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B A Katsnelson

Publications and source records attributed to B A Katsnelson.

At least 19 recordsLinked to original sources

Some considerations concerning multimedia-multipollutant risk assessment methodology: use of epidemiologic data for non-cancer risk assessment in Russia.

The highly industrialized small town of Verkhnyaya Pyshma (in the Urals region of Russia) was chosen as the site of a multimedia-multipollutant risk assessment using the U.S. Environmental Protection Agency methodology. The assessment was based on routine environmental pollution monitoring data for ambient air, soils, drinking water, and food, and the international environmental epidemiology literature. Using an a priori set of the preliminary health-based criteria, we selected nine pollutants for risk assessment: total suspended particles (TSP), sulfur dioxide, nitrogen dioxide, benzo(a)pyrene (BaP), ammonia arsenic, copper, cadmium, and lead. We used dose-response functions derived from epidemiologic studies to assess individual and population risks for TSP, SO2, NO2, As, Cd, and Pb. We assessed both cancer (for BaP, As, and Cd) and non-cancer (for all the chosen pollutants but BaP) responses, but in this paper we discuss only the assessments of noncarcinogenic risks due to TSP, SO2, NO2, Pb, and Cd as examples of how the quantitative estimates of health effects can be produced by using a risk function approach. We also schematically present a modified conceptual model of multimedia-multipollutant risk assessment taking into account the experience gained with this study.

Adolescent↗

Prediction of the comparative intensity of pneumoconiotic changes caused by chronic inhalation exposure to dusts of different cytotoxicity by means of a mathematical model.

A multicompartmental mathematical model has been used to simulate variations in the cytotoxicity of dusts in the kinetics of the retention, in the pulmonary region and tracheobronchial lymph nodes, of practically insoluble quartzite and titanium dioxide dust particles deposited on the free surfaces of the acini from alveolar air. Experiments with these dusts were conducted on rats exposed to virtually the same dust concentrations in the air for an experimental period of 20 weeks and a period of 10 weeks after exposure. Satisfactory approximation to the experimental data on the retention of these dusts is obtained by using the model parameters that depend either on damage to lung macrophages by phagocytosed particles or on the response of the host organism to this damage by enhanced recruitment of neutrophilic leucocytes; all the other variables of the model being unchanged. The values of the "action integral" computed from this model and multiplied by the index of comparative cytotoxicity of particles in vitro satisfactorily approximate to quantitative differences in the intensity of pneumoconioses caused by the dusts under study by the end of the experimental period. On the whole, the results of the mathematical model agree with the hypothesis that the cytotoxicity of particles plays a key part in both the process of retention of dust in the lung parenchyma and lung associated lymph nodes, and the pathological process caused by the retained dust. Thus given the factors and conditions on which the deposition of practically insoluble dusts in the pulmonary region depends, it is necessary to take into account the multiplicative nature of these two effects of cytotoxicity when predicting the comparative risk of pneumoconiosis.

Animals↗

An approach to detecting delayed effects of radioactive contamination on industrial-urban-area dwellers.

Detecting changes in humans that result from radioactive contamination of the area of residence many years after an incident (i.e., when the radiation has substantially decayed) presents a difficult epidemiological problem. Problems of this kind are even more complicated ina areas where the population is continually exposed to other harmful man-made factors. The city of Kamensk-Uralsky (Sverdlovsk region, Russia) is a good case in point. In 1957, part of Kamensk-Uralsky was contaminated as the result of an accident at the Kyshtym nuclear plant. In addition, the population of the contaminated area is being exposed to atmospheric emissions from several industrial enterprises. Two comparable groups of residents were formed: one in the contaminated are and another in a control area within the same city characterized by similar levels of chemical pollution but substantially lower radioactive contamination. The groups were composed of only those people who had been living in these areas continually since time of the accident and who were under 15 years of age at the time of the accident. The groups were matched by sex, age, and socio-occupational characteristics. For each subject, data were gathered on more than 50 parameters including hematological, immunological, and biochemical indices of the health status. All these data were obtained from blood tests taken in the fall of 1992. Data processing was carried out with the help of a computerized mathematical pattern recognition methodology, which ensured reliable discrimination between the generalized health status in the areas under study. We found that the health status of inhabitants of the area more contaminated with radioactive fallouts was adversely affected by radiation.

Adult↗

Development of a multicompartmental model of the kinetics of quartz dust in the pulmonary region of the lung during chronic inhalation exposure of rats.

A multicompartmental model for the kinetics of dust retention in the pulmonary region of the lung and in the tracheobronchial lymph nodes has been developed. The model reflects the following ideas concerning the basic features of this process: (1) penetration into the pulmonary interstitium and translocation to the lymph nodes are possible for non-phagocytized particles only; (2) these processes depend on the degree of damage to macrophages by dust and on the extent of compensatory enhancement in the recruitment of neutrophils taking part in the clearance of the pulmonary region free surface; (3) a certain proportion of initially penetrating particles is continuously returned to this surface together with recruited pulmonary macrophages. The model ensures a satisfactory approximation to experimental data on the retention of quartz in the lung and lymph nodes during long term inhalation exposure, and simulation of the kinetic effects associated with both the damage to and the protection of the macrophagal clearance mechanism.

