POPs and Human Health

B.A. Revich, Doctor of Sciences (Medicine), Professor,
the Centre of Demography and Human Ecology of the Institute of Economic Forecasts of the Russian Academy of Sciences
(abridged version)

In recent years, the role of environment as a major determining factor of quality of population health was broadly recognised. The European Charter on Health and Environment (1998) formulates principles of state policies in the sphere of health and environment, as a further development of "Health for All" strategy of the World Health Organisation. The Charter recognises rights of every individual for healthy environment, promoting maximal quality of health and well-being and emphasises mutual responsibilities of citizens, governmental officials and industries in the sphere of environmental protection. The Charter states, that any activity should be based on solid scientific facts, therefore accurate data pertaining to nature and intensity of health impacts of dioxins are of major importance. Accounting for particular toxicological properties of dioxins, data on dioxins' impact on human health are discussed with respect to functions and systems of a human body, individual diseases and integral health deviations of workers exposed.

1. Health of dioxin-exposed workers.

Workers of chemical facilities were under the most intensive dioxin exposure in workplace environments. Naturally, these dioxin-exposed population groups demonstrate the most clear consequences of contacts with these toxicants. They demonstrate higher incidence of chloracne, in some cases they were found to suffer depressions, alterations of lipid and immune status, functional disorders of central/peripheral nervous systems, reduction of libido. The majority of these health disorders were found among workers, who had contacts with dioxins for more than 25 years, however, some symptoms were observed for young workers as well.

In Russia, high levels of workplace contamination are assumed to exist in the period of production of chlorinated pesticides at facilities of "Khimprom" Production Association in Ufa, Chapaievsk, Dzerzhinsk, Sumgait, Vurnary, Volgograd, Novocheboksarsk, Slavgorod, Moscow, Stchelkovo; at PCB-production facilities in Dzerzhinsk and Novomoskovsk; at chlorine-producing facilities in Usolie-Sibirkoie, Sayansk, Zima, and Kemerovo. However, the most detailed studies of health of workers of dioxin-hazardous facilities were carried out only on Ufa.

Workers of herbicide facility of Ufa chemical plant of "Khimprom" Production Association. Production of 2,4,5-T herbicide at the facility was launched in 1965. Medical examination of workers in two subsequent years revealed a specific skin disease - chloracne. 85 workers of the age group from 20 to 25 years, employed at 2,4,5-T production facility had been diagnosed to suffer well-developed chloracne-type skin diseases, caused by relatively short-time contacts with the dioxin. Moreover, the majority of these workers demonstrated these symptoms after contacts with the substance from 2 months to 2 years. The majority of individuals with these skin diseases were represented by reactor operators, fitters and laboratory personnel (i.e. the ones, who had the most frequent contacts with products). Occupational nature of the disease was confirmed by development of similar skin disorders among the majority of workers of a single facility, who performed the same production-related functions. The most early and severe skin pathologies were observed in the case of workers, who contacted with 2,4,5-trichlorophenole, 2,4,5-trichlorophenoxyacetic acid and the acid's ester, and workers who served stations, operating at high temperatures and pressures (promoting, thus intensive gaseous and vapour emissions).

According to retrospective analysis, the examined workers' complains included: headache, drowsiness, irritability, asthenia, pains in the region of the heart. In the course of the medical examination, the following neurological symptoms were revealed: activation of tendon reflexes, changes of skin pigmentation and strongly marked dermographism, hydrosis, reduced sensitivity of distal limb sections. Instrumental medical examination methods allowed to identify capillary deformations and irregular blood flows, thermoassimmetry and elevated capillary permeability among 85% of the workers examined.

Neurological deviations were diagnosed for almost a half of the workers examined. Typical specific deviations included vegetative vascular disorders (mainly of symphato-adrenaline nature), which resulted in rise of arterial pressure within "interjacent" zone (both for diastolic and systolic pressure).

