Polychlorinated dibenzo-p-dioxins, dibenzofurans, biphenyls, and naphthalenes in plasma of workers deployed at the World Trade Center after the collapse.

Blood plasma samples (n = 43) collected retrospectively from New York State employees and National Guard personnel who had been assigned to work in the vicinity of the World Trade Center (WTC) during the week after the collapse of the buildings were analyzed for polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and polychlorinated naphthalenes (PCNs). On the basis of algorithms developed to rank individual exposures to dust and debris and to smoke, we categorized the samples as: more smoke exposure (MSE), more dust exposure (MDE), less smoke exposure (LSE), and less dust exposure (LDE). Mean concentrations of PCDDs were 1070, 223, 3690, and 732 pg/g lipid wt, and mean concentrations of PCDFs were 910, 1520, 230, and 117 pg/g lipid wt, for the MSE, MDE, LSE, and LDE groups, respectively. The concentrations of PCDFs were higher in the two "more exposure" groups than in the two "less exposure" groups. Calculated TEQ concentrations of coplanar PCBs and PCDD/Fs in plasma samples were, on average, 1.12 and 41.2 pg WHO-TEQ/g lipid wt, respectively. TEQ concentrations of PCDFs were higher than those of PCDDs in both "more exposure" groups but lower than those of PCDDs in "less exposure" groups. This result is suggestive of exposure of the WTC responders to PCDFs after the WTC collapse. PCDFs contributed the majority of TEQs and are therefore the critical dioxin-like compounds in MSE/MDE groups, whereas PCDDs are the critical compounds in the LSE/LDE groups.

Exploratory assessment of sportfish consumption and polybrominated diphenyl ether exposure in New York State anglers.

A cross-sectional study was conducted to examine the influence of sportfish consumption on body burden of nine polybrominated diphenyl ether (PBDE) congeners in 36 New York State (NYS) anglers. Participating anglers who had previously reported consuming sportfish from Lake Ontario and its tributaries were found to have significantly higher blood plasma levels of BDE-28, BDE-47, BDE-99, BDE-100, and the sum of measured PBDE congeners (SigmaPBDE), than anglers who had previously reported no consumption of sportfish from these waters. Bivariate analysis was used to evaluate potential dietary predictors of PBDE plasma levels, including indicators of consumption of sportfish, as well as commercial fish, wild waterfowl, dairy products, and beef. The number of years of reported consumption of Lake Ontario sportfish between 1980 and 1990 was found to be correlated with plasma levels of BDE-47, BDE-85, BDE-99, BDE-100, BDE-153, BDE-154, and SigmaPBDE. The number of meals, eaten in the year prior to study participation, of Lake Ontario sportfish species known to have high levels of other persistent organic pollutants (POPs) was correlated with plasma levels of BDE-28, BDE-47, BDE-85, BDE-99, BDE-100, BDE-154, and SigmaPBDE. Multiple linear regression revealed that the number of years consuming Lake Ontario sportfish between 1980 and 1990, after adjusting for plasma lipids, was a weak, but statistically significant, predictor of SigmaPBDE plasma levels (beta=0.130, 95% CI: 0.007-0.254). These results suggest that sportfish consumption can contribute measurably to PBDE body burden in NYS anglers, although there are likely to be additional, more significant, sources of exposure.

Use of newborn screening program blood spots for exposure assessment: declining levels of perluorinated compounds in New York State infants.

Temporal biomonitoring studies can assess changes in population exposures to contaminants, but collection of biological specimens with adequate representation and sufficient temporal resolution can be resource-intensive. Newborn Screening Programs (NSPs) collect blood as dried spots on filter paper from nearly all infants born in the United States (U.S.). In this study, we investigated the use of NSP blood spots for temporal biomonitoring by analyzing perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (PFOSA), perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) in 110 New York State (NYS) NSP blood spot composite specimens collected between 1997 and 2007, representing a total of 2640 infants. All analytes were detected in > or =90% of the specimens. Concentrations of PFOS, PFOSA, PFHxS, and PFOA exhibited significant exponential declines after the year 2000, coinciding with the phase-out in PFOS production in the U.S. Calculated disappearance half-lives for PFOS, PFHxS, and PFOA (4.4, 8.2, and 4.1 years, respectively) were similar to biological half-lives reported for retired fluorochemical workers. Our results suggest sharp decreases in perinatal exposure of NYS infants to PFOS, PFOSA, PFHxS, and PFOA and demonstrate, for the first time, the utility of NSP blood spots for assessment of temporal trends in exposure.

Biomonitoring of perfluorochemicals in plasma of New York State personnel responding to the World Trade Center disaster.

