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Depleted uranium (DU), a waste product of uranium enrichment, has several civilian and military applications. It was used as armor-piercing ammunition in international military conflicts and was claimed to contribute to health problems, known as the Gulf War Syndrome and recently as the Balkan Syndrome. This led to renewed efforts to assess the environmental consequences and the health impact of the use of DU. The radiological and chemical properties of DU can be compared to those of natural uranium, which is ubiquitously present in soil at a typical concentration of 3 mg/kg. Natural uranium has the same chemotoxicity, but its radiotoxicity is 60% higher. Due to the low specific radioactivity and the dominance of alpha-radiation no acute risk is attributed to external exposure to DU. The major risk is DU dust, generated when DU ammunition hits hard targets. Depending on aerosol speciation, inhalation may lead to a protracted exposure of the lung and other organs. After deposition on the ground, resuspension can take place if the DU containing particle size is sufficiently small. However, transfer to drinking water or locally produced food has little potential to lead to significant exposures to DU. Since poor solubility of uranium compounds and lack of information on speciation precludes the use of radioecological models for exposure assessment, biomonitoring has to be used for assessing exposed persons. Urine, feces, hair and nails record recent exposures to DU. With the exception of crews of military vehicles having been hit by DU penetrators, no body burdens above the range of values for natural uranium have been found. Therefore, observable health effects are not expected and residual cancer risk estimates have to be based on theoretical considerations. They appear to be very minor for all post-conflict situations, i.e. a fraction of those expected from natural radiation.

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Soil samples collected from locations in Kosovo where depleted uranium (DU) ammunition was expended during the 1999 Balkan conflict were analysed for uranium and plutonium isotopes content (234U, 235U, 236U, 238U, 238Pu, (239 + 240)Pu). The analyses were conducted using gamma spectrometry (235U, 238U), alpha spectrometry (238Pu, (239 + 240)Pu), inductively coupled plasma-mass spectrometry (ICP-MS) (234U, 235U, 236U, 238U) and accelerator mass spectrometry (AMS) (236U)). The results indicated that whenever the U concentration exceeded the normal environmental values (approximately 2 to 3 mg/kg) the increase was due to DU contamination. 236U was also present in the released DU at a constant ratio of 236U (mg/kg)/238U (mg/kg) = 2.6 x 10(-5), indicating that the DU used in the ammunition was from a batch that had been irradiated and then reprocessed. The plutonium concentration in the soil (undisturbed) was about 1 Bq/kg and, on the basis of the measured 238Pu/(239 + 240)Pu, could be entirely attributed to the fallout of the nuclear weapon tests of the 1960s (no appreciable contribution from DU).

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Selected soil samples, collected in Kosovo locations where DU ammunition was expended during the 1999 Balkan conflict, have been investigated by secondary ion mass spectrometry (SIMS), X-ray fluorescence imaging using a micro-beam (micro-XRF) and scanning electron microscopy equipped with an energy dispersive X-ray fluorescence detector (SEM-EDXRF), with the objective to test the suitability of these techniques to identify the presence of small DU particles and measure their size distribution and the 235U/238U isotopic ratio (SIMS). Although the results do not permit any legitimate extrapolation to all the sites hit by the DU rounds used during the conflict, they indicated that there can be "spots ' where hundreds of thousands of particles may be present in a few milligrams of DU contaminated soil. The particle size distribution showed that most of the DU particles were <5 microm in diameter and more than 50% of the particles had a diameter <1.5 microm. Knowledge on DU particles is needed as a basis for the assessment of the potential environmental and health impacts of military use of DU, since it provides information on possible re-suspension and inhalation.

