Organic Compounds Derived from Pliocene Lignite and the Etiology of Balkan Endemic Nephropathy

Acknowledged for the first time as a medical entity in the late 1950s, Balkan endemic nephropathy (BEN) is a chronic and irreversible kidney disease of unknown cause. BEN is geographically confined to several rural regions of central and southeastern Serbia, southwestern Romania, northwestern Bulgaria, southeastern Croatia, and parts of Bosnia and Kosovo, confined to the alluvial valleys of tributaries of the lower Danube River (Ceovic et al. 1992, Hall 1992, Tatu et al. 1998). It is estimated that several thousand people in the affected countries are currently suffering from the disease, and that thousands more will be diagnosed with BEN in the next few years. Although no single feature is sufficient for disease diagnosis, BEN has several characteristics that allow it to be distinguished from other chronic kidney diseases: These characteristics are: . . . ·The age of clinical onset is usually between 30 and 50 years, with a slightly higher frequency in women (female:male sex ratio is ~1.5:1), probably due to some social and genetic factors. . . . . . . ·There is a long subclinical “incubation” period and a rapid onset of end-stage renal disease; the only therapeutic solutions left are chronic renal dialysis or kidney transplantation. . . . . . . ·There is a family history of the disease, with an aggregation of the disease in certain households. . . . . . . ·BEN patients exhibit normal blood pressure in ~80% of the cases (a feature unusual for most other kidney diseases) and normochromic and normocytic anemia is common in BEN. . . . . . . ·BEN patients have lived for at least 10-20 years in one or more of the endemic villages. A slight decrease in the incidence of the disease has been noticed in the last two years in Serbia and Romania (Cukuranovic et al. 2000); however, this seems to follow the usual oscillating pattern of the disease, with lows and highs of incidence, and another epidemic outbreak is likely to occur in these areas in the future. . . .

Breast and Prostate Cancer: Sources and Pathways of Endocrine-disrupting Chemicals

Cancers of the breast and prostate, which together with those of the ovaries, endometrium and testes are hormone-dependent, are among the most common forms of cancers affecting women and men respectively throughout the developed world (IARC VII 1997, Miller and Sharp 1998). The incidence of breast, prostate, and testicular cancers has risen dramatically in most European and North American countries and in Japan and Australasia since cancer registries were first compiled in the 1960s (WHO/IARC Web site). For instance, women and men born in Generation X in the U.S. and Europe today have twice the risk of developing breast and prostate cancer than their grandparents faced (Dinse et al. 1999). Several lines of evidence indicate that environmental factors, broadly conceived, may account for some of the recent changes in patterns of hormonally dependent cancers. Although rates are about 4 times lower in Asian countries than in European ones, they are increasing most rapidly in the former (Hoel et al. 1992). People who migrate tend to develop the cancer rate of their new countries. Studies of highly exposed workers consistently find that those working with certain plastics, organic solvents, pesticides, and other toxic chemicals tend to have higher risks of several hormonally dependent cancers (Davis and Muir 1995). Dietary factors can be involved in these patterns in two ways. Food constituents, such as dairy and animal protein products, can affect hormonal metabolism directly. In addition, foods can contain contaminants such as growth stimulating substances, pesticides, and packaging materials that can function as endocrine disrupting chemicals (EDCs). In the past decade, a number of major national and international reports have noted the possible role of EDCs for hormone-related illnesses including breast and prostate cancer, including the Weybridge report of the European Environment Agency of 1996 (EUR 17549 1997) and the Royal Society Report on Endocrine Disrupting Chemicals (Royal Soc. 2000). This chapter presents some recent information on the sources of EDCs in the environment, outlines mechanisms by which these materials can increase the risk of hormonally dependent cancers, and discusses insights from geochemistry that may be pertinent to this work.

Surface and Groundwater Quality and Health, with a Focus on the United Kingdom

Freshwater environments are of major importance to health issues in both direct (e.g., drinking water and sanitation) and indirect (e.g., industry, agriculture, and amenity/recreation) ways. However, water resources are finite, and, though renewable, demands have multiplied over the last 100 years due to escalating human populations and the growing requirements of industry and agriculture. Hence, there are increasing global concerns over the extent of present and future good quality water resources. As Gleick (1998) emphasizes: . . . ·Per-capita water demands are increasing, but percapita water availability is decreasing due to population growth and economic development. . . . . . . ·Half the world’s population lacks basic sanitation and more than a billion people lack potable drinking water; these numbers are rising. Incidences of some water-related diseases are rising. . . . . . . ·The per-capita amount of irrigated land is falling and competition for agricultural water is growing. . . . . . . ·Political and military tensions/conflicts over shared water resources are growing. . . . . . . ·A groundwater overdraft exists, the size of which is accelerating; groundwater supplies occur on every continent except Antarctica. . . . . . . ·Global climate change is evident, and the hydrological cycle will be seriously affected in ways that are only beginning to be understood. . . . The chemical composition of surface and groundwaters is influenced by a wide range of processes, some of which are outside the influence of humans while others are a direct consequence of anthropogenic pollution or changing of the environment. Starting with the range and nature of the processes involved, the changing nature of surface and groundwater quality is illustrated here, based on the evolution of the United Kingdom from a rural to an industrial and to a post- industrial society. The issue of what constitutes a health risk is outlined in relation to the pragmatic approaches required for environmental management. Surface and groundwater exhibit a wide range of chemical compositions, and, in ecosystems uninfluenced by humans, the range of compositions can vary considerably.