More than a half of the examined were diagnosed to have gastro-intestine syndrome and moderate signs of reduction of liver antitoxic functions (based on results of santonine and salicylic tests). 64% of the worker were diagnosed to suffer gastritis and duodenitis, 57% of them were diagnosed to suffer stomach ulcers, and 45% of them were diagnosed to suffer cholecyctitis. Some patients were often found to suffer multiple pathologies of several gastro-intestinal organs.

Analysing results of laboratory tests, it is necessary to note, that 44% of persons with average age of 23 years were diagnosed to have statistically significant deviations of cholesterol levels in blood serum comparatively to normal parameters (hypercholesteremia). In peripheral blood of men, at the background of absence of leukopenia, the trend to cytopenia reactions was observed, mainly for band (30.1%) and segmented neutrophils (56.6%), monocytes (30.1%) and lymphocytes (37.3%). In the case of 28.9% of the examined, eosinephilia was observed with more that 5% deviations from lower margins of the normal state.

Examinations of kidneys, endocrine system and other organs did not reveal other pathologies. Notwithstanding rather diverse clinical parameters of the examined, the list of the most common disorders incorporates: chloracne, skin pigmentation, psychoneurological deviations, reduction of libido, lymphadenectasia, lipidosis, eye disorders.

Workers of Chapaievsk Fertiliser Plant. In early 1960-s, hexachlorocyclohexane production facility was launched at the plant. The facility's products included trichlorobenzene, hexachlorobenzene and sodium pentachlorophelolate. The production processes generated TCDD. In samples of the facility indoor air, concentrations of many hazardous substances exceeded relevant MACs, including dichloroethane. Dichloroethane air levels varied within the range from 9.1mg/m3 to 155 mg/m3, in the majority of cases these levels exceeded permitted air concentrations in 2.2 - 15.5 times (MAC for dichloroethane = 10mg/m3). Air levels of trichlorobenzene, sodium pentaphemolate and hexachlorobenzene also exceeded relevant MACs.

The hexachlorocyclohexane production facility was closed in 1985, but according to chemical technology experts, at some conditions, dioxins might be generated even now (as by products of production of sodium hypochloride or as a result of waste incineration on-site).

In 1984, 5 thousand workers were employed at the plant, including 2.3 thousand women. Later on, the plant workforce was reduced to 2.0 thousand workers, including 900 women. Chloracne is a commonly observed effect of chlorinated organic substances on health of the workers.

In recent years, new data were published on state of immune and macrophage-neutrophil systems of 126 workers of the chlorinated hydrocarbons production facility. Examination of the workers revealed the trend to development of a secondary immune deficiency state: small reduction of CD3+-limphocytes levels, reduction of immunoglobulin fractions. These changes were more marked among workers, who were under more prolonged dioxin exposure. In the course of analysis of unspecific protection mechanisms of a human body (the ones, based on reticoloendothelial system), increase of fibronectine levels was observed (the main factor, determining selectivity of phagocytic reactions).

The above results of medical examination of worker of facilities, producing chlorinated pesticides (Ufa and Chapaievsk) correspond to data of foreign researchers, who also found chloracne, liver dysfunctions, porphirine metabolism disorders, peripheral neuropathy among workers several years after termination of their dioxin exposure.

2. Levels of dioxins in breast milk and blood. Determination of concentration of dioxins in breast milk and blood is the direct indicator of their intake by a human body.

The highest levels of such toxic compounds as - 2,3,7,8-TetraCDD, 1,2,3,7,8-PentaCDD, 1,2,3,4,7,8-HexaCDD, and some octo-dioxins were found in breast milk of female residents of Chapaievsk and Usolie-Sibirskoie (Irkutsk Oblast).

Blood is another biological substrate, reflecting dioxin exposure. Comparative analysis of dioxin levels in blood of workers of Srednevolzhsly Chemical Plant and workers of other dioxin-risky facilities in other countries, suggests that the most high blood levels of these toxic substances are observed in Chapaievsk. The highest dioxin levels were observed in the case of those workers of "Khimprom" plant of Chapaievsk, who worked at 2,4,5-T production facility.