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Most assessments of possible deleterious outcomes from environmental and occupational exposures concentrate on single agents and neglect the potential for combined effects--that is, synergisms or antagonisms. Biomechanistic considerations based on multistep processes, such as carcinogenesis, indicate the potential for highly detrimental interactions if two or more consecutive rate-limiting steps are specifically effected by different agents. However, low specificity toward molecular structure or DNA sequence--and, therefore, exchangeability--of many genotoxic agents indicate little functional specificity and, hence, little vulnerability toward synergism in most occupational and environmental exposure situations. It is also evident that a low potential exists for the combined effects of common low-exposure situations wherein nongenotoxic agents with highly nonlinear dose-effect relationships and apparent thresholds are involved. A quantitative assessment of the contribution of synergistic interactions to the total detriment from natural and man-made toxicants based on experimental data is far away. There are important examples of combined exposures shown to lead to health effect risks that differ from those expected from simple addition-for example, the influence of smoking on radon- or asbestos-induced lung cancer and on ethanol-induced esophageal cancer. The existing data on combined effects is rudimentary, mainly descriptive, and rarely covers exposure ranges large enough to make direct inferences to present-day low-dose exposure situations. In view of the multitude of possible interactions among the large number of potentially harmful agents in the human environment, descriptive approaches will have to be supplemented by the use of mechanistic models for critical health endpoints, such as cancer. Finally, considering the shape of dose-effect relationships for ionizing radiation, an important question arises from the unresolved question of whether real or apparent thresholds may be used for any genotoxic agent, separately or one time, for an exposed genome.

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Nature and living organisms are separated into compartments. The self-assembly of phospholipid micelles was as fundamental to the emergence of life and evolution as the formation of DNA precursors and their self-replication. Also, modern science owes much of its success to the study of single compartments, the dissection of complex structures and event chains into smaller study objects which can be manipulated with a set of more and more sophisticated equipment. However, in environmental science, these insights are obtained at a price: firstly, it is difficult to recognize, let alone to take into account what is lost during fragmentation and dissection; and secondly, artificial compartments such as scientific disciplines become self-sustaining, leading to new and unnecessary boundaries, subtly framing scientific culture and impeding progress in holistic understanding. The long-standing but fruitless quest to define dose-effect relationships and thresholds for single toxic agents in our environment is a central part of the problem. Debating single-agent toxicity in splendid isolation is deeply flawed in view of a modern world where people are exposed to low levels of a multitude of genotoxic and non-genotoxic agents. Its potential danger lies in the unwarranted postulation of separate thresholds for agents with similar action. A unifying concept involving toxicology and radiation biology is needed for a full mechanistic assessment of environmental health risks. The threat of synergism may be less than expected, but this may also hold for the safety margin commonly thought to be a consequence of linear no-threshold dose-effect relationship assumptions.

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In Germany, the largest single cohort study on uranium miners to date is being conducted. The cohort includes about 64,000 workers of the former Wismut company in eastern Germany. Inclusion criteria were: a date of employment between 1946 and 1989, a minimum period of employment of 180 days, and complete information on working history. Due to poor working conditions in the late 1940s and early 1950s, miners were exposed to high levels of radiation, while later radiation exposure was significantly reduced. The aim of the cohort study is to evaluate the risk of lung cancer and other cancers associated with several indicators of exposure to radon and its progeny, with particular attention to low levels of radiation. Radon exposure will be estimated by a detailed job- exposure matrix. Some information about smoking, dust and arsenic is already available. About 49,000 miners are defined as exposed (underground or processing), while the internal control group (surface only) consists of 15,000 workers. A total of 1,436 lung cancer deaths among cohort members have been reported. The first mortality follow-up will be finished early in 2002, and a total of about 3,000 lung cancer deaths are expected by then.

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A registry of the rural population in the Altai region exposed to fallout from nuclear tests at the Semipalatinsk test site (STS) was established more than four decades after the first Soviet nuclear explosion on August 29, 1949. Information about individuals living in an exposed and a control area was collected using all available local sources, such as kolkhoz documentation, school registries, medical treatment records and interviews with residents. As a result, a database comprising an exposed group of 39 179 individuals from 53 Altai region villages, 6769 external and 3303 internal controls was compiled. For several settlements, effective dose estimates reached the level of 1.5 Sv, while the average effective dose estimate in the exposed group was 340 mSv. Dosimetric data, vital status information and health records gathered at rayon and village medical facilities are held in the registry. Cause-of-death information for deceased residents is obtained from death registration forms archived at the Altai region vital statistics office. At present, a follow-up of approximately 40% of the population exposed in 1949 has been done. More will be added by searching for migrants to the larger towns of the Altai region, i.e. Barnaul, Rubtsovsk and Biisk. In order to assess the influence of radiation exposure, analytical studies with a case-control design for stomach and lung cancer are currently being prepared. The number of known cases is sufficient to detect an odds ratio of 1.5 at the 95% confidence level. Epidemiological studies in populations affected by fallout from STS may be equally important to the atomic bomb survivors' study for the direct quantification of radiation effects. The range of exposure rates experienced will extend the acute high-dose-rate findings from Hiroshima/Nagasaki towards acute and protracted lower exposures, which are more relevant for radiation protection issues.

