Detailed polychlorinated biphenyl (PCB) signatures and chiral Enantiomer Fractions (EFs) of CB-95, CB-136 and CB-149 were measured for 30 workers at a transformer dismantling plant. This was undertaken to identify sources of exposure and investigate changes to the PCB signature and EFs over different exposure periods. Approximately 1.5g of serum was extracted and PCB signatures were created through analysis by comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (GC×GC–TOFMS) and EFs calculated following analysis by gas chromatography with high resolution mass spectrometry (GC–HRMS). A total of 84 PCBs were identified in the serum samples with concentrations of the 7 indicator PCBs ranging from 11–350ngg−1 of serum (1.2–39μgg−1 lipid). The PCB signatures were interpreted using principal component analysis (PCA) which was able to distinguish workers with background or recent minimal exposure from those with prolonged occupational exposure. Occupationally exposed individuals had a similar PCB profile to Aroclor A1260. However, individuals with prolonged exposure had depleted proportions of several PCB congeners that are susceptible to metabolism (CB-95, CB-101 and CB-151) and elevated proportions of PCBs that are resistant to metabolism (CB-74, CB-153, CB-138 and CB-180). The results also identified a third group of workers with elevated proportions of CB-28, CB-60, CB-66, CB-74, CB-105 and CB-118 who appeared to have been exposed to an additional source of PCBs. The results show near complete removal of the CB-95 E2 enantiomer in some samples, indicating that bioselective metabolism or preferential excretion of one enantiomer occurs in humans. By considering PCB concentrations along with detailed congener specific signatures it was possible to identify different exposure sources, and gain an insight into both the magnitude and duration of exposure.

Two new Standard Reference Materials (SRMs), SRM 3672 Organic Contaminants in Smokers' Urine (Frozen) and SRM 3673 Organic Contaminants in Non-Smokers' Urine (Frozen), have been developed in support of studies for assessment of human exposure to select organic environmental contaminants. Collaborations among three organizations resulted in certified values for 11 hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and reference values for 11 phthalate metabolites, 8 environmental phenols and parabens, and 24 volatile organic compound (VOC) metabolites. Reference values are also available for creatinine and the free forms of caffeine, theobromine, ibuprofen, nicotine, cotinine, and 3-hydroxycotinine. These are the first urine Certified Reference Materials characterized for metabolites of organic environmental contaminants. Noteworthy, the mass fractions of the environmental organic contaminants in the two SRMs are within the ranges reported in population survey studies such as the National Health and Nutrition Examination Survey (NHANES) and the Canadian Health Measures Survey (CHMS). These SRMs will be useful as quality control samples for ensuring compatibility of results among population survey studies and will fill a void to assess the accuracy of analytical methods used in studies monitoring human exposure to these organic environmental contaminants.

Background Few human studies have evaluated the impact of childhood exposure to organochlorine pesticides (OCP) on pubertal development. Objective We evaluated associations of serum OCP concentrations [hexachlorobenzene (HCB), β-hexachlorocyclohexane (βHCH), and p,p-dichlorodiphenyldichloroethylene (p,p´-DDE)] with age at attainment of sexual maturity among boys. Methods From 2003 through 2005, 350 8- to 9-year-old boys from Chapaevsk, Russia, with measured OCPs were enrolled and followed annually for 8 years. We used multivariable interval-censored models to evaluate associations of OCPs (quartiles) with three physician-assessed measures of sexual maturity: Tanner stage 5 for genitalia growth, Tanner stage 5 for pubic hair growth, or testicular volume (TV) ≥ 20 mL in either testis. Results In adjusted models, boys with higher HCB concentrations achieved sexual maturity reflected by TV ≥ 20 mL a mean of 3.1 months (95% CI: –1.7, 7.8), 5.3 months (95% CI: 0.6, 10.1), and 5.0 months (95% CI: 0.2, 9.8) later for quartiles Q2, Q3, and Q4, respectively, compared with Q1 (p trend = 0.04). Tanner stage 5 for genitalia growth was attained a mean of 2.2 months (95% CI: –3.1, 7.5), 5.7 months (95% CI: 0.4, 11.0), and 3.7 months (95% CI: –1.7, 9.1) later for quartiles Q2, Q3, and Q4, respectively, of βHCH compared with Q1 (p trend = 0.09). Tanner stage 5 for pubic hair growth occurred 6–9 months later on average for boys in the highest versus lowest quartile for HCB (p trend < 0.001), βHCH (trend p = 0.01), and p,p´-DDE (p trend = 0.04). No associations were observed between p,p´-DDE and Tanner stage 5 for genitalia growth or TV ≥ 20 mL. Conclusions and relevance Higher prepubertal serum HCB and βHCH concentrations were associated with a later age at attainment of sexual maturity. Only the highest quartile of serum p,p´-DDE was associated with later pubic hair maturation. Citation Lam T, Williams PL, Lee MM, Korrick SA, Birnbaum LS, Burns JS, Sergeyev O, Revich B, Altshul LM, Patterson DG Jr, Hauser R. 2015. Prepubertal serum concentrations of organochlorine pesticides and age at sexual maturity in Russian boys. Environ Health Perspect 123:1216–1221; http://dx.doi.org/10.1289/ehp.1409022