In Chapaievsk, in 1997, dioxin levels were measured in blood of female residents of two residential districts located nearby the chemical plant (at distances of 1 - 3km) and at a higher distances (5 - 8km). In the case of women, who lived nearby the chemical plant, dioxin accumulation was found to be substantially higher (in 3 times). In 1998, another study was carried out, in that case dioxin blood levels were measured for 24 residents of the city. Measurements of dioxin levels were made in the leading World centre of dioxin analysis - in the US Disease Control Centre. These studies were sponsored by a grant of the International Cancer Research Agency (Lyons, France), project manager - Prof. Paolo Toniolo. Comparative analysis of dioxin levels in blood of Chapaievsk residents in 1997 and 1998 allows to conclude, that comparatively to residents of other cities of Russia and some other countries, blood samples of female residents of areas nearby the chemical facility of Chapaievsk contain high levels of dioxins and furans, moreover, within the city itself there are sharp differences of dioxin levels between residents of areas, located nearby the facility and the ones, living at higher distances.

3. Impacts of dioxins on reproductive health and status of the endocrine system. Dioxins have some estrogen activity, however the precise mechanism of the effect is still unknown. Compounds, containing chlorine atoms in ortho positions (or at least some of them) are very similar to estrogen receptors (due to stereospecific and conformational properties, associated with substitution of hydrogen atoms by chlorine atoms). Dioxins may induce multipurpose oxidases in liver and placenta, which may affect metabolism and functioning of estrogens at pregnancy and in other periods of life. Animal tests suggest that dioxins produce different toxic effects for reproductive system, the most likely, these effects are associated with disruption of endocrine functions.

In environmental epidemioiologic studies, pertaining to health impacts of environmental media, contaminated by dioxins and PCBs, these substances were found to act as risk factors, facilitating infertility, spontaneous abortions, stillbirth, birth defects and other neonatal pathologies.

Sperm quality and male hormonal status. In recent years, numerous medical publications were dedicated to discussion of issues, associated with reduction of quantity and quality of sperm of male populations of several European countries (France - Paris, Belgium, Scotland) and US, and some of them claimed contamination of the environment by chlorinated organic substances as a relevant risk factor. Some specialists rather sceptically assess conclusions on reduction of sperm quality and quantity in 20 recent years, and argue that there are no reliable data on healthy men, that databases of sperm analysis incorporate only men with different health disorders. However, there are convincing data on statistically significant reduction of sperm counts and alteration of morphologic forms of spermatozoa in the case of workers of formerly operational facility, that produced chlorinated pesticides in Chapaievsk.

Reduction of spermatozoa mobility may result in higher infertility incidence.

Infertility. This pathology, associated with environmental contamination, was studied in Chapaievsk (dioxin contamination) and Serpukhov (PCB contamination). In Chapaievsk, higher infertility incidence comparatively to the control group was found to be statistically significant for both men and women. Duration of stay in Chapaievsk in excess of 20 years increases risks of infertility among women up to 3.1 times; while the fact of employment at Srednevolzsky Chemical Plant (the major source of dioxin emissions in the city) increases these risks in 2.1 - 11.5 times. In the case of male residents of Chapaievsk, incidence of idiopathic infertility forms, associated with reduced sperm quality, was found to be statistically significantly higher, comparatively to men of another city of Samara Oblast (Kinel). The latter city was not polluted by organochlorine substances, therefore, the effect may be attributed to impacts of chlorinated organic compounds. Clinical examination of infertile married couples also confirmed, that comparatively to Kinel residents, in Chapaievsk, incidence of the following endocrine status related risk factors was higher: lutein phase deficiencies and endometriosis (for women); idiopathic infertility forms, associated with reduced sperm counts (for men). These results correspond to our understanding of disruptions of reproductive functions of men and women. Studies of reproductive functions of US veterans of the Vietnam war allowed to reveal statistically significant reduction of sperm counts and lower density of normal sperm comparatively to the unexposed control group.

