Country-specific chemical signatures of persistent environmental compounds in breast milk.

Recent reports have confirmed a worldwide increasing trend of testicular cancer incidence, and a conspicuously high prevalence of this disease and other male reproductive disorders, including cryptorchidism and hypospadias, in Denmark. In contrast, Finland, a similarly industrialized Nordic country, exhibits much lower incidences of these disorders. The reasons behind the observed trends are unexplained, but environmental endocrine disrupting chemicals (EDCs) that affect foetal testis development are probably involved. Levels of persistent chemicals in breast milk can be considered a proxy for exposure of the foetus to such agents. Therefore, we undertook a comprehensive ecological study of 121 EDCs, including the persistent compounds dioxins, polychlorinated biphenyls (PCBs), pesticides and flame retardants, and non-persistent phthalates, in 68 breast milk samples from Denmark and Finland to compare exposure of mothers to this environmental mixture of EDCs. Using sophisticated, bioinformatic tools in our analysis, we reveal, for the first time, distinct country-specific chemical signatures of EDCs with Danes having generally higher exposure than Finns to persistent bioaccumulative chemicals, whereas there was no country-specific pattern with regard to the non-persistent phthalates. Importantly, EDC levels, including some dioxins, PCBs and some pesticides (hexachlorobenzene and dieldrin) were significantly higher in Denmark than in Finland. As these classes of EDCs have been implicated in testicular cancer or in adversely affecting development of the foetal testis in humans and animals, our findings reinforce the view that environmental exposure to EDCs may explain some of the temporal and between-country differences in incidence of male reproductive disorders.

Molar-incisor-hypomineralisation and dioxins: new findings.

AIM: According to our earlier study, molar-incisor-hypomineralisation (MIH) was associated with the exposure of a child via mother's milk to polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) in a group of Finnish children born in 1987. Since the levels of PCDD/Fs and PCBs in mother's milk/placenta have remarkably decreased, it was important to find out if an association still exists. METHODS: The study group was composed of 167 mothers and their children. Placental samples from the mothers were collected in maternity hospitals in Helsinki and Oulu in 1995--1999 and concentrations of the 17 most toxic PCDD/PCDF and 36 PCB congeners were measured. After 7-10 years the children were examined for MIH and the mothers were interviewed on the duration of breast-feeding. RESULTS: MIH was found in 24 children (14.4%). The duration of breast-feeding ranged from 0 to 30 months (mean=7.2+/-4.7). WHOPCDD/FTEQ ranged from 2.5 to 39.1 pg/g fat (mean=13.7+/-6.8) and WHOPCBTEQ from 0.7 to 9.8 pg/g fat (mean=2.7+/-1.4). The mean sum of PCDD/Fs was 196+/-105 pg/g fat and that of PCBs was 57.2+/-28.1ng/g fat. The total exposure to PCDD/Fs, which was calculated from the placental concentration (used as a proxy for the milk concentration) and duration of breastfeeding, was not associated with the occurrence or severity of MIH. Neither was the total exposure to PCBs associated with the occurrence or severity of MIH. CONCLUSION: At prevailing levels, exposure of a child via placenta/mother's milk to PCDD/Fs and PCBs is not associated with MIH.

Polychlorinated biphenyls (PCBs) and hydroxy-PCBs in adipose tissue of women in Southeast Spain.

Polychlorinated biphenyls (PCBs) and hydroxylated PCBs (OH-PCBs) were investigated in human adipose tissue samples collected from 20 women undergoing surgery. Mean sum of PCB and sum of OH-PCB levels were 737ng/g of lipid and 8pg/g of lipid, respectively. Among PCBs, congeners 180, 153, 138 and 170 were the most frequent and abundant, and together constituted 72% of the total amount of PCBs in adipose tissue. The PCB congener pattern and the frequencies and concentrations of non-dioxin-like and non-hydroxylated congeners observed in adipose tissue were similar in distribution and order of magnitude to the profile previously published in Spain but lower than that found in other European countries. Among OH-PCB congeners studied, 4-OH-PCB 107/118 was found at the highest concentrations followed by 3'-OH-PCB 180 and 3-OH-PCB 138. To date, no information on levels of PCB metabolites in the Spanish population is available for comparison. These three predominant OH-PCBs contributed 97% of all OH-PCBs. Twelve dioxin-like PCBs contributed around 8% of the total PCB exposure, and all were present in all study subjects. Further research is required to determine trends in human exposure to PCBs and OH-PCBs and how existing banning measures affect exposure.

