.40-42 The principal target organs of tobacco smoke-induced respiratory tract carcinogenesis (lung, bronchus bronchial epithelium, and larynx) consistently exhibit high adduct levels in smokers, while adduct levels in these tissues are absent or low in nonsmokers.1536 Smoking-related DNA adducts have also been detected in other target and nontarget tissues, including kidney, bladder, esophagus, pancreas, ascending aorta, liver, and cervix.42-44 BPDE-dG adducts have also been detected by immunohistochemistry in human sperm and in embryos from smoking couples.45 shorter half-life of 8 h.55 Therefore, in those studies in which the WBC samples consisted mainly of short-lived granulocytes, the inability to detect differences in adduct levels between smokers and nonsmokers may have been because there was insufficient time to accumulate stable adducts in these cells....

Role of Pahdna adducts in human carcinogenesis

PAHs are products of incomplete pyrolysis of organic matter and are widespread in the environment.3839 Humans are largely exposed to complex mixtures of these compounds. Sizable amounts of PAHs are generated as a result of industrial coke and iron and other metal production. In addition, PAHs are found in combustion emissions of fuels, including diesel and biomass, in certain types of cooked food, and in tobacco smoke. It is believed that the largest concentrations of PAHs are inhaled by smokers with the mainstream smoke of cigarettes.4041 Smoking is considered to be the major cause of upper aerodigestive tract cancers including cancer of the lung.42 Lung cancer is a leading cause of cancer death for American women and men43 and is one of the most common types of cancer worldwide. Therefore, smoking-related PAHs are strongly implicated as agents responsible for initiation and development of lung cancer. Interestingly, recent work still does not ascribe a role of diesel engine exhaust...

Other DNA adducts other types of cancer

Monitoring of the sequence-specific formation of PAH-DNA adducts along the p53 gene has provided important clues as to the potential origin of G to T transversion mutations in human lung cancers. A similar case can be made for the involvement of sunlight-induced cyclobutane pyrimidine dimers and p53 mutations in human nonmelanoma skin tumors.89,111 Interestingly, the DNA base 5-methylcytosine also plays an important role in enhancing formation of DNA damage by sunlight although the mechanism is, of course, completely different from that of enhanced PAH adduct formation at methylated CpG sites.112 One other obvious example, where an exogenous agent has been clearly implicated in human carcinogenesis, is the connection between aflatoxin B1 and human liver cancer. Hepatocellular carcinomas from geographic areas of the world with high suspected food contamination by aflatoxin B1 carry a unique G to T transversion mutation signature at codon 249 of the p53 gene. LMPCR and terminal...

Malignant Neoplasms Cancer

Cancer is any malignant growth in the body. It is an uncontrolled multiplication of abnormal body cells. The cause of the various types of cancer is unknown, circumstantial, or unclear except for cigarette smoking and exposure to ionizing radiation. There does not appear to be a dosage or level of exposure to cigarette smoking or ionizing radiation below which there is no risk. Viruses, genetic background, poor health, and exposure to various agents in our air, water, food, drugs, and cosmetics are believed to contribute to the disease. Some environmental substances become carcinogenic only after metabolism within the body, and gene-environment interactions are believed to be crucial in determining an individual's risk to developing cancer from exposure to toxins.

Toxicodynamic Modeling of cancerRelated Effects of chemicals and a Binary chemical mixture

A further example of biologically based toxicodynamic modeling is computer simulation of clonal growth of initiated liver cells in relation to carcinogenesis. The impetus of this research development came from the desire to finding a way to evaluate carcinogenic potentials of chemicals or chemical mixtures without going through the resource-intensive chronic cancer bioassays (Yang 1994, 1997 Yang et al. 2004). The experimental animal model used for this research development involved a modification of the medium-term initiation-promotion bioassay of Ito et al. (1989a, 1989b). It is an initiation-promotion assay of a relatively short duration, and the modification incorporated toxicokinetics into the experimental design. This protocol allows the evaluation of carcinogenic potential within 8 weeks by identification of hepatic pre-neoplastic foci expressing glutathione S-transferase placental form (GST-P) as an endpoint marker. The clonal growth model is based on the 2-stage model of...

Molecular epidemiological studies of aflatoxin and human liver cancer

HCC is one of the most common cancers worldwide, and there is a striking geographic variation in incidence. For example, in the People's Republic of China, HCC accounts for over 300,000 deaths annually, the third leading cause of cancer mortality.5 During the 1960s and 1970s, several epidemiolog-ical studies were conducted in Asia and Africa that showed there was an association between high aflatoxin exposure, estimated by sampling foodstuffs or by dietary questionnaires, and increased incidence of HCC.6 While these early studies could not account for additional factors such as hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, this information provided a strong motivation to further investigate the circumstantial relationship between aflatoxin ingestion and liver cancer incidence. There have been two major cohort studies to address the relationship of aflatoxin exposure to HCC incidence reported to date. The first comprises over 18,000 people in Shanghai from whom urine...

Health Risk Calculations For Noncarcinogens

In considering the carcinogenic effects of chemicals, there is no threshold dose of a chemical to which an animal species can be exposed safely. In risk calculations for noncarcinogens, though, it is accepted that there is a threshold chemical concentration, below which the chemical is not harmful. These values are calculated by taking a population of animals, exposing them to increasing doses of the chemical, and observing health effects. A generic plot of such an experiment is shown in Figure 10.2, where the response is shown on the y-axis and the chemical concentration is on the x-axis. Note the presence of the threshold, which is essentially just an estimate. There are several important points on the plot that need to be mentioned. The first is the lowest-observed-effect level (LOEL not shown in Figure 10.2) which is lowest dose administered to the animal that results in a response (death or health effect). The next point is the no-observed-effect level (NOEL not shown in Figure...

Biomarkers and liver cancer prevention

Several approaches can be considered for the prevention of liver cancer. A first approach is vaccination against HBV. Unfortunately, many people living in high-risk areas for liver cancer acquire the HBV infection before age three. Thus, an immunization program for total population protection would have to occur over several generations, provided that mutant strains of HBV do not arise, thereby eliminating the utility of current vaccines. Despite these problems, vaccination programs for HBV have been implemented in many areas of Africa and Asia. A second approach for cancer prevention would be the elimination of aflatoxin exposures. Primary prevention of aflatoxin exposures could be accomplished through large expenditures of resources for proper crop storage and handling however, this approach is not economically feasible in many areas of the world. Secondary prevention measures using chemopreventive agents, which block the activation and enhance the detoxification of AFB1 are being...

Solutions Cancer And Other Chronic Diseases

Cancer Clusters Acute environmental illnesses constitute a minority of all health problems handled by specialists in environmental health. More frequently, chronic diseases are at issue. A particularly common perception or complaint coming to the attention of environmental health practitioners is the concern that a given community has an excessive number of cancer cases. Although the steps required have been clarified in recent years, much time and effort is required to address effectively these concerns (CDC 2005). The first step in evaluating such a complaint is to verify that the numbers of cases actually justify concern. The investigator first establishes the geographical and temporal boundaries (place and time) of concern about increased risk. The cancer cases that occur (observed cases) are compared with the expected numbers calculated by applying tumor type-, age-, and gender-specific rates from population-based cancer registries to the numbers of persons in the same age and...

Developmental Effects and Cancer

The potential of phthalate esters to produce cancer following long-term exposure will be discussed below. Occasionally, questions arise about the potential to develop cancer following short-term exposure. Based on animal studies, liver cancer associated with exposure to some high-MW phthalates occurs only after prolonged exposure 45,51,52 .

Table 23 Types of cancers reported following exposure to benzene

The role of benzene in some of these cancers is controversial, see text for details. Lung cancer Lung cancer Some mortality studies on benzene exposure have identified individuals with lung cancer (Aksoy, 1985 Yin et al., 1989 Hayes et al., 1996 Yin et al., 1996). However, the relative risk of lung cancer from benzene exposure is difficult to distinguish from the risks associated with cigarette smoking.

Health Risk Calculations For Carcinogens

Perhaps the most disputed, but very important, aspect of determining the effects of a pollutant on human health is our attempt to estimate the increase in cancer risk in a population exposed to the pollutant at a specific concentration. We start with the standard approach of developing a dose-response curve, such as the one shown in Figure 10.1, by exposing an animal to increasing concentrations of pollutant. After a given time period days, months, or even a lifetime the animal is sacrificed and examined for signs of cancer development. In rare cases, human data are available, not from experiments, of course, but from legal, illegal, or in many cases accidental exposures to pollutants. The obvious problem with animal experiments is determining how nonhuman responses in exposure studies relate to human responses to the same pollutant. In most cases, we do not know but rather approximate the relationship. To complicate the situation further, dose-response experiments are conducted at...