Molybdenosis Leading to Type 2 Diabetes Mellitus in Swedish Moose

The “mysterious moose disease” also called “wasting disease” is affecting moose in a strongly acidified region of southwestern Sweden. Chemical investigations of animals from the affected region have been performed since 1988 and several articles are already published (Frank et al. 1994, Frank 1998, Frank et al. 1999, 2000a, b, c, d). The numerous clinical signs and necropsy findings have included diarrhea, loss of appetite, emaciation, discoloration and loss of hair, apathy, osteoporosis, and neurological signs such as behavioral and locomotor disturbances (Rehbinder et al. 1991, Stéen et al. 1993). Further findings were mucosal oedema, hyperemia, hemorrhages and lesions of the mucosa in the gastrointestinal tract, hemosiderosis of the spleen and liver, dilated flabby heart, alveolar emphysema, and uni- or bilateral corneal opacity. Not all the symptoms appear simultaneously in one and the same animal. About 150—180 affected animals have been reported annually since the late 1980s. An increase in molybdenum (Mo) and a decrease in copper and cadmium (Cu, Cd) content in organ tissues (e.g., liver) are signs of a disturbed trace element balance found in affected animals (Frank 1998). To confirm the findings and to elucidate the mechanisms leading to molybdenosis and Cu deficiency, experimental studies were performed in goats. The feeding studies were performed in a controlled laboratory environment and a semi-synthetic diet was supplied (Frank et al. 2000c). Despite considerable differences in species and living conditions between goat and moose, similar changes in trace element pattern and clinical chemical parameters were observed in both species. The study shows that the etiology of the moose disease is basically molybdenosis followed by Cu deficiency, inter alia (Frank et al. 2000a,b,d). Mo is an essential trace element that controls the metabolism of Cu in ruminants. Increased Mo concentrations relative to Cu in feed results in Cu deficiency, whereas the converse leads to an accumulation of Cu, even to Cu poisoning (e.g., in sheep). In an acidified environment, the molybdate anion is adsorbed in the soil, contrary to positively charged metals. The presence of Mo and Cu in the environment is basically dependent mainly on geochemistry, influenced by numerous physical and chemical parameters (Selinus et al. 1996, Selinus and Frank 2000).

Mitigation of Endemic Arsenocosis with Selenium: An Example from China

Endemic arsenocosis (chronic arsenic poisoning) in China comes from two sources of arsenic (As). One source is drinking water, with As concentrations 2-40 times that of the state standard of 0.05 mg/l As. The second is smoke pollution from combustion of coal with high concentrations of As; this can be inhaled or ingested from smoke-contaminated food. Over 2,000,000 people live in areas of high geological As concentrations (Cao 1996), and more than 17,000 arsenocosis patients in 21 counties of five provinces or Autonomous Regions have been identified. Long-term exposure to As in air, diet, or drinking water can result in permanent and severe damage to health, including lesions of the skin, mucous membranes of the digestive, respiratory, circulatory, and nervous systems, and rhagades (skin cleft on palm and feet). Elevated As intake is also associated with skin, liver, and lung cancers (Centeno 2000, Liang 1999, Wang Lianfang 54-61 1997). At present, there are few studies of efficient measurement of treatment of endemic arsenocosis patients. Our study demonstrates that treatment of these patients with dietary selenium (Se) can cause both excretion (elimination) of As accumulated in the human body and remediation of some health damages. We report the results of this experiment. Data were collected on 3 test groups of people: 186 patients, from BaYinMaoDao Farm in Inner Mongolia suffering from endemic arsenocosis, were divided into a treatment group (100 patients) and a control group (86 patients). A third group, consisting of 70 families, received no treatment but drank ambient well water, >0.10 mg/l As. All participants had been exposed to high-As drinking water (>0.10 mg/l) since 1983. Throughout the experiment, water containing 0.05 mg/1 As was supplied for both treatment and control groups. Of the 186 patients, 100 were treated with Se-enriched yeast tablets, containing 100 μg Se/tablet. The treatment lasted 14 months. Treated patients received 100-200 μg Se/day. All patients were examined for clinical criteria of arsenocosis: characteristic pigmentation, depigmentation, hyperkeratosis, rhagades (skin cleft), and incidence of secondary symptoms of headaches, dizziness, thoracalgia (chest pain), numbness of hands or feet, convulsions, or lumbago.