Selenium in pregnancy: is selenium an active defective ion against environmental chemical stress?

Transportation of selenium from mother to fetus and its possible effects on mother's zinc, copper, cadmium, and mercury levels were studied together during the first trimester and at term in 216 mothers. Mothers came from three geographical places with different selenium intakes. The role of selenium as a biomarker for the vital function was estimated by studying the associations between tissue or blood selenium content and placental cytochrome P450 enzyme activities and the newborn's birth weight. Regardless of the selenium intake of the mothers, higher concentrations were found in the cord blood than in mother's blood reflecting active transportation of selenium to the fetus. Active smoking was associated with higher placental selenium concentrations like it is associated with higher placental zinc concentrations. When the cadmium concentrations were high in placenta, as in smokers, the transfer of selenium from blood to placenta was increased, decreasing the selenium levels in blood. On the other hand, the high selenium concentrations in blood were connected to lower cadmium concentrations in placenta also in nonsmokers. Selenium had correlations with copper and zinc. ECOD activity in placental tissue, mercury in mothers' hair, mothers' age, and selenium concentrations in cord blood and placental selenium all seem to have connections with xenobiotic-metabolizing enzymes linked effects among mothers. These data suggest that selenium has an active role in the mother's defense systems against the toxicity of environmental pollutants and the constituents of cigarette smoke.

Gas chromatographic-mass spectrometric detection of 2- and 3-hydroxy fatty acids as methyl esters from soil, sediment and biofilm.

Hydroxy fatty acids (OH-FAs) can be used in the characterization of microbial communities, especially Gram-negative bacteria. We prepared methyl esters of 2- and 3-OH-FAs from the lipid extraction residue of soil, sediment, and biofilm samples without further purification or derivatization of hydroxyl groups. OH-FA methyl esters were analyzed using a gas chromatograph equipped with a mass selective detector (GC-MS). The ions followed in MS were m/z 103 for 3-OH-FAs and m/z 90 and M-59 for 2-OH-FAs. The rapid determination of 3- and 2-OH-FAs concomitantly with phospholipid fatty acids provided more detailed information on the microbial communities present in soil, sediment, and drinking water biofilm.

Determination of gallic acid in wood dust as an indicator of oak content.

A high-performance liquid chromatography (HPLC) method was developed for the detection of extracted gallic acid in wood dust. Gallic acid is a polyphenol present in carcinogenic oak wood dust, but not in beech, ash, pine or spruce dusts, as confirmed by HPLC analyses. The method involved the extraction of gallic acid from the oak dust, followed by liquid chromatographic analysis. The correlation coefficient for the share of oak dust vs. the gallic acid concentration of wood dust was 0.995. The method was tested with oak wood dust samples collected on polycarbonate membrane filters during an 8 h workshift in a floor board factory, where the dust content of the air samples was determined gravimetrically. The oak dust and the gallic acid concentrations varied from 0.2 to 13.8 mg m-3 and from 0.03 to 3.8 micrograms m-3, respectively. These parameters were linearly correlated with a correlation coefficient of 0.95. The airborne gallic acid determination is a useful technique to confirm occupational exposure to oak wood dust, a recognized human carcinogen.

Changes in selenium, zinc, copper and cadmium contents in human milk during the time when selenium has been supplemented to fertilizers in Finland.

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 < 0.001) and in fat contents (3.4% and 4.0%, p < 0.001), whereas significant decreases were seen in mean zinc (3.00 mg/l and 1.47 mg/l, p < 0.001), copper (0.52 mg/l and 0.43 mg/l, p < 0.001) and cadmium contents (0.095 microg/l and 0.062 microg/l, p < 0.01). In 1987, zinc had a positive correlation with copper and fat. Copper correlated inversely with the mothers' age. In 1993-1995, selenium correlated positively with copper, and zinc correlated inversely with mothers' age. Mothers living area had an effect on copper content in milk. Our results confirm that selenium supplementation to fertilizers in Finland has increased the selenium level in human maternal milk and most likely it also has an effect on the zinc and copper concentrations in maternal milk.

Use of olive oil for soil extraction and ultraviolet degradation of polychlorinated dibenzo-p-dioxins and dibenzofurans.

