Assessment of the exposure of breast milk to persistent organic pollutants in Latvia.

According to the National Implementation Plan on persistent organic pollutants (POP) for the years 2004-2020 the situation on POP was actualised in Latvia. The aim of the study was to assess the contamination of breast milk with polychlorinated biphenyls (PCB), polychlorinated dibenzodioxins, dibenzofurans (PCDD/PCDF) and some pesticides. Breast feeding mothers (together 30) were selected from probably polluted area, and a control group on the basis of WHO criteria for donor selection. The concentration of POP in milk was detected by gas chromatography with HRGC/HRMS, HRGC/ECD and GC/ECD detection after extraction of milk fat and purification. The results of the survey show comparability of both groups in age, weight, habits, occupation as well as age of the children and the weight at birth and at the time of collecting the samples. PCB were not observed in 15.9%, PCDD/PCDF in 6.6% and pesticides in 14% analyses of the target group and in 26.3%, 7% and 8.6% analyses correspondingly of the control group. The concentration of 18 detected PCB, 17 detected PCDD/PCDF and 8 chlorinated pesticides and its metabolites varied in wide range and the differences of mean values within groups were not statistically significant (p>0.05). The concentration of POPs corresponds to lowest levels detected in European countries. The concentration of dioxine-like PCBs and PCDD/PCDF according to toxicity equivalents does not exceed the WHO accepted level of 15 TEQ pg/g milk fat.

Fish from industrially polluted freshwater as the main source of organochlorinated pollutants and increased frequency of thyroid disorders and dysglycemia.

In a certain area of Michalovce district in East Slovakia, heavy industrial pollution by polychlorinated biphenyls (PCBs) developed in 1955-1984 and very high PCB levels in environmental and human samples are still persisting. Recently, a total of 2045 adults from this and the surrounding background pollution area have been examined using questionnaire data, thyroid volume by ultrasound (ThV), urinary iodine and serum levels of 15 PCB congeners, hexachlorobenzene (HCB), 2,2'-2-bis(4-chlorobiphenyl)-1,1-dichloroethylene (DDE), 2,2'-bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT), alpha-, beta- and gamma-hexachlorocyclohexane (HCH), thyrotropin (TSH), free thyroxine (FT4), anti-thyroperoxidase antibodies (TPOab) and fasting glucose. As based on our previous findings of strikingly high level of PCBs in fish from high pollution area (e.g. mean level of 375430 ng/g lipid) and considerably lower, but still relatively high level in background pollution area (e.g. mean PCB level of 5150 ng/g), the information on the frequency of fish meals and approximate annual consumption of fish from local waters was obtained by questionnaires. The association of contaminated fish consumption with very high blood levels of PCBs, DDE and HCB and increased ThV as well as with increased frequency of positive TPOab, high values of FT4 and impaired fasting glucose (IFG) was found. These associations were also confirmed in 16 marital pairs from high pollution area with very high PCB level in both members associated with high fish consumption. It was concluded that, due to persistent heavy pollution of waters, soil and food chain namely by PCBs, but also by pesticides (e.g. DDE and HCB) resulting from their previous extensive use in agriculture, the fish from local waters still remains the most important source of these toxic pollutants which results in considerable adverse health effects.

Possible effects of persistent organochlorinated pollutants cocktail on thyroid hormone levels and pituitary-thyroid interrelations.