Natural Dust and Pneumoconiosis in High Asia

High Asia, defined here as that great tract of land from the Himalaya- Karakoram in the south to the Tian Shan in the north and the Pamir in the west to the Qinling Mountains in the east, is a very dusty place. Whole communities of people in this region are exposed to the adverse effects of natural (aerosolic) dusts at exposure levels reaching those encountered in some high-risk industries. Outdooor workers are at particular risk. However, few data are available on the magnitude of the dust impact on human health. The effect of such far-travelled particles on the health of the human population in the Loess Plateau, and including major Chinese cities, has received relatively little attention to date. A combination of the highest known uplift rates, rapid river incision (up to 12 mm/yr: Burbank et al. 1996), unstable slopes, glaciation and widespread rock breakup by crystal growth during freezing (frost action), and by hydration of salts (salt weathering) makes the High Asia region the world’s most efficient producer of silty (defined as between 2 and 63 μm) debris. The earliest written records of the dust hazard come from China, most notably in the “Yu Gong” by Gu Ban (ca 200 BC) (Wang and Song 1983). Here, deposits of wind-blown silt (known as ‘loess’) cover the landscape in a drape that is locally 500 m thick. In North China, the loess covers an area of over 600,000 km², most of it in the Loess Plateau, situated in the middle reaches of the Huang He (Yellow River). The characteristic properties of loess include high porosity and collapsibility on wetting (Derbyshire et al. 1995, Derbyshire and Meng 2000).Thus, it is readily reworked and redistributed by water. This process concentrates silts in large alluvial fans (up to 50 x 50 km) in the piedmont zones of 6,000 m high glacier- and snow-covered mountain ranges of western China, including the Altai Shan (‘shan’ = mountains), Tian Shan, Kunlun Shan, Qilian Shan, and Karakoram. These zones are loci for human populations, and also a major source of wind-blown dust.

Environmental Iodine in Iodine Deficiency Disorders, with a Sri Lankan Example

Iodine is an essential element for human and other animal health and forms an important constituent of the thyroid hormones thyroxine (T4, also known as tetraiodothyronine) and triiodothyronine (T3). These hormones play a fundamental biological role in controlling growth and development (Hetzel and Maberly 1986). If the amount of utilizable iodine reaching the thyroid gland is inadequate, or if thyroid function is impaired, hormone production can be reduced, resulting in a group of conditions collectively referred to as Iodine Deficiency Disorders (IDD) (Fernando et al. 1987, Hetzel 1989). The World Health Organization (WHO 1993) estimate that in excess of one billion people worldwide are at risk from IDD, the most common manifestation of which is goiter (Fig. 9.1). Iodine deficiency is the world’s most common cause of preventable mental retardation and brain damage, and has a significant negative impact on the social and economic development of communities. Although it is likely that IDD are multifactorial diseases involving other trace element deficiencies and goitrogens (goiter-promoting substances) in foodstuffs, a lack of adequate dietary iodine remains a major concern (Stewart and Pharaoh 1996). The link between environmental iodine and IDD has been known for the last 80 years. During this time, the medical community has become well organized when tackling the problem, exemplified by the work of the International Council for the Control of IDD (ICCIDD) ( <http:// www.tulane.edu/~icec/icciddhome.htm>), which provides an excellent dissemination point for discussion and information. Remediation strategies often focus on enhancing dietary intakes of iodine via the introduction of iodinated salt and iodinated oil programs (Stanbury and Hetzel 1980). However, these methods are not always successful and other strategies, including environmental interventions, require development (DeLong et al. 1997) In contrast to the wealth of information about the symptoms, assessment, and treatment of IDD, there is very little on the primary cause, a lack of readily available iodine in the environment and diet. Our knowledge of environmental iodine geochemistry is limited, mainly because the analytical methods for assessment are not routine and iodine is not an element that has been systematically determined in geochemical surveys. However, in the past two decades, improved analytical methodologies and an interest in iodine from different perspectives have added much to our knowledge.