Tamoxifen is a carcinogen

The antiestrogen tamoxifen is widely used as first-line endocrine therapy for breast cancer patients more than 500,000 women in the United States are currently being treated with this drug.5 A randomized clinical trial designed for healthy women at high risk of developing this disease showed that therapeutic doses of tamoxifen reduced the risk of invasive breast cancer by approximately 50 .6 Subsequently, tamoxifen was approved in 1998 for use as a chemopreventive agent. Unfortunately, the use of tamoxifen in breast cancer patients is associated with an increased risk of endometrial cancer.712 A similar observation was made during the breast cancer chemo-prevention trial.6 Tamoxifen is listed as a human carcinogen by the IARC.13 The cellular mechanism responsible for this carcinogenic effect has not been defined.1416 Since tamoxifen induces hepatocellular carcinomas in rats1719 and tamoxifen-DNA adducts have been detected in rat liver, 1420-22 it is possible that tamox-ifen or its...

Lung cancer incidence predisposition and environment

Lung cancer is the paradigm of an environmentally induced disease. It is estimated that there will be 169,400 new cases and an estimated 154,900 deaths accounting for 28 of cancer-related deaths in the United States in 2002.1 The prognosis for lung cancer remains poor, with a 13 overall 5-year relative survival rate. About 87 of the cancer cases are attributed to cigarette smoking and the relative risk for lung cancer in current smokers compared with those who have never smoked is up to 20-fold higher.2 However, fewer than 20 of the cigarette smokers develop lung cancer. In genetic epidemi-ological studies, which utilize twin comparisons, the effects of genetic and environmental factors on current smoking, smoking initiation, and smoking persistence have been estimated. One of the conclusions that may be drawn from these studies is that, for most individuals, the liability to become and remain a smoker is explained by additive genetic factors.3 It has been reported that smoking and...

Molecular epidemiology of human cancer and DNA adducts

The emerging field of molecular epidemiology is based on the detection of biological markers of human chronic disease with environmental components for the purpose of identifying its causes and outcomes.912 Identification of human carcinogens is considered most accurate when supported by cancer epidemiology data.13 The biomarkers used in the molecular epidemiology of human cancer include specific changes at the gene and chromosome level (polymorphisms, mutations and cytogenetic alterations), concentrations of potential carcinogens and or metabolites in cells, tissues and biological fluids, and levels of covalent carcinogenic adducts to proteins and to DNA.14 In certain cases changes found at the molecular level may give insights into possible origins of the disease.915 Development of a biomarker normally involves thorough laboratory characterization in order to recognize its utility for molecular epidemiological studies. The ultimate level of validation of a biomarker is achieved...

Cancer

A retrospective mortality study of 887 male and 874 female patients that were observed for an average of 11 years following official registration as Yusho victims found no significant increase in male deaths (79 observed, 66.13 expected) or female deaths (41 observed, 48.90 expected) from all causes (Kuratsune et al. 1987). Mortality for cancer at all sites, however, was significantly increased in males (33 observed, 15.51 expected, standardized mortality ratio SMR 2.13) based on Japanese national rates. This is attributable to significantly increased mortality from liver cancer (9 observed, 1.61 expected, SMR 5.89) and cancer of the lung, trachea, and bronchus (8 observed, 2.45 expected, SMR 3.26). The increased mortality from liver cancer remained statistically significant when based on local death rates (SMR 2.53) and when early liver cancer cases (those occurring < 9 years after poisoning) were excluded (SMR 3.85). However, because the geographic distribution of liver cancer...

Carcinogenicity

First classified as probably carcinogen for humans (class B2) by the US EPA in 1987 71 , aldrin and dieldrin were then described as ''not likely human carcinogen'' 72,73 , since reported epidemiologic studies showed no correlation between pesticide exposure and cancer 74,75 . POPs and PCBs contamination of the environment is suspected to be the cause of the increasing incidence of breast cancer in European countries 76 . DDT is classified by International Agency for Research on Cancer (IARC) as possibly carcinogenic to humans (group 2B) 30 . Dioxins are carcinogenic in several animal species 77 and humans, and increased risk of cancer has been demonstrated at exposure levels more than 100 times the normal intake of the general population 78 . Dioxins are classified as human carcinogenic by the IARC 79-81 and either ''carcinogenic to humans'' or ''likely to be a human carcinogen'' by EPA 35 . This is consistent with the observations of Bertazzi et al. 82,83 , showing an increase of...

F UV carcinogenesis

The role played by free radicals in carcinogenesis has been debated for many years. There is little doubt that carcinogenesis involves free radical events and changing these events can effect the rate if not the final outcome of carcinogenesis. However, it is not clear how or at what stage antioxidants or other agents that affect free radical processes interfere with carcinogenesis. This discussion will focus on the early phases of carcinogenesis. Skin tumors are a good example because they are largely due to UV radiation and the ROS-mediated processes caused by UV.42 UV-mediated tumor formation in rodents was studied by Black and colleagues in the 1970s under the basic premise that ROS are important mechanistically.43-46 They determined that a cholesterol epoxide formed by ROS intermediates was important in the carcinogenic process.43 They showed that UV-mediated tumor formation decreased significantly in animals fed a diet containing antioxidants (i.e., 1.2 ascorbate, 0.5 butylated...

Assessment of current status of biomarker research

Nevertheless, there are exemplary results with biomarkers that can be mentioned. A recent summary highlighted the success achieved with biomarkers of exposure to aflatoxin.7 A biologically plausible model based on adverse effects of aflatoxin bioadducts supports the strong epidemiological link between adduct level and risk of liver cancer. In both animal models and human studies, DNA adduct level correlates with known or estimated external dose of aflatoxin. A urinary metabolite of the aflatoxin DNA adduct has also been used effectively as a quantitative biomarker of exposure. In addition, large-scale epidemiological studies (cross-sectional, longitudinal, and case-control) have been carried out using these biomarkers. Prospective studies are also ongoing and biomarkers of aflatoxin exposure have been used to monitor efficacy of intervention during clinical trials of the drug oltipraz. The aflatoxin biomarker is a unique example of a well-developed and useful molecular biomarker of...

The Need For Bioremediation

Tanks have caused widespread soil and aquifer contamination, threatening the safety of various potable water supplies. Polycyclic aromatic hydrocarbons (PAHs), dioxins, and dibenzofurans formed during the incomplete combustion of organic materials such as coal, diesel, wood, and vegetation are major airborne contaminants these complex and sometimes carcinogenic compounds ultimately are deposited from the air and contaminate terrestrial and aquatic systems. Oil spills, such as the 1967 Torrey Canyon spill in the English Channel, the 1978 Amoco Cadiz oil spill off the coast of Brittany, and the 1989 Exxon Valiez oil spill in Prince William Sound, Alaska, have the potential to cause maj or marine ecosystem damage. The complex and diverse range of petroleum-derived organic compounds released from such spillages is of major environmental concern. These consist of aliphatic (e.g., al-kanes and alkenes) and aromatic (e.g., benzene, toluene, ethylbenzene, and xylene BTEX ) hydrocarbons and...

Perfluorinated organic substances

Perfluorinated compounds (PFCs) or perfluorinated organic substances (PFOS) are used in a wide variety of industrial applications 13 . As a consequence these compounds show a global distribution in the environment 14 . They have been detected not only in environmental samples and fish but also in human blood and liver, and in several wildlife species 15 . PFOS show persistence in the environment and some of them have been related to different carcinogenic actions, for example, perfluorooctanoic acid has been identified as a potent hepatocarcinogen in rodents 16 . Meanwhile PFOS have been recognized by the EFSA and concentration levels, contamination pathways and toxicological potency should be assessed in the food chain.

Surface Water Treatment Rule

Cancer risk liver effects Kidney liver nervous system effects Kidney liver blood cell nervous system effects Cancer risk liver circulatory effects Liver nervous system effects cancer risk Cancer risk liver kidney nervous system effects Kidney liver effects Nervous system liver circulatory effects Cancer risk liver effects Cancer risk neurologic liver effects kidney liver nervous system effects

Can an Energy Source Be Isolated from Matter

Chapter 5 characterizes lights from various sources and based on their sources. It shows that with such scientific characterization it becomes evident why sunlight is the essence of life and artificial light (dubbed as white light) is the essence of death. The problems associated with artificial lights, ranging from depression and breast cancer to myopia (Chhetri and Islam 2008), are explained in terms of the characterization done in this chapter. It is shown that a natural light source is a necessary condition of sustainability. However, it is not sufficient as the process of converting the energy source into light must not be unsustainable.

Regulations and Phthalate Esters

Phthalate esters have undergone comprehensive risk assessments regarding virtually all aspects of environmental and human health under existing substances regulations in the US, Canada, the EU, and at the Organization for Economic Cooperation and Development (OECD) level. These risk assessments have used the extensive data that has been generated for phthalate esters. The results of the various risk assessments completed to date have led to varying conclusions ranging from no further information needed and or no need for further restrictions on use, to proposed requirements for some use-specific risk reduction measures. Some of the recent reviews include cancer classifications for DEHP and BBP by the International Agency for Research on Cancer, reviews of seven phthalate esters by an Expert Panel of the U.S. National Toxicology Program Center for the Evaluation for Risk to Human Reproduction, and review of DINP in children's toys by the U.S. Consumer Product Safety Commission Chronic...