Another "case - control" epidemiological study was carried out in Serpukhov. In Serpukhov, PCB contamination was caused by production operations of the capacitor-producing plant. In the course of selecting women for the study, the researchers focused on their gynaecologic case histories, because earlier experienced inflammatory genital disorders belong to the main infertility-causing factors. The main causes of primary female infertility include genital infantilism and associated ovary dysfunctions, followed by inflammations of female reproductive organs. Generally, the share of endocrine forms of female infertility reaches almost 30 - 42% of all female infertility causes. In 44.4% of families, infertility is caused by diseases of female reproductive system, in 19.3% of families infertility is caused by diseases of male reproductive system, while in 34.2% of cases pathologies of the both spouses are observed (mainly inflammatory diseases of internal reproductive organs).

In the case of infertile women, PCB blood levels were found to be statistically significantly higher, comparatively to the control group. These data confirm, that infertility risks increase in line with growth of PCB levels in women's blood.

If exposed women become pregnant, there is high probability of pregnancy disorders (e.g. spontaneous abortions and gestation toxicosis).

Spontaneous abortions. Causal links between DDT blood levels and spontaneous abortions was identified as early as in 1970s. Higher risks of spontaneous abortions were registered also in families of US servicemen, who participated in the Vietnam war and among residents of Sevezo area. In the latter case, incidence of spontaneous abortions increased after the accident, in 1976 the rate of spontaneous abortions in the area reached 21% of all pregnancies, comparatively to 14% (р < 0.05) in other regions of Italy. Similar situation is observed in Russia, in Chapaievsk and Serpukhov cities. In the case of Chapaievsk women, substantial pregnancy dysfunctions were observed. Comparatively to other cities of Samara Oblast, incidence of spontaneous abortions in Chapaievsk is substantially higher. In 7 recent years, average incidence of spontaneous abortions in Chapaievsk reached 24.4% (comparatively to 15.2% in Samara, 10.6% in Tolliatty, 15.6% in Syzran, 16.9% in Novokuibyshevsk and 11.3% in small towns).

Incidence of new-born children with birth weight lower than 2500g. The incidence of the underweight new-born is used as an indicator of health impacts of environmental contamination. In Chapaievsk, the incidence reaches 7.14 ± 0/3%, while Russian national averages vary within the range between 5.7% and 6.2%, and incidence of the underweight new-born in the majority of urban settlements of Samara Oblast falls within the above range. It is necessary to note, that similar underweight incidence parameters (7.1%) are observed in Serpukhov as well. Correlation between maternal blood levels of dioxins and PCBs and disruptions of foetal growth and development (underweight and premature birth) was also demonstrated (see Fein et al.,1984). Average weight of new-born children of women, who had workplace contacts with PCBs, was lower (by 60g), comparatively to children of female workers of the same facility, who did not contacted these substances. Similar reduction of weight of the new-born (the phenomenon is more common for boys, than for girls - relevant chances reach 2.1 to 1.1, respectively) was observed among fishermen's families at the Baltic coast of Sweden. The phenomenon is also attributed to excessive intake of chlorinated organic compounds. In Finland, children are also underweight, mothers of the country were found to have higher levels of dioxins and furans in breast milk.

In recent years, gender balance ratio of the new-born was increasingly used as an indicator of environmental risks (e.g. growing shares of girls among the new-born, that were registered at dioxin-contaminated areas of Sevezo). To some extent, the phenomenon is visible in Chapaievsk, where boys/girls ratio reached 1.03 in 16 recent years.

Birth defects and multiple congenital anomalies. The most reliable evidence of dioxin-induced birth defects was observed in Vietnam, at territories, affected by "Orange Reagent", where incidence of these pathologies was found to increase in 2 - 3 times.

