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Nevertheless hypertension workup metoprolol 25 mg purchase amex, histopathological analysis has played an important role in confirming chemically mediated tissue damage in numerous laboratory and field studies. For example, Pacheco and Santos (2002) integrated histopathological analysis with biochemical studies of the effects of various environmental contaminants on the European eel (Anguilla anguilla), and Devlin (2006) similarly incorporated this approach in studies of the effects of methylmercury in fathead minnows (Pimephales promelas). In subsequent sections concerning organismal-level impacts, other examples of the use of histopathology will be provided. Target Organs Descriptions of chemical impacts on all organ systems of the myriad species relevant to ecotoxicology are beyond the scope of this chapter. Other chapters in this volume address key target organs in the mammalian context, and much of this is relevant to other vertebrates. Target organ toxicology is also the subject of comprehensive reviews by Schlenk and Benson (2001) concerning marine and freshwater fish, and by Gardner and Oberdorster (2005) concerning reptiles. Although we are unaware of similar reviews for birds or invertebrates, understanding target organ toxicity can be crucial for these taxa as in the recent case of widespread renal poisoning of vultures exposed to the veterinary drug diclofenac during scavenging on cattle carcasses (Oaks et al. Further, the unique properties of the avian respiratory system and its utility for investigating respiratory system toxicity and air pollution were reviewed by Brown et al. Another important target organ in ecotoxicology that is not covered elsewhere in this text is the respiratory organ of nonmammalian aquatic vertebrates and many invertebrates, the gill; gills of fish have received the most attention as targets of toxicants. The gill epithelium is the major site of gas exchange, ionic regulation, acidbase balance, and nitrogenous waste excretions for fish and other aquatic animals (Evans, 1987). Gills are immersed in a major exposure medium for these animals (surface water), so metabolically active epithelial cells are in direct contact with this medium. They also receive blood supply directly from the heart, through the ventral aorta. Thus, it is not surprising that gills comprise a very important target for many environmental pollutants, due to their critical physiological functions, central position in blood circulation pathways, and intimate relationship with the environment. The basic structure of fish gills is composed of branchial arches from which extend numerous filaments; from the filaments extend the lamellae (Wendelaar Bonga and Lock, 2008). Common structural lesions in gills caused by a diverse array of chemicals include cell death (via necrosis and apoptosis), rupture of the epithelium, hyperplasia and hypertrophy of various cell populations that can lead to lamellar fusion, epithelial swelling, and lifting of the respiratory epithelium from the underlying tissue (Wendelaar Bonga and Lock, 2008). Chloride cells have received particular attention due to their key role in ionic homeostasis. For example, metals such as cadmium, copper, lead, silver, and zinc have been shown to interfere with their function in ion transport. The stress response, which results in elevated blood concentrations of epinephrine and cortisol, and associated responses such as increased cardiac output and elevated blood pressure, can also perturb ionic balance by promoting passive loss of ions such as Na+ and Cl (Wendelaar Bonga and Lock, 2008).
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Shellfish accumulate relatively high levels of cadmium (1 to 2 mg/kg) blood pressure yeast infection discount metoprolol 12.5 mg with mastercard, and animal liver and kidney can have levels higher than 50 g Cd/kg. Cereal grains such as rice and wheat, and tobacco concentrate cadmium to levels of 10 to 150 g Cd/kg. With nearby industrial emission, air can be a significant source of direct exposure or environmental contamination (Jarup and Akesson, 2009). Total daily cadmium intake from all sources in North America and Europe ranges from 10 to 30 g Cd per day. The increase in lung cancers is linked to high exposure levels that occurred prior to stricter exposure regulations introduced in the 1950s. The likelihood of lung cancer was greater in workers with acute beryllium disease than 1120 Tobacco leaves accumulate high levels of cadmium from the soil making cigarette smoking a major nonoccupational source of cadmium exposure. Smoking is thought to roughly double the lifetime body burden of cadmium (Satarug et al. Historically, levels of cadmium in the workplace have dramatically improved with the appreciation of its potential toxicity in humans, development of safety restrictions, and improved industrial hygiene. Occupations potentially at risk from cadmium exposure include those involved with refining zinc and lead ores, iron production, cement manufacture, and industries involving fossil fuel combustion, all of which can release airborne cadmium. Toxicokinetics Gastrointestinal absorption of cadmium is limited to 5% to 10% of a given dose. Cadmium absorption can be increased by dietary deficiencies of calcium or iron and by diets low in protein. In the general population, women have higher blood cadmium levels than men, possibly due to increased oral cadmium absorption because of relatively low iron stores in women of childbearing age. For instance, 5% to 50% of cadmium fumes, as generated in cigarette smoke, may be absorbed. Cadmium is transported in blood by binding to albumin and other higher-molecular-weight proteins. It is rapidly taken up by tissues and is primarily deposited in the liver and to a lesser extent in the kidney. Cadmium is nephrotoxic, and when renal pathology is present the urinary excretion of cadmium is increased due to decreased renal absorption of filtered cadmium (Zalups and Ahmad, 2003). Acute cadmium toxicity from the ingestion of high concentrations of cadmium in the form of heavily contaminated beverages or food causes severe irritation to the gastrointestinal epithelium. Inhalation of cadmium fumes or other heated cadmiumcontaining materials may produce acute pneumonitis with pulmonary edema.
