Environmental Hygiene III

Public awareness of environmental problems has steadily increased during the past two decades. According to interviews in the Federal Republic of Germany and the EEC two thirds of the population consider it a political task of high priority that effective measures are taken in order to protect against environmental hazards. In this respect, air pollution by chemicals evoked the highest concern in 60 % of the subjects interviewed. As a consequence of this pronounced awareness of environmental health hazards, a more critical behaviour not only of consumers, but also of patients is developing. With increasing frequency people do not only inquire into possible adverse effects of therapeutic measures, but also express the suspicion that some of their health problems might be caused by exposure to chemicals from the environment. Hence, physicians find themselves more and more confronted with environmental issues.

The carcinogen cadmium causes direct genotoxic effects as well as epigenetic changes. Cadmium (II) evokes DNA strand breaks in mammalian cells (Snyder, 198 8) and, if combined with thiol compounds, in isolated DNA, too (Müller et al., 1991; Oetken and Beyersmann, 1991) . Cd2+ is a weak mutagen only but it enhances the mutagenicity of UV irradiation in mammalian cells by interfering with the repair of damaged DNA (Hartwig and Beyersmann, 1989). An important epigenetic mechanism in carcinogenesis is the interference with the control of cell proliferation. Here, we discuss evidence for the interaction of cadmium (II) with the inositol trisphosphate/calcium signalling pathway which controls growth and which also is susceptible to tumor promoters.

Squamous cell carcinoma of the cervix is a major public health problem worldwide, as a cause of cancer death in women it is number two after breast cancer. The first documented data concerning marital or sexual events was published by Rigoni-Stern in 1842 (1) who concluded from a statistical analysis of death records that cancer of the uterus occurred rarely in virgins and nuns. Since then, evidence has been accumulating consistent wit the premise that cervical cancer behaves as a venereally transmitted disease. Two important factors in the development of cancer appear to be the age of onset of sexual activity and the number of partners. Today, it is accepted that a subset of human papillomaviruses (HPV) are linked with neoplastic events in the epithelia of the female genitalia In fact, over 95% of invasive cervical cancers are associated with a specific subset of HPVs (2). However, the evidence also indicates that while HPV is necessary it is not sufficient to induce cancer. Cervical cancer is an ideal model for studying human carcinogenesis because the normal, benign and malignant stages can be distinguished in vivo and in vitro.

Both Golgi apparatus and lysosomes are associated with turnover of cell compartments and extracellular processes. The role of the microtubules maintaining the location of Golgi vesicles as well as the intracellular transport of lysosomes is demonstrated in many experiments dealing with microtubule poisons. Due to the sensitivity of the microtubule system to chemicals, a direct correlation between the spatial distribution of the lysosomal apparatus and the biochemical condition of the cell can be assumed.

Intracellular dissolution of a large variety of inhaled inorganic environmental particles — which are not readily soluble in the epithelial lining fluid of the lungs — is the first step of an important long-term clearance mechanism of the lungs by which the dissolved material is eliminated to blood (Kreyling, 1992). Intracellular particle dissolution (IPD) occurs in phagolysosomal vacuoles of phagocytes (Kreyling et al., 1990). IPD was shown to be more effective for a number of materials than dissolution in extracellular body fluids as recently reviewed (Kreyling, 1992). Since the intraphagolysosomal pH (PLpH) at about 5 is lower than that of the surrounding cell plasma at about 7.2 (Nyberg et al., 1989a, 1989b), PLpH is believed to be an important co-factor of IPD and thereby of an important long-term clearance mechanism of the lungs.

Over the recent years the bio-hazardous effects of UV-C- as well as electromagnetic radiation have increasing impact in discussions concerning the enviromental hygiene. At the cellular level considerable data exist that UV-C is a severe hazard for eukaryotic cells in terms of cell killing and/or induction of skin cancer. However, little is known about the biological effects of UV-C- and electromagnetic radiation as inducers of terminal differentiation processes in cells, especially mammalian cells. Although, low frequency electromagnetic fields (EMF) have been administered in bone fracture healing with reasonable success for almost 20 years (Bassett et al 1982; Kraus and Lechner 1972), the cellular and/or molecular basis of the mechanisms involved are still unknown.