In Russia, incidence of birth defects was studied in several cities, experiencing risks of dioxin and PCB contamination, however, results of these studies are hardly compatible, because, at the moment of implementation, no uniform methodologies and standard lists of birth defects were available.

Survey of 369 children of the age group between 3 and 7 years, who attended Chapaievsk kindergartens, revealed that the number of congenital morphogenetic developmental variations per child varies within the range from 0 to 10. The most often, the following symptoms were diagnosed: epicanthus, clinodactyly, wide first fingers etc. Average numbers of congenital variations per child were found to reach 4.5 for boys and 4.4 for girls - these figures exceed relevant figures for other environmentally unhealthy cities. Average incidence of congenital development variations (at 95% significance levels) reach 3.4 per child for Moscow girls and 3.44 for Moscow girls; relevant figures for Novomoskovsk reach 2.98 and 2.82, respectively, in Yaroslavl - 2.63 and 2.63, in Plavsk - 2.0 and 3.79, in Novobyzkovo - 1.92 and 1.76 (N.Subbotina, 1994). Results of statistical analysis of impacts of such risk factors as occupational contacts of children's parents with adverse workplace factors and duration of their stay in Chapaievsk (c 2 least square analysis ) reveal that only period of stay of the both parents in Chapaievsk in excess of 15 years is a statistically significant factor of growth of incidence of congenital development variations. Therefore, the results confirm higher incidence of congenital development variations among examined children in Chapaievsk and significance of duration of stay of their parents in the city as a risk factor.

Sexual development of boys. Studies of health impacts of dioxins are increasingly focused on endocrine system dysfunctions. In some cases, dioxins act as hormones, in other cases these substances disrupt natural endocrine processes in a human body. Chronic dioxin exposure may result in diverse endocrine diseases and disorders, associated with hormonal changes. Dioxin exposure was found to correlate with deviations of sexual development, hypogonadism, cryptorchism and hypospadias of boys; breast cancer and endometriosis of women, etc. Health impact of dioxins on population in general (without gender-specific differentiation) may result in higher incidence of diabetes, adiposity and thyroid gland pathologies.

In the course of studies in Chapaievsk, incidence of the following types of boys' endocrine pathologies was studied: cryptorchism, hypogonadism, phimosis. Dioxins, entering a boy's body (in prenatal and postnatal periods), may reduce testosterone levels, causing deviations in testicles' development and cryptorchism (absence of one or two testicles in the scrotum).

The study of sexual development of 2.5 thousand boys of the age group between 11 and 16 years in Chapaievsk revealed high incidence of pathologies of sexual development and minor development disorders (e.g. cryptorchism and hypospadias). Natural processes of urethra formation and descendence of testicles into the scrotum in perinatal period are androgen-dependent and dioxins may severely disrupt these processes. Cryptorchism, hypospadias and phimosis were registered for 1.7%, 0.7% and 7.8% of boys of the age group, respectively. In the process of antenatal development, 19.4% of boys had different stages of varicocele, 8.7% of adolescents over 14 were diagnosed to have retardation of sexual development (diagnosed by testicles' volume and pubarche stages). In the case of Chapaievsk adolescents, the study also revealed decrease of testosterone blood levels, accompanied by elevated levels of lutropine (LH) and follitropine (FSH).

The hormone deviations, diagnosed for adolescents, to some extent might be identified for adult men as well. These deviations are revealed by reliable increase of FSH levels (the hormone regulates functions of seminiferous tubules, stimulating development of spermatozoa, so the increase of FSH levels manifests a marked disruption of spermatogenesis).

The above hormonal deviations correlate with results of medical examinations of workers, exposed to PCBs. Increase of dioxin levels in blood was found to correlate reliably with reduction of testosterone and FSH blood levels.

3. Malignant tumours. The International Agency for Research on Cancer incorporated dioxins into its list of carcinogen substances, facilitating human cancer. Organochlorine compounds either disrupt metabolism of human sex hormones or act as hormone-imitators. These effects may facilitate development of malignant tumours of some localisations.