Cavity-Enhanced Direct Frequency Comb Spectroscopy has been applied to buffer gas cooled acetylene achieving a Doppler-limited spectral resolution of 90 MHz. Additionally Time Resolved Frequency Comb Spectroscopy allows for the detection of trans-DOCO in photolysis reaction kinetics with a molecular sensitivity of 1010 cm−3.

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.

This chapter first discusses the various aspects of human biomonitoring that are important to be able to use human data in a forensic context. Important aspects include: (1) toxicokinetics—absorption, distribution, metabolism, and elimination; (2) sensitive analytical chemistry methods; (3) characterizing normal background population levels such as in the US National Report on Human Exposure to Environmental Chemicals as well as in other countries; (4) development of reference values and biomonitoring equivalents; and (5) environmental exposure pathways, such as food, soil, dust, clay, and beef. Various human exposures are then discussed related to accidental exposures, poisonings, food contamination incidents, and occupational exposures such as e-waste and various manufacturing processes.

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.

In human exposure studies involving Polychlorinated Biphenyls (PCBs), it is useful to establish when an individual was potentially exposed. Age dating PCB exposure is complex but assessments can be made because different PCB congeners have different residence times in the human body. The less chlorinated congeners generally tend to have shorter residence times because they are biotransformed and eliminated faster than more chlorinated congeners. Therefore, the presence of high proportions of less chlorinated congeners is often indicative of recent exposure. The 2003–04 National Health and Nutrition Examination Survey (NHANES) dataset contains results for the concentration of 37 PCBs in a sub-sample of the US population. Multivariate statistical analysis of the NHANES data showed that less chlorinated congeners are not always biotransformed faster than higher chlorinated compounds. For example, PCB 28 (a tri-chlorobiphenyl) appears to be more resistant to biotransformation than PCB 101 and 110 (penta-chlorobiphenyls). Using statistical analysis of the NHANES data in conjunction with previously published studies on PCB persistence in humans, it was possible to identify the structural relationships that determine if a PCB is likely to be from a recent exposure (termed ‘episodic’) or from steady state exposure. Congeners with chlorine atoms in the 2,5- and 2,3,6-positions appear to be more susceptible to biotransformation whereas congeners with chlorine bonds in the 2,3,4- 2,4,5- 3,4,5- and 2,3,4,5-positions appear to be more persistent. This work shows that future investigations to date PCB exposure would benefit from the analysis of a wide range of congeners, including the selection of key congeners based not only on the degree of chlorination but also on the positions of the chlorine atoms on the biphenyl.

A GC × GC-TOFMS installed with a Rtx-PCB (60 m × 0.18 mm × 0.18 μm) in the first dimension and Rxi- 17 (1.5 m × 0.1 mm × 0.1 μm) column in the second dimension was used to separate 188 out of 209 congeners. A further 12 congeners were identified through additional data processing resulting in the identification of a total of 200 congeners. However, caution is advised if these 12 congeners were to be used in quantitative assessments. The remaining 9 co-eluting congeners were three doublets (CB65 + CB62, CB160 + CB163 and CB201 + CB204) and one triplet (CB20 + CB21 + CB33). This method was tested on five Aroclors and resulted in the separation of all congeners present in the heavier Aroclor mixtures A1254 and A1260. The suitability of this method for applications in biological matrices was demonstrated on extracted whiting and guillemot liver samples which resulted in the identification of 137 individual PCBs in the whiting liver sample and 120 in the guillemot sample. Fingerprinting was able to show clear differences in the PCB signature of the two animals. This highlights the potential of this method for PCB fingerprinting in environmental forensics studies and other assessments that require congener specific analysis.

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.