OBJECTIVE:To determine if occupational exposure to dioxins is associated with an increased frequency of t(14;18) translocations.METHODS:A cross-sectional analysis of serum dioxin levels and t(14;18) frequencies in peripheral blood mononuclear cells in 218 former chemical plant workers and 150 population controls.RESULTS:The workers had significantly higher geometric mean serum levels of 2,3,7,8-TCDD (26.2 vs 2.5 ppt) and TEQ (73.8 vs 17.7 ppt) than controls. There were no significant differences in the prevalence or frequency of t(14;18) translocations in the workers compared to controls. Among former workers with current or past chloracne who were t(14;18) positive, the frequency of translocations significantly increased with quartiles of 2,3,7,8-TCDD and TEQ.CONCLUSION:Chloracne appears to modulate the association between dioxin exposure and increased frequency of t(14;18) translocations.

In 2002, a cross-sectional study designed to compare the serum dioxin toxic equivalent concentrations (TEQ) of a population-based sample of Calcasieu Parish, Louisiana residents, to Lafayette Parish was conducted. The mono-ortho polychlorinated biphenyls (PCBs) were measured in order to calculate the TEQ. We compared the sum of lipid adjusted serum concentrations of 27 PCB congeners (total PCBs) in residents of these two parishes and also by their demographic characteristics.The geometric means (GM) [standard errors (SE)] of the concentrations (ngg−1 lipids) of total PCBs in participants from Calcasieu Parish and Lafayette Parish were 154 (11.8) and 168.6 (20.8) (T-test p=0.54), respectively. Various percentiles of the distribution of serum total PCB concentrations were similar in the two parishes. After adjusting by age and race in the ANCOVA regression model, the adjusted GM for the lipid adjusted total PCBs was statistically higher in the residents in Lafayette than in Calcasieu Parish regardless of age or race (P=0.007). The adjusted GM of lipid adjusted total PCBs for African Americans was significantly higher than for Whites (p<0.001). Serum total PCB levels in residents of both parishes increased linearly with age (P<0.001). The congener profiles were similar in residents of both parishes. We also compared the GMs of a sum of 8 PCBs in Calcasieu and Lafayette Parish residents to those from a representative sample of the U.S. general population in 2001–2002 and they were not significantly different between parishes or between the parish data and the U.S. general population.

Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) have been measured in surplus serum collected in 2009 from a convenience sample of 300 Texas children (boys and girls) in the birth to 13 years of age range. Serum concentrations of traditional persistent organic pollutants such as 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and p,p'-DDE did not change consistently with age. By contrast, serum concentrations of tetra-, penta-, and hexa-BDEs were lowest in the youngest children (birth to two year old) and increased 3.0 to 7.9 times, depending on the analyte, for children in the >4 to 6 years of age group. From the apex concentration to the 10 to 13 years of age group, concentrations decreased significantly except for 2,2',4,4',5,5'-hexabromodiphenyl ether (PBDE-153), which also had a longer apex concentration of >4 to 8 years of age. This concentration trend for PBDE-153 is most likely due to a longer half-life of PBDE-153 than of other PBDE congeners. The observed PBDEs concentration patterns by age may be related, at least in part, to ingestion of residential dust containing PBDEs through hand-to-mouth behavior among toddlers, preschoolers, and kindergarteners. Further studies to characterize young children's exposure to PBDEs are warranted and, in particular, to determine the lifestyle factors that may contribute to such exposures.