Industrial processes, power generation, traffic, waste incineration and coal or fuel combustion for space heating are the most important sources of atmospheric pollutants (Fishbein, 1990). Between 500–2,000 mostly organic compounds have been detected as atmospheric pollutants, among them potential and recognized mutagens and carcinogens (Helmes et al., 1983; Schlip-köter, 1983; Fishbein, 1990). Beside gaseous pollutants airborne particulates are of special medical concern. They are composed of a very large number of chemical substances and with a diameter smaller than 5 µm they represent respirable dust, which by inhalation reaches broncho-alveolar space in human lung. Alveolar space in human lung contains an “inner surface” of 100–150 m2 (Burri, 1982). Each day this “inner surface” of human lung is exposed to a volume of air of 12–14 m3 and contaminants such as airborne particulates, noxious gases, infectious agents, immunogenic and allergic particles (Green et al., 1977). Alveolar macrophages, which are found on the “inner surface” serve as an important line of defense, keeping alveoli clean by ingesting inhaled particles and micro-organisms (Brain, 1986). Adverse effects on alveolar macrophages could impair the pulmonary defense system contributing to the causation of diseases. There is evidence that particulate pollutants affect the process of phagocytosis by macrophages. A strong inhibition of phagocytosis of alveolar macrophages of the Syrian golden hamster was reported by Beck et al. (1988) after intratracheal instillation of respirable particles of waste oil heater. Van Houdt and Rietjens (1988) observed a strong dose-dependent inhibition of phagocytosis of rat alveolar macrophages in vitro by polluted outdoor and indoor samples of particulates.

Numerous hazardous substances show neurotoxic effects after acute incorporation as well as after chronic exposure. Some organic solvents for example are known to cause polyneuropathy (e.g. Konietzko 1981, Greeersen et al. 1984, McCunney 1988). Exposure to heavy metals such as mercury or lead may result in an impairment of the central as well as of the peripheral nervous system (e.g. Zielhuis 1975, Triebig et al. 1981). Since knowledge about neurotoxicity is rather incomplete, the need for experimental test systems to investigate the mechanisms involved is quite obvious (Triebig et al. 1989). Furthermore, a test system allowing for the prediction of neurotoxicity would be of great importance with regard to the prevention of — in some cases irreversible — neuronal damages.

Earlier, we found with Epstein Barr virus and Type 2 Herpes simplex that copper acetate added after virus attachmment reduced significantly virion production as measured by immunofluorescence microscopy on fixed monolayers (Orsi et al 1988, Obradovic & Orsi 1990). However with similar conditions lead acetate did not modify virus replication. Our microscopy methods provided insufficient emission intensity for measuring the low levels of fluorescence associated with viral DNA formation and the early stages of virion maturation. We then devised a method based on procedures used for fixed cell visualization (Narin 1964, Brigati et al 1983). In our method, cell monolayers were infected, metal added, cells fixed and permeabilized for addition of the fluorescent probe which was then extracted and the emission intensity measured by fluorometry.

In past experiments (Orsi et al 1988, Orsi et al 1990) mice born and raised in an urban area (SHU) showed less weight gain, decreased lysosome enzyme activity and higher levels of lead and copper in their hearts and lungs than those born and raised in cleaner (BW) air. Studies of the effects of lead on cytoskeleton depletion in cell cultures ( Orsi et al 1987) suggested that the (SHU) progeny might show a similar depletion. Consequently, fixed heart and lung tissues saved from the third experiment (Orsi et al 1990) and those from this experiment a year later were utilized for comparing cytoskeleton levels in progeny from high and low air pollution regions.

In previous investigations chromates were proven to be highly toxic for different cell systems of rat and human origin (Popper et al., 1990). In addition it causes severe organ injury in the respiratory and alimentary tract and in the spleen (see Popper et al., this volume). Different chromates and especially water soluble dichromates exert their toxic effects on mammalian cell systems at least in part by the liberation of oxygen radicals (Popper, Woldrich, 1991). Our knowledge about VC’s is very limited. There are some reports on the toxicity of VC’s (Rhoads et al., 1985, Waters, 1977) and some dealing more specifically with the mechanisms of VC toxicity (Zychlinski et al., 1990, Owusuyaw et al., 1990, Roldan et al., 1990). There is one report which suggests a similar mechanism of vanadium-5-oxide reduction as it is described for dichromates (Shi et al., 1990). We therefore investigated different VC’s in a pneumocyte cell culture system and compared the results with the effects of dichromate.

