Cadmium, zinc, and copper from placental tissue and blood samples at the first trimester (n = 64) and at term (n = 152) were analyzed; the welfare of newborns and placental 7-ethoxycoumarin O-deethylase (ECOD) activities in vitro were determined. The study material was collected from Finland, Estonia, and Russia. The results demonstrate that Cd starts to accumulate in the placenta during the first trimester and that Zn and Cu contents were significantly higher at the first trimester than at term. Among nonsmokers a negative correlation was found between placental Cu content and birth weight of neonates. Among smokers a positive correlation between placental Zn content and birth weight and ECOD activity was found. The birth weights correlated inversely with the length of time the mothers smoked. The highest Cd concentrations were detected in the samples collected from St. Petersburg. The data demonstrate an inverse accumulation of Zn and Cd throughout the pregnancy in the placenta and maternal blood samples. Zn may act as a positive marker or even an enzymatic enhancement for the human placental vital functions. Smoking, parity, age, and especially the place of residence affect the Cd, Zn, and Cu contents and ratios in placenta and mother's blood.
During the past four decades, there has been an increase in the incidence rate of male reproductive disorders in some, but not all, Western countries. The observed increase in the prevalence of male reproductive disorders is suspected to be ascribable to environmental factors as the increase has been too rapid to be explained by genetics alone. To study the association between complex chemical exposures of humans and congenital cryptorchidism, the most common malformation of the male genitalia, we measured 121 environmental chemicals with suspected or known endocrine disrupting properties in 130 breast milk samples from Danish and Finnish mothers. Half the newborns were healthy controls, whereas the other half was boys with congenital cryptorchidism. The measured chemicals included polychlorinated biphenyls (PCBs), polybrominated diphenyl-ethers, dioxins (OCDD/PCDFs), phthalates, polybrominated biphenyls and organochlorine pesticides. Computational analysis of the data was performed using logistic regression and three multivariate machine learning classifiers. Furthermore, we performed systems biology analysis to explore the chemical influence on a molecular level. After correction for multiple testing, exposure to nine chemicals was significantly different between the cases and controls in the Danish cohort, but not in the Finnish cohort. The multivariate analysis indicated that Danish samples exhibited a stronger correlation between chemical exposure patterns in breast milk and cryptorchidism than Finnish samples. Moreover, PCBs were indicated as having a protective effect within the Danish cohort, which was supported by molecular data recovered through systems biology. Our results lend further support to the hypothesis that the mixture of environmental chemicals may contribute to observed adverse trends in male reproductive health.
In animal studies, exposure to dioxins has been associated with disrupted development of the male reproductive system, including testicular maldescent. Some polychlorinated biphenyls (PCBs) have also dioxin-like effects. In addition, one previous case-control study has reported an association between congenital cryptorchidism and colostrum PCB levels. We performed a case-control study to evaluate whether congenital cryptorchidism in boys was associated with increased levels of dioxins or PCBs in placenta reflecting foetal exposure. In addition, associations between placenta levels of these chemicals and reproductive hormone levels in boys at 3 months were studied. Placentas were collected in a Danish-Finnish joint prospective cohort study on cryptorchidism (1997-2001). The boys were examined for cryptorchidism at birth and at 3 months. Altogether, 280 placentas [112 Finnish (56 cases, 56 controls) and 168 Danish (39 cases, 129 controls)] were analysed for 17 toxic polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and 37 PCBs (including 12 dioxin-like PCBs). Infant serum samples taken at 3 months were analysed for reproductive hormones. No significant differences between cases and controls were observed in either country in dioxin WHO-TEq levels (median 9.78 vs. 8.47 pg/g fat, respectively, in Finland, and 11.75 vs. 10.88 pg/g fat in Denmark) or PCB WHO-TEq levels (median 2.12 vs. 2.15 pg/g fat in Finland, 2.34 vs. 2.10 pg/g fat in Denmark) or total-TEq levels (median 11.66 vs. 10.58 pg/g fat in Finland, 13.94 vs. 13.00 pg/g fat in Denmark). Placenta WHO-TEq levels of dioxins were not associated with infant reproductive hormone levels at 3 months. In Finland, PCB WHO-TEq levels in placenta associated positively with infant LH levels. WHO-TEq levels of dioxins and PCBs and total-TEq levels were higher in Danish than Finnish samples. In conclusion, no association between placenta levels of dioxins or PCBs and congenital cryptorchidism was found. Significant country differences in chemical levels were observed.
Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) were analyzed in 167 random human milk samples from urban and rural areas in Finland. Dietary habits and background information on each mother and child were gathered by questionnaire. Body mass indexes (BMI) before pregnancy and delivery in the rural area were 5-10% higher than in the urban area, but fat content of mother's milk was about 10% higher in the urban area. The mean weights of children (+/- standard deviation) were similar in the rural and urban areas among primiparae, 3,500 +/- 597 g and 3,505 +/- 454 g, respectively, although dioxin international toxic equivalents (I-TEQs) were significantly higher in the urban area. The mother's level of education did not affect the weight of the child, but concentrations of PCDDs/PCDFs (I-TEQ, 2,3,4,7,8-Cl5 dibenzofuran,1,2, 3,7,8-Cl5 dibenzodioxin) and PCBs [sum of PCBs (sumPCB), PCB-TEQ, and most PCB congeners] increased with advanced education. This is considered to be due to differences in the mother's consumption of fish. The birth weight, especially of boys, slightly decreased with increasing concentrations of I-TEQ, 2,3,4,7,8-Cl5 dibenzofuran, 1,2,3, 7,8-Cl5 dibenzodioxin, and 2,3,7,8-Cl4 dibenzodioxin; however, when the analysis was restricted to primiparae, there was no statistically significant correlation between birth weight and the concentrations of PCDDs/PCDFs. No correlation was found between the weight of the child and PCBs, PCB-TEQs, or individual PCB congeners in the whole material or among primiparae, or among boys or girls. The concentrations of PCDDs/PCDFs and PCBs inhuman milk were modeled for primiparae by weighing fish consumption, age of mother, milk fat content, and BMI before pregnancy. The linear regression resulted in values of R = 0.67 and 0.30 for the modeled dioxin I-TEQs in the urban and rural areas, respectively, and the corresponding values for sumPCBs of R = 0.60 and 0.11. The increase of PCDD/PCDF body burden was calculated to be on average 0.58 pg I-TEQ/g milk fat/year in the urban area and 0.39 pg I-TEQ/g milk fat/year in the rural area.
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The aim of the study was to create a rapid method for estimating cancer risk in areas defined by exact map coordinates and to test it using as an example incidence of leukemia near an oil refinery. The method can be used to investigate possible local excesses of cancer of suspected environmental origin in Finland. Map coordinates with an accuracy of 10 m for the place of residence of each Finn were obtained from national registers. Based on this data set, numbers of inhabitants and expected number of cancer cases by sex and age in squares of 500 x 500 m were calculated for all of Finland. Observed number of cancer cases in each square were obtained based on record linkage of the map coordinates with the Finnish Cancer Registry. The ratio of observed and expected number of cancer cases was modeled using Poisson regression. The example analysis included all 23 leukemia and 531 any cancer cases registered in an area around an oil refinery in 1983-1986. There was no significant association between distance from the oil refinery and risk of leukemia or any cancer. The method proved fast and efficient in comparing areal differences in cancer incidence in Finland. In cases of environmental concern, geographical analyses of existing registers is a rapid method to perform first analyses when evaluating the need for further studies.
Sodium selenate has been supplemented to all agricultural fertilizers used in Finland since 1984. We followed the changes in selenium, cadmium, zinc and copper content in Finnish human milk between the years 1987 and 1993-1995. A total of 257 milk samples was collected, four weeks after delivery, in two areas: In Helsinki, an urban area, and in Kuopio, a rural area, where elevated copper concentrations have been found in the bedrock. Direct atomic absorption spectrophotometric methods without digestion were used for the analyses. The dependence of trace element content on study time, living area, smoking habits, fish eating frequency, and parity of mothers was studied by analysis of covariance. Inter-element correlations and correlations with mothers' age and fat content in milk were studied by partial correlation. Significant increases were observed in mean selenium (16.4 microg/l and 18.9 microg/l, p
The authors determined that demarcated hypomineralizations of developing teeth are a biological indicator of an early dioxin exposure in a healthy population of children. In the current study, the authors examined the prevalences of the demarcated hypomineralization lesions of teeth in 2 Finnish towns by the Kymijoki River--a river that is severely contaminated by dioxins and furans. The 4,120 permanent first molars of 1,030 children were studied. The prevailing levels of dioxins and furans in human milk were measured. The prevalences of the defects in children in Kotka and Anjalankoski were 14.2% and 5.6%, respectively, and the corresponding dioxins and furans in human milk were 13.4 pg/gm fat and 10.9 pg/gm fat (International Toxic Equivalents). In Anjalankoski, the duration of total breast-feeding was associated with the prevalence of the defects. Compared with the figures reported earlier in Finland, neither the prevalence of dental lesions nor the levels of dioxins and furans in human milk were increased in riverside residents.