Serum polychlorinated biphenyls (PCBs) in Anniston, AL, residents have been associated with hypertension and diabetes. There have been no systematic interventions to reduce PCB body burdens in Anniston or other populations. Our objective was to determine the efficacy of 15 g/day of dietary olestra to reduce PCBs in Anniston residents. Blood PCBs and 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene were measured at baseline and 4-month intervals in a double-blind, placebo-controlled, 1-year trial. Participants with elevated serum PCBs were randomized into two groups of 14 and received potato crisps made with olestra or vegetable oil (VO). Elimination rates during the study period were compared with 5-year prestudy rates. Eleven participants in the olestra group and 12 in the VO group completed the study. Except for one participant in the VO group, reasons for dropout were unrelated to treatments. The elimination rate of 37 non-coplanar PCB congeners during the 1-year trial was faster during olestra consumption compared to the pretrial period (−0.0829±0.0357 and −0.00864±0.0116 year−1, respectively; P=.04), but not during VO consumption (−0.0413±0.0408 and −0.0283±0.0096 year−1, respectively; P=.27). The concentration of PCBs in two olestra group participants decreased by 27% and 25% during the trial. There was no significant time by group interaction in change from baseline. However, group main effects for total PCBs and PCB 153 were of borderline significance. This pilot study has demonstrated that olestra can safely reduce body burdens of PCBs and supports a larger intervention trial that may also determine whether reduction in PCBs will reduce the risk of hypertension and diabetes.

Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and persistent pesticides have been measured in pooled samples representative of the general noninstitutionalized population of the United States. The pools were made from individual sera from the National Health and Nutrition Examination Survey (NHANES) during 2005/06 and 2007/08. The pooled concentrations have been contrasted to NHANES 2003/04 individual measurements to evaluate changes in concentration over time and within survey period differences among age groups, race/ethnicity groups (Mexican American, non-Hispanic Black, non-Hispanic White), and sex. The arithmetic mean serum concentrations of several PCB congeners decreased from NHANES 2003/04 through 2007/08. Larger percentage reductions were seen for younger subjects (12-19 years) compared with older subjects (≥60 years). For example, the arithmetic mean concentration of 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) was 36% lower in 12-19 year old adolescents when comparing NHANES 2007/08 with 2003/04; while for subjects over the age of 60 a 14% lower concentration was seen, although, the 95% confidence intervals overlapped. Similarly, the arithmetic mean serum concentrations of tri- to hexaBDEs were lower in NHANES 2007/08 than in 2003/04; however, most confidence intervals of the arithmetic means overlapped. These findings suggest that a reduction in PBDE serum concentrations cannot yet be detected following the discontinuation of pentaBDE in 2004.

We measured serum concentrations of seven dibenzo-p-dioxin congeners (PCDDs), ten dibenzofurans (PCDFs), four non-ortho polychlorinated biphenyls (noPCBs) and six mono-ortho polychlorinated biphenyls (moPCBs) in 1950 veterans of the Vietnam War. The veterans were participants in the Air Force Health Study (AFHS) who attended the final medical examination in 2002. Blood samples were collected from 777 Ranch Hands involved in the aerial spraying of herbicides in Vietnam and a comparison group of 1173 veterans ("Comparisons") who served in Southeast Asia during the same time period. Results for moPCBs were based on a random subsample of 800 veterans. The median 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations in 2002 were 5.0 pg g(-1) lipid in Ranch Hands and 2.2 pg g(-1) lipid in Comparisons. No substantial differences were found in measured concentrations of other PCDDs, PCDFs, and noPCBs. Similarly, no substantial differences were found for moPCBs in the subsample. The median total dioxin toxic equivalent (TEQ) in Ranch Hands was 18.7 pg g(-1) lipid for PCDDs, 3.4 pg g(-1) lipid for PCDFs, and 3.2 pg g(-1) lipid for noPCBs. Median TEQs in Comparisons were 14.4 pg g(-1) lipid for PCDDs, 3.5 pg g(-1) lipid for PCDFs, and 3.3 pg g(-1) lipid for noPCBs. These TEQs, with the exception of PCDD TEQ in Ranch Hands (primarily due to elevated TCDD), were similar to or lower than those reported for similar age and gender groups in the 2001-2002 National Health and Nutrition Examination Survey (NHANES). These findings support the assumption that the Ranch Hand veterans were not more highly exposed to dioxin-like compounds other than TCDD than were Comparison veterans or the general US population.