Peptide and protein growth promoters

The use of growth promoters in food producing animals has been banned in many countries since 1988 31 . Thanks to harmonization efforts most of the EU member states are capable of detecting steroids and b-agonists at the required level, although large differences in specific analyte coverage still exist. Hormone criminality is believed to be linked with sports doping and to occur via international networks. As in sports doping it can be predicted that the abuse will shift from classical growth promoters such as steroids and b-agonists to peptides and proteins when the veterinary control of the former becomes more effective. Bovine and porcine somatotropin (bST and pST), the equivalents of human growth hormone, are 22 kDa proteins and commercially available as recombinant preparations. They are important endocrine factors influencing metabolic and somatogenic processes including growth, immune function, reproduction and lactation. Their species specificity implies low toxicity in...

The Nature Of The Problem

DDT, the chemical for which Carson is most noted for highlighting, was banned in the United States at the end of 1972, eight years after her untimely death from cancer. Although the DDT ban spread to many temperate countries, few tropical countries acceded to the ban, largely due to the pesticide's efficacy to control the spread of malaria and other insect-borne diseases. DDT has been shown to dissipate much more rapidly in tropical than temperate soils 12 . The mechanism for the latter is partly attributed to increased temperature-mediated volatility, but more importantly increased microbial biodegradation. The mechanisms underpinning chemical persistence in the environment are complex but are thought to be heavily influenced by the rarity of the chemical's structure and substituents.

Bernard K Gadagbui Lynne T Haber and Michael L Dourson

Hazard identification explores potential concerns about a chemical. It involves an evaluation of the nature, quality, and relevance of scientific data on the specific chemical, the characteristics and relevance of the experimental routes of exposure, and the nature and significance of the observed effects. In this step, scientific studies are reviewed to determine if exposure to an agent could cause increased incidence of adverse health effects (noncancer or cancer effects) in humans, and to identify which effects the chemical can cause. For cancer toxicity, hazard identification depends on professional judgment as to the overall weight-of-evidence of carcinogenicity, including epidemiological information, chronic animal bioassays, mechanistic data, mutagenicity tests, other short-term tests, structure-activity relationships, metabolic and pharmacokinetic properties, toxicological effects, and physical and chemical properties. The outcome of this judgment is the placement of the...

Environmental health science for the next century

This risk management debate has often been conducted using political, economic, or social rhetoric. Yet the key determinant is the availability of valid and robust scientific methodology pertinent to understanding the etiology of disease. This methodology must first enable the necessary definition and surveillance of diseases caused by environmental factors. Then, it must be able to determine causes. Fortunately, the recent rapid advances in molecular biology and in other biologically relevant technologies provide the necessary tools to develop indicators of cause and effect relationships by starting first with the disease and working backward to the cause. Whether by fingerprinting specific patterns of DNA codons altered by a chemical carcinogen or by understanding the subtle alterations in the immune system underlying pulmonary asthma, our new biology provides an opportunity to understand causation.

Pollution Classifications

Mixed waste, a very difficult waste to treat, usually refers to organic and radioactive waste being present in the same waste product. Inorganic waste can be further broken down into nontoxic and toxic metals, metalloids, and nonmetals. Metal waste can be subdivided into heavy metals and transition metals. Toxic wastes can be grouped as carcinogens, terratogens, and mutagens (discussed in Chapter 10). Compounds that are subjects of heightened public awareness, such as PCBs, are divided out even further. Other wastes are listed as hazardous based solely on their origin from a specific industrial process (for example, metal plating wastes) or when a specific chemical is present in the waste stream (for example, the presence of PCBs). As you see, there are many ways to categorize or list a waste, and each country will have their own system for classifying pollutants.

Lead Contamination Causes Warnings State Journal Register Springfield IL September 28 2006

A decision has been made by officials to close the Fairbanks Motorsports Park until further notice following the discovery of asbestos contamination at the site. The asbestos originates from illegally dumped soil that was contaminated with the hazardous substance, which is known to cause a number of health problems including a deadly cancer known as mesothelioma. The illegal dumping of the contaminated soil, which surrounds a dirt bike racing track, is currently being investigated by the Environmental Protection Authority. It has been confirmed that the soil in question was found to be missing from a Mitchell industrial waste holding yard last week. An EPA spokesperson confirmed that the soil had been used in the construction of noise barriers. a product of the coke process, was released directly into Muggah Creek, thus creating the infamous tar ponds. Compared to Nova Scotia and the rest of Canada, Sydney shows significantly higher rates of cancer, cancer mortality and congenital...

New European Chemicals Policies

Chemicals of greatest concern based on their inherent characteristics (carcinogens, mutagens, reproductive hazards, persistence and bioaccumulative potential) would need to be specifically authorized for continued use by the appropriate agencies of the member states or by the European Union (Tickner and Geiser, 2003).

Toxic Soup under Navy Base Creeps toward Water Supply Los Angeles Times February 22 1999

(trichloroethylene) that is 195 feet deep and 2,500 feet wide. This is a concern to the community that uses the groundwater for drinking since the TCE is a cancer-causing toxic solvent. TCE levels were found to be 165,000 ppb and the federal drinking limit is 5 ppb. The Navy is currently removing and treating some of the material and continuously monitoring the surrounding area drinking water.

Debrisoquinesparteine oxidation CYP2D6

CYP2D6 is now known to metabolize more than 72 drugs19 but few environmental pollutants. Numerous epidemiological studies, associating the CYP2D6 allelic differences with toxicity and cancer, however, have been reported. MPTP (N- methyl-4-phenyl-1,1,3,6- tetra-hydropyridine, formed as a byproduct during the illegal drug synthesis of a meperidine analog), and similar addictive compounds, can cause Parkinsonian tremors in humans MPTP inhibits CYP2D6-mediated metabolism in vitro. Individuals having the PM phenotype also appear to have a twofold to 2.5-fold increased risk of developing Parkinson's disease. The EM phenotype appears to be correlated with an increased incidence of tumors in the bladder, liver, pharynx, and stomach, and especially in cigarette smoking-induced lung cancer. These data suggest that enhanced CYP2D6-mediated metabolism of one or more unknown dietary or other environmental agents over decades of life, i.e., formation of a reactive intermediate, might play a role in...

How Can Cdfs Affect My Health

We do not definitely know if CDFs caused cancer in any of the accidentally poisoned people. There are no cancer studies in animals that ate or breathed CDFs. One study found that CDFs alone did not cause skin cancer in animals when they were applied to the skin for several months. However, when researchers applied another carcinogen to the animals' skin before applying CDFs, skin cancer developed. Although skin cancer developed in these animals, the Department of Health and Human Services, the International Agency for Research on Cancer, and the Environmental Protection Agency have not classified the carcinogenicity of CDFs.

How Can Chlorophenols Affect My Health

One way to see if a chemical will hurt people is to learn how the chemical is absorbed, used, and released by the body for some chemicals, animal testing may be necessary. Animal testing may also be used to identify health effects such as cancer or birth defects. Without laboratory animals, scientists would lose a basic method to get information needed to make wise decisions to protect public health. Scientists have the responsibility to treat research animals with care and compassion. Laws today protect the welfare of research animals, and scientists must comply with strict animal care guidelines. One man who splashed pure 2,4-dichlorophenol on his arm and leg died shortly after the accident. Workers who made pesticides from chlorophenols and were exposed to chlorophenols as well as other chemicals through breathing and through the skin developed acne and mild injury to their livers. According to some studies, the risk of cancer was also slightly higher among workers who had made...

Aryl hydrocarbon receptor AHR

The AHR is a ligand-activated transcription factor that controls a number of genes, including drug-metabolizing enzymes such as CYP1A1, CYP1A2, and CYP1B1.25 AHR ligands include dioxin, halogenated aromatic hydrocarbons, and polycyclic hydrocarbons commonly found in cigarette smoke and combustion processes. Inbred mice having a high-affinity receptor allele (Ahrb1, Ahrb2, Ahrb3) are more sensitive to CYP1A1 1A2 1B1 inducibility at lower doses of AHR ligands and exhibit more toxicity and cancer, compared with resistant mice having the low-affinity receptor (Ahrd).26 More than a 12-fold difference in affinity of the AHR for dioxin, similar to that found in mice, is known to exist in human populations.19 From numerous studies, at any given dose of an AHR ligand, the animal having the high-affinity AHR exhibits more polycyclic hydrocarbon-induced toxicity and cancer than the animal having the low-affinity AHR.26 Thus, it seems likely that a high-affinity AHR human might develop cigarette...