Polycyclic aromatic compounds alone are relatively inert chemically blood pressure medication causing low blood pressure generic 100 mg metoprolol visa, but they can accumulate in cellular membranes and thus perturb function if not removed. They are hydroxylated by a number of cytochrome P450 isoenzymes, primarily 1A1 and 1B1 in epidermal cells, and then conjugated for disposal from the body. While the role of AhR polymorphisms in the development of skin cancers has been well demonstrated in murine models (Shimizu et al. The best studied example, and one of the most potent, is the active ingredient of croton oil, 12-O-tetradecanoylphorbol-13-acetate, which transiently stimulates then chronically depletes protein kinase C in epidermis (Fournier and Murray, 1987). Another groups of promoting agents, for example, okadaic acid, act as phosphatase inhibitors. Calcium channel modulators and free radical generators can also act as skin cancer promoters. Sensitivity to tumor promotion is an important factor in the relative sensitivity to skin carcinogenesis among different animal species (Poland et al. Much effort is currently focused on the signal transduction pathway(s) that is (are) perturbed by the treatment with these chemicals. Around the world, substantial exposures can occur as a result of dust from mining operations, smelting fumes, or from leachate in waterways. Glass manufacturing and food dried using coal with high arsenic content can also contribute to exposures. The environmental burden is increased by disposal of large volumes of wood preserved with chromated copper arsenic, among other sources. Well water derived from geological formations with high arsenic content is now recognized as a major health concern, highlighted by populations in the tens of millions at risk in Bangladesh and India (Tapio and Grosche, 2006). However, even in the United States, arsenic in drinking water remains a concern (Mayer and Goldman, 2016). Studies in Southwestern Taiwan have shown an association between high arsenic exposure and altered skin pigmentation, hyperkeratosis of the palms and soles, impaired circulation reflecting endothelial cell damage ("black foot" disease), and carcinoma (skin, lung, bladder, liver, and other organs). More recent concentration dependent studies in Bangladesh show hyperpigmentation and keratoses occurring with drinking water concentrations close to 50 ppb (Argos et al. Furthermore, there appears to be synergism between the toxic effects of arsenic and smoking (lung and bladder), sun exposure (skin), and fertilizer use (liver) (Melkonian et al. Due to the observation that even low exposures to arsenic can have adverse health effects, much effort has been devoted to understanding its mechanism of action. Skin Tumor Promotion As with all cancers, the development of skin cancers can be simplistically viewed as a three-step model: initiation, promotion, and progression.
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Abbas, 27 years: After menopause, follicles are no longer present in the ovary (Knobil and Neill,1994). Chronic maternal methanol inhalation in nonhuman primates (Macaca fascicularis): exposure and toxicokinetics prior to and during pregnancy. Monosaccharides are transported into the enterocytes by active transport (glucose, galactose) or via facilitated diffusion (fructose). Most spider peptide toxins appear to have basic pI in the 9 to 11 range (Escoubas et al.
Lares, 30 years: Cadmium-induced renal toxicity is reflected by proteinuria as a result of renal tubular dysfunction. Implications of C-5, C-6 unsaturation as a key structural factor in steroidal alkaloid-induced mammalian teratogenesis. Dermal exposure is by far the major route of unintentional exposure to 2,4-D in humans. Species are selected based not only on their traditional use as laboratory animals, but also on ecological relevance, which further complicates global harmonization of ecological testing.
Ronar, 24 years: Carbon disulfide also modifies low-density lipoprotein in vitro and enhances arterial fatty deposits induced by a high-fat diet in mice (Lewis et al. Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate. Air-liquid interface exposure to aerosols of poorly soluble nanomaterials induces different biological activation levels compared to exposure to suspensions. The toxic effects are attributed to tremetone, a benzofuran, which blocks gluconeogenesis from lactate, resulting in acidosis, tremor, and ultimately death (Polya, 2003).
Mason, 44 years: The prevalence of chromium sensitivity is less than 1% among the general population and up to 4% in occupational settings (Shelnutt et al. It modulates the solubility of -amyloid in the brain and protects against -amyloid toxicity, but excess zinc may trigger neuronal death that is independent or synergistic with the toxic effect of -amyloid (Greenough et al. Ironically, this prescribed remedy for an air problem evolved into an unexpected problem: groundwater contamination. Again, understanding effects at the population and higher levels can be viewed as the ultimate goal of ecotoxicology.
Sigmor, 34 years: These mediators include interleukins, prostaglandins, free radicals, and eicosanoids. Many of the most severe exposures to solvents have occurred as a result of their use in confined spaces with inadequate ventilation. In his article Kinlen (2011) focuses on the nuclear power plant studies and the German results in particular. Glycolate causes the acidosis in ethylene glycol poisoning and is effectively removed by hemodialysis.
Candela, 31 years: Community ecotoxicologists spend considerable effort trying to understand and predict ecotoxicant influences on community structure and essential functions. Water transport through aquaporins occurs in response to osmotic gradients created by active solute transport. All latrotoxins stimulate massive release of neurotransmitters after binding to specific neuronal receptors. During chemical exposure, these mechanisms may be affected individually or jointly resulting in a disturbance in the integration of the regulatory mechanisms.
Renwik, 64 years: This section, normally applied to occurrences of unsafe levels of toxicants in food, is applied to new plant varieties whose composition has been altered by an added substance. The extensive use of organochlorines and their environmental persistence made them widespread pollutants. Thus, when a test animal strain is selected where such nuances are unclear or unknown, the replication of responses in multiple species builds confidence in the finding as being homologous or having speciesconserved modes of action that are relevant to the human and bear careful consideration in a risk assessment. Arsenite interacts selectively with zinc finger proteins containing C3H1 or C4 motifs.
Jaroll, 35 years: Nonselective herbicides will kill all vegetation, while selective compounds are those used to kill weeds without harming the crops. Changes in xenobiotic biotransformation during maturation may have the greatest impact on susceptibility to chemical toxicity and carcinogenicity. Only certain critical species such as dominant or keystone species are essential to the community. Fatal cases, while rare, usually are preceded by intravascular hemolysis, hemolytic anemia, thrombocytopenia, hemoglobinuria, and renal failure (Russell, 2001).
