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BACKGROUND: Polychlorinated biphenyl (PCB) exposures have been associated with liver injury in human cohorts, and steatohepatitis with liver necrosis in model systems. MicroRNAs (miRs) maintain cellular homeostasis and may regulate the response to environmental stress. OBJECTIVES: We tested the hypothesis that specific miRs are associated with liver disease and PCB exposures in a residential cohort. METHODS: Sixty-eight targeted hepatotoxicity miRs were measured in archived serum from 734 PCB-exposed participants in the cross-sectional Anniston Community Health Survey. Necrotic and other liver disease categories were defined by serum keratin 18 (K18) biomarkers. Associations were determined between exposure biomarkers (35 ortho-substituted PCB congeners) and disease biomarkers (highly expressed miRs or previously measured cytokines), and Ingenuity Pathway Analysis was performed. RESULTS: The necrotic liver disease category was associated with four up-regulated miRs (miR-99a-5p, miR-122-5p, miR-192-5p, and miR-320a) and five down-regulated miRs (let-7d-5p, miR-17-5p, miR-24-3p, miR-197-3p, and miR-221-3p). Twenty-two miRs were associated with the other liver disease category or with K18 measurements. Eleven miRs were associated with 24 PCBs, most commonly congeners with anti-estrogenic activities. Most of the exposure-associated miRs were associated with at least one serum hepatocyte death, pro-inflammatory cytokine or insulin resistance bioarker, or with both. Within each biomarker category, associations were strongest for the liver-specific miR-122-5p. Pathways of liver toxicity that were identified included inflammation/hepatitis, hyperplasia/hyperproliferation, cirrhosis, and hepatocellular carcinoma. Tumor protein p53 and tumor necrosis factor α were well integrated within the top identified networks. DISCUSSION: These results support the human hepatotoxicity of environmental PCB exposures while elucidating potential modes of PCB action. The MiR-derived liquid liver biopsy represents a promising new technique for environmental hepatology cohort studies. [ABSTRACT FROM AUTHOR]

Anniston, Alabama was home to a major polychlorinated biphenyl (PCB) production facility from 1929 until 1971. The Anniston Community Health Survey I and II (ACHS-I 2005–2007, ACHS-II 2013–2014) were conducted to explore the effects of PCB exposures. In this report we examined associations between PCB exposure and DNA methylation in whole blood using EPIC arrays (ACHS-I, n = 518; ACHS-II, n = 299). For both cohorts, 35 PCBs were measured in serum. We modelled methylation versus PCB wet-weight concentrations for: the sum of 35 PCBs, mono-ortho substituted PCBs, di-ortho substituted PCBs, tri/tetra-ortho substituted PCBs, oestrogenic PCBs, and antiestrogenic PCBs. Using robust multivariable linear regression, we adjusted for age, race, sex, smoking, total lipids, and six blood cell-type percentages. We carried out a two-stage analysis; discovery in ACHS-I followed by replication in ACHS-II. In ACHS-I, we identified 28 associations (17 unique CpGs) at p ≤ 6.70E-08 and 369 associations (286 unique CpGs) at FDR p ≤ 5.00E-02. A large proportion of the genes have been observed to interact with PCBs or dioxins in model studies. Among the 28 genome-wide significant CpG/PCB associations, 14 displayed replicated directional effects in ACHS-II; however, only one in ACHS-II was statistically significant at p ≤ 1.70E-04. While we identified many novel CpGs significantly associated with PCB exposures in ACHS-I, the differential methylation was modest and the effect was attenuated seven years later in ACHS-II, suggesting a lack of persistence of the associations between PCB exposures and altered DNA methylation in blood cells. [ABSTRACT FROM AUTHOR]