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In 1991, an increased rate of childhood leukaemia was reported from the small northern German community of Elbmarsch, which is located on the banks of the River Elbe opposite the Kruemmel nuclear power plant. Owing to the fact that the increase occurred six years after the start-up of the plant, radioactive discharges were suspected as being implicated in the development of the cases. Previous investigations have failed to identify any exposure which might be associated with the cluster. Nonetheless, concern regarding the increased tritium burden in the environment remains. To further assess the impact of tritium releases to the environment upon population cancer rates, the releases and leukaemia rates at the Savannah River site, USA, were compared with the Kruemmel site. Based on the data from 1991 to 1995, the incidence of childhood leukaemia in the vicinity of the Savannah River site was non-significantly less than expected compared with the significantly higher than expected rates close to the German plant. In contrast, tritium releases from the Savannah River site exceed those from the Kruemmel site by several orders of magnitude. The results of this observational study suggest that factors other than environmental tritium releases are associated with the increased number of leukaemia cases near the Kruemmel site.

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An understanding of damage pattern in critical cellular structures such as DNA is an important prerequisite for a mechanistic assessment of primary radiation damage, its possible repair, and the propagation of residual changes in somatic and germ cells as potential contributors to disease or ageing. Important quantitative insights have been made recently on the distribution in time and space of critical lesions from direct and indirect action of ionizing radiation on mammalian cells. When compared to damage from chemicals or from spontaneous degradation, e.g. depurination or base deamination in DNA, the potential of even low-LET radiation to create local hot spots of damage from single particle tracks is of utmost importance. This has important repercussions on inferences from critical biological effects at high dose and dose rate exposure situations to health risks at chronic, low-level exposures as experienced in environmental and controlled occupational settings. About 10,000 DNA lesions per human cell nucleus and day from spontaneous degradation and chemical attack cause no apparent effect, but a dose of 4 Gy translating into a similar number of direct and indirect DNA breaks induces acute lethality. Therefore, single lesions cannot explain the high efficiency of ionizing radiation in the induction of mutation, transformation and loss of proliferative capacity. Clustered damage leading to poorly repairable double-strand breaks or even more complex local DNA degradation, correlates better with fixed damage and critical biological endpoints. A comparison with other physical, chemical and biological agents indicates that ionizing radiation is indeed set apart from these by its unique micro- and nano-dosimetric traits. Only a few other agents such as bleomycin have a similar potential to cause complex damage from single events. However, in view of the multi-stage mechanism of carcinogenesis, it is still an open question whether dose-effect linearity for complex primary DNA damage and resulting fixed critical cellular lesions translate into linearity for radiation-induced cancer. To solve this enigma, a quantitative assessment of all genotoxic and harmful non-genotoxic agents affecting the human body would be needed.

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Living organisms are exposed every day to a multitude of physical, chemical and biological agents. However, assessments of possible deleterious outcomes from these exposures concentrate on single agents and neglect the potential for combined effects, i.e., synergisms or antagonisms. Biomechanistic considerations based on multistep processes such as carcinogenesis indicate the potential for highly detrimental interactions, if two or more consecutive rate limiting steps are specifically effected by different agents. However, this depends on the specificity of the individual agents for well defined molecular structures or DNA sequences. Low specificity towards molecular structure or DNA-sequence-and therefore exchangeability-of many genotoxic agents indicate little functional specificity of most agents and therefore little vulnerability towards synergism at most occupational and non-occupational exposure situations. In addition, the relative insignificance of combined actions for those common exposure situations where highly non-linear dose effect relationships for non-genotoxic acting agents are involved is also evident. However, an experimental proof of the quantitative assessment of the contribution of synergistic interactions to the total detriment from natural and man-made toxicants is remote. Surprises therefore cannot be excluded.

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Ionizing radiation from natural or man-made sources may affect human health. The main consequence of low and moderate radiation doses is the induction of cancer. To quantify these effects both epidemiological studies and experimental radiobiological research are needed. The ensuing results of the studies are used to establish radiation protection principles and dose limits to protect the public from the effects of ionizing radiation.