Cadmium toxicity and CDM

Cadmium (Cd++) is a trace metal that exists at high concentrations in cigarette smoke, contaminated fish, and food, water, and soil in certain contaminated regions around the world. Cd++ has been designated a Group I human carcinogen, and inhaled Cd++ has been linked with respiratory tumors. Epidemiological evidence suggests that Cd++ exposure in humans might lead to testicular tumors, renal and pulmonary toxicity, and possibly osteoporosis. Striking interindividual variations have been found among people from the same area, same age group, and presumed to be exposed to the same amounts of Cd++.31 These findings suggest allelic differences probably exist in one or more human genes involved in relative sensitivity or resistance to heavy metal toxicity.

How Can Hccpd Affect My Health

One way to see if a chemical will hurt people is to learn how the chemical is absorbed, used, and released by the body for some chemicals, animal testing may be necessary. Animal testing may also be used to identify health effects such as cancer or birth defects. Without laboratory animals, scientists would lose a basic method to get information needed to make wise decisions to protect public health. Scientists have the responsibility to treat research animals with care and compassion. Laws today protect the welfare of research animals, and scientists must comply with strict animal care guidelines. No information is available on whether HCCPD causes cancer in people. The Department of Health and Human Services (DHHS) has determined that HCCPD does not cause cancer in rats and mice under the conditions of the study conducted by the National Toxicology Program. The International Agency for Research on Cancer (IARC) has not evaluated HCCPD as a possible cancer-causing chemical. The EPA...

Environmental genomics applications and issues

The basic techniques used in environmental genomics have already been mentioned under pharmacogenomics. In the case of environmental genom-ics, the studies are more complex for several reasons. The association of a single chemical and a disease response may not be well-established. Even if it is, the genes involved have probably not been defined well. The latter problem is manifested in cancer, a multifactorial disease often of poorly established etiology. Second, numerous examples of interactions of genetic and environmental factors exist. Examples include the resistance of individuals with sickle cell hemoglobin trait to malaria, the resistance of individuals with a lack of CCR5 gene function to human immunodeficiency virus, and the genetic influence (genes not well characterized) on development of lung cancer from smoking. Another example presented by Yokoyama et al.24 deals with aldehyde dehy-drogenase (ALDH2), ethanol, and the risk of head and neck cancer. Homozy-gous poor...

Poly cyclic Aromatic Hydrocarbons

The applications of microorganism for degradation of organics have been growing partly because of better understanding of microbial processes in soil. Especially sites contaminated with polycyclic aromatic hydrocarbons (PAHs). PAHs are aromatic compounds made up of two or more fused benzene rings. It represents a large group of soil pollutants (e.g. naphthalene, phenanthrene, flouranthene, pyrene, chrysene, benzo(a)pyrene etc.). PAHs are recalcitrant and can persist in the environment for long periods, and described to be toxic, mutagenic, or carcinogenic therefore, they are an important risk to the environment and human health (Kuiper et al. 2004) . The main input sources of PAHs are leaches from old storage tanks, road surfaces, and domestic waste oil spills tanker leakage incomplete fossil fuel combustion and seepage from natural oil reservoirs.

Variation in DNA repair capacity

DNA repair systems are responsible for maintaining the integrity of the genome by minimizing replication errors, removing DNA damage and minimizing deleterious rearrangements arising via aberrant recombination. The important role of DNA repair in maintenance of genomic integrity is most obvious in cancer families, where the presence of highly penetrant variant alleles of several genes are associated with a high risk of cancer. A classic example is xeroderma pigmentosum (XP), a prototypic cancer gene syndrome associated with an extreme risk of developing UV-induced skin cancers as the result of the loss of function of one of the genes of NER.49,51 Ataxia telangiectasia, Bloom's Syndrome, Fanconi's anemia, and Nijmegen Breakage Syndromes are other examples of human genetic diseases associated with reduced DNA repair and increased cancer proneness.1 Similarly, the high cancer risks associated with inherited loss-of-function variants of p53, BRCA1, and BRCA243,46 emphasize the important...

Variation in DNA repair genes

Substitutions to be associated with reduced protein function. This screening effort provides a catalog of variants that are reagents for subsequent biochemical and molecular epidemiology studies to address questions of the relationship of genetic variation and cancer risk. This has been described as a genotype to phenotype approach for molecular epidemiology studies.

Extent of variation

In addition, because of the linearity of the steps in the repair process or pathway, different variants may have a similar impact on repair capacity. That is, different variants in a gene or variants in different genes in a pathway could be considered to be equivalent in terms of impact on individual susceptibility and cancer risk. The amount of variation and the complexity of the genotypes when considering a process or pathway rather than individual variants or genes present significant challenges for molecular epidemiology studies.

Discussion Of Health Effects By Route Of Exposure

To help public health professionals and others address the needs of persons living or working near hazardous waste sites, the information in this section is organized first by route of exposure--inhalation, oral, and dermal and then by health effect--death, systemic, immunological, neurological, reproductive, developmental, genotoxic, and carcinogenic effects. These data are discussed in terms of three exposure periods--acute (14 days or less), intermediate (15-364 days), and chronic (365 days or more). Levels of exposure associated with carcinogenic effects (Cancer Effect Levels, CELs) of CDFs are indicated in Table 2.2.

Biomarkers of Exposure

Variation in biomarkers of exposure to chemical carcinogens has also been associated with genetic variation in the carcinogen metabolizing enzymes.22-27 The increase in adduct level associated with the XRCC3 241Met genotype was more marked in smokers with the NAT2-slow phenotype,119 emphasizing the interaction between metabolism or damage induction and repair capacity. The sum of these studies emphasizes the complexity of the role of genetic variation in the individual response to an exposure. These studies documenting a role for individuals differences in response to common exposures begins to provide plausible explanations for the observation that the level of cytogenetic damage in lymphocytes is a better predictor of individual cancer risk than it is an estimator of historical exposure.121, 122 This is consistent with the accumulating data indicating that the health consequences of exposure to environmental agents result from the interaction of dose and the genetic constitution of...

Biodegradation of Aromatic Amines

Aromatic amines formed from reductive decolorization of azo dyes, either by biotic or abiotic processes, are generally toxic and are known or suspected carcinogens (Ekici et al. 2001). Further, they may undergo transformations, when they are released into water bodies. These may be more or less toxic than the parent compounds. Thus, the total degradation of the products formed is the only solution for abating the toxicity of these xenobiotics. In this section, mineralization of aromatic amines under different red-ox conditions, is briefly discussed.

Fundamentals of Cyclodextrin Chemistry 221 Structure and Properties

On the toxicological point of view, none of the a-, P- and y-CD shows major harmful effects for human being (Szejtli 1982, 1996a). No mutagenic, teratogenic or carcinogenic effects have been observed. As a result, an increasing number of commercial products or processes involves native or modified CDs.

YanJu Liu l2 Qing Jun Liu1 and Hui Ding1

Soil plays an important role of medium for material and energy exchanges among the atmosphere, hydrosphere, biosphere and lithosphere (Qishlaqi, 2009). After being polluted, it does bring adverse effects to plants, animals and humans (DalCorso et al., 2008). At Ardai, for example, mature mountain pine forest with significant scenic value was severely damaged and killed due to the toxic emission far away from a smelter l0-20 km (Braanaas et al., 1970). In Asia, large amounts of hazardous materials were considered closely related to humans' reproductive toxicity, neurotoxicity, teratogenesis, immunotoxicity and carcinogenesis (Pringle and Rondinelli, 1998). Up till now, soil pollution has been spreading over many countries of the world (Franzius, 1994). Soil contaminants can input into subsurface arising from agriculture, municipal landfills, informal dumps, and leaking storage tanks (Pringle and Rondinelli, 1998) and thus raise potential risks to the ecosystem. As one of the most heavy...

Health Effects of Chemicals

There are some health problems in this latter class which seem to have grown over the period of growth of the chemical industry. In particular, while most of the rise in cancer is attributable to the fact that we are living longer and therefore stand a greater chance of getting it, some increases in cancer cannot be totally thus explained. Cancers of concern include testicular cancer, which increased in incidence by 55 between 1979 and 1991 in England and Wales breast cancer, which has been estimated to have increased in incidence by 1 a year in the USA since the 1940s prostate cancer, which increased by 40 between 1979 and 1991 in England and Wales, though at least some of this increase is due to improved diagnosis, as well as longer life. There also seems to be a rise in asthma, and possibly in reproductive health problems additional to cancers. diet, including greatly increased consumption of soya, which contains powerful endocrine modulators, and increased consumption of coffee,...

Phenotypic studies methods A Epidemiologic methods 1 Study design

Phenotypic studies of DNA repair are cell-based assays that measure the response to in vitro damaging agents. The design of these studies is presented in Table 7.1. Most phenotypic studies are case control studies (n 12)4-6,8-9,1113,16-2o while one assessed families,7 one examined a cohort of subjects and cases who developed second primary cancers.10 Two were cohort Cancer Site Colorectal cancer Head and neck cancer Lung cancer Head and neck cancer Head and neck cancer Study Method, Ethnic Group Design Cancer Site No. Cases Controls Study Method, Ethnic Group Design Cancer Site No. Cases Controls Lung cancer Lung cancer All cancers All cancers Lung cancer Lung cancer cancer Lung cancer The source of controls is not usually described in detail. Controls are often obtained in a similar manner to the cases, either as a subset of a larger study or as a convenience sample. Sometimes, they are matched by age and sex or other characteristics that might be important to cancer susceptibiltiy,...