In polluted district of Michalovce in East Slovakia (POLL) and two districts with background pollution (BCGR) 2046 adults (834 males and 1212 females aged 20-75 years) were examined. Serum levels of thyrotropin (TSH), free thyroxine (FT4), total triiodothyronine (TT3) and antithyroperoxidase antibodies (TPOab) were estimated by electrochemiluminiscent assay and also these of 15 polychlorinated biphenyl congeners (PCBs), p,p'-DDE, p,p'-DDT, hexachlorobenzene (HCB) and hexachlorocyclohexane were measured by high resolution gas chromatography/mass spectrometry. In addition, also dioxins, furans, coplanar- and mono-ortho-PCBs as well as selected hydroxylated and methylsulphonated PCBs and DDE metabolites were measured by appropriate methods based on gas chromatography/mass spectrometry principle. In POLL significantly higher levels of all organochlorines were found than these in BCGR. When pooled values from both areas were stratified in terms of PCBs level and treated as continuous variables, positive association of PCBs with FT4 and TT3 was found, the latter two being also mutually associated. However, within the category of PCBs level <530 ng/glipid (n=232) the association between PCBs and both the FT4 (p<0.09) and TT3 (p<0.03) was negative and any association of these was not found within the category of PCBs level of 531-1000 ng/g (n=691). In contrast, in the category of 531-2000 ng/g (n=1307) positive association appeared between PCBs and FT4 (p<0.001) as well as TT3 (p<0.05). Highly significant association of PCBs with FT4 (p<0.001) was further found in the categories with PCBs level of 1001-101414 ng/g (n=1307) and 2001-101414 (n=1123), while significant association with TT3 was observed only in the category of 531-2000 ng/g. Such findings suggest possible threshold level in positive effect of PCBs on FT4 and TT3 level which seems to be individual and located somewhere around the PCBs level of 1000 ng/g. However, highly significant negative association of both FT4 and TT3 with TSH was found in each of above indicated PCBs categories. Considerable difference in FT4 and TT3 level between large groups of subjects with the same range of PCBs level was also found suggesting different individual susceptibility to the effects of organochlorines. Among a total of 26 cases from POLL with very low TSH level (<0.5 mU l(-1)) 13 cases showed very high level of PCBs, FT4 and TT3, thus supporting a hypothesis on a novel sporadic form of high PCBs related peripheral subclinical hyperthyroidism possibly resulting from the long-term disruption of equilibrium between bound and free thyroxine in plasma by high PCBs level followed by a striking inhibition of TSH release from the pituitary.

Thyroid ultrasound volume, structure and function after long-term high exposure of large population to polychlorinated biphenyls, pesticides and dioxin.

We examined 2,046 adults (834 males and 1,212 females aged 20-75 years) from polluted district in East Slovakia (POLL) and two neighboring upstream and upwind located districts of background pollution (BCGR). By ultrasound we estimated the thyroid volume (ThV), hypoechogenicity (HYE), nodules and cysts. Serum levels of thyrotropin (TSH), thyroperoxidase antibodies (TPOab) and thyroglobulin were estimated by electrochemiluminiscent assay and these of 15 PCB congeners, p,p'-DDE, p,p'-DDT, hexachlorobenzene (HCB) and hexachlorocyclohexane by high-resolution gas chromatography. In 320 subjects also selected hydroxylated and methylsulfonated PCB metabolites, polychlorinated dibenzo-dioxins (PCDDs), -furans (PCDFs), five dioxin-like coplanar and eight mono-ortho PCB congeners were estimated. Urinary iodine was measured by automatic microplate method. Reciprocal positive association was found between three major POPs (PCBs, DDE and HCB), the levels of these and also PCDDs plus PCDFs in polluted area being considerably higher than in background pollution area. ThV in groups of males and females from POLL with high PCBs level was significantly higher (p<0.001 by t-test) then in age and sex matched groups from BCGR with low PCBs level. In 1,048 males and females aged <60 years with serum PCBs level >1,000 ng g(-1) lipid (median=1,756 ng g(-1)) a significant effect of age on ThV was found (p<0.01 by ANOVA), while in 921 respective subjects with PCBs level <1,000 ng g(-1) (median=661 ng g(-1)) it was not. These findings supported the view on the additional effect of PCBs on ThV other than that of age. Since the urinary iodine in both districts showed optimal range, any interfering effect of unsatisfactory iodine intake on ThV may be excluded. The frequency of autoimmune thyroiditis signs such as HYE, increased serum level of TPOab and TSH resulting in subclinical or overt thyroid hypofunction was positively associated with sex, age and organochlorine levels. The increase of such frequency in males with POPs levels was much more abrupt than that in females. No considerable differences in the frequency of thyroid nodules as related to PCBs level were found.

