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Background: Global DNA methylation levels have been reported to be inversely associated with blood levels of persistent organic pollutants (POPs), xenobiotics that accumulate in adipose tissue. Whether these associations extend to a population with much lower concentrations of POPs is not known., Objectives: This study was performed to examine whether low-dose exposure to POPs was associated with global DNA hypomethylation in Koreans., Methods: The amount of global DNA hypomethylation was estimated by the percent 5-methyl-cytosine (%5-mC) in Alu and LINE-1 assays in 86 apparently healthy Koreans. Among various POPs, organochlorine (OC) pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenylethers (PBDEs) were measured., Results: Most OC pesticides were inversely and significantly associated with %5-mC in the Alu assay, with correlation coefficients in the range 0.2 to 0.3 after adjusting for age, sex, body mass index, smoking, and alcohol. The strongest OC pesticide associations with %5-mC in the Alu assay were observed with oxychlordane, trans-nonachlor, and p,p -dichlorodiphenyldichloroethylene. The correlation coefficient of age with %5-mC in the Alu assay was 0.24, similar to correlations of OC pesticides with %5-mC in the Alu assay. Most PCBs and PBDEs showed nonsignificant inverse trends with %5-mC in the Alu assay, but for some PCBs the U-shaped association was significant. On the other hand, POPs were not associated with %5-mC in the LINE-1 assay., Conclusions: We found that low-dose exposure to POPs, in particular OC pesticides, was associated with global DNA hypomethylation in apparently healthy Koreans.

Background: Several ubiquitous polyhalogenated compounds (PHCs) have been shown to alter thyroid function in animal and in vitro studies. So far, epidemiologic studies have focused on the potential effect of a small number of them, namely, polychlorinated biphenyls (PCBs) and some organochlorines (OCs), without paying attention to other important PHCs., Objectives: We investigated the relationship between exposure to several PHCs and thyroid hormone homeostasis in Inuit adults from Nunavik., Methods: We measured thyroid parameters [thyroid-stimulating-hormone (TSH), free thyroxine (fT(4)), total triiodothyronine (tT(3)), and thyroxine-binding globulin (TBG)] and concentrations of 41 contaminants, including PCBs and their metabolites, organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), perfluorooctanesulfonate (PFOS), and a measure of dioxin-like compounds, detected in plasma samples from Inuit adults (n = 623)., Results: We found negative associations between tT(3) concentrations and levels of 14 PCBs, 7 hydroxylated PCBs (HO-PCBs), all methylsulfonyl metabolites of PCBs (MeSO(2)-PCBs), and 2 OCPs. Moreover, we found negative associations between fT(4) levels and hexachlorobenzene concentrations. TBG concentrations were inversely related to 8 PCBs, 5 HO-PCBs, and 3 OCPs. Exposure to BDE-47 was positively related to tT (3), whereas PFOS concentrations were negatively associated with TSH, tT(3,) and TBG and positively with fT(4) concentrations., Conclusion: Exposure to several PHCs was associated with modifications of the thyroid parameters in adult Inuit, mainly by reducing tT(3) and TBG circulating concentrations. The effects of PFOS and BDE-47 on thyroid homeostasis require further investigation because other human populations display similar or higher concentrations of these chemicals.

Background: It has been suggested that pre- and postnatal exposure to persistent organic pollutants (POPs) can promote several adverse effects in children, such as altered neurodevelopment. Epidemiologic studies to date have relied on the analysis of biological samples drawn pre- or post-natally for exposure assessment, an approach that might not capture some key events in the toxicokinetics of POPs., Objectives: We aimed to build a generic physiologically based pharmacokinetic (PBPK) modeling framework for neutral POPs to assess infant toxicokinetic profiles and to validate the model using data on POP levels measured in mothers and infants from a Northern Québec Inuit population., Methods: The PBPK model developed herein was based upon a previously published model to which an infant submodel was added. Using the model and maternal blood levels at the time of delivery, exposure to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT), hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), 2,2',3,4,4',5'-hexachlorobiphenyl (PCB-138), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), and 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB-180) in mothers was estimated to subsequently simulate infant blood, breast milk, and cord blood POP concentration. Simulations were then compared with corresponding measured levels through Spearman correlation analyses., Results: Predictions were highly correlated with measured concentrations for PCB-153, PCB-180, PCB-138, HCB, and p,p'-DDE (r = 0.83-0.96). Weaker correlations were observed for p,p'-DDT and beta-HCH for which levels were near the limits of detection., Conclusion: This is the first study to validate a PBPK model of POPs in infants on an individual basis. This approach will reduce sampling efforts and enable the use of individualized POP toxicokinetic profiles in the epidemiologic studies of POP adverse effects on child development.

Background: Persistent organic pollutants (POPs), which are endocrine disruptors that accumulate in adipose tissue, can increase the risk of periodontal disease through the disturbance of the immune system., Objective: We examined associations of background exposure to POPs with periodontal disease in the general population., Design: Cross-sectional associations of concentrations of serum POPs with the prevalence of periodontal disease were investigated in 1,234 adults > or = 20 years of age in the National Health and Nutrition Examination Survey 1999-2002., Results: Among several POPs, organochlorine (OC) pesticides were most strongly associated with periodontal disease. Adjusted odds ratios across quintiles of OC pesticides were 1.0, 1.3, 1.7, 2.4, and 2.7 (p for trend < 0.01) for the presence in any site of clinical attachment loss > or = 4 mm and 1.0, 1.7, 2.6, 3.4, and 3.7 (p for trend < 0.01) for the presence of pocket depth > or = 4 mm. Polychlorinated biphenyls and polychlorinated dibenzo-p-dioxins also showed significant positive associations with one or both definitions of periodontal disease. Results did not materially change when continuous variables of clinical attachment loss or pocket depth were used as outcomes. Although participants with periodontal disease had higher white blood cell and neutrophil counts, neutrophil counts were inversely related to OC pesticides (p for trend < 0.01). These inverse associations did not change after excluding subjects with C-reactive protein >/= 3 mg/L., Conclusion: POPs, especially OC pesticides, were positively associated with periodontal disease, possibly through immunomodulation due to OC pesticides.