This paper represents a successful laboratory-scale photolysis of soil-bound tetra- to octachlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in olive oil. The irradiation source consisted of two blacklight lamps emitting light at a near-ultraviolet range. Samples used in the experiments included pure 1,2,3,4,6,7,8-heptachlorodibenzofuran, PCDD/F extract made of a wood preservative (chlorophenol product Ky 5), and soil that was highly contaminated with PCDD/Fs. Degradation of 1,2,3,4,6,7,8-heptachlorodibenzofuran dissolved in olive oil proceeded rapidlywith a first-order reaction half-life of 13 min. Irradiation of a soil sample resulted in an 84% reduction in PCDD/F toxicity equivalent (I-TEQ) in 17.5 h. A more complete degradation of soil-bound PCDD/Fs was achieved after extraction of the soil with olive oil. The oil was effective in solubilizing PCDD/Fs. After one extraction at room temperature, only 9% of I-TEQ remained in soil. Irradiation of the resulting extract reduced toxicity of the extract by 99%, and even the highly chlorinated congeners octachlorodibenzo-p-dioxin and octachlorodibenzofuran degraded easily (97 and 99% degradation, respectively). Photodegradation byproducts found included diphenyl ether and small amounts of dechlorination products, which were mainly nontoxic PCDD/Fs. Degradation was probably mediated by light absorption of unsaturated fatty acids and phenolic compounds in olive oil, leading to sensitized photolysis of PCDD/Fs.

Accumulation of cadmium, zinc, and copper in maternal blood and developmental placental tissue: differences between Finland, Estonia, and St. Petersburg.

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.

Liver tumor-promoting activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in TCDD-sensitive and TCDD-resistant rat strains.

Risk assessment of dioxins is currently based on induction of liver tumors in rats. The toxicity of dioxins is characterized by large sensitivity differences among animal species and even strains of the same species, which complicates the risk assessment. The significance of these differences in dioxin-induced carcinogenicity is not known. We therefore studied the liver tumor-promoting activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the sensitive Long-Evans (L-E) and the resistant Han/Wistar (H/W) rats differing >1000-fold in their sensitivity to the acute lethaity of TCDD. Female rats were partially hepatectomized, initiated with nitrosodiethylamine, and treated with TCDD for 20 weeks. Altered hepatic foci (AHF) were stereologically quantitated using glutathione S-transferase P as a marker. AHF were significantly (P < 0.001) and dose dependently increased in L-E rats at 10 and 100 ng/kg/day, but in H/W rats only at 1000 ng/kg/day and above, indicating a remarkable (approximately 100-fold) sensitivity difference between L-E and H/W rats. The same sensitivity difference but 10-fold less foci were observed between nonhepatectomized/noninitiated L-E and H/W rats. Induction of AHF was related to hepatotoxicity but not to cytochrome P4501A1 activity in the liver. Liver TCDD concentrations were similar in both strains. H/W rats are exceptionally resistant to induction of AHF by TCDD, and the resistance is associated with an altered transactivation domain of the aryl hydrocarbon receptor. Genetic differences may account for significant interindividual/intraspecies sensitivity differences in dioxin-induced carcinogenesis. Understanding the role of transactivation domain of the aryl hydrocarbon receptor in carcinogenesis is therefore likely to improve dioxin risk assessment.

Environmental chemicals and changes in sex ratio: analysis over 250 years in finland.

It has been proposed that environmental chemicalization is responsible for the recent decline in male ratio, but these speculations are based on statistics going back only a few decades. The objective of this study was to evaluate whether Finnish long-term data are compatible with the hypothesis that the decrease in the ratio of male to female births in industrial countries is caused by environmental factors. We analyzed the sex ratio of births from the files of Statistics Finland and all live births in Finland from 1751 to 1997. Running averages of 9 years (1751-1904) or 5 years (1905-1997) were analyzed for sex ratios. Additionally, to identify potential explanations for the findings, births from 1990 to 1997 were correlated with various family parameters. We found an increase in the proportion of males from 1751 to 1920; this was followed by a decrease and interrupted by peaks in births of males during and after World War I and World War II. None of the family parameters (paternal age, maternal age, age difference of parents, birth order) could explain the time trends. The turning point of male proportion precedes the period of industrialization or the introduction of pesticides or hormonal drugs, rendering a causal association unlikely. Moreover the trends are similar to those observed in other countries with worse pollution and much greater pesticide use.

Drinking water mutagenicity and urinary tract cancers: a population-based case-control study in Finland.