Samples of cow milk, pork, beef eggs, rainbow trout, flours and vegetables were analysed for 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) and 36 polychlorinated biphenyls (PCB). Daily dietary intake of PCDD/Fs as toxic equivalent (I-TEq) and PCBs (PCB-TEq) was assessed using food consumption data from a 24-h dietary recall study for 2862 Finnish adults. The calculated intake of PCDD/F was 46 pg I-TEq day(-1). The current level was about half of the earlier estimation of intake in Finland made in 1992. The assessed PCB intake was 53 pg PCB-TEq day(-1). Thus, the total intake of PCDD/Fs and PCBs was 100 pg TEqday(-1) (1.3pg TEqkg(-1) b.w. day(-1)), which is within the range of tolerable daily intake (TDI) proposed by the WHO (1-4pg TEqkg(-1) b.w. day(-1)).
Chlorination of water rich in organic material is known to produce a complex mixture of organochlorine compounds, including mutagenic and carcinogenic substances. A historical cohort study of 621,431 persons living in 56 towns in Finland was conducted in order to assess the relation between historical exposure to drinking water mutagenicity and cancer. Exposure to quantity of mutagenicity was calculated on the basis of historical information of raw water quality and water treatment practices using an empirical equation relating mutagenicity and raw water pH, KMnO4 value and chlorine dose. Cancer cases were derived from the population-based Finnish Cancer Registry and follow-up time in the study started in 1970. Age, gender, time period, social class, and urban residence were taken into account in Poisson regression analysis of the observed numbers of cases using expected numbers of cases standardized for age and gender as a basis. Excess risks were calculated using a continuous variable for mutagenicity for 3,000 net rev/l exposure representing an average exposure in a town using chlorinated surface water. After adjustment for confounding, a statistically significant excess risk was observed for women in cancers of the bladder (relative risk [RR] = 1.48, 95 percent confidence interval [CI] = 1.01-2.18), rectum (RR = 1.38, CI = 1.03-1.85), esophagus (RR = 1.90, CI = 1.02-3.52), and breast (RR = 1.11, CI = 1.01-1.22). These results support the magnitude of excess risks for rectal and bladder cancers found in earlier epidemiologic studies on chlorination by-products and give additional information on exposure-response concerning the mutagenic compounds. Nevertheless, due to the public health importance of water chlorination, uncertainty related to the magnitude of observed risks, and the fact that excess risks were observed only for women, the results of the study should be interpreted with caution.
The purpose of this study was to investigate the relationship between exposure to mutagenic drinking water and cancers of the gastrointestinal and urinary tract.
Past exposure to drinking water mutagenicity was assessed in 56 Finnish municipalities for the years 1955 and 1970. The cases of bladder, kidney, stomach, colon, and rectum cancers were derived from two periods (1967 to 1976 and 1977 to 1986). Age, sex, social class, urban living, and time period were taken into account in the Poisson regression analysis.
Statistically significant exposure-response association was observed between exposure and incidence of bladder, kidney, and stomach cancers. In an ordinary municipality using chlorinated surface water, this exposure would indicate a relative risk of 1.2 for bladder cancer and of 1.2 to 1.4 for kidney cancer compared with municipalities where nonmutagenic drinking water was consumed.
The acidic mutagenic compounds present in drinking water may play a role in the etiology of kidney and bladder cancers, but, because the results are based on aggregate data, they should be interpreted with caution.
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