Genotyping studies methods A Epidemiologic methods

Cancer Site Head and neck cancer Lung cancer 288 292 Lung cancer Colorectal cancer Lung cancer Cancer Site cancer Esophageal cancer cancer Lung cancer Breast cancer breast cancer Lung cancer BCC Lung cancer Bladder cancer Bladder cancer Breast and or ovarian cancer Esophageal cancer Chinese cases living in the United States with Chinese controls living in China. One study29 used cadaveric transplant donors as controls, and one used friends of the cases.26 Several studies match for exposure (typically, studies on lung cancer match on smoking). The response rate was usually not reported although the study by Duell et al.25 reported an important difference in response rates between cases and controls.

Laboratory methods

Three studies used a relatively high-throughput genetic technology (Taqman or LightCycler).23 25 38 PCR-RFLP was the most frequently used method although one study used PCR SSCP with sequencing.45 Genotype-pheno-type correlation and cancer status were sought in one study,17 with a comparison between the HCRA assay and genotyping for XPD in lung cancer patients. Cases and controls with the wild genotype had the most proficient DNA repair capacity as measured by the host cell reactivation assay. One study compared PCR-RFLP and DHPLC,40 others compared RFLP or SSCP with sequencing in a subgroup.

Assessment of causality

Strength of association Phenotypic studies tend to have relatively high odds ratios (ORs). As the sample sizes are quite small, the variabilities of the assays are often not reported, the reliability most often not measured, and the populations generally subsets of larger and hospital-based studies the large estimates of effect (i.e.,, odds ratios) are common. Larger studies are needed to determine whether phenotypes of low DNA repair capacity do actually have such large effects. The cohort study should demonstrate the most reliable results as measurement of phenotype would be made prior to the development of disease. It should be noted that ORs vary widely with the referent group used. Phenotyping is generally expensive and time consuming. Therefore, studies that attempt to correlate phenotype and genotype in such a way that genotyping, which is far less time consuming and expensive, would be valuable. Only one study17 to date has correlated phenotype and genotype among cancer cases...

Statistical considerations sample size power multiple comparisons

Phenotypic studies are generally small to moderate in size and often consist of a highly selected sample. The differences reported between cases and controls are difficult to evaluate. A large issue is that of separating the results from cases who have cancer and the effects that cancer may exert on the phenotype from a susceptibility to develop cancer. As phenotyping to date is labor intensive, this issue is unlikely to be resolved soon. The cohort studies represented by Bonassi et al.14 give the best insight into the likely true nature of the effect of lower DNA repair capacity on cancer, an approximately twofold increase for those with a higher level of aberrations. In phenotypic studies the statistical power is much stronger than genotyping studies because continuous variables can be used. Multiple comparisons can become a problem whenever the group is split into subgroups, as in any study.

Function and mechanistic interactions

A great deal of progress has been made in developing methods for population-based study of DNA repair in the last several years however, there is room for much more progress in the future. Researchers are genotyping large numbers of subjects for newly identified repair gene polymorphisms and association studies are being carried out. Information on the function and mechanistic interactions of these genotypic alterations is urgently needed. New technologies are being developed rapidly. It may soon be possible to determine whether a small decrement in DNA repair capacity predisposes to cancer. Ultimately, measures of DNA repair capacity may be developed as viable biomarkers for human susceptibility to cancer and possibly other human disease.

Analysis of smokingrelated DNA adducts

With recent advances in analytical biochemistry techniques, DNA adducts have been detected and quantified in target and nontarget tissues or surrogate tissues of smokers using highly sensitive methods, such as immunoas-says, the 32P-postlabeling assay, and fluorescence assays, with detection limits of one adduct per 106-1010 normal nucleotides.30,31 Immunological methods such as competitive enzyme-linked immunosorbent assay (ELISA) require the development of antibodies to the specific adduct of interest. Several polyclonal and monoclonal antibodies are available which can be used in large population studies.30,31 However, some of these antibodies frequently cross react with structurally related DNA adducts formed by other carcinogens. For example, the antibody raised against BPDE-dG cross reacts with diol epoxide adducts of other PAH carcinogens. Recently, immu-noslotblot assays are becoming increasingly popular owing to their high sensitivity (detects one adduct in 108 nucleotides)...

Oxidative DNA damage in smokers

Cigarette smoke, which is a complex mixture of chemical carcinogens, also contains high levels of oxidants. These ROS generated from cigarette smoke can induce DNA single strand breaks in vitro61 as well as cause oxidative DNA damage in cultured human cells62,63 and are known to be involved in chemical carcinogenesis.64 Among the various forms of oxidative lesions, 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) is the most abundant product of oxidative DNA damage and is a sensitive marker of free radical-mediated DNA damage.17 Formation of 8-oxodG in DNA has been shown to be associated with mutagenesis65,66 and carcinogenesis,67,68 and in several animal studies this oxidative lesion has been shown to be associated with the incidence of cancer.69-71 Urinary excretion of 8-oxodG has been used extensively as a noninvasive biomarker of oxidative DNA damage in humans in vivo.72 Cigarette smoking has also been shown to generate high levels of 8-oxodG, which is detected in urine.73 However,...

Metabolic polymorphisms

Inherited polymorphisms in phase I (CYP enzymes) and phase II (predominantly GSTM1) drug metabolizing enzymes have been suggested to contribute to DNA damage and cancer susceptibility of an individual and may contribute to interindividual differences following exposures to carcinogens or mutagens.83,95,96 Aromatic DNA adduct levels in lung tissue of cigarette smokers have been related to the presence of particular CYP1A1, GST M1, and GST P1 polymorphisms in smokers.8, 97 In the CYP1A1 gene (CYP1A1*1 or wt), which encodes for the P4501A1 enzyme involved in the metabolic activation of PAH carcinogens, an Mspl polymorphism in the 3' noncoding region (CYP1A1*2) and an Ile-Val polymorphism in exon 7 (CYP1A1*3 or m2) both of which are found predominantly in Japanese populations and rarely if at all in Caucasians as well as a CYP1A1*4 polymorphism specific to African-Americans, have been shown to be associated with increased risk of developing lung cancer in several studies.98 Higher levels...

The Cradleto Cradle Approach to Material Assessment and Product Design

Once a material's chemical ingredients have been identified, each ingredient is profiled based on the attributes listed in Table 5.3. The attribute set is used to provide a profile of a chemical's potential human and environmental health effects and the profile can be modified as new tests, data, and discoveries become available. Some of the data relating to the attributes of chemical ingredients are available from numerous lists, that is, federal and state regulatory lists, international classifications, lists of carcinogens (National Toxicology Program Report on Carcinogens, NTP International Agency for Research on Cancer Carcinogens, IARC U.S. EPA Integrated Risk Information System, IRIS American Conference

Mutagenic potential of dGN2tamoxifen DNA adducts

Among several tamoxifen-DNA adducts described above, the mutagenic potential of dG-N2-TAM were established using site-specific mutagenesis.51 dG-N2-TAM adducts promoted primarily G T transversions, along with small numbers of G A transitions (Table 9.1). Except for a trans-diastereoi-somer (fr-1) of dG-N2-TAM, mutational frequencies were 12.4-14.0 , slightly higher than that observed with dG-C8-AAF, a model chemical carcinogen.52 The mutagenic specificities were similar to those observed in primer extension reactions catalyzed by mammalian DNA polymerases on dG-N2-TAM-modified DNA templates53 and in the liver DNA of lambda lac transgenic rats.54 Thus, dG-N2-TAMs are mutagenic lesions in mammalian cells.

Detection of tamoxifenDNA adducts in human endometrium

32P-postlabeling combined with chromatography has been used to detect tamoxifen-DNA adducts in endometrial tissue.2325,55 However, conflicting evidence has been published regarding the detection of tamoxifen-DNA adducts in human tissues. Using a 32P-postlabelling-TLC technique, Car-michael and his colleagues failed to detect tamoxifen adducts in the endometrium of tamoxifen-treated patients.23 Applying a 32P-postlabeling HPLC analysis, Hemminki et al. detected a putative tamoxifen-induced adduct in endometrial tissues obtained from breast cancer patients 25 the level of tamoxifen adducts reported was 0.29-0.82 adducts 108 bases standard markers were not used. Also using a 32P-postlabeling-HPLC analysis, Carmichael et al.24 reported they were unable to reproduce the results of the study by Hemminki et al.25 with tamoxifen (Table 9.2). The level of tamoxifen adducts were 0.2-18.0 adducts 108 bases, reproducing the results described in our previous study with 32P-postlabeling-TLC.55 We...