The detection of mutagenic and carcinogenic chlorination by-products in chlorinated drinking water has raised concern in many countries over the potential health effects of long-term exposure to these products. The relation between estimated exposure to historical drinking water mutagenicity and cancer was studied in Finland by using a population-based case-control study comprising 732 bladder cancer cases, 703 kidney cancer cases, and 914 controls. The cases were obtained from the nationwide Finnish Cancer Registry for the years 1991-1992. The controls, frequency matched by age and sex, were randomly selected from the national population registry. Information on past drinking water sources and confounding factors was acquired through a questionnaire. Historical exposure to drinking water mutagenicity was estimated by using information on past residence, past water source, and historical data on water quality and treatment. Odds ratios were calculated for an increase of 3,000 net revertants per liter (net rev/liter) in average exposure from 1950 to 1987, adjusting for age, sex, socioeconomic status, and smoking in logistic regression models. A small, statistically significant, exposure-related excess risk was found for kidney cancer for men (odds ratio = 1.49, 95 percent confidence interval (CI) 1.05-2.13) for 3,000 net rev/liter exposure level. For women, the association remained nonsignificant, with a lower odds ratio of 1.08 (95% CI 0.69-1.68). For bladder cancer, the odds ratio for both men and women was 1.22 (95% CI 0.92-1.62) for 3,000 net rev/liter exposure. However, a higher odds ratio of 2.59 (95% CI 1.13-5.94) for 3,000 net rev/liter exposure was observed for male nonsmokers.

Mutagenicity and amount of chloroform after chlorination of bank filtered lake water.

Chlorinated drinking waters produced from humus-rich waters often have a high content of halogenated organic by-products which increases the mutagenicity of drinking water. With in vitro chlorination experiments we studied the formation of chloroform (CHCl3) and mutagenicity of artificially recharged ground water samples. The water samples where obtained from an artificial ground water plant which infiltrates humus-rich lake water through an esker island. The chlorination experiments showed that bank filtration reduced strongly the formation of chloroform and mutagenicity of chlorinated water. Reduction in the amount of chloroform and mutagenicity in chlorinated waters was strongly associated with the decrease in the total content of organic carbon and with the decrease in molecular weight of organic matter during bank filtration.

Carcinogenicity of the drinking water mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone in the rat.

BACKGROUND: Several epidemiologic studies have suggested that the consumption of chlorinated drinking water may be associated with the development of certain cancers in humans. 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a byproduct of the chemical reactions that occur in chlorinated drinking water, has been found to be mutagenic in bacteria and mammalian cells; however, its potential to cause tumors in animals has not been tested previously. PURPOSE: The objective of this study was to evaluate the carcinogenicity of MX in rats given MX in their drinking water. METHODS: MX was administered to male and female Wistar rats (50 rats per dose group) in drinking water for 104 weeks at concentrations yielding the average daily doses of MX of 0.4 mg/kg of animal weight (low dose), 1.3 mg/kg (mid dose), and 5.0 mg/kg (high dose) for males and 0.6 mg/kg, 1.9 mg/kg, and 6.6 mg/kg for females, respectively. Control rats received water from the same source used for preparation of the MX dose formulations (after its adjustment to the same pH range). Body weight, clinical signs, and food and water consumption were recorded regularly. At the end of the treatment period, the animals were killed and full histopathologic analysis was performed on 47 tissues and all lesions. RESULTS: Dose-dependent increases in tumor incidence were observed in rats given MX-containing drinking water; the same MX doses had no obvious toxic effects on animals. MX consumption increased most drastically the prevalence of follicular adenoma (up to 43% and 72% in high-dose males and females, a test [one-sided] for positive trend in all dose groups P = .0045 and P = .0000, respectively) and carcinoma (55% [P = .0000] and 44% [P = .0000], respectively) in thyroid glands and cholangioma in the liver (8% [P = .0009] and 66% [P = .0000] in the high-dose males and females, respectively). Among rats given the higher doses of MX in their drinking water, cortical adenomas of the adrenal glands were increased in both sexes, alveolar and bronchiolar adenomas of the lungs and Langerhans' cell adenomas of the pancreas were increased in males, and lymphomas, leukemias, and adenocarcinomas and fibroadenomas of the mammary glands were increased in females. Even the lowest MX dose studied was carcinogenic. CONCLUSION: MX is a potent carcinogen in both male and female rats, and it causes tumors at doses that are not overtly toxic to rats. IMPLICATIONS: Although these findings cannot be extrapolated to humans, MX should be studied as a candidate risk factor in the possible association between consumption of chlorinated drinking water and cancer in humans.

Drinking water chlorination by-products and cancer.