Environmental Geochemistry on a Global Scale

Recent population growth and economic development are extending the problems associated with land degradation, pollution, urbanization, and the effects of climate change over large areas of the earth’s surface, giving increasing cause for concern about the state of the environment. Many problems are most acute in tropical, equatorial, and desert regions where the surface environment is particularly fragile because of its long history of intense chemical weathering over geological timescales. The speed and scale of the impact of human activities are now so great that, according to some authors, for example, McMichael (1993), there is the threat of global ecological disruption. Concern that human activities are unsustainable has led to the report of the World Commission on Environment and Development Our Common Future (Barnaby 1987) and the establishment of a United Nations Commission on Sustainable Development responsible for carrying out Agenda 21, the action plan of the 1992 Earth Summit in Rio de Janeiro, Brazil. Considerable research into the global environment is now being undertaken, especially into issues such as climate change, biodiversity, and water quality. Relatively little work has been carried out on the sustainability of the Earth’s land surface and its life support systems, however, other than on an ad-hoc basis in response to problems such as mercury poisoning related to artisanal gold mining in Amazonia or arsenic poisoning as a result of water supply problems in Bangladesh (Smedley 1999). This chapter proposes a more strategic approach to understanding the distribution and behavior of chemicals in the environment based on the preparation of a global geochemical baseline to help to sustain the Earth’s land surface based on the systematic knowledge of its geochemistry. Geochemical data contain information directly relevant to economic and environmental decisions involving mineral exploration, extraction, and processing; manufacturing industries; agriculture and forestry; many aspects of human and animal health; waste disposal; and land-use planning. A database showing the spatial variations in the abundance of chemical elements over the Earth’s surface is, therefore, a key step in embracing all aspects of environmental geochemistry. Although environmental problems do not respect political boundaries, data from one part of the world may have important implications elsewhere.

Some Environmental Problems of Geomedical Relevance in East and Southern Africa

Medical geology studies the influence of geo-environmental factors on the geographical distribution of diseases of humans and animals. In the east and southern African subregion, there has been little attention paid to date on the extent to which these factors may be important in disease causation, even though developing countries in general can be shown to hold tremendous promise for specific research in this field. This chapter highlights some problems of geomedical relevance in the subregion and submits that interdisciplinary research among scientists can help provide practical solutions. The iodine deficient regions of east and southern Africa have been identified and the widespread occurrence of goiter and related conditions, collectively referred to as iodine deficiency disorders (IDD), firmly established (e.g., Davies 1994, Jooste et al. 1997). These are serious and debilitating consequences, particularly for poor populations, as the capacity of children is severely restricted and they become a burden to the family. The reported geographical distribution of endemic goiter in East Africa is shown in Figure 22.1. Many aid agencies and governments have attempted to solve the problem by increasing dietary intake of iodine via the introduction of iodized salt and iodized oil programs. Despite these interventions, IDD remain a major problem in the subregion. It is likely that IDD are multi-causal diseases involving factors such as trace element deficiencies, goiter-inducing substances in foodstuffs (known as goitrogens), and genetics (Fordyce 2000). However, geochemists have an important role to play in determining the environmental cycling of iodine and its uptake into the food chain if levels of dietary iodine are to be enhanced successfully. It has now been established that excessive fluorine (mainly in the form of fluoride) is present in parts of the hydrological system of Kenya as well as other countries in the subregion, particularly those that are associated with rift formation (Gaciri and Davies 1993). Fluoride in minor amounts (around 1.3 ppm) reduces dental decay and enhances the proper development of the bone. A similar level of fluoride intake may also be beneficial to animals.

Biogeochemical Monitoring in Medical Geology

How can we determine the distribution of metals and other elements in our environment? The Geological Survey of Sweden started an innovative monitoring of metals in a monitoring/mapping program in 1980. Before 1980, traditional inorganic stream sediments were used, a method still employed all over the world, but not really suitable for medical work. A new method is used, whereby metal concentrations are determined in organic material consisting of aquatic mosses and roots of aquatic higher plants. These are barrier-free with respect to trace metal uptake and reflect the metal concentrations in stream water (Brundin 1972, 1988, Kabata-Pendias,1992, Selinus 1989). Aerial parts of many plant species do not generally respond to increasing metal concentrations in the growth medium because of physiological barriers between roots and above-ground parts of plants. These barriers protect them from uptake of toxic levels of metals into the vital reproductive organs. The roots and mosses, however, respond closely to chemical variations in background levels related to different bedrock types in addition to effects of pollution. The biogeochemical samples provide information on the time-related bioavailable metal contents in aquatic plants and in the environment. One great advantage of using biogeochemical samples instead of water samples is also that the biogeochemical samples provide integrated information of the metal contents in the water for a period of some years. Water samples suffer from seasonal and annual variations depending on, for example, precipitation. The mapping program now covers about 65% of the land area of Sweden (40,000 sample sites, one sample every 6 km²), where about 80% of the population of Sweden is living. This means that there is now available an extensive analytical data base for use in environmental and medical research (Freden 1994). One example of the use of biogeochemical monitoring concerns high cadmium contents in Sweden. In noncontaminated, noncultivated soils, Cd concentration is largely governed by the amount of Cd in the parent material (Thornton 1986). If the substrate concentration is higher than in background concentrations, Cd is readily taken up by roots and is distributed throughout the plants.