Background: In animal studies, organochlorine pesticide (OCP) exposure alters pubertal development; however, epidemiological data are limited and inconsistent.Objective: To evaluate the associations of serum OCP concentrations [hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE)] with male pubertal onsetMethods: In Chapaevsk, Russia, a town environmentally contaminated with OCPs, 350 8-9 year old boys with measured OCPs were enrolled during 2003-2005 and were followed annually for eight years. We evaluated three measures of pubertal onset: testicular volume (TV) >3 mL in either testis, or stage 2 or greater for genitalia (G2+), or pubic hair (P2+). We used multivariable interval-censored models to evaluate associations of OCPs (quartiles) with physician-assessed pubertal onset. Results: In adjusted models, boys with higher HCB concentrations had later mean ages of TV > 3 mL and P2+ (but not G2+). Mean age at attaining TV > 3 mL was delayed 3.6 (95% CI: -2.6, 9.7), 7.9 (95% CI: 1.7, 14.0), and 4.7 months (95% CI: -1.4, 10.9) for HCB Q2, Q3, and Q4, respectively, compared to Q1 (trend p: 0.06). Boys with higher HCB concentrations reached P2+ 0.1 months earlier (95% CI: -5.8, 5.6) for Q2, 4.7 months later (95% CI: -1.0, 10.3) for Q3 and 4.6 months later (95% CI: -1.1, 10.3) for Q4 compared to Q1 (trend p: 0.04). There were no associations of serum beta-HCH and p,p'-DDE concentrations with age of pubertal onset.Conclusion: Higher prepubertal serum HCB concentrations were associated with later age of gonadarche and pubarche. (C) 2014 Elsevier Ltd. All rights reserved.

BACKGROUND: Few studies have evaluated predictors of childhood exposure to organochlorine pesticides (OCPs), a class of lipophilic persistent chemicals. Objectives: Our goal was to identify predictors of serum OCP concentrations-hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), and p,p-dichlorodiphenyldichloroethylene (p,p'-DDE)-among boys in Chapaevsk, Russia.METHODS: Between 2003 and 2005, 499 boys 8-9 years of age were recruited in a prospective cohort. The initial study visit included a physical examination; blood collection; health, lifestyle, and food-frequency questionnaires; and determination of residential distance from a local factory complex that produced HCB and beta-HCH. Fasting serum samples were analyzed for OCPs at the U.S. Centers for Disease Control and Prevention. General linear regression models were used to identify predictors of the boys' serum HCB, beta-HCH, and p,p'-DDE concentrations.RESULTS: Among 355 boys with OCP measurements, median serum HCB, beta-HCH, and p,p'-DDE concentrations were 158, 167, and 284 ng/g lipid, respectively. Lower body mass index, longer breastfeeding duration, and local dairy consumption were associated with higher concentrations of OCPs. Boys who lived < 2 km from the factory complex had 64% (95% CI: 37, 96) and 57% (95% CI: 32, 87) higher mean HCB and beta-HCH concentrations, respectively, than boys who lived >= 5 km away. Living > 3 years in Chapaevsk predicted higher beta-HCH concentrations, and having parents who lacked a high school education predicted higher p,p'-DDE concentrations.CONCLUSIONS: Among this cohort of prepubertal Russian boys, predictors of serum OCPs included consumption of local dairy products, longer local residence, and residential proximity to the local factory complex.