Extracorporeal shock wave treatment is mainly used to destroy renal-, ureteral-, and gall-stones (Chaussy et al. 1983, 1984; Hood et al. 1988; Sackmann et al. 1988; Staritz et al. 1989). This application raises the question whether shock waves also exert effects on the surrounding tissue, especially since mechanical stress may induce cellular damage and alterations in intracellular organization. Studies with various tumor cell lines revealed different sensitivities of these cells to high energy shock waves (HESW) implicating that HESW might also be a tool for treatment of tumor tissue (Berens et al. 1989; van Dongen et al. 1989; Russso et al. 1985, 1986). Whereas these investigations were performed with different cell types, it is useful to study cell lines originating from the same clone for direct comparison of effects.

During the early stages of development, the chick embryo with the surrounding yolk sac blood vessels offers a good model for vascular and circulatory studies. At days 3–6 of incubation the test-system mainly consists of the chambered heart with embryonic and extraembryonic blood vessels. The system has been proofed to be a suitable model for the assessment of acute toxicity of irritant substances (Rosenbruch and Holst, 1990).

Analysis of macromolecular adducts of ethylene oxide is a tool which allows determination of internal target doses of this carcinogen (Bolt et al., 1988). An important aspect is that ethylene is converted in the living organism to ethylene oxide, and that ethylene is produced endogenously (Filser and Bolt, 1983; Schmiedel et al., 1983).

Relatively little is known about the histogenesis and the underlying mechanisms of lung cancer; in particular about the target cell type(s) of carcinogens (Schüller 1987). The same can be said about the mechanisms of epithelial regeneration in the lung after injury by toxic chemicals. One of the morphologically appreciable responses of the lung to such injury is a hyperplastic growth of bronchiolo-alveolar epithelium. There is speculation that type II pneumocytes or Clara cells may give rise to the hyperplasia. Neuroendocrine (APUD) cells and type I pneumocytes are supposed to be less capable of initiating hyperplasia because of their low activity of cell division, although hyperplasia of the former cell type is experimentally inducible (Schuller et al. 1988). Mutual transformation has even been postulated between type II pneumocytes and Clara cells in certain cases (Schüller 1987). There is another cell type which, occurring in a fetal as well as regenerating adult airway epithelium (McDowell et al. 1984; Emura 1985; Strum et al. 1990), closely resembles the small mucus granule cells (SMGC) postulated to be one of the carcinogen targets in the lung (McDowell and Trump 1983). In our cell culture study (Emura et al. 1990) a large population of cells possessing SMGC characteristics are inducible in vitro from an undifferentiated population of airway epithelial cells.

Most environmental mutagens and carcinogens require metabolic activation to electro- philic intermediates capable of reacting with cellular target structures, such as DNA. These electrophilic intermediates are in addition subject to metabolic detoxification. This metabolism is mainly controlled by enzymes whose expression is very variable. Among other things, various enzymes are inducible by environmental chemicals. Understanding the toxicology of chemicals (for example, species differences, idiosyncrasias, organotropisms) therefore requires knowledge of critical host factors. One approach towards this goal involves the use of purified enzymes in metabolism and toxicological studies (Glatt et al., 1983; Glatt and Oesch, 1986). This approach, however, is laborious, the purification may alter enzymatic properties, and it may be difficult to rule out the influence of impurities in the enzyme preparation, especially when large families of structurally closely related enzymes exist, as is common in xenobiotic metabolism.