BACKGROUND: In 2014, we conducted a longitudinal study [Anniston Community Health Survey (ACHS II)] 8 y after the baseline (ACHS I). OBJECTIVES: We investigated the relationship between persistent chlorinated compounds and hypertension in residents living around the former polychlorinated biphenyl (PCB) production plant in Anniston, Alabama. We also examined the potential role of inflammatory cytokines in those with hypertension. METHODS: A total of 338 participants had their blood pressure measured and medications recorded, gave a blood sample, and completed a questionnaire. Prevalent hypertension was defined as taking antihypertensive medication or having systolic blood pressure >140 mmHg and/or diastolic pressure >90 mmHg; incident hypertension used similar criteria in those who developed hypertension since the baseline in 2005-2007. PCB congeners were categorized into structure-activity groups, and toxic equivalencies (TEQs) were calculated for dioxin-like compounds. Descriptive statistics, logistic and linear regressions, as well as Cox proportional hazard models, were used to analyze the associations between exposures and hypertension. RESULTS: Prevalent hypertension (78%) in ACHS II showed statistically significant adjusted odds ratios (ORs) for PCBs 74, 99, 138, 153, 167, 177, 183, and 187, ranging from 2.18 [95% confidence interval (CI): 1.10, 4.33] to 2.76 (95% CI: 1.14, 6.73), as well as for two estrogenic-like PCB groups, and the thyroid-like group [ORs ranging from 2.25 (95% CI: 1.07, 4.75) to 2.54 (95% CI: 1.13, 5.74)]. Furthermore, analysis of quartiles demonstrated a monotonic relationship for dioxin-like non-ortho (non-o)-PCB TEQs [fourth vs. first quartile: 3.66 (95% CI: 1.40, 9.56)]. Longitudinal analyses of incident hypertension supported those positive associations. The results were strongest for the di-o-PCBs [hazard ratio (HR)=1.93 (95% CI: 0.93, 4.00)] and estrogenic II PCB group [HR=1.90 (95% CI: 0.96, 3.78)] but were weaker for the dioxin TEQs. DISCUSSION: Findings supportive of positive associations were reported for dioxin-like mono-o- and non-o-PCBs as well as for nondioxin-like estrogenic and thyroid-like congeners with prevalent and incident hypertension, suggesting that multiple pathways may be involved in hypertension development. [ABSTRACT FROM AUTHOR]

Endocrine and metabolism disrupting chemicals (EDCs/MDCs) have been associated with environmental liver diseases including toxicant-associated steatohepatitis (TASH). TASH has previously been characterized by hepatocellular necrosis, disrupted intermediary metabolism, and liver inflammation. Polychlorinated biphenyls (PCBs) are environmental EDCs/ MDCs associated with the genesis and progression of steatohepatitis in animal models and human liver injury in epidemiology studies. The cross-sectional Anniston Community Health Survey (ACHS) investigates ortho-substituted PCB exposures and health effects near a former PCB manufacturing complex. The rates of obesity, diabetes, and dyslipidemia were previously determined to be high in ACHS. In this study, 738 ACHS participants were categorized by liver disease status using the serum cytokeratin 18 biomarker. Associations between PCB exposures and mechanistic biomarkers of intermediary metabolism, inflammation, and hepatocyte death were determined. The liver disease prevalence was high (60.2%), and 80.7% of these individuals were categorized as having TASH. Sex and race/ethnicity differences were noted. TASH was associated with increased exposures to specific PCB congeners, insulin resistance, dyslipidemia, proinflammatory cytokines, and liver necrosis. These findings are consistent with PCB-related steatohepatitis. RPCBs was inversely associated with insulin resistance/production, leptin, and hepatocyte apoptosis, while other adipocytokines were increased. This is possibly the largest environmental liver disease study applying mechanistic biomarkers ever performed and the most comprehensive analysis of PCBs and adipocytokines. It provides insight into the mechanisms of PCB-related endocrine andmetabolic disruption in liver disease and diabetes. In the future, associations between additional exposures and liver disease biomarkers will be evaluated in the ACHS and follow-up ACHS-II studies. [ABSTRACT FROM AUTHOR]

We examined serum levels of persistent organic pollutants (POPs) among geographical regions of the United States as defined by the US Census Bureau. National Health and Nutrition Examination Survey (NHANES) data for adults aged 20 years and older are presented for selected survey periods between 1999 and 2010. From NHANES 1999 through 2004, dichlorodiphenyldichloroethylene (DDE) concentration levels were consistently higher among people living in the West than in the Midwest, Northeast, or South. In 2003–2010, perfluorinated compound concentrations tended to be highest in the South. The sum of 35 polychlorinated biphenyls (PCBs) congeners was significantly higher in the Northeast [GM: 189; 95% CI: 173–204 ng/g lipid] than the remaining regions. The regional differences in higher body burdens of exposure to particular POPs could be attributed to a variety of activities, including region-specific patterns of land use and industrial and agricultural chemical applications, as well as different levels of regulatory activity. [ABSTRACT FROM AUTHOR]