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A temporary increase in the incidence of infant leukaemia in Greece was reported by Petridou et al., which was attributed to in utero exposure to ionising radiation resulting from the Chernobyl accident. We performed a similar analysis based on the data of the German Childhood Cancer Registry in order to check whether the observation could be confirmed by means of independent data. Applying the same definitions as Petridou et al., we also observed an increased incidence of infant leukaemia in a cohort of children born after the Chernobyl accident. More detailed analyses, regarding areas with different contamination levels and dose rate gradients over time after the accident, showed, however, no clear trend with regard to exposure. It would therefore appear less likely that the observed effect was caused by exposure to ionising radiation due to the Chernobyl accident.

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319 Patients are retrospectively competed, which underwent an inpatient or outpatient gynecological laparoscopy in 1992. Equality exists for martial status, education degree, nationality, anesthesiological risk and social structure. Outpatients are older, more rarely private assured, more often abdominal preoperated, have more children and live closer to the providing clinic. The satisfaction with the chosen medical care was outpatiently higher than inpatiently (97% vs 86%). In this context hesitation of security, quality of care and involvement at home are important. The inpatient group is characterized by patients with infertility, endometriosis and extrauterine gravidity, distance to employment and intensity of troubles have been important for the decision of medical providing. Outpatients were less anxious, sterilization and adhesions were main diagnoses. Here decisive factors for the choice of medical care have been care requiring relatives and financial aspects. By mean of these characteristics predictors are diverted for both kinds of care for being help to the advising doctor.

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For 44 individuals living in areas of the Southern Urals with historical 90Sr contamination, whole-body activities of this radionuclide were investigated using a new mobile detection system. Beta-particles from 90Sr/90Y decay were measured in vivo via two proportional counters mounted in front of the forehead and above the head, respectively. In order to correct for absorption by the skin, scalp thickness was measured using ultrasonic techniques. Corrections are given with respect to self-absorption by the bone matrix and absorption by hair. A procedure is described to extrapolate from measured 90Sr activity of the skull bone to total 90Sr skeleton burden. As a result, 90Sr whole-body activities of up to 50 kBq were recorded in the selected cohort. For the same individuals, 90Sr was measured via the detection of bremsstrahlung using an established whole-body counting device. The overall results of both systems agree within 15%, but differences exceeding a factor of 2 were observed in some cases.

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A region between Chelyabinsk and Ekaterinburg in the Southern Urals has been heavily contaminated due to operational and accidental releases from the first Soviet plutonium production facility Mayak. In 1992 and 1993, the German Federal Office for Radiation Protection organized a measuring campaign involving two Russian institutes to assist with the validation of former Soviet measurement data. The results of this measuring campaign are reported here. Environmental samples were collected from areas affected by significant radioactive releases into the Techa river, which started in 1948, and by fallout from the explosion of a fission product storage tank in 1957. Soil, sediment, water, milk and food samples were independently analysed for 90Sr, 137Cs and plutonium by the three institutes involved. This paper presents data on the present levels of environmental radioactivity. The highest contamination of areas accessible to the local population was found in the vicinity of the Techa river around Muslumovo. Activity concentration of floodplain samples reached up to 37,000 Bq.kg-1 137Cs, 5,600 Bq.kg-1 90Sr and 9.9 Bq.kg-1 Pu. Milk and potatoes from private farms in Muslumovo showed low activity in the range from 0.7 Bq.kg-1 to 25 Bq.kg-1 90Sr. The results of the three independent measurement teams showed sufficient agreement. One Russian laboratory obtained plutonium activities that exceeded the results of the other laboratories by about 20%. Contrary to the International Chernobyl Project, there was no overestimation of 90Sr activities in the Russian analyses. Therefore, the validity of earlier data sets acquired with same methodology and quality control can be considered a valuable basis for further assessments and for dose reconstruction in epidemiological projects.

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In the inhomogeneous radiation field surrounding small beta-particle sources, nonlethally and heavily damaged cells are in proximity, permitting interaction via extracellular signals. This situation is typical of hot particles such as those released during the accident at Chernobyl. Beta-particle-emitting yttrium-90 wires (average energy 934 keV) were employed to investigate radiation-induced neoplastic transformation under these conditions. Integrated 24-h doses ranging from 0 to 750 Gy across the exposure field were applied. At equal levels of toxicity a 10-fold enhancement of neoplastic transformation frequency in C3H 10T1/2 cells was observed in the presence of heavily damaged cells. Homogeneous fields of low-dose-rate beta-particle radiation produced neoplastic transformation frequencies typical for comparable photon exposures reported in the literature.

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