This review discusses the relation between by-products of drinking water chlorination and cancer in the light of present toxicological and epidemiologic evidence. During the chlorination of drinking water, a complex mixture of by-products forms from chlorine and the organic and inorganic compounds present in raw water. The quality and quantity of such compounds depend on the specific nature of the organic material in raw waters, the inorganic material in raw water, pH, temperature, other water treatment practices, and the chlorine timing and dose added. Chlorination by-products are important mainly when surface water is used for drinking water as more organic compounds are present in surface waters than in ground waters. The gastrointestinal and urinary tract are the cancer sites that are most often associated with the use of chlorinated surface water or with the quantity of chlorination by-products in the water-supply network. Yet the microbial quality of drinking water should not be compromised by excessive caution over the potential long-term effects of disinfection by-products because the risk of illness and death resulting from exposure to pathogens in untreated drinking water may be several orders of magnitude greater than the cancer risks from chlorination by-products.

Drinking water chlorination and cancer-a historical cohort study in Finland.

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.

Subchronic toxicity of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in Wistar rats.

The subchronic (14-18 wk) toxicity of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a mutagenic by-product in chlorinated drinking water, was evaluated in Wistar rats. In a range-finding study, MX was administered daily for 14 days by gavage in deionized water to male rats (five animals per group) at doses of 12.5, 25, 50, 100 or 200 mg/kg body weight. The doses above 50 mg/kg were lethal and three out of five animals also died during treatment at 50 mg/kg. The range-finding study was repeated with doses of 5, 10 and 20 mg MX/kg, given on 5 days a week, to both males and females (10 animals per group). These doses were not overtly toxic but caused several changes in plasma clinical chemistry at 10 and 20 mg MX/kg in comparison with the controls. These included increased urea, creatinine and bilirubin and decreased inorganic phosphate and potassium in females and increased cholesterol in males. In the subchronic toxicity study, rats (15 per group, were given MX by gavage, on 5 days a week, at doses of 0 (controls) or 30 md/kg (low dose) for 18 wk, or, in the high-dose group, at doses increasing from 45 to 75 mg/kg over 14 wk. The high dose was finally lethal (two males and one female died) and caused hypersalivation, wheezing respiration, emaciation and tangled fur in animals. The body weights of the high-dose males decreased by 15%, and food consumption was decreased by 15 to 20%, but the water consumption increased by 15% to 60%. Plasma cholesterol and triglycerides were elevated and urine excretion was increased. Urine specific gravity was decreased and the relative weights of the liver and kidneys were increased in both sexes at both doses in comparison with the controls. At both doses, duodenal hyperplasia occurred in males and females, and slight focal epithelial hyperplasia in the forestomach was observed in males. Splenic atrophy and haemosiderosis were seen in two high-dose females, and epithelial cell atypia in the urinary bladder of one high-dose male and female. The frequency of bone marrow polychromatic erythrocytes with micronuclei was slightly increased in low-dose males. The results indicate that repeated administration of MX disturbs the fluid-electrolyte balance and induces diuresis, causes mucosal hyperplasia in the gastro-intestinal tract as a local effect, and affects lipid metabolism.

Cancer incidence around an oil refinery as an example of a small area study based on map coordinates.

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.

Drinking water mutagenicity and leukemia, lymphomas, and cancers of the liver, pancreas, and soft tissue.

The acid, mutagenic compounds present in chlorinated drinking water have caused concern about the potential cancer risk of drinking-water mutagenicity. In this study, past exposure to drinking water mutagenicity was assessed for the years 1955 and 1970 in 56 Finnish municipalities, using the historical information on water quality and treatment. Cases of leukemia, lymphomas, and cancers of the liver, pancreas, and soft tissue were derived from the Finnish Cancer Registry for two periods: 1966-1976 and 1977-1989. Relative risk was estimated in an additive Poisson regression model, adjusting for age, gender, social class, urbanity, and time period. In an ordinary municipality that was supplied with mutagenic drinking water (3,000 net rev/l), the observed exposure-response relationship indicated a relative risk of 1.1-1.3 for lymphomas and 1.1-1.2 for pancreatic cancer, compared with municipalities in which nonmutagenic drinking water was consumed.

Drinking water mutagenicity and gastrointestinal and urinary tract cancers: an ecological study in Finland.

OBJECTIVES: The purpose of this study was to investigate the relationship between exposure to mutagenic drinking water and cancers of the gastrointestinal and urinary tract. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.