In former studies we could demonstrate that environmental pollutants such as atmospheric particulates and particulate automotive exhaust induce genotoxic effects. They were found to induce sister chromatid exchanges and chromosomal aberrations in human and rodent tissue culture cells and to enhance the number of transformed colonies of SV40-infected Syrian hamster kidney cultures (Hadnagy et al., 1986; Hadnagy and Seemayer, 1988; Hadnagy et al., 1989; Hadnagy and Seemayer, 1990; Seemayer et al., 1988). Furthermore, it was shown that these complex chemical mixtures interfere with the mitotic spindle apparatus to produce abnormal mitotic figures and mitotic arrest in mouse macrophages (line IC-21) and Chinese hamster lung cells V79 (Hadnagy and Seemayer, 1986; Hadnagy and Seemayer, 1988; Hadnagy and Seemayer, 1990; Seemayer et al., 1989). As a consequence of this effect aneuploidy and polyploidy were induced in subsequent cell divisions. There is increasing evidence that aneuploidy and events leading to aneuploidy are mechanistically involved in malignant cell transformation and tumor formation in vivo (Oshimura and Barrett, 1986). This led to the conclusion that the carcinogenic potential of particulates from the atmosphere and particulate automotive exhaust may be the result of genotoxic and epigenetic mechanisms. Until now little is known about aneugenic (aneuploidy-inducing) compounds present in environmental pollutants. Therefore, the aim of this study was the detection of suspicious compounds contributing to the observed epigenetic effect.

Methyl bromide is a colourless gas with excellent qualities as an insecticide, nematocide and fungicide. It is especially useful for the fumigation of soil, due to its relatively high specific weight, which enables it to penetrate the soil very deeply. Methyl bromide is also used as a fumigant for foodstuffs, animal fodder, and various commodities. Its relevance to environmental hygiene is stressed by the fact that traces of it can be found in various foodstuffs, spices and drugs (Laug, 1941; Reeves et al., 1985). Methyl bromide is highly neurotoxic, is mutagenic and can alkylate DNA (Gansewendt et al., 1991).

As an essential element in humans, iron is involved in many biochemical reactions; however, it is also known to catalyse the production of highly reactive oxygen species like hydroxyl radicals and superoxide anions, which produce DNA damage in cell free systems (Inoue and Kawanishi, 1987). Since in intact cells iron is mainly bound to storage proteins like ferritin and cellular defense systems exist to detoxify free oxygen radicals, toxic reactions in vivo are prevented to a high degree (for review see Halliwell and Gutteridge, 1984).

For more than a decade it is known that extracts of outdoor and indoor airborne particulate matter (APM) are genotoxic. However, little attention has been paid to non-genotoxic mechanisms by which APM could play a role in the development of (lung)cancer. As there is increasing evidence that inhibition of gap junctional intercellular communication (IC) is an important mechanism in tumor promotion (for a review see Yamasaki, 1990), we investigated in the present study if extracts of APM are able to inhibit IC in V79 cells. To compare dose-effect relationships for inhibition on IC with initiating activity of extracts of APM, mutagenicity in Salmonella typhimurium TA98 was also studied.

A precondition to replace animal experiments on the carcinogenicity of ecotoxicologically relevant compounds by in vitro studies is a comparable metabolism of the latter in both systems. To this end we have studied the metabolism of chrysene and benzo[a]pyrene in hamster, rat and human lung cell cultures.

Neoplastic transformation occurs with chemical carcinogens that interact with DNA such as carcinogenic polycyclic hydrocarbons, inorganic metals, N-Acetoxy-florenylacetamide and its derivatives and alkylating agents (1). Transformation resulting in malignancy also occurs with non-mutagenic agents including SO₂− (sodium bisulfite). With chemicals alone or in combination with X-irradiation the incidence of transformed hamster colonies fits a one hit curve indicating that the phenomenon is inductive (2).

Up to now no simple and sensitive experimental test system is available to assess the carcinogenic properties of substances which are suspected to cause bladder cancer in humans. The usual animal model in this case is the oral application (IARC, 1987). The data show, however, that it is greatly a matter of chance to select a species which is sufficiently sensitive to a certain tested substance. Bladder carcinogens were detected in the past especially with dogs. High doses and long observation periods have to be used with this species. It can be deduced from some studies, that a total of more than one kilogram of benzidine or ß-naphthylamine had to be applied (Bonser et al., 1956; Walpole et al., 1954). Naturally this leads to many technical problems. Therefore, we started to investigate the applicability of two other test models which we expected to allow successful carcinogenicity testing with much smaller amounts of test substances.