The collapse of the World Trade Center (WTC) on September 11, 2001 resulted in the release of several airborne pollutants in and around the site. Perfluorochemicals including perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA), which are used in soil- and stain-resistant coatings on upholstery, carpets, leather, floor waxes, polishes, and in fire-fighting foams were potentially released during the collapse of the WTC. In this pilot study, we analyzed 458 plasma samples of New York State (NYS) employees and National Guard personnel assigned to work in the vicinity of the WTC between September 11 and December 23, 2001, to assess exposure to perfluorochemicals released in dust and smoke. The plasma samples collected from NYS WTC responders were grouped based on estimated levels of exposure to dust and smoke, as follows: more dust exposure (MDE), less dust exposure (LDE), more smoke exposure (MSE), and less smoke exposure (LSE). Furthermore, samples were grouped, based on self-reported symptoms at the time of sampling, as symptomatic and asymptomatic. Eight perfluorochemicals were measured in 458 plasma samples. PFOS, PFOA, perfluorohexanesulfonate (PFHxS), and perfluorononanoic acid (PFNA), were consistently detected in almost all samples. PFOA and PFHxS concentrations were approximately 2-fold higher in WTC responders than the concentrations reported for the U.S. general population. No significant difference was observed in the concentrations of perfluorochemicals between symptomatic and asymptomatic groups. Concentrations of PFHxS were significantly (p < or = 0.05) higher in the MDE group than in the LDE group. Concentrations of PFNA were significantly higher in the MSE group than in the LSE group. Significantly higher concentrations of PFOA and PFHxS were found in individuals exposed to smoke than in individuals exposed to dust. A significant negative correlation existed between plasma lipid content and concentrations of certain perfluorochemicals. Our initial findings suggest that WTC responders were exposed to perfluorochemicals, especially PFOA, PFNA, and PFHxS, through inhalation of dust and smoke released during and after the collapse of the WTC. The potential health implications of these results are unknown at this time. Expansion of testing to include all archived samples will be critical to help confirm these findings. In doing so, it may be possible to identify biological markers of WTC exposure and to improve our understanding of the health impacts of these compounds.

Environmental exposure to PBDEs and thyroid function among New York anglers.

Experimental studies suggest that polybrominated diphenyl ethers (PBDEs) can influence thyroid function, although the few human studies reported provide little support for this premise. Great Lakes sportfish anglers represent a population with potentially elevated dietary exposure to PBDEs due to the lipophilic nature of these compounds. Thirty-six licensed anglers who participated in the New York State Angler Cohort Study donated blood and completed questionnaires regarding demographic, clinical and sportfish consumption information. Archived blood specimens were analyzed for thyroid stimulating hormone, total and free thyroxine, total triiodothyronine, total serum lipids and nine PBDE congeners. PBDE congener profiles were dominated by BDE-47 (median=7.9ng/g lipids), BDE-153, and BDE-99 (medians=1.8ng/g lipids). No significant associations were observed between congeners, or their sum (ΣPBDEs), and thyroid function. However, the possibility of a positive association between ΣPBDEs and fT(4), detectable with an approximate ninefold increase in sample size, suggests that additional studies are needed.

Mercury exposure in young children living in New York City.

Residential exposure to vapor from current or previous cultural use of mercury could harm children living in rental (apartment) homes. That concern prompted the following agencies to conduct a study to assess pediatric mercury exposure in New York City communities by measuring urine mercury levels: New York City Department of Health and Mental Hygiene's (NYCDOHMH) Bureau of Environmental Surveillance and Policy, New York State Department of Health/Center for Environmental Health (NYSDOHCEH), Wadsworth Center's Biomonitoring Program/Trace Elements Laboratory (WC-TEL), and Centers for Disease Control and Prevention (CDC). A previous study indicated that people could obtain mercury for ritualistic use from botanicas located in Brooklyn, Manhattan, and the Bronx. Working closely with local community partners, we concentrated our recruiting efforts through health clinics located in potentially affected neighborhoods. We developed posters to advertise the study, conducted active outreach through local partners, and, as compensation for participation in the study, we offered a food gift certificate redeemable at a local grocer. We collected 460 urine specimens and analyzed them for total mercury. Overall, geometric mean urine total mercury was 0.31 microg mercury/l urine. One sample was 24 microg mercury/l urine, which exceeded the (20 microg mercury/l urine) NYSDOH Heavy Metal Registry reporting threshold for urine mercury exposure. Geometric mean urine mercury levels were uniformly low and did not differ by neighborhood or with any clinical significance by children's ethnicity. Few parents reported the presence of mercury at home, in a charm, or other item (e.g., skin-lightening creams and soaps), and we found no association between these potential sources of exposure and a child's urinary mercury levels. All pediatric mercury levels measured in this study were well below a level considered to be of medical concern. This study found neither self-reported nor measured evidence of significant mercury use or exposure among participating children. Because some participants were aware of the possibility that they could acquire and use mercury for cultural or ritualistic purposes, community education about the health hazards of mercury should continue.