Other antiestrogen drugs

Tamoxifen is a hepatocarcinogen in rats while toremifene, a chlorinated tamoxifen analog (Figure 9.2), is not.19,59 Although toremifene, like tamoxifen, has estrogenic effects on the human endometrium,60 the formation of toremifene-DNA adducts in the liver of rats was two-orders of magnitudes less than that of tamoxifen.19 Therefore, genotoxic effects of tamoxifen are thought to be involved in development of rat hepatocarcinoma. Toremifene has been used for breast cancer chemotherapy in the United States since 1998. Raloxifene (Figure 9.2), a selective estrogen response modifier, reduced the incidence of breast cancer in women at high risk of developing this disease.61 Unlike tamoxifen, raloxifene is unlikely to react with DNA due to the absence of the ethyl moiety and does not demonstrate proliferative effects on the uterus of postmenopausal women.62 The incidence of endometrial cancer was not increased in women enrolled in the raloxifene chemopreven-tive trial.61 In view of their...

Other Novel Bioreactor Configurationsfor Volatile Organic Compound Treatment

Gas-phase benzene, toluene, ethylbenzene and xylene, commonly reported as BTEX, are usually present in emissions from petrochemical and pharmaceutical industries. The deleterious effects of these aromatics are well documented in the literature, and several studies have demonstrated their toxic and carcinogenic health effects. Shim et al. (2002) inoculated a novel fibrous-bed bioreactor with a co-culture of Pseudomonas putida and Pseudomonas fluorescens, and studied the kinetics of BTEX biodegradation in liquid-phase. The authors observed that the biodegradation rates of BTEX increased with increasing BTEX concentration and reactor loading rate. The maximum biodegradation rates for BTEX observed in that study were the highest for toluene (45 mg l.h at a loading rate of 100 mg l.h), followed by benzene, ethyl benzene and xylene isomers. The authors reported that the fibrous-bed bioreactor also had a stable long-term performance, maintaining its cell activity for efficient BTEX...

Air pollution and health

It appears that more than 10 of the benzene used by society (33 M tonne yr-1) is ultimately lost to the atmosphere. High concentrations of benzene can be found in the air of cities and these concentrations may increase the number of cancers. Exposure is complicated by the importance of other sources of benzene to humans, for example tobacco smoke. Toluene (C6H5CH3 Fig. 3.4d) is another aromatic compound present in large concentrations in petrol. Toluene is less likely to be a carcinogen than benzene but it has some undesirable effects. Perhaps most importantly it reacts to form a PAN-type compound, peroxybenzoyl nitrate, which is a potent eye irritant. As emphasized in the previous section, particles have increasingly come to be seen as an important influence on the environmental health of modern populations. The fine PM-2.5 is able to penetrate through the respiratory system all the way to the alveoli. Normally particles are removed from the...

Mass spectrometry and other methods

Gas chromatography-mass spectrometry (GC-MS) offers both high sensitivity and specificity of damage detection. Adducts of PAH, nitrosamines, mal-ondialdehyde and oxidatively damaged bases have been measured in human samples by this technique. The high cost of necessary equipment has limited the use of GC-MS in human biomonitoring. Also, the thermal stability and volatility GC-MS requirements of the sample are not always met by carcinogen-adducted DNA.13 These limitations may be overcome by combining liquid chromatography electrospray ionization with mass spectrometry (LC ESI-MS) or tandem MS.79 LC ESI-MS MS is extremely useful for analysis of DNA adducts, which are not amenable to GC and derivatization owing to the presence of several adjacent polar functional groups.79 Another

Fungal Biodegradation of Polycyclic Compounds

Lignin- and manganese- peroxidases (known as MnP and LiP) (Hammel 1992) and laccases (Majcherczyk et al. 1998). One of the main roles of lignin-degrading enzymes is to attack lignin. The latter is a complex molecule containing different structures, rings and links between the rings. Ligninolytic enzymes are, therefore, non-specific and highly versatile in their biodegradation capabilities, which allow them to biodegrade many different molecules, such as PAHs. On the other hand, the cytochrome P-450 system is also found in mammals, where PAH degradation follows similar pathways as in fungi. The biodegradation products, with the cytochrome P-450 system, are mainly epoxides and dihydrodiols which may show carcinogenic properties. In theperodixase-linkedpathway, quinones are formed (Kennes and Lema 1994a), which are much less harmful. In many cases, these metabolites tend to accumulate as dead-end products.

Human Health Risk Assessment

Human health risk assessments have been performed for pyrethrins and pyr-ethroids by the United States Environmental Protection Agency (USEPA), other government regulatory agencies around the world and university researchers. The USEPA has found that dietary exposure to pyrethrins and pyrethroids is below reference doses 10,11,68,118 these results are supported by the current weight of evidence based on urinary metabolites (see section 3.8). Permethrin has been observed in animal models to be a carcinogen and the USEPA estimated the worst-case lifetime average daily exposure based on a tier 1 conservative model to be 0.117 mgkg day-1. This exposure does not result, however, in an increase in incidents of cancer to the general US population.10 One commonly overlooked use of pyrethrins and pyrethroids is with ultra-low volume (ULV) application techniques, which are applied from trucks, helicopters or airplanes and are used for the control of public health pests such as adult mosquitoes...

Risk Associated with Exposure to Pyridine

Pyridine is 5 ppm (16 mg m3) and a concentration of 3,600 ppm is immediately dangerous to life. A concentration of 10 ppm becomes objectionable to unaccustomed individual and a concentration above 5 ppm leads to olfactory fatigue. EPA regulates pyridine as a toxic waste under the Resource Conservation and Recovery Act (RCRA) a maximum pyridine concentration of 5.0 mg per litre of leachate is allowed using analysis determined by the Toxicity Characteristic Leaching Procedure. Pyridine is listed as a chemical known to the State of California to cause cancer under the safe Drinking Water and Toxic Enforcement Act of 1986 (Proposition 65).

Future directions

The QPCR assay holds great promise for measuring DNA repair capacity and levels of endogenous DNA damage in human populations. However a number of questions remain about the use of the QPCR assay as well as others listed in Table 11.1 for the measurement of DNA damage in human populations. If endogenous DNA damage is 100-fold higher than xenobiotic damage, as has been suggested, then it is unclear whether the more infrequent lesions from exogenous chemicals pose a real threat to biological systems.19 Peripheral lymphocytes are often used as surrogate markers for DNA, but does this cell population serve as a good marker for DNA damage throughout the body More studies must be done in animals to compare levels of adducts in target tissue versus peripheral blood cells. Since cancer can take as long as 20 years to develop in humans following the initial injury, any study of persistent DNA adducts must take into account the biological half-life of these DNA adducts. Finally, molecular...

Characterization of the Toxic Organic Compounds

Exposure to chlorinated dioxins and dibenzofurans causes chloracne which is mostly seen on the cheeks, behind the cheeks, in the armpits and groin region. Chloracne persists for more than 10 years. Abnormal reproductive effects such as decreased testosterone, reduced sperm count, male feminization are seen among males while females experience decreased fertility, miscarriage and endometriosis. Other effects that result from exposure to chlorinated dioxins include immune suppression, liver enzyme changes, nervous system damage and thymus, spleen and bone marrow damage (Mandal 2005). Both PCBs and dioxins are known carcinogens (Fig. 13.2).

Noninfectious And Noncommunicable Diseases And Conditions Associated With The Water Environment

Treatment of the environment supplements treatment of the individual but requires more effort and knowledge. The total environment is the most important determinant of health. A review of more than 10 years of research conducted in Buffalo, New York, showed that the overall death rate for people living in heavily polluted areas was twice as high, and the death rates for tuberculosis and stomach cancer three times as high, as the rates in less polluted areas.118 Rene Dubos points out that many of man's medical problems have their origin in the biological and mental adaptive responses that allowed him earlier in life to cope with environmental threats. All too often, the wisdom of the body is a shortsighted wisdom.119 Whereas microbiological causes of most communicable diseases are known and are under control or being brought under control in many parts of the world (with some possible exceptions such as malaria and schistosomiasis), the physiologic and toxicologic effects on human...

Effect Of Radiation On Humans

Radiation effects on humans are classified as somatic or genetic. Somatic effects are those that cause damage to the individual and include anemia, fatigue, loss of hair, cataracts, skin rash, and cancer. Genetic effects include inheritable changes ) resulting from mutations in reproductive cells. It is widely held that even small dosages of radiation can have some adverse effects, genetic effects being of most concern. Humans are exposed to varying levels of natural radiation, especially from extraterrestrial sources. It is generally felt that radiation created through human activities should be kept well within the bounds of the natural background radiation. What should be the upper acceptable levels within these bounds is a subject of much debate. J Radon is reported to be second only to smoking as a leading cause of lung cancer deaths in the United States. The National Research Council in a 1999 report9 indicated that about 19,000 lung cancer deaths in the United States each year...

