M. Judith Charles

In utero polychlorinated biphenyl exposures in relation to fetal and early childhood growth.

Background: Polychlorinated biphenyls (PCBs) are industrial chemicals that were used widely for approximately 50 years. Now banned, they are still ubiquitous because of their persistence in the environment, the food chain, and human fatty tissue. High in utero exposures cause developmental deficits accompanied by growth retardation. Studies examining intrauterine growth at lower exposures have been inconsistent, with most such investigations having relied on surrogate exposure indicators such as consumption of fish from contaminated bodies of water. Methods: In the 1960s, serum specimens were collected from pregnant women participating in the Child Health and Development Study in the San Francisco Bay Area. The women were interviewed and their serum samples stored at −20°C. At 5 years of age, detailed anthropometric measurements were made on children born in the years 1964–1967. We measured PCBs in specimens from 399 mothers using gas chromatography/electron capture detection. We conducted multiple linear regression to examine the relationship between these organochlorine concentrations and both intrauterine and 5-year growth, with adjustment for medical, lifestyle, sociodemographic, and specimen characteristics. Results: In male infants, higher total in utero PCB exposure was associated with reduced birth weight, head circumference, and weight-for-gestational age. An increase from the 10th to 90th percentile in total PCBs was related to 290 g lower birth weight, a 0.7-cm decrease in head circumference, and for weight for gestational age, a reduction in z-score of 0.6. In girls, smaller head circumference and shorter gestations were observed. In contrast, prenatal PCBs were associated with greater growth in 5-year-old girls, with no apparent effect in 5-year-old boys. Conclusions: Maternally mediated exposure to PCBs may be detrimental to fetal growth, particularly in boys. These effects apparently are not persistent. Interpretation of greater childhood growth of girls is unclear.

Polychlorinated biphenyls and their hydroxylated metabolites (OH-PCBS) in pregnant women from eastern Slovakia.

Objective Our aim in the present study was to characterize and quantify the levels of polychlorinated biphenyls (PCBs) and specific polychlorobiphenylol (OH-PCB) metabolites in maternal sera from women delivering in eastern Slovakia. Design During 2002–2004, blood samples were collected from women delivering in two Slovak locations: Michalovce district, where PCBs were formerly manufactured, and Svidnik and Stropkov districts, about 70 km north. Participants A total of 762 and 341 pregnant women were sampled from Michalovce and Svidnik/Stropkov, respectively, and OH-PCBs were measured in 131 and 31. Evaluation/Measurements We analyzed PCBs using gas chromatography (GC)/electron capture detection. OH-PCBs and pentachlorophenol (PCP) were determined as methyl derivatives using GC-electron capture negative ionization/mass spectrometry. We characterized distributions in the full cohort using inverse sampling weights. Results The concentrations of both PCBs and OH-PCB metabolites of Michalovce mothers were about two times higher than those of the Svidnik/Stropkov mothers (p < 0.001). The median weighted maternal serum levels of the sum of PCBs (∑PCBs) were 5.73 ng/g wet weight (Michalovce) and 2.82 ng/g wet weight (Svidnik/Stropkov). The median sum of OH-PCBs (∑OH-PCBs) was 0.55 ng/g wet weight in Michalovce mothers and 0.32 ng/g wet weight in Svidnik/Stropkov mothers. 4-OH-2,2′ ,3,4′ ,5,5′ ,6-Heptachlorobiphenyl (4-OH-CB187) was a primary metabolite, followed by 4-OH-2,2′ ,3,4′ ,5,5′ -hexachlorobiphenyl (4-OH-CB146). Only four PCB congeners—CBs 153, 138, 180, and 170—had higher concentrations than 4-OH-CB187 and 4-OH-CB146 (p < 0.001). The median ratio of the ∑OH-PCBs to the ∑PCBs was 0.10. Conclusions Mothers residing in eastern Slovakia are still highly exposed to PCBs, and their body burdens of these pollutants and OH-PCB metabolites may pose a risk for adverse effects on health for themselves and their children.

Secondary organic aerosols formed from oxidation of biogenic volatile organic compounds in the Sierra Nevada Mountains of California

Received 7 February 2006; revised 14 April 2006; accepted 17 May 2006; published 25 August 2006. [1] Biogenic volatile organic compound (BVOC) emissions, such as isoprene and terpenes, can be oxidized to form less volatile carbonyls, acids, and multifunctional oxygenated products that may condense to form secondary organic aerosols (SOA). This research was designed to assess the contribution of oxidized BVOC emissions to SOA in coniferous forests by collecting high-volume particulate samples for 6 days and 5 nights in the summer of 2003. The samples were analyzed for acids, carbonyls, polyols and alkanes to quantify oxidized BVOCs. Terpene and isoprene oxidation products were among the most abundant chemical species detected with the exception of hexadecanoic acid, octadecanoic acid and two butyl esters of unknown origin. The terpene oxidation products of pinonic acid, pinic acid, nopinone and pinonaldehyde showed clear diurnal cycles with concentrations two- to eight-fold higher at night. These cycles resulted from the diurnal cycles in gaseous terpene concentrations and lower temperatures that enhanced condensation of semivolatile chemicals onto aerosols. The terpene-derived compounds averaged 157 ± 118 ng/m 3 of particulate organic matter while the isoprene oxidation compounds, namely the 2-methyltetrols and 2-methylglyceric acid, accounted for 53 ± 19 ng/m 3 . Together, the terpene and isoprene oxidation products represented 36.9% of the identified organic mass of 490 ± 95 ng/m 3 .P M10 organic matter loadings in the region were approximately 2.1 ± 1.2 mg/m 3 , so about 23% of the organic matter was identified and at least 8.6% was oxidized BVOCs. The BVOC oxidation products we measured were significant, but not dominant, contributors to the regional SOA only 75 km downwind of the Sacramento urban area.