Cyanide adducts with human plasma proteins: albumin as a potential exposure surrogate.

Cyanide (CN) is a ubiquitous environmental toxicant. The measurement of CN in whole blood is a common exposure assay, but values are error prone because of CN's rapid metabolism and clearance (t1/2 < 1 h) from this compartment. This study was undertaken to determine whether CN forms covalent adduct(s) with plasma proteins that could serve as stable biomarker(s) and potential surrogate(s) of exposure. When added to human blood, plasma, or serum, CN formed covalent adducts with immunoglobulin G (IgG) and serum albumin (HSA) in the plasma fraction. Covalent adducts were not detected in the cellular, primarily erythrocyte, fraction. With human, mouse, and rabbit IgGs, the reaction with CN occurred at intra- and/or interchain disulfide linkages in the heavy and light chains. Digestion of CN-treated HSA with trypsin or the endoproteinase Lys-C at basic pH produced tautomeric 2-iminothiazoline-4-carboxylyl/2-aminothiazolidine-4-carboxylyl (itcCys) N-terminal peptides exclusively, consistent with prior model peptide/protein studies showing that under basic conditions internal S-cyanylated-Cys residues cyclize with concomitant release of the upstream peptide. The most readily detectable reaction of CN with purified HSA was at Cys34, the only Cys of the 35 present not connected as internal cystines. Because CN does not react with free sulfhydryl groups, it is probable that S-cyanylation at Cys34 occurs at those residues that carry GSH, Cys, or other small molecules as mixed disulfides. Relatively less detectable, modified Cys residues were also identified at positions 53, 124, 392, 477, and 487. When 14CN was added to human serum or whole blood at concentrations spanning a putative nontoxic to lethal range, stable adduct formation with HSA occurred in a linear, concentration-dependent reaction that was complete within 2 h. These attributes of the reaction, coupled with a plasma compartment location, suggest that quantitation of CN bound to HSA would provide a much more reliable assessment of exposure than does measurement of CN in blood.

Characterization and quantitative analysis of DNA adducts formed from lower chlorinated PCB-derived quinones.

Polychlorinated biphenyls are wide pollutants readily detected in environmental and human specimens. DNA adduction occurs through the corresponding quinones. Polychlorinated biphenyls are first metabolized to arene oxides, which can be further oxidized to dihydroxy metabolites by microsomal cytochrome p450s. The catechol and hydroquinone products are further oxidized by peroxidases to quinones, which are electrophilic and capable of reacting with DNA to form adducts. DNA adduction is initiated by Michael addition preferentially to guanosine followed by stabilization through enolization. Another nucleophilic attack forms a five-membered ring, which aromatizes by dehydration to form the final adduct. This report describes the characterization and quantitative study of DNA adducts formed from lower chlorinated PCB-derived quinones. Quantitative study by HPLC/ESI-MS/MS and (32)P-postlabeling-HPLC gave the adduct levels in the range of 3-1200 adducts per 10(8) nucleotides. These results demonstrate that increasing chlorine substitution is associated with lower yields of DNA adduct. Although (32)P-postlabeling is more sensitive than HPLC/ESI-MS/MS for the quantitative analysis of DNA adducts, modification levels were severely underestimated by the (32)P-postlabeling assay as compared to the HPLC/ESI-MS/MS assay.

Detection and characterization of DNA adducts formed from metabolites of the fungicide ortho-phenylphenol.

The significance of DNA adduction in ortho-phenylphenol-induced carcinogenesis remains unclear. Establishing adduct structures may contribute to resolving this issue. The chemical structures of the DNA adduction products resulting from the in vitro reaction of phenylbenzoquinone, the putative ultimate carcinogenic metabolite of the fungicide/disinfectant ortho-phenylphenol, are reported here. Three isomeric adducts that resulted from reaction of deoxyguanosine were characterized by UV, LC-ESI-MS, and MS/MS, and 1D and 2D COSY-NMR spectroscopy. The proposed mechanism of product formation is nucleophilic attack by the deoxyguanosine exocyclic amine nitrogen on an electrophilic quinone carbon, followed by stabilization through enolization. Another nucleophilic attack forms a five-membered ring, which aromatizes by dehydration to form the final product. Adducts were also characterized from deoxyadenosine and deoxycytidine, although conversions were at least 10 times lower. Structures are also proposed for these products. Cell culture studies confirmed that HepG2 cells incubated with phenylbenzoquinone at concentrations associated with cytotoxicity form the same DNA adducts.