Animals↗

Trends and perspectives of the biological prophylaxis of silicosis.

Based on earlier paper in this journal, as well as on new data concerning factors predetermining individual susceptibility to silicosis, we propose a comprehensive system of recommendations aimed at increasing the working population's resistance against the harmful action of silica dust. These recommendations consider, on one hand, the criteria of possible selection for employment in dusty industries of individuals who do not possess characteristics making them especially sensitive to this harmful action (collective biological prophylaxis), and on the other hand, the influences that could diminish such sensitivity (individual biological prophylaxis). Some ethical and practical problems of the biological prophylaxis of occupational diseases and a mathematical approach to predicting its effectiveness are also discussed.

Age Factors↗

Some peculiarities of the pulmonary phagocytotic response: dust retention kinetics and silicosis development during long term exposure of rats to high quartz dust levels.

Rats were exposed to quartz dust (about 90 mg/m3) for five hours a day, five times a week either throughout the 48 weeks of the experiment or for a total of 40 weeks plus eight weeks of "rest." Cytological study of bronchoalveolar lavage showed that at a certain level of silicotic changes in the lungs, a pronounced breakdown in pulmonary dust clearance by macrophages could be observed. There was, however, a concomitant compensatory increase in the contribution to pulmonary phagocytosis by the neutrophil leukocytes (NL). As a result, pulmonary dust kinetics could be mathematically described using a constant clearance rate both throughout the 48 weeks of exposure and during the eight weeks after the end of the 40 week exposure. It is shown in a separate experiment that enhanced recruitment of NL into the airways may be due not only to an attractant effect of the products of macrophage breakdown (PMB) themselves but also to the release of an NL attractant factor by viable macrophages activated under influence of the PMB.

Animals↗

Some aspects of the problem of individual predisposition to silicosis.

Based on experimental and epidemiological data findings presented here, as well as on data of other investigators, the authors conclude that a wide interindividual variability of susceptibility to silicosis is a real phenomenon. This susceptibility depends on both intrinsic features of the host and the influence of many environmental factors. The effect of any such factor is realized at different stages of silicosis pathogenesis and in close interrelation with the influence of other factors. The necessity of multifactorial analysis is stressed, and an example of such analysis is presented.

Acclimatization↗

A further experimental study of the antisilicotic effect of glutamate.

Two groups of rats were exposed to quartz dust for six months and in addition one group was given drinking water containing 1.5% sodium glutamate while the second received only water. In the rats receiving glutamate we observed (a) evidence for a considerably reduced cytotoxic effect of the quartz on cells obtained by bronchopulmonary lavage, (b) a reduction in dust retention in the lungs, especially in the tracheobronchial lymph nodes, (c) a considerable reduction in the weight gain in the lungs and in their hydroxyproline and lipid contents, and (d) the inhibition of the formation of silicotic nodules. Polarographic studies of the oxygen consumption of peritoneal macrophages from rats receiving glutamate showed that glutamate prevents the adverse effects of quartz on mitochondrial oxidative processes.

Animals↗

Recruitment of phagocytizing cells into the respiratory tract as a response to the cytotoxic action of deposited particles.

Recruitment of phagocytizing cells into the lower respiratory tract plays a very important role in the pulmonary dust clearance, depending both on the number of particles deposited therein and on their aggressiveness. The higher cytotoxicity of the particles, the greater the number of such cells recruited and the higher the contribution of the neutrophilic leukocytes (NL) into the free cellular population of airways which normally is represented chiefly by alveolar macrophages (AM). Adaptation of the alveolar dust phagocytosis to properties of inhaled particles operates through autoregulation of this process in which a key role is played by macrophage breakdown products (PMB). A series of experiments in vitro and in vivo showed that PMB stimulate AM and NL, enhance their recruitment into airways with a dose-dependent increase of the NL/AM ratio, promote recruitment of their precursors via blood and replenishment of such precursor reserves. The most active factor of the PMB appears to be lipidic by nature. The variability between individuals and between groups of alveolar phagocytosis response to particles of a given cytotoxicity may be due to differences of the host's neurohormonal status. It was shown that influencing the latter significantly shifts response to a standard dose of the PMB.

Animals↗

On the defensive action of glutamate against the cytotoxicity and fibrogenicity of quartz dust.