The causal relation between tobacco consumption and human cancer has been recognized for more than 50 years and NNK was considered to be the most potent carcinogenic tobacco specific nitrosamine. In present studies the cytotoxic, genotoxic and transforming effects of NNK in vivo and in vitro in rat tracheal epithelial (RTE) cells were investigated by the assays of colony forming efficiency (CFE), micronuclei formation (MN) and cell transformation frequency (TF).

This inhalation study with Wistar rats aims to present an investigation concept that helps authorities and industry in the replacement of toxic smoke screens among which several mixtures of ZnO/hexachloroethane (HC-) smoke had been preferentially used for decades in military and fire-service training.

A few air pollutants, in particular certain gases, have been recognized as being noxious. The noxious effects are generally observed in acute or subchronic animal and human exposure studies with agents at concentrations exceeding by far average ambient concentrations, or as a result of observations during environmental episodes with high levels of air pollution. However, the effects resulting from inhalation of these agents over long periods of time at or close to ambient concentrations have only been studied rarely.

Ozone (O₃) has become a common air pollutant in urban areas and in the workplace. Because O₃ is highly reactive and potentially toxic, it has received increasing attention regarding effects on pulmonary function. However, the precise mechanisms which lead to O3-induced lung injury are still not completely understood. A role for cytochrome P-450 enzymes in the development of oxidant-induced lung injury has recently been suggested. Rietjens et al. (1988) found that prolonged exposure to 0.8 ppm O₃ caused qualitative and quantitative changes in pulmonary cytochrome P-450-linked enzyme characteristics in whole lung and within specific lung cells of rats. Takahashi and Miura (1990) showed that prolonged exposure to 0.2 ppm O₃ caused increased content of specific isoforms of cytochrome P-450 in lungs of rats. Although these studies suggest P- 450 inducibility by O₃ may be important, a physiologic or pathologic correlate to the activity of these enzymes has not been demonstrated.

In 1989 aerosols of the oxide (CdO), the sulfate (CdSO₄) and the sulfide (CdS) of Cadmium had been classified by the german Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) as substances with a carcinogenic potential for humans. Lung tumors had been observed by exposing rats to these chemical species (Glaser et al., 1990); no carcinogenic effect occured in hamsters or mice (Heinrich et al., 1989).

The U.S. Environmental Protection Agency is presently preparing a Health Assessment Document of inhaled diesel engine emissions which will also address the question of an assessment of its carcinogenic potency. The evidence of a carcinogenic potential of inhaled diesel exhaust from epidemiological studies is limited whereas it is sufficient from long-term rat inhalation studies (IARC, 1989). Table 1 lists several of those rat inhalation studies, and the question arises whether the result of these studies could be used for assessing a carcinogenic risk for human exposure.

Chromates have been shown by many authors to be highly toxic to mammalian cells and animals. In cell cultures using pneumocytes, fibroblasts and alveolar macrophages we have demonstrated toxic reactions (Popper et al., 1990). Also genotoxic effects have been shown using the micronucleus assay. To further extend our data we investigated an inhalation experiment using Fisher 344 rats. In these experiments we looked for toxic and carcinogenic effects at the onset of inhalation and for the late outcome.

Specific volatile N-nitrosamines (e.g. N-nitrosodimethylamine, NDMA) have been detected in different sources of the human environment, such as in tobacco smoke (Tricker and Preussmann, 1989) or in several work places (rubber, leather, chemical industries; ECETOC, 1990). In these exposure situations, amounts of up to several hundred micrograms per cubic metre have been found. For this reason, we initiated a long-term inhalation study with NDMA in Sprague-Dawley rats using exposure schedules in which the lowest concentration was comparable to peak concentrations at those work places (Klein et al. 1991). It is feasible to make risk assessments on the basis of such inhalation experiments with animals at dose levels relevant to the human situation. For this purpose, it is furthermore important to know the actual absorption rate in the respiratory tract. Therefore, in addition to the longterm assay, several short-term experiments were performed to study the exhalation rate of NDMA and some other volatile N-nitrosamines in rats. In earlier inhalation experiments with endotracheally intubated rats, we had shown that some volatile nitrosamines including NDMA are not completely absorbed in the respiratory tract and several % of the nitrosamines inhaled for a few minutes were exhaled again within the subsequent hour (Klein and Schmezer, 1984).