Applications of TK and TD Modeling in Risk Assessment

Improving risk assessment can possibly be attained from TK and TD modeling, where it is physically impossible or not practically or ethically feasible to make direct measurements. Biologically based modeling may allow for informed extrapolation (e.g., between species). The most obvious example related to infeasible direct testing is the ethical limitations of human toxicological studies. Most mixture toxicity considerations for humans can only be undertaken by extrapolation from data obtained in experiments on other species. Especially, (suspected) carcinogenic chemicals cannot be administered to humans, but toxicological endpoints and models can be based on data from surrogate species (e.g., rats) or gained from subjects that are exposed to these chemicals on a daily basis from their own consent (e.g., smoking) or after an accident (e.g., radioactivity). In wildlife toxicology, similar issues apply, as it is impossible or impractical to test protected organisms. Furthermore, TK TD...

Detoxification Studies

Bioremediation using microorganisms is very attractive option but it is not always the case, it might increase toxicity (van de Wiele et al. 2005). The measurement for toxicity after microbial treatment suggests whether we should take the microbe for bioremediation further. There are many techniques reported so far to measure the toxicity. Effect of toxicity can be many ways such as genotoxity, carcinogenesis, teratogenesis, mutagenesis and stress caused by toxicant on physological activity. Genotoxic effect can be measured by many ways such as comet assay, end labeling of DNA to visualize the nicking in DNA. For carcinogenesis studies, a comprehensive study is required to established relationship. For mutational effect one can choose Salmonella mutagenesis test. The physiological stress can be measured by many ways depending on type of stress such as metabolic, neuronal, reproductive stress etc. Some specific biochemical and cell based assays are very much popular due to rapid and...

Grouping of chromiuminduced spectra with others

Recently, we began to investigate the mutagenic activity of chromate, Cr(VI), a known human carcinogen. Although chromate had been found to be mutagenic in a variety of test systems,72 73 the mechanism of mutagenesis was less understood. There was evidence that chromate was reduced in the cell by glutathione and other cellular reducing agents, generating reactive intermediates that cause oxidative damage to DNA.74 75 It had also been demonstrated that Cr(III), the stable end product of intracellular reduction of chromate, bound tightly to DNA.48 76 We reasoned that the mutational mechanism could be revealed through an analysis of mutation spectra. For these studies we used both protocols outlined in Figure 13.2. First, we treated

Regulatory Authorities In Health

Communicable and certain noninfectious diseases can usually be regulated or brought under control. In the United States, the local or municipal (often at the county level) health department is the fundamental unit of health intervention and surveillance. A health department having a complete and competent staff to prevent or control diseases that affect individuals and animals is usually established for this purpose. The preventive and control measures conducted by a municipal health department might include supervision of water supply, wastewater, and solid wastes housing and the residential environment milk and food production and distribution stream pollution recreational areas, including camps, swimming pools, and beaches occupational health and accident prevention insects and rodents rural and resort sanitation air pollution noise radiological hazards hospitals, nursing homes, jails, schools, and other institutions medical clinics, maternal and child health services, school...

Toxic Compounds from Plastic

Plastic products and their production processes release numerous types of toxic compounds (Islam 2003). Table 8.2 shows the release of toxic compounds from plastics and their related effects. More than 70,000 synthetic chemicals and metals are currently commercially used in the U.S. The toxicity of most of these is unknown or incompletely studied. In humans, exposure to some may cause mutation, cancer, reproductive and developmental disorders, adverse neurological and immunological effects, and other injuries. Reproductive and developmental effects are a concern because of the important consequences for couples attempting to conceive and because exposure to certain substances during critical periods of fetal or infant development may have lifelong and even intergenerational effects. The industry responsible for creating raw plastic materials is by far the biggest user of listed chemicals, reportedly using nearly 270 million pounds in 1993 alone. Plastic materials and resins are the...

Illnesses Associated with Air Pollution Lung Diseases

The particulate and gaseous contaminants in polluted air may irritate the eyes and respiratory system or damage the clearance mechanism of the lungs, thereby increasing susceptibility to upper respiratory diseases and aggravating existing chronic illnesses. Diseases mentioned as also being associated with air pollution include bronchial asthma (restriction of the smaller airways or bronchioles and increase in mucous secretions), chronic bronchitis (excessive mucus and frequent cough), pulmonary emphysema (shortness of breath), lung cancer, heart diseases, and conjunctivitis (inflammation of the lids and coatings of the eyeballs) (also with lead and carbon monoxide poisoning as previously discussed). In an example of the built environment influencing health, one study found the higher prevalence of asthma in poor neighborhoods of Hartford, Connecticut, to be due in large part to a heavy burden of dust laden with cockroach antigen.73 Certain air contaminants, depending on the body...

Future Perspectives

It is well known that bacteriophages have been successfully applied as therapeutic agents to treat many notorious bacterial pathogens. There are few reports in which phages have been applied in food and agriculture field to kill infectious bacterial pathogens. Traditional chemical disinfectants that are used in water treatment process can form by-products that are carcinogenic in nature. Besides, antimicrobials resistant bacterial strains are ever emerging that are showing resistance to traditional chemical disinfectants. Therefore, now this is the time to think of an alternative antibacterial strategy. It seems possible that phages can be used in environmental problems especially in case of water borne epidemic diseases where it is difficult to control the pathogenic bacteria sources by chemicals. There are very few reports in which bacteriophages have been used as disinfectant in water bodies to kill bacterial pathogens. Bacteriophages could be applied as disinfectant to overhead...

Skin Damage from Sunlight

The ultraviolet light in sunlight can injure the skin and cause skin cancer (melanoma), depending on the exposure. Melanoma appears as a pigmented mole or tumor that may or may not be malignant. Melanomas are almost always curable if detected early and can be usually removed by surgery or freezing with liquid nitrogen. Cataracts can also result from too much sun.

Environmental Governance

Moreover these alternative methods, while more expensive, have the added advantage of not generating trihalomethanes (THMs), which are a byproduct of chlorination and which, if ingested in drinking water over a period of decades, can result in some increase in THM-induced cancer. Hence, the international waterworks literature of today (which is IC-oriented) gives major of attention to use of these alternative disinfection methods.

Molecular responses of mammalian cells to nickel and chromate exposure

Abstract Previous studies from our laboratory have developed biomarkers to assess exposure and early toxicological effects to hexavalent chromium (Cr). Hexavalent Cr reacts with the phosphate backbone of DNA forming ternary complexes of protein Cr DNA, as well as glutathione and amino acid crosslinks with DNA. Recently, we have utilized the Uvr-ABC system and ligation mediated PCR to study and detect Cr DNA adducts in exon 5 and 7 of the p53 gene in human A549 cells. Preliminary results suggest that this technique can detect and map the sites of Cr DNA adducts at a single nucleotide level in exon 5 and 7 of the p53 gene. Interestingly, some of these sites appear to be at hotspots for p53 mutations in human cancer. We are also investigating whether Cr DNA adducts that were tightly bound to the DNA form these coordinate covalent bonds preferentially at guanines that are neighbored by methylated cytosines since previous studies have suggested that guanines near methylated cytosines are...

Biomarkers of chromate exposure

Humans are exposed to two major oxidation states of Cr, Cr(III) and Cr(VI).1 Cr(VI) is the most toxic and carcinogenic form of Cr. The high toxicity of Cr(VI) results from its active accumulation into cells, whereas Cr(III) is much A second indicator of Cr(VI) exposure involves its adduction with DNA. In the cell, the hexavalent form of Cr is reduced to the trivalent form which actually binds to the phosphate backbone of DNA and can cause the formation of ternary complexes involving glutathione, amino acids such as cys-teine and histidine, and DNA.7 Cr(III) can also adduct protein to DNA forming ternary protein-Cr(III)-DNA complexes.89 There has been a substantial amount of work using the DNA-protein crosslinks induced by chromate in white blood cells of humans as a biomarker of chromate exposure and early toxic effects.1011 Recently, we have utilized a UvrABC system and ligation-mediated PCR to study and detect Cr-DNA adducts in exons 5 and 7 of the p53 gene in human A549 cells....

Oxidative state of Cr and toxicity

Exposure to hexavalent Cr compounds has been consistently found to be associated with an elevated incidence of respiratory cancers and other adverse health effects.3-5 Squamous cell carcinoma is the most prevalent form of lung cancer among Cr(VI)-exposed workers.6 The genotoxic potential of Cr(VI) has been confirmed in animal experiments and in several cell-based assays6a7 Inhalation of Cr(VI)-containing acid mists in electroplating industry leads to nasal septum ulceration and perforation, as well as impaired lung function such as decreased vital capacity and forced expiratory vol-ume.8 Other health consequences of exposure to Cr(VI) include pulmonary fibrosis, chronic bronchitis, emphysema, and bronchial asthma.9 Ingestion of Cr(VI) can result in the irritation of mucous membranes and, in severe cases, intestinal bleeding. High doses of Cr(VI) cause renal tubular necrosis and can be lethal. Animal studies have also detected teratogenic activity of Cr(VI).9a Cr(VI) is the second most...