In Chapaievsk, cancer morbidity levels among male residents in 1998 exceeded Russian national averages in 1.3 times and Samara Oblast averages in 1.2 times (in the case of Chapaievsk women, these excess factors reached 1.5 and 1.4 respectively). In the case of men, the most high cancer incidence rates was observed for malignant tumours of buccal cavity, larynx, lungs, liver and bladder. In the case of women, the most high cancer incidence rates were observed for malignant tumours of stomach, skin (including black cancer), mammary gland, cervix uteri and hemoblastosis.

The share of malignant tumours among the main causes of death of Chapaievsk residents reaches 17.5%. Every year, malignant tumours cause death of more that 200 people (or 4 - 5 death cases weekly). In the case of men, cancer-related mortality levels were found to be reliably higher comparatively to Russian averages for lung cancer (139 cases per 100 thousand residents in Chapaievsk and 87 cases in Russia) and larynx cancer (14 and 10 cases, respectively), while in the case of women these levels were higher for breast cancer (27 and 22 cases ) hemoblastosis (13 and 7 cases, respectively).

Age profiles of lung cancer morbidity for men of Chapaievsk, Russia and Samara Oblast demonstrate that morbidity parameters are substantially higher for all age groups. A man over 45, who lives in Chapaievsk has higher risk of lung cancer.

We analysed expected and actual incidence of cancer cases and cancer-induced deaths in the period from 1995 to 1998, relative death risks and their confidence margins for several different localisation (using indirect standardisation technique). We used data for Samara Oblast as a baseline. Actual incidence levels of malignant tumours of many localisations was found to be higher than expected ones.

In the case of men, the main localisations, associated with reliably higher cancer risks (comparatively to Samara Oblast) were represented by tumours of liver and bile ducts (excess in 4.3 times), bladder (excess in 3.6 times), lungs (excess in 3.3 times), prostate gland (excess in 2.1), stomach (excess in 1.9 times) and rectum (excess in 1.6 times). Overall, actual average cancer morbidity for all localisations was found to be higher than expected in 1.9 times.

Actual cancer-induced mortality levels for male residents of Chapaievsk were found to exceed expected mortality levels in 1.8 times. The highest cancer-induced death risks were observed for lung cancer (excess in 3.1 times), tumours of urinary system (excess in 2.6 times), larynx cancer (excess in 2.3 times), stomach and intestine tumours (excess in 1.7 times). Besides that, higher cancer-induced death risks were observed for malignant tumours of bone and soft tissue. Naturally, among the men, who died from cancer, there were some individuals, who were exposed to carcinogenic factors of occupational nature. However, it is practically impossible to identify these cases in the course of retrospective analysis of official statistical data.

In the case of Chapaievsk women, we did not found so serious differences between expected and actual cancer mortality and morbidity levels, as in the case of Chapaievsk men. Some excessive morbidity was observed for breast cancer (actual morbidity is 1.9 times higher than expected one), tumours of cervix uteri (in 2.1 times) and ovaries (in 1.7 times). Actual levels of cancer-induced mortality were found to exceed expected ones for breast cancer (in 2.1 times) and malignant tumours of internal reproductive organs (in 1.9 times). For both men and women higher death risks, associated with malignant tumours of bone/soft tissues, were observed, but due to the small number of cases these higher risks are not statistically significant.

In recent years, intensive research works were initiated world-wide to assess impacts of organochlorine substances on development of breast cancer, but so far no there are no universally agreed views on the matter. Moreover, the fact of excretion of these substances with breast milk allows one to assume their direct impacts on cells and tubule tissues of the mammary gland. Numerous research publications on the matter emphasised the need to carry out detailed studies of correlation between adverse environmental factors (including quasi-estrogens) and development of breast cancer.