Up to now the behaviour of inert aerosol particles within the human respiratory tract has primarily been studied in young healthy people. The application of bronchoconstrictive or brochodilatory pharmaca to this group results in a corresponding variation of aerosol derived effective airway dimensions (EADs). Each subject has been measured at least twice, once without pharmacon and then after drug application. By this way, each subject has been his own reference. It turned out that variations in EADs are most pronounced in proximal airways; the effect decreases continuously towards the lung periphery until it disappears. For the antagonistic drugs carbachol (bronchoconstrictor) and oxitropiumbromide ((VentilatR) bronchodilator) the sites of action are in almost identical volumetric lung depths V_LDs. The percental changes in EADs are equivalent for the applied doses of pharmaca (Schiller-Scotland (1990)).

The measurement of the remanent magnetic field of the human lung contains a lot of information about the behavior of magnetic material, either in the lung or in the macrophages. Iron oxide can be used as a test aerosol for studies of particle clearance and macrophage activity.

Cobalt is a relatively rare element, which takes the 32nd place on earth in distribution of elements. It is mainly found in copper ores of Katanga in Zaire as well as in Pyrites of Ontario in Canada. The evident glitter of some parts of these ores pretended to contain silver, copper or tin, but didn’t forward any precious metal when dressed and washed. Therefore the ancient miners believed in a specter called “imp” — in German called “Kobold”.

According to a WHO task group on environmental health criteria for methylmercury the average daily intake of mercury in the general population not occupationally exposed to mercury can be described as shown in Table 1. Taking into account the low mercury concentration in air the fraction of mercury absorbed by inhalation is very small. Mercury in non-fish foodstuffs normally occurs in the form of inorganic mercury compounds. The average daily intake is estimated to be 3,6 µg per day in industrialized countries. Mercury in fish mainly consists of methylmercury (mean intake: 2,4 µg per day). Therefore, fish consumption represents the main source of exposure to methylmercury.

The purpose of human genetic monitoring is to detect exposures to chemical mutagens and to evaluate genotoxic effects from different exposure situations. Cytogenetic changes in somatic cells of in vivo exposed workers are an acceptable approach to occupational risk assessment. 5 different groups of chemical workers employed in synthesis and processing of several industrial chemicals (parathion-methyl, dimethylsulphate, ß-naphthol, hair dyes, chromate) from one of the formerly most important factories of the Bitterfeld region in Sachsen-Anhalt and 2 non-exposed control groups were analyzed for chromosomal aberrations (CA) and sister chromatid exchanges (SCE) in lymphocytes. Altogether 103 exposed and 117 non-exposed individuals were investigated. The investigations were performed from 1977 — 1984. Till 1990 there was no possibility to publish the results in East Germany. Both genetic endpoints are widely used to monitor human populations to environmental mutagens. A lot of epidemiological studies have shown that workers occupationally exposed to mutagens have higher frequencies of CA and SCE than non-exposed controls (Nordic Study, 1990; Hüttner, 1990).

In connection with the national Cardiovascular Prevention Study in the Federal Republic of Germany (FRG), which includes adults between 2 5 and 69 years of age, it was decided to take advantage of the availability of a representative population to know more about the relationship between health and the environment. Thus, in 1985/86, the nationwide representative survey “Environment and Health” was conducted. While in one part of the study questionnaires were used to acquire a better knowledge of the personal opinion of German citizens on their health status and the environment, the study was mainly directed at getting objective information by passing the participants through a medical examination and assessing their exposure to environmental pollutants. The final population sample included some 2700 persons and was representative for the West German population with regard to age, sex and community size.