The concentrations of indicator polychlorinated biphenyls (PCBs No. 28, 52, 101, 138, 153 and 180) and organochlorine pesticides (HCB, p,p′-DDE and p,p′-DDT) in 121 blood serum specimens collected from non-occupationally exposed adults living in contaminated and comparison areas were determined using high-resolution gas chromatography/electron capture detection (HRGC/ECD). The sum of the serum concentrations of the three most abundant PCB congeners (No. 138, 153 and 180) found in participants ( N = 81) living in industrial areas near incinerators, metallurgical and chemical plants (Krompachy, Kosice, Nemecka and Sala) was significantly higher ( p < 0.001) than in participants living in villages and towns without known sources causing persistent organic pollutant (POP) contamination ( N = 40). Similarly, significant differences were observed for p,p′-DDE ( p < 0.0001) and p,p′-DDT ( p < 0.002). However, a Mann-Whitney U test between groups showed that the difference for HCB was not statistically significant ( p = 0.089). Age was positively correlated with the sum of PCBs (No. 138, 153 and 180), HCB and the sum of p,p′-DDE and p,p′-DDT ( p < 0.01 for all). [ABSTRACT FROM AUTHOR]

Background: Anniston, Alabama, is the site of a former Monsanto plant where polychlorinated biphenyls (PCBs) were manufactured from 1929 until 1971. Residents of Anniston are known to have elevated levels of PCBs. The objective of the study was to test the hypothesis that levels of the various lipid components (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides) are differentially associated with concentrations of total PCBs and total pesticides, and further that different congeners, congener groups and different pesticides do not have identical associations in serum samples obtained from Anniston residents in a cross-sectional study.Methods: Fasting serum samples were obtained from 575 residents of Anniston who were not on any lipid-lowering medication and were analyzed for 35 PCB congeners, nine chlorinated pesticides, total cholesterol, LDL and HDL cholesterol and triglyceride concentrations. Associations between toxicant concentrations and lipid levels were determined using multiple linear regression analysis.Results: We observed that elevated serum concentrations of lipids were associated with elevated serum concentrations of ΣPCBs and summed pesticides in analyses adjusted for age, race, gender, BMI, alcohol consumption, smoking and exercising status. The strongest associations were seen for PCB congeners with three, four, or at least eight substituted chlorines. Mono-ortho substituted congeners 74 and 156, di-ortho congeners 172 and 194, and tri- and tetra-ortho congeners 199, 196-203, 206 and 209 each were significantly associated with total lipids, total cholesterol and triglycerides. Serum concentrations of HCB and chlordane also had strong associations with lipid components.Conclusions: Increased concentrations of PCBs and organochlorine pesticides are associated with elevations in total serum lipids, total cholesterol and triglycerides, but the patterns are different for different groups of PCBs and different pesticides. These observations show selective effects of different organochlorines on serum concentrations of different groups of lipids. This elevation in concentrations of serum lipids may be the basis for the increased incidence of cardiovascular disease found in persons with elevated exposures to PCBs and chlorinated pesticides. [ABSTRACT FROM AUTHOR]

A dose-response relationship between serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) and adult diabetes risk has been reported among U.S. Vietnam veterans in the Ranch Hand (RH) cohort. We examine the hypothesis that diabetes progression leads to higher serum dioxin (reverse causation) rather than higher serum dioxin leading to diabetes (causation) across the longitudinal medical monitoring data on these airmen. Lipid-adjusted serum dioxin levels and clinical parameters relating to diabetes progression were examined. Potential confounding due to age, race, diabetes family history, serum total lipid, and body mass index (BMI) was accounted for. The similar incidence of diabetes in RH and Comparison veterans, along with generally similar incidence trends with dioxin decile and lipid decile despite the large differential in serum dioxin, is evidence consistent with reverse causation. Of 135 RH diabetics with at least two dioxin measurements, 32.6% had a temporary serum dioxin increase more than a decade after Vietnam tour and another 22.2% had an interval of unusually slow half-life (>15.5 years); these diabetes-related changes shifted more diabetics into the higher dioxin deciles. Further, the increased diabetes odds ratio among the generally younger RH veterans in the highest dioxin decile is associated with a higher incidence of adult obesity in this RH subgroup, both at tour of duty and decades later. Change in serum dioxin levels is likely due to diabetes progression or poor control and is not independently related to serum dioxin concentrations. In summary, the data from the Ranch Hand studies does not indicate that dioxin increases adult diabetes risk. [ABSTRACT FROM AUTHOR]