Dioxin-like and non-dioxin-like PCBs in human serum of Slovak population.

In the present study, non-ortho, mono-ortho and other ortho-substituted PCB congeners were analysed in individual blood serum samples taken from healthy adults (196 males and 119 females) in the polluted area of the Michalovce district and in the background area of the Stropkov/Svidnik districts in Eastern Slovakia by high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS). The samples from general population living in villages and towns of two regions were taken between August 2001 and February 2002 within the project of the EC's 5th Framework Programme (PCBRISK, ). The medians of dioxin-like PCBs (dl-PCBs)--expressed as TEQs on lipid basis--of all males (24.7 pg g(-1) lipid) and females (21.4 pg g(-1) lipid) were comparable, but there was a significant difference between both of the areas studied. In the district of Michalovce, the medians of males (47.3 pg g(-1) lipid) and females (41.1 pg g(-1) lipid) were 2.3 times higher than in the area of the Stropkov/Svidnik districts. The medians of total non-dioxin-like PCB concentration were 1,835 and 1,033 ng g(-1) lipid in males and females, respectively. The data show a trend toward higher concentrations of both dl- and non-dioxin-like PCBs in the older age groups. The substantial increase was observed for the 60+ age group. PCB-126 was the most abundant non-ortho congener. PCBs-118 and 156 were the predominant mono-ortho congeners. They were quantitated in all samples analysed. Congeners 153, 138(+163), 180 and 170(+190) were the main contributors to total non-dioxin-like PCB concentrations. Mean mutual ratio HexaCBs:HeptaCBs:OctaCBs in the non-dioxin-like group was 37:50:1. The results of this study represent the overall information about the congener distribution of dioxin-like and non-dioxin-like PCBs in human serum blood of adult Slovaks.

Serum PCBs and organochlorine pesticides in Slovakia: age, gender, and residence as determinants of organochlorine concentrations.

We measured organochlorine concentrations of 15 polychlorinated biphenyl congeners and six organochlorine pesticides (PCB28, 52, 101, 123(+149), 118, 114, 153, 105, 138(+163), 167, 156(+171), 157, 180, 170, 189, alpha-, beta-, gamma-HCH, HCB, p,p'-DDT and p,p'-DDE) in 2047 subjects from contaminated and background areas of eastern Slovakia. Data were collected in 2001 and analyzed by high-resolution gas chromatography with electron capture detection in 2002-2003. Elevated levels persist in subjects from Michalovce district, site of former production facility, after almost 20-years since the end of the PCB manufacturing. Sum of 15 PCB congeners was 3105 ng/g of lipid in the Michalovce district versus 871 ng/g of lipid for subjects from the background districts of Svidnik and Stropkov. Relatively high concentration in children from the Michalovce district, sum PCB = 766 ng/g of lipid versus 372 ng/g of lipid in children from background area suggest ongoing exposure from environmental reservoirs and contaminated food. Consistent differences between genders in both contaminated and background areas are reported here. Levels in males are about 20% higher in both districts. Levels of organochlorine pesticides, particularly of DDT metabolite DDE and hexachlorobenzene are also elevated in the Michalovce district, reflecting intensive use of pesticides in agriculture in the past. About 30% decrease in serum organochlorine levels was observed in comparison with our earlier samples collected in 1998. These results suggest that contamination with PCBs still remains a source of relatively high environmental exposure for subjects in the Michalovce district.

PCDDs, PCDFs and dioxin-like PCBs in food of animal origin (Slovakia).