The mechanism of action of many carcinogens is considered to involve the formation of electrophilic alkylating agents which react with nucleophilic sites in DNA giving rise to a range of adducts (Miller, 1978). All of the nitrogen and oxygen atoms in purines and pyrimidines are known to form adducts with various carcinogens, although the relative amounts of each adduct vary greatly depending on the reactivity of the alkylating species (Singer and Kusmierek, 1982). O6-alkylguanine adducts are promutagenic lesions which can be repaired by alkyltransferases which remove the alkyl group. In contrast, N7- and N3-purine adducts are repaired by glycosylases which excise the alkylated base (Karran and Lindahl, 1985). Excised alkylpurines are known to be resistant to catabolism and are excreted in urine. These observations are the basis of methods for the non-invasive measurement of human exposure to alkylating carcinogens using excreted DNA adducts (Shuker, 1989). This approach has been particularly successful in studies on human exposure to aflatoxin B₁ (Groopman et al., 1991).

In an area with a lead smeltery, concentrations of lead and cadmium in airborne particles, depositions and household dust, and biological indicators of lead exposure have been followed over 20 years. The environmental lead levels, particularly concentrations of lead in the air, have shown a marked decrease after the introduction (in 1978) of efficient bag filters for the control of smeltery emissions (Fugas et al., 1984), while biological indicators of lead exposure have improved gradually over the years (Prpić-Majić et al., 1984). The purpose of this study was to assess approximately the range of possible total personal exposures to lead and cadmium and to determine the share of their absorption from air, food and beverages.

Chronic, pulmonary fibrosis caused by the inhalation of asbestos has a very clear etiology, although its pathogenesis remains obscure. Macrophages are a key element in the response of the host to asbestos. Dust clearance from the alveoli is the function of the macrophages. Whereas these cells phagocytize short fibres and remove them from the respiratory pathways they cannot encompass and transport the longer fibres, which tend to be retained in the lumens of the bronchioles and the alveolar ducts (Craighead and Mossman, 1987). The appearance of asbestos bodies represents the endogenous reaction of the pulmonary defense mechanism to the inhaled needlelike asbestos. Asbestos bodies are inhaled asbestos fibres which have been coated with ferroprotein by macrophages (Morgan and Holmes, 1985). It is generally accepted that coating neutralises the pathogenic potential of the fibre. The coated fibres are less toxic to pulmonary alveolar macrophages (McLemaire et al., 1980). The fibres, the lengths of which exceed the diameter of the human alveolar macrophage (ca. 15 μm) are poorly cleared. As asbestos bodies are rarely formed on fibres less than 10 µm in length, the majority will be retained in the lungs indefinitely, unless broken into smaller fragments, which undergo phagocytosis and are cleared by macrophages (Timbrel, 1982).

Mercury burden can be caused by intake of contaminated food (e.g. fish), by amalgam fillings and most importantly by occupational exposure, e.g. chlor-alkali plants, production of electrical equipment, production of thermometers. Hg vapor is the most common form of exposure from occupational sources and amalgam fillings. In food, Hg can be found in organic form (e.g. methylmercury). It has been shown that Hg intake from amalgam fillings has been reduced to levels that do not pose a health risk to dental patients (Zander et al., 1990). Furthermore Hg in fish is regulated by threshold limit values that are very rarely surpassed in recent years.

Aluminium (A1) is the most abundant metal. It is present in tap water, beverages, food, cosmetics and pharmaceutical preparations. Human exposure is unavoidable. An essential role has not been established but the element is now known to be toxic.

In Germany, possible associations between air quality and obstructive bronchitis as well as croup syndrome had been intensively discussed during the last decade. Meanwhile it is mostly accepted that air quality can only explain a relatively small part of the variance of these diseases (LAI, 1990), compared with the dominant role of viral infections and individual disposition.

Since 1976, the Medical Institute of Environmental Hygiene conducts epidemiological studies the results of which form a part of the Clean-air plans (Luftreinhaltepläne) of North-Rhine- Westphalia. These studies are intended to monitor the effects of air pollution on human health. Since 1985, six year old children who take part in the compulsory school entrance examination are investigated by our group on a voluntary basis. Response rates of above 90 % could be achieved.