The cytotoxic action of quartz (DQ12) particles on cultures of rat peritoneal macrophages, as estimated by the inhibition of the TTC-reductase activity, is considerably reduced by preincubation with glutamic acid and by adding sodium glutamate (15 mg/ml) to the drinking water of the rats donating the macrophages. This increase in macrophage resistance under the influence of glutamate is the most probable cause of the delay in the development of silicotic fibrosis shown in several experiments on rats intratracheally injected with quartz and then treated by prolonged administration of glutamate. This effect is probably connected with the influence of glutamate on the stability of the macrophage membranes, which can in its turn be explained by different mechanisms, including the influence on the synthesis and phosphorylation of adenosine nucleotides. Such an influence was shown in rats receiving glutamate by the change of the ATP/ADP ratio in macrophages, but not in erythrocytes. The resistance of rat erythrocytes to the haemolytic action of quartz is also not influenced by the action of glutamate neither in vitro nor in vivo. Such differences in the influences of glutamate on two types of cells, equally susceptible to quartz cytotoxicity but considerably differing in the character of energy metabolism, is an indirect proof of the role of the latter in the realisation of the anticytotoxic, and thereby antifibrogenic, effect of glutamate.

Animals↗

Response of a phagocyte cell system to products of macrophage breakdown as a probable mechanism of alveolar phagocytosis adaptation to deposition of particles of different cytotoxicity.

The adaptation of the alveolar phagocytosis response to the quantitative and qualitative features of dust deposited during inhalation consists not only in enhanced recruitment of alveolar macrophages (AM), but also in adding a more or less pronounced neutrophil leukocyte (NL) recruitment as an auxiliary participant of particle clearance. The NL contribution to clearance is especially typical for response to cytotoxic particles (quartz, in particular). An important feature of the adaptation considered is the limitation of the number of AM and NL recruited when an efficient clearance can be achieved by a lesser number of cells due to increased AM reistance to the damaging actin of phagocytized particles. The main mechanism providing the adequacy of the alveolar phagocytosis response is its self-regulation thrugh the products of macrophage breakdown (PMB). In a series of experiments with intraperitoneal and intratracheal injections of syngenetic PMB into rats and mice, it was shown that these products stimulate respiration and migration of phagocytic cells, their dose-dependent attraction to the site of PMB formation with the predominant NL contribution, increasing with the increase of amount of PMB, the AM and NL precursor cells recruitment from reserve pools, and the replenishment of these reserves in the process of hemopoiesis. At least some of the above effects are connected with the action of the lipid components of PMB. The action of specialized regulative systems of the organism can modify the response to PMB, judging by the results obtained by hydrocortisone injection. Autocontrol of alveolar phagocytosis requires great care in attempts at artificial stimulation of this process, as an excessive cell recruitment may promote the retention of particles in lungs.

Air Pollutants, Occupational↗

Non-fibrous mineral dusts and malignant tumors: an epidemiological study of mortality.

The connection between enhanced oncological risk and the exposure to non-fibrous mineral dusts receives a contradictory but mostly negative estimation in the literature. The present authors estimated the death rate by relating the number of deaths from cancer, registered at different companies during a 21 to 27-year span, to the number of man-years of work for all employees during the same period. The death rates, calculated as above, were compared with the age standardized analogous death rates of the control population. The ratio of these indices, which statistically significantly exceeded 1.0, was taken as evidence of risk connected with exposure to the industrial environment. Frequency of registration of deaths from malignant tumors among other causes of death of silicotic patients was also studied. The results are in favor of accepting talc dust (even that not containing fibrous minerals) as a carcinogen, and silica containing dust only as a cocarcinogenic agent. The percent silica content in dust either plays no role at all, or plays a much lesser role than the total dust load. Tbc as the competing cause of death in silicotic patients, in grave forms of the disease, eliminates the susceptibility of patients to death from cancer.

Dust↗

The principles of predicting the individual risk of silicosis and silicotuberculosis.

A series of investigations conducted in different "silicosis-risk" industries using a methodology based on the mathematical theory of pattern recognition has shown that in the given conditions of dust exposure, the probability of contracting pneumoconiosis depends for each individual on a complex influence of many factors, both environmental and intrinsic for the individual. Genetic predisposition was one of the most important factors and while the direction in which a factor influences predisposition was the same in every industry, its relative contribution to predisposition to simple silicosis was different in the studied working populations. So a reliable prediction of the high probability of this form of pneumoconiosis on the basis of such a multifactorial analysis is possible only with respect to specific conditions of a particular industry. The complex of factors determining predisposition to silicotuberculosis is more general: this complex comprises both factors influencing susceptibility to silica dust and specially those influencing susceptibility to tuberculosis. Despite the low prevalence of genetic resistance to pneumoconiosis in working populations, the risk of contracting the disease in modern industrial conditions of relatively low dust exposure is high only for a proportion of workers for whom the genotype of predisposition to silicosis or to silicotuberculosis coincides with a most unfavourable combination of non-genetic factors enhancing this predisposition. In the opinion of the authors, the task of screening off those applicants for a "silicosis-risk" employment for whom the risk may be estimated as high on the basis of the developed methodology, is quite feasible.

Discriminant Analysis↗