The apparent decline in the age at puberty in the United States raises a general level of concern because of the potential clinical and social consequences of such an event. Nutritional status, genetic predisposition (race/ethnicity), and environmental chemicals are associated with altered age at puberty. The Exposure to Chemical Agents Working Group of the National Children's Study (NCS) presents an approach to assess exposure for chemicals that may affect the age of maturity in children. The process involves conducting the assessment by life stages (i.e., in utero, postnatal, peripubertal), adopting a general categorization of the environmental chemicals by biologic persistence, and collecting and storing biologic specimens that are most likely to yield meaningful information. The analysis of environmental samples and use of questionnaire data are essential in the assessment of chemicals that cannot be measured in biologic specimens, and they can assist in the evaluation of exposure to nonpersistent chemicals. Food and dietary data may be used to determine the extent to which nutrients and chemicals from this pathway contribute to the variance in the timing of puberty. Additional research is necessary in several of these areas and is ongoing. The NCS is uniquely poised to evaluate the effects of environmental chemicals on the age at puberty, and the above approach will allow the NCS to accomplish this task.

Biomonitoring of exposure is a useful tool for assessing environmental exposures. The matrices available for analyses include blood, urine, breast milk, adipose tissue, and saliva, among others. The sampling can be staged to represent the particular time period of concern: preconceptionally from both parents, from a pregnant woman during each of the three trimesters, during and immediately after childbirth, from the mother postnatally, and from the child as it develops to 21 years of age. The appropriate sample for biomonitoring will depend upon matrix availability, the time period of concern for a particular exposure or health effect, and the different classes of environmental chemicals to be monitored. This article describes the matrices available for biomonitoring during the life stages being evaluated in the National Children's Study; the best biologic matrices for exposure assessment for each individual chemical class, including consideration of alternative matrices; the analytical methods used for analysis, including quality control procedures and less costly alternatives; the costs of analysis; optimal storage conditions; and chemical and matrix stability during long-term storage.

Blood concentrations of 11 volatile organic compounds (VOCs) were measured up to four times over 2 years in a probability sample of more than 150 children from two poor, minority neighborhoods in Minneapolis, Minnesota. Blood levels of benzene, carbon tetrachloride, trichloroethene, and m-/p-xylene were comparable with those measured in selected adults from the Third National Health and Nutrition Examination Survey (NHANES III), whereas concentrations of ethylbenzene, tetrachloroethylene, toluene, 1,1,1-trichloroethane, and o-xylene were two or more times lower in the children. Blood levels of styrene were more than twice as high, and for about 10% of the children 1,4-dichlorobenzene levels were greater than or equal to 10 times higher compared with NHANES III subjects. We observed strong statistical associations between numerous pairwise combinations of individual VOCs in blood (e.g., benzene and m-/p-xylene, m-/p-xylene and o-xylene, 1,1,1-trichloroethane and m-/p-xylene, and 1,1,1-trichloroethane and trichloroethene). Between-child variability was higher than within-child variability for 1,4-dichlorobenzene and tetrachloroethylene. Between- and within-child variability were approximately the same for ethylbenzene and 1,1,1-trichloroethane, and between-child was lower than within-child variability for the other seven compounds. Two-day, integrated personal air measurements explained almost 79% of the variance in blood levels for 1,4-dichlorobenzene and approximately 20% for tetrachloroethylene, toluene, m-/p-xylene, and o-xylene. Personal air measurements explained much less of the variance (between 0.5 and 8%) for trichloroethene, styrene, benzene, and ethylbenzene. We observed no significant statistical associations between total urinary cotinine (a biomarker for exposure to environmental tobacco smoke) and blood VOC concentrations. For siblings living in the same household, we found strong statistical associations between measured blood VOC concentrations.

A 1999 study heightened long-standing concerns over persistent organic pollutant contamination in the Aral Sea area, detecting elevated levels in breast milk and cord blood of women in Karakalpakstan (western Uzbekistan). These findings prompted a collaborative research study aimed at linking such human findings with evidence of food chain contamination in the area. An international team carried out analyses of organochlorine and organophosphate pesticides, polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) on samples of 12 foods commonly produced and consumed in Karakalpakstan. Analysis consistently detected long-lasting organochlorine pesticides and their metabolites in all foods of animal origin and in some vegetables such as onions and carrots--two low-cost components of many traditional dishes. Levels of PCBs were relatively low in all samples except fish. Analyses revealed high levels of PCDDs and PCDFs (together often termed "dioxins") in sheep fat, dairy cream, eggs, and edible cottonseed oil, among other foodstuffs. These findings indicate that food traditionally grown, sold, and consumed in Karakalpakstan is a major route of human exposure to several persistent toxic contaminants, including the most toxic of dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). Intake estimations demonstrate that consumption of even small amounts of locally grown food may expose consumers to dioxin levels that considerably exceed the monthly tolerable dioxin intake levels set by the World Health Organization. Data presented in this study allow a first assessment of the risk associated with the consumption of certain food products in Karakalpakstan and highlight a critical public health situation.