Epidemiological studies provide evidence that air pollution influences incidence, prevalence, course of the disease and lethality of asthma (McDONNEL,1983; MENZEL, 1984; MOSBECH, 1987). With an increasing degree of pollution, the results become more distinct, especially during episodes of extremely severe air pollution. A study in Donora (USA) showed that 87.6% of asthmatics developed acute symptoms.

In order to integrate the environmental medicine into the necessary redevelopment programmes for the Bitterfeld region we tried to compile during the last half year every still available data for a first assessment of the complex effect. This study contains apart from a renewed analysis of the own field studies additional pilot examinations.

The proper estimation of industrial risk associated with the activities of industrial enterprise can be a complicated problem for the enterprise managerial staff. The reason is that the risk comprises several relevant components and there are no friendly methodologies at hand for their comparative estimation. Thus the approach was suggested called an Integrated Quality Concept (Boutoussov, 1988) to evaluate simultaneously (and in comparable terms) major positive and negative impacts of industrial activity at the level of industrial enterprise. These impacts correspond to economical, environmental and occupational components of the enterprise activity.

Environmental tobacco smoke (ETS) is a major cause of indoor air pollution (Repace and Lowrey, 1980). Exposure to ETS is known to cause irritation (Cummings et al., 1991), increased risks for respiratory infections (Samet, 1989), atopy (Kershaw, 1987), heart disease (Glantz and Parmley, 1991) and cancer (Pershagen, 1989). The exposure to ETS has often been evaluated by the presence or absence of smokers in the family. Exposure is, however, possible in all environments whenever smoking occurs. We have earlier analyzed ETS using the Ames Salmonella mutagenicity assay on extracts of particulate matter collected in homes (Löfroth and Lazaridis, 1986) offices (Löfroth et al., 1983) and public places (Löfroth et al., 1988). These latter studies have now been extended with comparisons between smoking and non-smoking areas and amended with analysis of airborne nicotine as a specific marker for ETS.

In the federal countries of West Germany 160.000 persons annually die of cancer among them 25.000 of lung cancer. After subtraction of smoking effect and working place caused burden one has to assume that air pollution is an important factor for the etiopathogenesis of lung cancer.

Based on estimations of the German ministry of science and technology (BMFT), in the Federal Republic of Germany 70,000 sites exist which are in suspect of remediatory need. These old sites are typically found in industrial regions and urban areas and include undefined disposal of wastes, regions surrounding mining and industry sites, as well as old sites which used to harbor metal and coking works, chemical and power plants, refineries and gas work plants.

Polychlorinated dibenzodioxins (PCDD) and dibenzofurans (PCDF) — often refered to simply as “dioxins” — constitute a group of 210 closely related chemicals. They are mainly formed as byproducts in combustion or heating processes in the presence of substances containing chlorine as well as during the synthesis of chemical compounds structurally based on chlorinated aromatics.

In Germany, we have a number of solid waste depositions out of World War I and II that are contaminated with high toxic chemical weapon agents (Spyra 1988). During the cleaning up of such depositons, contaminations of the total environment with the original agents ore with some decomposition products of it are possible and have to be measured.

For an industrial large-scale production of alpha amylase with an rDNA B. subtilis a case study was performed in the former G.D.R. from 1986–1990. Unintended releases of production strains are expected to occur in most cases of large-scale fermentations under safety level 1 conditions. Dominant release routes are via air (exhaust air from aerobic fermentation), biomass (after separation of the production strain from the extracellular enzymes) and waste water (Smalla et al. 1991). Our investigations were focussed on monitoring the extent and routes of release, characterization of microbial composition of bioprocessing waste, the fate of rDNA B. subtilis in sterile and nonsterile environmental media (potential recipient habitats such as soil, river water or waste water) and transfer of rDNA to indigenous microbes.

The environment in the GDR was considerably damaged due to the structure of its source of energy which is unique in the world. The country covered 70 per cent of its primary energy consumption by the extraction of 320 million tonnes of raw lignite; oil and natural gas amounting to 12 and 10 per cent, respectively. As a result, since the oil crisis in the early seventies there has been a continuous increase in sulphur dioxide and dust emissions in the GDR, which included emissions from households and residential areas because of the strategy of replacing coke and gas by lignite.