Competition between resonance ejection and ion dissociation during resonant excitation in a quadrupole ion trap

The competition between ion dissociation and ion ejection during resonant excitation in a quadrupole ion trap is investigated. Ions of similar mass but with a range of critical energies for the onset of dissociation have been examined. The effects of the amplitude and duration of the resonant excitation, the well depth in which the ions are trapped, and the pressure and nature of the collision gas are explored. Once the onset of ion ejection is reached, the rate of ion ejection increases with increased amplitude of the resonant excitation signal. The rate of ejection decreases or stays constant as a function of the duration of the resonant excitation, depending upon the ion species being excited. Increasing the trapping well depth increases the relative amount of dissociation versus ejection as does increasing the pressure of the bath gas. Adding heavier bath gases lowers the onset of ion dissociation and raises the onset of ion ejection.

A cohort study of in utero polychlorinated biphenyl (PCB) exposures in relation to secondary sex ratio

BackgroundPolychlorinated biphenyls (PCBs) are ubiquitous industrial chemicals that persist in the environment and in human fatty tissue. PCBs are related to a class of compounds known as dioxins, specifically 2,3,7,8-TCDD (tetrachloro-dibenzodioxin), which has been implicated as a cause of altered sex ratio, especially in relation to paternal exposures.MethodsIn the 1960s, serum specimens were collected from pregnant women participating in the Child Health and Development Study in the San Francisco Bay Area. The women were interviewed and their serum samples stored at -20°C. For this study, samples were thawed and a total of eleven PCBs were determined in 399 specimens. Secondary sex ratio, or sex ratio at birth, was evaluated as a function of maternal serum concentrations using log-binomial and logistic regression, controlling for hormonally active medications taken during pregnancy.ResultsThe relative risk of a male birth decreased by 33% comparing women at the 90th percentile of total PCBs with women at the 10th percentile (RR = 0.67; 95% CI, 0.48–0.94; p = 0.02), or by approximately 7% for each 1 μg/L increase in total PCB concentration. Although some congener-specific associations with sex ratio were only marginally statistically significant, all nine PCB congeners with < 30% of samples below the LOQ showed the same direction of association, an improbable finding under the null hypothesis.ConclusionMaternal exposure to PCBs may be detrimental to the success of male sperm or to the survival of male embryos. Findings could be due to contaminants, metabolites or PCBs themselves.

Quantitative analysis of the DNA adduct N2,3-ethenoguanine using liquid chromatography/electrospray ionization mass spectrometry.

The need for specificity and sensitivity in the analysis of DNA adducts has led the development of GC/MS methods. Such methods require chemical derivatization (i.e. silylation, electrophore labelling), which can also bring its own sets of problems, including the production of artifacts, interferences and sample to sample variability in derivatization. To obviate such problems, a liquid chromatographic/electrospray ionization mass spectrometric (LC/ESI-MS) method was developed to quantify N2,3-ethenoguanine (epsilon Gua), a promutagenic DNA adduct of vinyl chloride exposure. The response of epsilon Gua to isotopically labelled internal standard [13C4]epsilon Gua was linear (r2 = 0.999) and reproducible from 0.027 to 0.538 pmol microliter-1. We obtained an accuracy of 86 +/- 14% by analyzing chloroethylene oxide (CEO)-treated calf thymus DNA enriched with authentic epsilon Gua. The analysis of CEO-treated calf thymus DNA samples not enriched with authentic epsilon Gua provided a precision of 15%. The detection limits with a signal-to-noise ratio (S/N) 2.5:1 were obtained in the determination of authentic epsilon Gua at 5 fmol per injection. The detection limit obtained in the routine analysis of the biological samples was 50 fmol epsilon Gua with S/N = 3:1. The applicability of the method was established by determining epsilon Gua in rats treated with CEO by portal vein injection and an unexposed human liver. It was observed that the concentration of epsilon Gua in the rat livers increased with increase in dose and was inversely related to the time after, CEO exposure. This trend suggests rapid repair of the adduct in rat livers. In the human liver DNA sample, epsilon Gua was quantitated at 0.06 +/- 0.01 pmol mg-1 DNA.