Four new Standard Reference Materials (SRMs) have been developed to assist in the quality assurance of chemical contaminant measurements required for human biomonitoring studies, SRM 1953 Organic Contaminants in Non-Fortified Human Milk, SRM 1954 Organic Contaminants in Fortified Human Milk, SRM 1957 Organic Contaminants in Non-Fortified Human Serum, and SRM 1958 Organic Contaminants in Fortified Human Serum. These materials were developed as part of a collaboration between the National Institute of Standards and Technology (NIST) and the Centers for Disease Control and Prevention (CDC) with both agencies contributing data used in the certification of mass fraction values for a wide range of organic contaminants including polychlorinated biphenyl (PCB) congeners, chlorinated pesticides, polybrominated diphenyl ether (PBDE) congeners, and polychlorinated dibenzo-p-dioxin (PCDD) and dibenzofuran (PCDF) congeners. The certified mass fractions of the organic contaminants in unfortified samples, SRM 1953 and SRM 1957, ranged from 12 ng/kg to 2200 ng/kg with the exception of 4,4'-DDE in SRM 1953 at 7400 ng/kg with expanded uncertainties generally <14 %. This agreement suggests that there were no significant biases existing among the multiple methods used for analysis.

The Seveso Women’s Health Study (SWHS) is a historical cohort study of the female population residing near Seveso, Italy, on 10 July 1976, when a chemical explosion resulted in the highest known residential exposure to 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD). Individual TCDD concentration was measured in serum collected near the time of the explosion, and in 1996, we collected adequate blood for TCDD and total dioxin toxic equivalent (TEQ) measurement. Polychlorinated dibenzo- p -dioxins, dibenzofurans, and biphenyls were measured in 1996 serum for a sample ( n =225, 23%) of the SWHS cohort and WHO 2005 TEQs were calculated. We examined characteristics that predict 1996 TCDD concentrations and estimated TCDD elimination half-life over the 20-year period since the explosion. Median lipid-adjusted TCDD and total TEQ concentrations in 1996 serum were 7.3 and 26.2 p.p.t., respectively. Initial 1976 TCDD and age at explosion were the strongest predictors of 1996 TCDD. The TCDD elimination half-life was 7.1 years for women older than 10 years in 1976, but was shorter in those who were younger. Twenty years after the explosion, TCDD concentrations in this SWHS sample, the majority of who were children in 1976, remain elevated relative to background. These data add to the limited data available on TCDD elimination half-life in children.

Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and persistent pesticides have been measured in serum pools from participants 3-5, 6-11, 12-19, 20-39, 40-59, and ≥60 years of age from the 2001-2002 National Health and Nutrition Examination Survey. For 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47), the unweighted (not adjusted for sampling weights) arithmetic mean concentration (±95% confidence interval) was 3.4 times higher in 3-5-year-olds (216 ± 30 ng/g of lipid) than in 12-19-year-olds (64 ± 11 ng/g of lipid), with no apparent change with increasing age for adults ≥20 years of age. By contrast, unweighted arithmetic mean concentrations of traditional persistent organic pollutants (POPs) such as hexachlorobenzene (HCB) and 2,2',3,3',4,4',5,5'-octachlorobiphenyl (PCB194) were 2- and 20-fold higher, respectively, in persons ≥60 years than in 12-19-year-old adolescents. Findings suggest higher exposures to PBDEs but lower exposures to traditional POPs in 3-5-year-old children than in adults.

Background We recently reported increased risks for all cancers and urinary cancers in workers exposed to chlorophenoxy herbicides using data from the Dutch herbicide cohort study. These risks could not be linked to the qualitative exposure proxies available. Here, we re-investigate exposure-response relationships using a (semi) quantitative measure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure.Methods Plasma TCDD levels of 187 workers were used to develop a predictive model for TCDD exposure. Cox proportional hazards model was used to investigate associations between time-varying TCDD exposure and cause-specific mortality. Sensitivity analyses were performed to assess the impact of key assumptions in exposure assessment.Results Predicted TCDD levels were associated with mortality from all causes (HR 1.08; 95% CI 1.03 to 1.13), ischaemic heart disease (IHD; HR 1.19; 95% CI 1.08 to 1.32) and non-Hodgkin's lymphoma (NHL; HR 1.36; 95% CI 1.06 to 1.74). No relationships were found between TCDD exposure and mortality from all cancers, respiratory or urinary cancers, which were previously linked to qualitative proxies of TCDD exposure in this cohort. Sensitivity analyses showed that results were relatively robust to slight changes in exposure estimation.Conclusions Modelled TCDD exposure does not explain the previously reported increased risks for cancer mortality in this cohort except for a possible association with NHL. A small increase in ischaemic heart disease was observed, however we cannot exclude that this finding was due to residual confounding. Although risk estimates for some of the rarer outcomes were still rather imprecise, we do not expect more precise estimates from longer follow-up of this cohort due to the long time-span since last exposure to TCDD.