In the case of Chapaievsk, accounting for simultaneously observed higher mortality of women from breast cancer and unfavourable morbidity dynamics (as well as the trend of development of breast cancer in relatively young age groups - under 55), it is necessary both to study the problem more seriously and to implement special cancer-prevention actions. It is necessary to note, that the analysis of Chapaievsk workers under heavy occupational dioxin exposure revealed rather high shares of women among these workers - in the range from 30% to 35% (the phenomenon is not typical for other countries). Average duration of employment of these women at chemical facilities reaches 11.5 years.

Changes of different health parameters, observed for residents of Ufa, Chapaievsk and Serpukhov are rather typical for symptoms of adverse health impacts of dioxins and PCBs. Workers of chemical facilities of Ufa and Chapaievsk, who has occupational contacts with dioxin-like compounds, typically suffer chloracne, serious immune disorders and other adverse health impacts. Results of medical examination of workers, employed in production of chlorinated products, generally are in good similarity with findings of foreign researchers. Health changes, observed for the both groups, are very similar to findings of medical examination of Vietnamese, who were affected by "Orange Reagent" (V.Antoniuk, 1995; V.Rumak, 1993), and results of medical examination of dioxin-exposed workers of chemical facilities.

Findings of studies in Chapaievsk provided evidence in favour of the hypothesis that dioxins produce carcinogenic effects for all members of a population, not for dioxin-exposed workers only. There is an extremely limited body of evidence of carcinogenic impacts of dioxins on general population. So far, only some minor trend of growing cancer morbidity among victims of Sevezo accident has been reported (two decades after the accident). Relative risks of death from lung cancer for men were found to vary between 2.1 - 3.1 (these figures are similar to relative risks suggested by other authors - from 1.2 - 1.4 to 2.4). Growth of breast cancer morbidity in Chapaievsk in 10 - 15 recent years cannot be attributed to already known risk factors only (genetic predisposition, particular features of reproductive function, age, nutrition patterns, etc.) and improvement of diagnostics. Growing breast cancer morbidity on Chapaievsk might be attributed to use of contaminated local food. It is possible to suggest also, that insufficiently differentiated cells and tissue of the mammary gland, in the case of young nonparuous women are more sensitive to carcinogenic effects of quasi-estrogens. Population statistics data for Chapaievsk suggest once again, that it is necessary to carry out "case - control" cancer epidemiological studies or long-term prospective studies with coverage of several generations in order to reveal casual links between dioxin exposures in different periods of life and development of malignant tumours.

Results of studies in Chapaievsk, pertaining to reduction of male reproductive function, higher infertility incidence, spermatogenesis disruptions, observed among the city residents, are similar to results of medical examination of US veterans of the Vietnam war (reliable reduction of sperm counts and lower density of normal sperm). In the course of animal studies, dioxins were found to affect development of genitals, induce development defects of reproductive system and levels of sex hormones for male rats. Dioxins in environmental media impair sexual development of boys, cause higher incidence of some forms of birth defects and multiple congenital anomalies. In the case of adults, cytogenetical impairments are typical.

Besides that, dioxins create preconditions for inadequate responses of body systems to different environmental factors (including drug treatment) and reduce body resistance to viruses, bacteria, effects of alcohol and tobacco (IARC, 1997; Poznyakov et al., 1996; A.Alschbacher et al., 1986). Therefore, to some extent, higher TB mortality and morbidity levels in Chapaievsk and substance abuse levels might be also attributed to impacts of dioxins. According to (V.Antoniuk, 1995), dioxin-exposed patients experience premature accelerated ageing and suffer some diseases of "old age" in their younger years.

According to our expert assessments, at the territory of Russia, up to 1.5 - 2.0 million residents of cities, where facilities of former "Khimprom" were operational or are operational now, could be exposed to dioxins in the past or are being exposed now, therefore, it is necessary to carry out eco-epidemiological studies to assess health status of residents of these cities and to implement a comprehensive set of programs for environmental improvement, health treatment and disease prevention.