Maternal DDT Exposures in Relation to Fetal and 5-Year Growth

Background: Dichlorodiphenyltrichloroethane (DDT) is an organochlorine pesticide still used in areas of the world where malaria vector control is needed. Few studies have examined in utero exposures to DDT in relation to fetal and early childhood growth in populations with substantial exposure to DDT. Furthermore, only a portion of these studies have investigated in utero exposures and growth during childhood. Methods: To assess the role of in utero exposures to DDT on fetal and early childhood growth, we analyzed data from mothers and children who participated in the Child Health and Development Study (CHDS), a cohort study of 20,754 women and their pregnancies conducted in the San Francisco Bay area during the 1960s. We measured p,p′-DDE, o,p′-DDT, and p,p′-DDT concentrations from the stored sera of 399 women collected during pregnancy. Outcomes were measured at the childs birth and at 5 years of age. Results: Maternal p,p′-DDE concentrations were considerable in this study, averaging 6.9 micrograms per gram lipid. After covariate adjustment, a small increase in gestational age was observed with increases in p,p′-DDT and o,p′-DDT, but there was no association with p,p′-DDE. At 5 years of age, an increase from the 25th to the 75th percentile in p,p′-DDE was related to a 2-mm increase in head circumference (95% confidence interval = 0 to 4). Overall effect sizes were small and imprecise. Furthermore, there was little evidence of specificity for a given outcome or exposure at either age. Conclusions: At the concentrations studied in this sample, DDT compounds did not appear to impair fetal or 5-year growth.

Processes that affect electrospray ionization-mass spectrometry of nucleobases and nucleosides

Due to the complexity of electrospray ionization processes and the many factors that affect the ion signal, optimization of electrospray ionization methods to gain ultimate sensitivity for analysis of nucleobases and nucleosides may not be straightforward. In this work, we investigated the effect of the pKa and the gas-phase basicity of analyte and other electrolytes on the [M+H]+ ion signal for 11 select nucleobases and nucleosides in 50% methanol:water solution. Solution chemistry plays a role in the electrospray signal for all analytes, but gas-phase chemistry may be important for compounds with pKa<3 depending on the solution composition. For compounds with pKa<3, gas-phase proton transfer reactions can be promoted to increase analyte electrospray response by the addition of ammonium acetate to the solution.

Optimization of a hybrid-mass spectrometer method for the analysis of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans

Abstract Experiments were conducted to evaluate the effect of collision energies and argon pressure on the formation of daughter ions (M-COCI) selective to the analysis of PCDDs and PCDFs. The results show that sensitivity is enhanced at higher pressures and lower collision energies. The detection sensitivity of the method for the analysis of 2, 3, 7, 8 - TCDD and 2, 3, 7, 8 - TCDF is S N =43 : 1 on 8.7 pg and S N =34 : 1 on 11.6 pg, respectively. The selectivity of the method is demonstrated through the analysis of municipal incinerator ash and pulp effluent extracts. In these cases, interferences were eliminated by HRGC/MS/MS and not by HRGC/MS at resolving powers of 10,000 and 18,000.

Ion trap mass spectrometry affords advances in the analytical and atmospheric chemistry of 2-hydroxy-2-methylpropanal, a proposed photooxidation product of 2-methyl-3-buten-2-ol

In the western United States, in areas where emissions of the biogenic hydrocarbon, 2-methyl-3-buten-2-ol (MBO) are high, MBO contributes significantly to the oxidative capacity of the atmosphere. Hydroxyl radical oxidation of MBO can play an important role in forming tropospheric ozone, and MBO reaction products may contribute to the formation of secondary organic aerosols [1–3]. Although 2-hdyroxy-2-methylpropanal was tentatively identified as a product from the reaction of MBO with ·OH in indoor chamber studies, the identity of the compound was not confirmed due to the lack of an authentic standard. Further, no data exists on the atmospheric generation and fate of 2-hydroxy-2-methylpropanal in the ambient environment. Herein, we provide further evidence that 2-hydroxy-2-methylpropanal is generated by ·OH reaction with MBO by identifying 2-hydroxy-2-methylpropanal in an indoor chamber experiment and in ambient air sampled in the Blodgett Forest, where MBO emissions are high. We analyzed 2-hydroxy-2-methylpropanal by using a method that relies on O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) and bis-(trimethylsilyl) trifluoroacetamide (BSTFA) derivatization along with ion-trap mass spectrometry. Tentative identification of 2-hydroxy-2-methylpropanal was possible by using knowledge gained in this study regarding the mass spectrometry of PFBHA-BSTFA derivatives of carbonyls with primary, secondary, and tertiary -OH groups, and ado- and keto-acids. The identification was confirmed by comparing the methane CI mass spectra and relative gas chromatographic retention time obtained by analyzing 2-hydroxy-2-methylpropanal in a sample extract and a synthesized authentic standard. Since the standard became available at the end of this study (after all samples were analyzed), we also developed a method for semi-quantification of 2-hydroxy-2-methylpropanal, with a detection limit of 27 pptv in air. We used the method to provide the first ambient air measurements of 2-hydroxy-2-methylpropanal. The analyte is not commercially available, and hence other researchers who have not synthesized an authentic standard can employ the method.