Background: Exposure to dioxins has been associated with delayed pubertal onset in both epidemiologic and animal studies. Whether genetic polymorphisms may modify this association is currently unknown. Identifying such genes could provide insight into mechanistic pathways. This is one of the first studies to assess genetic susceptibility to dioxins.Objectives: We evaluated whether common polymorphisms in genes affecting either molecular responses to dioxin exposure or pubertal onset influence the association between peripubertal serum dioxin concentration and male pubertal onset.Methods: In this prospective cohort of Russian adolescent boys (n = 392), we assessed gene–environment interactions for 337 tagging single-nucleotide polymorphisms (SNPs) from 46 candidate genes and two intergenic regions. Dioxins were measured in the boys' serum at age 8–9 years. Pubertal onset was based on testicular volume and on genitalia staging. Statistical approaches for controlling for multiple testing were used, both with and without prescreening for marginal genetic associations.Results: After accounting for multiple testing, two tag SNPs in the glucocorticoid receptor (GR/NR3C1) gene and one in the estrogen receptor-α (ESR1) gene were significant (q < 0.2) modifiers of the association between peripubertal serum dioxin concentration and male pubertal onset defined by genitalia staging, although not by testicular volume. The results were sensitive to whether multiple comparison adjustment was applied to all gene–environment tests or only to those with marginal genetic associations.Conclusions: Common genetic polymorphisms in the glucocorticoid receptor and estrogen receptor-α genes may modify the association between peripubertal serum dioxin concentration and pubertal onset. Further studies are warranted to confirm these findings.

BACKGROUND:Limited human data suggest an association of organochlorine pesticides (OCPs) with adverse effects on children's growth. OBJECTIVE:We evaluated the associations of OCPs with longitudinally assessed growth among peripubertal boys from a Russian cohort with high environmental OCP levels. METHODS:A cohort of 499 boys enrolled in the Russian Children's Study between 2003 and 2005 at 8-9 years of age were followed prospectively for 4 years. At study entry, 350 boys had serum OCPs measured. Physical examinations were conducted at entry and annually. The longitudinal associations of serum OCPs with annual measurements of body mass index (BMI), height, and height velocity were examined by multivariate mixed-effects regression models for repeated measures, controlling for potential confounders. RESULTS:Among the 350 boys with OCP measurements, median serum hexachlorobenzene (HCB), β-hexachlorocyclohexane (βHCH), and p,p´-dichlorodiphenyldichloroethylene (p,p´-DDE) concentrations were 159 ng/g lipid, 168 ng/g lipid, and 287 ng/g lipid, respectively. Age-adjusted BMI and height z-scores generally fell within the normal range per World Health Organization standards at entry and during follow-up. However, in adjusted models, boys with higher serum HCB, βHCH, and p,p´-DDE had significantly lower mean [95% confidence interval (CI)] BMI z-scores, by -0.84 (-1.23, -0.46), -1.32 (-1.70, -0.95), and -1.37 (-1.75, -0.98), respectively, for the highest versus lowest quintile. In addition, the highest quintile of p,p´-DDE was associated with a significantly lower mean (95% CI) height z-score, by -0.69 (-1.00, -0.39) than that of the lowest quintile. CONCLUSIONS:Serum OCP concentrations measured at 8-9 years of age were associated with reduced growth, particularly reduced BMI, during the peripubertal period, which may affect attainment of optimal adult body mass and height.