Background: Polychlorinated biphenyls (PCBs) manufactured in Anniston, Alabama, from 1929 to 1971 caused significant environmental contamination. The Anniston population remains one of the most highly exposed in the world. Objectives: Reports of increased diabetes in PCB-exposed populations led us to examine possible associations in Anniston residents. Methods: Volunteers (n = 774) from a cross-sectional study of randomly selected households and adults who completed the Anniston Community Health Survey also underwent measurements of height, weight, fasting glucose, lipid, and PCB congener levels and verification of medications. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the relationships between PCBs and diabetes, adjusting for diabetes risk factors. Participants with prediabetes were excluded from the logistic regression analyses. Results: Participants were 47% African American, 70% female, with a mean age of 54.8 years. The prevalence of diabetes was 27% in the study population, corresponding to an estimated prevalence of 16% for Anniston overall; the PCB body burden of 35 major congeners ranged from 0.11 to 170.42 ppb, wet weight. The adjusted OR comparing the prevalence of diabetes in the fifth versus first quintile of serum PCB was 2.78 (95% CI: 1.00, 7.73), with similar associations estimated for second through fourth quintiles. In participants < 55 years of age, the adjusted OR for diabetes for the highest versus lowest quintile was 4.78 (95% CI: 1.11, 20.6), whereas in those ≥ 55 years of age, we observed no significant associations with PCBs. Elevated diabetes prevalence was observed with a 1 SD increase in log PCB levels in women (OR = 1.52; 95% CI: 1.01, 2.28); a decreased prevalence was observed in men (OR = 0.68; 95% CI: 0.33, 1.41). Conclusions: We observed significant associations between elevated PCB levels and diabetes mostly due to associations in women and in individuals < 55 years of age. [ABSTRACT FROM AUTHOR]

BACKGROUND: Residents of Anniston, Alabama, live near a Monsanto plant that manufactured polychlorinated biphenyls (PCBs) from 1929 to 1971 and are relatively heavily exposed. OBJECTIVES: The goal of this study was to determine the relationship, if any, between blood pressure and levels of total serum PCBs, several PCB groups with common actions or structure, 35 individual PCB congeners, and nine chlorinated pesticides. Methods: Linear regression analysis was used to determine the relationships between blood pressure and serum levels of the various contaminants after adjustment for age, body mass index, sex, race, smoking, and exercise in 394 Anniston residents who were not taking antihypertensive medication. RESULTS: Other than age, total serum PCB concentration was the strongest determinant of blood pressure of the covariates studied. We found the strongest associations for those PCB congeners that had multiple ortho chlorines. We found the associations over the full range of blood pressure as well as in those subjects whose blood pressure was in the normal range. The chlorinated pesticides showed no consistent relationship to blood pressure. CONCLUSIONS: In this cross-sectional study, serum concentrations of PCBs, especially those congeners with multiple ortho chlorines, were strongly associated with both systolic and diastolic blood pressure. [ABSTRACT FROM AUTHOR]

US Air Force veterans of Operation Ranch Hand sprayed herbicides contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Vietnam from 1962 to 1971. Comparisons served in Southeast Asia (SEA) during the same time period but did not spray herbicides. Here we investigate a potential association between exposure to TCDD and prostate cancer. Data were available for 2516 veterans (1019 Ranch Hand and 1497 Comparison) who participated in at least one of six physical examinations starting in 1982 and had a measurement of serum TCDD. We assigned Ranch Hands to two exposure categories: Lower and Higher, based on their median 20-year cumulative TCDD level. In total, 81 Comparison and 59 Ranch Hand prostate cancers were identified between 1 January 1982 and 31 December 2003. We found no overall increase in the risk of prostate cancer in Ranch Hand veterans versus the Comparisons. There was a positive association in Ranch Hand veterans in the Higher TCDD category who served in SEA before 1969 (RR=2.27, 95% CI 1.11–4.66) when more contaminated herbicides were used, but the number of cases was small (n=15). A within-group comparison found that in Comparison veterans, time served in SEA was associated with an increased risk of prostate cancer (RR=2.18, 95% CI 1.27–3.76, >789 days versus ≤789 days). No increase in the risk of prostate cancer was observed within the Ranch Hand group in association with TCDD or time served in SEA. These analyses suggest that a longer service in SEA and exposures other than TCDD may have increased the risk of prostate cancer in Comparison veterans.Journal of Exposure Science and Environmental Epidemiology (2006) 16, 184–190. doi:10.1038/sj.jea.7500448; published online 27 July 2005 [ABSTRACT FROM AUTHOR]