Post Synthesis Procedures

ZnO quantum dots-chitosan folate carrier loaded with anticancer drug and prepared following a post synthesis method, has shown a drug loading efficiency of ca. 75 (Yuan et al. 2010). The hydrophobicity and the positive charged character of the chitosan have enhanced the stability of the quantum dots. An initial rapid drug release followed by a controlled process has been observed for anticancer drug-loaded ZnO quantum dots -chitosan folate carrier.

Human and Mammalian Toxicology

In cancer research the resource-intensive chronic cancer bioassays originally needed to evaluate carcinogenic potentials of chemicals or chemical mixtures has led to the development of computer simulation of clonal growth of initiated liver cells in relation to carcinogenesis. This model describes the process of carcinogenesis based on the 2-stage model with 2 critical rate-limiting steps 1) from normal to initiated cells and 2) from initiated cells to malignant states. Because this approach can incorporate relevant biological and kinetic information available, it usefully facilitates description of the carcinogenesis process with time-dependent values without the need for chronic exposures.

Analysis of chromium in biological samples

The toxicological significance of Cr measurements in erythrocytes remains unclear due to the lack of data about the cellular uptake of Cr(III) complexes with lipophilic ligands. Cr(III) complexes with amino acids can cross cell membranes although less readily than the carcinogenic Cr(VI) form.67 Published animal studies comparing the distribution of Cr between different compartments of the blood typically used commercial chro-mium(III) chloride that forms Cr(H2O)4Cl2+ ion in a freshly prepared solution. This is not a toxicologically important Cr(III) compound and, therefore, is highly desirable to examine environmentally relevant Cr(III)-aqua ions and dietary Cr(III) complexes with organic ligands. (See introduction (I) and section concerning dietary chromium.) Analysis of the Cr content of biological tissues is not a trivial task even when expensive instrumentation is available because contamination and background problems are frequently encountered. The development of background...

Chemical Hazard Assessment

In assessing risks posed by chemicals to the environment, there are certain characteristics that are commonly taken to be important. These parameters are persistence (P), the propensity for a substance to withstand degradation and therefore remain in the environment in an unchanged state for a prolonged period of time bioaccumulation (B), the propensity to build up in biota (through, for example, accumulation in fatty tissues) resulting in bioconcentration that can especially impact top predators and toxicity (T), resulting in measurable harm to organisms in the environment (normally measured in aquatic organisms). In addition, chemicals are considered to be of concern if they are carcinogenic (C), that is they cause neoplasms, or are muta-genic (M) with the ability to cause cancers or affect the heritable genetic material, or are toxic to reproduction (R), causing measurable impacts on reproductive function (e.g. fertility) or outcome (i.e. defects in offspring). validated through...

Children S Susceptibility

Komori 1990 Vieira et al. 1996 NRC 1993). Whether differences in xenobiotic metabolism make the child more or less susceptible also depend on whether the relevant enzymes are involved in activation of the parent compound to its toxic form or in detoxification. There may also be differences in excretion, particularly in the newborn who has a low glomerular filtration rate and has not developed efficient tubular secretion and resorption capacities (Altman and Dittmer 1974 West et al. 1948 NRC 1993). Children and adults may differ in their capacity to repair damage from chemical insults. Children also have a longer lifetime in which to express damage from chemicals this potential is particularly relevant to cancer.

Ingestion of Pollutants in Soil

Where CS is the pollutant concentration in the soil (mg kg), IR is the ingestion rate (mg soil day) suggested values (EPA, 1989c) 200mg day children 1-6 years old, 100mg day > 6 years old , CF is a conversion factor (10-6kg mg), FI is the fraction of soil ingested from the polluted site (versus soil ingested from a nonpolluted site or playground this value varies based on population activity patterns), EF is the exposure frequency (365 days year), ED is the exposure duration years 70 years for a lifetime exposure, 30 years (national upper-bound time (90th percentile) at one residence), 9 years (national median time (50th percentile) at one residence , BW is the body weight 70 kg for an average adult, 16 kg for children aged 1 to 6 years (50th percentile) , and AT is the averaging time period over which the exposure is averaged, in days (for noncarcinogenic effects, this is equal to ED x 365 days year for carcinogenic effects, use 70 years x 365 days year) .

Safer Chemicals Within Reach

Sustainable chemical policies are being proposed at regional and national levels. Sweden's new chemical policy has the objective of a nontoxic environment. Here a variety of goals and strategies include the phase-out of the most harmful substances increasing the information of chemical content in products promoting more ecolabelling and product declarations using public procurement to stimulate the market for safer materials and establishing ongoing dialogs with companies in various sectors to move towards safer chemical use (Geiser and Tickner, 2003). The new draft European chemical policy is itself a paradigm shift in the way chemicals are regulated. The proposed legislation, called REACH, requires the registration, evaluation, and authorization of chemicals and requires companies to provide environmental and human health toxicity data. This reverses the onus of proof and effectively ensures that by the year 2012, all chemicals must be registered prior to marketing. Chemicals found...

Inhalation of Airborne Vapor Phase Pollutants

Where CA is the pollutant concentration in the air (mg m3), IR is the inhalation rate (m3 day) suggested values are adult (upper-bound) 30m3 day, adult (average) 20m3 day for hourly rates see EPA (1989b) use 0.6m3 hr for showering events , ET is the exposure time (days) use 12 minutes converted to days for upper-bound shower duration (90th percentile), use 7 minutes converted to days for average shower duration (50th percentile) , EF is exposure frequency (times day), ED is the exposure duration (years) use 70 years for a lifetime exposure, use 30 years at one residence (national upper-bound time (90th percentile)), use 9 years at one residence (national median time (50th percentile)) , BW is the body weight (kg) use 70kg for an average adult, age-specific values are given in EPA (1989b) , and AT is the averaging time (time period over which the exposure is averaged, days) for non-carcinogenic effects upper-bound shower duration use ED x 365 days year, for carcinogenic effects use 70...

Ingestion of Contaminated Fish and Shellfish

Where CF is the pollutant concentration in the fish or shellfish (mg kg), IR is the ingestion rate (kg meal) suggested values 0.284 kg meal (90th percentile for fin fish Pao et al., 1982), 0.113kg meal (50th percentile for fin fish Pao et al., 1982), 132 g day (95th percentile daily intakes averaged over 3 days for consumers of fin fish Pao et al., 1982), 38g day (50th percentile daily intake, averaged over 3 days for consumers of fin fish Pao et al., 1982), 6.5 g day (daily intake averaged over a year EPA 1989b) other specific values for age, sex, race, region, and other fish species are available in EPA (1989b) , FI is the fraction of the daily fish intake from the polluted source (a case-specific value), EF is the exposure frequency (meals year) general value 48 days year (average per capita for fish and shellfish EPA, 1989d) , ED is the exposure duration for lifetime exposure use 70 years, for 30 years at one residence (national upper-bound time (90th percentile) EPA, 1989b), for...

Toxic Effect Without a Threshold

Two types of toxic response are commonly believed not to have a threshold below which the possibility of an adverse effect can be discounted mutagenicity and geno-toxic carcinogenicity. Clearly, the deliberate exposure of humans to chemicals with such properties would be unacceptable and, wherever possible, such chemical usage should be banned (with the obvious exception of a pharmaceutical where the balance between risk and potential clinical benefit might be such as to warrant its use). However, particularly in environmental situations, humans may be inadvertently or unavoidably exposed to chemical mutagens and genotoxic carcinogens (of either 'natural' or anthropogenic origin). In such cases, particularly in the USA, mathematical models are used to quantify the expected level of response using the results of highdose animal experiments to predict low-dose human exposure situations. Examples include Multi-hit, Weibull and multi-stage models, with the US Environmental Protection...

Childrens Susceptibility

Are proportionately larger (Altman and Dittmer 1974 Fomon 1966 Fomon et al. 1982 Owen and Brozek 1966 Widdowson and Dickerson 1964). The infant also has an immature blood-brain barrier (Adinolfi 1985 Johanson 1980) and probably an immature blood-testis barrier (Setchell and Waites 1975). Many xenobiotic-metabolizing enzymes have distinctive developmental patterns, and at various stages of growth and development, levels of particular enzymes may be higher or lower than those of adults sometimes unique enzymes may exist at particular developmental stages (Komori 1990 Leeder and Kearns 1997 NRC 1993 Vieira et al. 1996). Whether differences in xenobiotic metabolism make the child more or less susceptible also depends on whether the relevant enzymes are involved in activation of the parent compound to its toxic form or in detoxification. There may also be differences in excretion, particularly in the newborn who has a low glomerular filtration rate and has not developed efficient tubular...

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

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