Background: We sought to identify possible gene-environment interactions for congenital heart malformations (hypoplastic left heart (HLH) and coarctation of the aorta (CoAo)). We have previously shown geospatial aggregations of HLH and CoAo, higher maternal solvent exposure, and potential interaction with GST-theta activity.(Loffredo) Methods: Mother/infant pairs, where infants were < 1 yr of age were studied. Cases werei infants undergoing cardiac surgery for HLH or CoAo (N=14 pairs). Controls were unrelated cardiac malformation (N=16 pairs). Bloods were obtained at the time of surgery. Mothers completed a questionnaire about environmental exposures. Blood DNA was genotyped for 14 toxicogenomics loci. Blood concentrations of 37 lipid-adjusted PCB isomers, and 9 pesticides were determined in all pairs. Statistical analyses were made for the sum of total PCBs, dioxin like (DLPCB) and non dioxin like (NDL) PCBs. Blood AhR transactivation was also measured. Results: Mean infant age was 53 days for cases and 92 days for controls. Total PCBs, DLPCBs, NDLPCB levels were associated with CoAo (*N=7) (P= 0.008 for total PCB), but not with HLH (N=7). Covariates for PCB levels included history of alcohol consumption and maternal age. By non parametric analysis, blood concentrations of summed pesticides were associated with case status (p=0.0034), and separately for HLH and for CoAo specifically (ppDDE and t-NONA). 4 gene loci showed positive associations of low metabolizer alleles with infant cases (ARNT T19, PON1 rs# 662, CAT C26T rs # 1001179and CYP1A2 rs # 726551). Conclusions: Our data are consistent with gene-environment interactions leading to genospatial clustering of congenital heart malformations. Blood levels of PCBs and pesticides in infants with HLH or CoAo and their mothers were higher than controls. DL and NDL PCB and pesticides were associated with CoAo; DDE and t NONA were associated with both HLH and CoAo. This pilot study should be confirmed in larger cohorts

A liquid nitrogen jet-cooled thermal modulator dedicated to comprehensive two-dimensional gas chromatography has been mounted in a GC oven coupled to a high resolution magnetic sector mass spectrometry instrument. The data acquisition parameters of the slow double-focusing magnetic sector MS instrument have been optimized to accommodate the description of the narrow modulated GC peaks. Acquisition rates were increased to 20Hz, while maintaining high mass resolution. Selected ion monitoring (SIM) descriptors, typically including several ions for both native and labeled analytes, were thus reduced to one or two to ensure enough MS cycle time. For maximization of the sensitivity enhancement due to cryogenic zone compression (CZC), the entire GC peak of interest was trapped and remobilized in one event. Optimization of the method resulted in the ability to detect low attogram (ag) amounts of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) (313ag gives a S/N of 400:1), a level that had not yet been attained using classical GC-HRMS. An isotope-dilution calibration curve was constructed using (13)C(12)-2,3,7,8-TCDD as the internal standard over the range of 500ag/μL to 35,000ag/μL (R(2)=0.9953). Analyses of a standard natural human reference serum-matrix NIST SRM 1589a containing 223ag of 1,2,3,7,8-pentachlorodibenzo-p-dioxin (1,2,3,7,8-PeCDD) (70% recovery rate assumed) resulted in a peak with a S/N of 188:1 (4 sigma, m/z=355.8546). Measurement of 2,2-bis (4-chlorophenyl-1,1,1-trichloroethane) (DDE) and 2,2',4,4',5,5'-hexabromobiphenyl (BB-153) in human dried-blood spot (DBS) samples is also reported to illustrate the usefulness of such a sensitive technique. Finally, some of the challenges related to sample preparation, blank levels, and to the fact of measuring of such a limited number of molecules (less than 600,000 TCDD molecules) are discussed.