During the Vietnam War, a phenoxy-herbicide mixture called Agent Orange, which was contaminated with 2,3,7,8-tetrachlorodibenzodJoxin, or TCDD, was used primarily for destruction of forest and other foliage in order to prevent enemy troop movement and protect American and allied troops and military bases in the south of Vietnam. Smaller areas of Laos and Cambodia were also sprayed with Agent Orange between 1962 and 1971 from fixed-wing aircraft. In 2001, 28 food samples consisting of meat, fish, and dairy products were collected in sprayed and nonsprayed areas of Laos and analyzed for dioxins, dioxin-like dibenzofurans, and selected polychlorinated biphenyl (PCB) congeners by high-resolution gas chromatography/high-resolution mass spectrometry at laboratories in Germany and Canada. Low levels of dioxin and other dioxinlike substances were found in Laotian food, similar to levels present in recent exported Vietnamese food to United States. Vietnam is geographically adjacent to Laos. Total dioxin toxic equivalent (TEQ) levels were similar in samples from sprayed and nonsprayed areas, ranging from 0.009 to 0.851 pg/g or parts per trillion (ppt) in sprayed Sepone, and from 0.022 to 0.537 pg/g or ppt wet weight in non sprayed Vientiane. However, the Laotian fish samples from the Agent Orange-sprayed area had, on average, a higher proportion of total TEQ from TCDD (31.7% vs. 9.4%) compared to the nonsprayed area. Some other food items, duck eggs and pork liver from Sepone, also had several fold higher TCDD levels than similar food samples from Vientiane, 0.029 vs. 0.011 pg/g and 0.070 vs. 0.004 pg/g wet weight, respectively. There were no substantial differences in levels of dibenzofuran and PCB congeners. In general, elevated TCDD levels were not found in Laotian food samples. It is possible that dioxin-contaminated areas, or "hot spots," exist in Laos as they do in Vietnam, although they have not yet been identified. [ABSTRACT FROM AUTHOR]

Investigates the concentration and distribution of polybrominated diphenyl ether (PBDE) congeners in milk from mothers in Austin, Texas. Utilization of PBDE as flame retardants; Increase PBDE concentration in the U.S. compared to Europe; Potential toxicity to nursing infants; Role of PBDE in causing neurodevelopmental toxicities; Need to determine if animal fat in food is the major route of exposure.

In this study the levels of dioxins and dioxinlike compounds, dibenzofurans, and polychlori-nated biphenyls (PCBs) were measured in food exported from Vietnam to the United States. In the past, some Vietnamese fish was found to be contaminated with dioxin, 2,3,7,8-TCDD, or TCDD, from Agent Orange. U.S. commercial catfish farmers recently claimed that exported Vietnamese food, especially catfish, was contaminated with dioxin from Agent Orange and was thus a matter of concern to the U.S. Congress. In 2001, twenty-two exported Vietnamese food samples (mostly fish) were purchased in the United States and Laos to evaluate possible contamination with dioxin from Agent Orange. Dioxin, dibenzofuran, and coplanar PCB congeners were measured by high-resolution gas chromatography-high-resolution mass spectrometry by laboratories in Germany and Canada certified for dioxin analysis by the World Health Organization (WHO). In the current study, only low levels of dioxins and dioxinlike compounds were present in all exported Vietnamese food analyzed, despite recent findings of elevated levels of one dioxin, 2,3,7,8-TCDD, from Agent Orange exposure in some Vietnam-ese individuals, presumably due to food consumption. It appears unlikely that exported Vietnamese food is, in general, contaminated with large amounts of dioxin (TCDD) from Agent Orange or other sources. Further food sampling from areas of heavy Agent Orange spraying in Vietnam is warranted to map out where the source of TCDD contamination of food may be originating. [ABSTRACT FROM AUTHOR]