The levels of 17 toxic polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and 12 non-ortho and mono-ortho polychlorinated biphenyls (PCBs) in 73 foodstuff samples of animal origin collected from shops and small farms in selected districts of Slovak Republic are presented in this paper. The concentrations expressed as WHO-TEQ in analysed samples ranged for PCDDs/PCDFs from 0.25 pg/g fat in pork to 75 pg/g fat in cod liver. The TEQ concentrations of non-ortho PCBs were between 0.007 and 181 pg/g fat and mono-ortho PCBs between 0.0083 and 66.5 pg/g fat. The mean concentrations in freshwater fish and imported species of marine fish were 0.089 pg TEQ/g fresh weight for PCDDs/PCDFs, 0.17 pg TEQ/g fresh weight for non-ortho PCBs and 0.034 pg TEQ/g fresh weight for mono-ortho PCBs. The mean total concentration of PCDDs/PCDFs and dioxin-like PCBs in samples of infant milk formula imported from EU countries was 0.98 pg TEQ/g fat.

Possible effects of polychlorinated biphenyls and organochlorinated pesticides on the thyroid after long-term exposure to heavy environmental pollution.

The purpose of this work was to study the effects of high environmental exposure to polychlorinated biphenyls (PCBs) and other organochlorines on the thyroid. Thyroid volume, hypoechogenicity and nodules (by ultrasound), presence of antithyroid peroxidase (anti-TPO) antibodies, and abnormal thyroid-stimulating hormone (TSH) levels in serum (by radioimmunoassay) were examined in 101 adults from the PCB-polluted area in 360 controls. Serum levels of PCBs, hexachlorobenzene, gamma-hexachlorocyclohexane (HCH), p,p'-DDT(1,1,1-trichloro-2,2'-bis(p-chlorophenyl)ethane), and p,p'-DDE(1,1-dichloro-2,2'-bis(p-chlorophenyl)ethene) were measured by high-resolution gas chromatography. Very high levels of PCBs were found in the polluted area (7300 +/- 871 ng/g lipids) compared with controls (2045 +/- 147 ng/g). Positive correlations (P < 0.001) were found between the levels of all organochlorines and their total except for hexachlorocyclohexane (HCH). In the polluted area, the highest thyroid volumes (18.7 +/- 2.32 mL; mean +/- SE) were clustered among 23 subjects (17 males and six females) with PCB levels above 10,000 ng/g (range 10,000-58,667 ng/g). In the remaining 438 subjects the thyroid volume was 14.2 +/- 0.29 mL. These data suggest that there might be a threshold serum PCB level of approximately 10,000 ng/g that may influence the thyroid volume. A two-way ANOVA showed that all thyroid volumes in the polluted area were significantly higher (P < 0.001) than in the control area. In males from the polluted area, the frequencies of thyroid hypoechogenicity, thyroid nodules, positive anti-TPO, and abnormal TSH level were higher than in males from the control area, whereas such differences were not observed in females. Increased thyroid volume and indicators of potential thyroid dysfunction were associated with long-term environmental exposure to PCBs. These effects on the thyroid were confined to subjects with PCB levels above 10,000 ng/g of lipid (thyroid volume) and to males from the polluted area (thyroid hypoechogenicity, thyroid nodules, positive anti-TPO, and abnormal TSH).

High prevalence of anti-glutamic acid decarboxylase (anti-GAD) antibodies in employees at a polychlorinated biphenyl production factory.

An increased prevalence of thyroid antibodies was seen in employees of a factory that formerly produced polychlorinated biphenyls (PCBs). In this study, the authors expand the evaluation of possible long-term PCB effects by comparing the prevalence of glutamic acid decarboxylase (anti-GAD) antibodies with the development of diabetes mellitus. The sera of 240 factory employees and 704 control subjects were analyzed. Anti-GAD antibody values exceeded 1.20 U/ml in all employees (40.4%), was 4 times higher (p < .001) than in all controls (10.5%), and were 5 times higher in employees aged 51-60 yr (53.2%) than in age-matched controls (10.5%) (p < .001). Although the prevalence of diabetes could not be determined from this retrospective study, this is the first report of a possible relationship between xenobiotics and the prevalence of anti-GAD antibodies, and it supports the concept of an immunomodulatory effect of PCBs. However, such antibodies may be present decades before the development of clinical diabetes, and not all anti-GAD antibody-positive individuals become diabetic. Presently, it is unknown whether there is an increased prevalence of diabetes among the former factory employees.