This case-control study was designed to investigate association between polychlorinated biphenyls (PCBs) and risk of breast cancer in an area of high environmental exposure in the Michalovce district of eastern Slovakia. Incident breast cancer cases from the Michalovce district diagnosed between May 1997 and May 1999 were recruited through the Oncology Department of the District Hospital. A total of 15 individual PCB congeners, 2,2'-bis(4-chlorophenyl)-1,1-dichloroethylene (DDE), 2,2-bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT), and hexachlorobenzene (HCB) were measured in the serum of 24 breast cancer patients and 88 population controls in 1998-1999. The median levels of total PCBs were similar in cases (2586?ng/g of lipid) and controls (2682?ng/g of lipid). Higher serum levels (highest vs. lowest tertile) of total PCBs (odds ratio (OR)=0.42, 95% CI 0.10-1.82, p-for trend=0.31), group 1 congeners (OR=0.37, 95% CI 0.10-1.43, P-for trend=0.02), group 2 congeners (OR=0.32, 95% CI 0.07-1.56, P-for trend=0.60), and group 3 congeners (OR=0.49, 95% CI 0.12-2.04, P-for trend=0.51) were inversely associated with risk of breast cancer. Higher serum levels of DDE (OR=3.04, 95% CI 0.65-14.3, P-for trend=0.10) were positively associated with risk of breast cancer, while there was no association for DDT (OR=1.19, 95% CI 0.27-5.23, P-for trend=0.68), and an inverse association for HCB (OR=0.45, 95% CI 0.06-3.19, P-for trend=0.67). While generally not statistically significant, PCB and HCB levels were inversely associated with risk of breast cancer in this highly exposed population. DDE, but not DDT, was positively associated with risk.Journal of Exposure Analysis and Environmental Epidemiology (2003) 13, 267-275. doi:10.1038/sj.jea.7500277 [ABSTRACT FROM AUTHOR]

This is the first known study of dioxins, dibenzofurans, and polychlorinated biphenyls (PCBs) in commercial American bottled baby foods purchased in the United States. Dioxins, persistent chlorinated organics, are inadvertent by-products of chemical synthesis or combustion and are toxic to humans and other animals. Almost all dioxins enter the body through food consumption, specifically from food products containing animal fat. Major-brand bottled baby food containing meat was purchased at U.S. supermarkets and 12 pooled samples were analyzed for dioxins using high-resolution gas chromatography with high-resolution mass spectrometry. Low levels of dioxins were found in these products. The range was from 28 to 226 parts per quadrillion (ppq) dioxin toxic equivalents (TEQ). This is reported on a whole or wet weight (as eaten) basis. As a comparison, findings of dioxins in U.S. supermarket meat ranged from 28 to 540 ppq. Although dioxin levels are generally lower in these baby foods than in meat or poultry, the presence of dioxins in commercial baby food containing meat is cause for concern. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article in the previous issue concerning agent orange exposure and the development of prostate cancer in American Vietnam veterans by K. Chamie, D. Lee and L. M. Ellison.

We examined serum levels of persistent organic pollutants (POPs) among geographical regions of the United States as defined by the US Census Bureau. National Health and Nutrition Examination Survey (NHANES) data for adults aged 20 years and older are presented for selected survey periods between 1999 and 2010. From NHANES 1999 through 2004, dichlorodiphenyldichloroethylene (DDE) concentration levels were consistently higher among people living in the West than in the Midwest, Northeast, or South. In 2003-2010, perfluorinated compound concentrations tended to be highest in the South. The sum of 35 polychlorinated biphenyls (PCBs) congeners was significantly higher in the Northeast [GM: 189; 95% CI: 173-204 ng/g lipid] than the remaining regions. The regional differences in higher body burdens of exposure to particular POPs could be attributed to a variety of activities, including region-specific patterns of land use and industrial and agricultural chemical applications, as well as different levels of regulatory activity. [ABSTRACT FROM AUTHOR]