Faculty Bibliography

The study was conducted in a Chinese population with occupational or environmental exposures to polycyclic aromatic hydrocarbons (PAHs). A total of 106 subjects were recruited from coke-oven workers (workers), residents in a metropolitan area (residents) and suburban gardeners (gardeners). All subjects were monitored twice for their personal exposures to PAHs. The biological samples were collected for measurements of 1-hydroxypyrene (1-OHP) and cotinine in urine. The geometric means of personal exposure levels of pyrene, benz(a)anthracene (BaA) and benzo(a)pyrene (BaP) in workers were 1.470, 0.978 and 0.805 microg m-3, respectively. The corresponding levels in residents were 0.050, 0.034 and 0.025 microg m-3; and those in gardeners were 0.011, 0.020 and 0.008 microg m-3, respectively. The conjugate of 1-OHP with glucuronide (1-OHP-G) is the predominant form of pyrene metabolite in urine and it showed strong associations with exposures not only to pyrene, but also to BaA, BaP and total PAHs. Most importantly, a significant difference in 1-OHP-G was even detected between the subgroups with exposures to BaP at < 0.010 and > 0.010 but < 0.020 microg m-3, suggesting that 1-OHP-G is a good marker that can be used for the risk assessment of BaP exposure at levels currently encountered in ambient air. Furthermore, multiple regression analyses of 1-OHP-G on PAHs exposure indicated that cigarette smoke was a major confounding factor and should be considered and adjusted for while using 1-OHP to estimate PAHs exposure

This report is part of an extensive biomarker study conducted in a Chinese occupational population with benzene exposures ranging from 0.06 to 122ppm (median exposure of 3.2ppm). All urinary benzene metabolites measured in this study were significantly elevated after exposure to benzene at or above 5ppm. Among these metabolites, however, only S-phenylmercapturic acid (S-PMA) and trans,trans-muconic acid (t,t-MA) showed a significant exposure-response trend over the exposure range from 0 to 1ppm (for S-PMA, p<0.0001 and for t,t-MA, p=0.006). For benzene exposure monitoring, both S-PMA and t,t-MA were judged to be good and sensitive markers, which detected benzene exposure at around 0.1 and 1ppm, respectively. Polymorphisms of the metabolic genes, including CYP2E1, quinone oxidoreductase (NQO1), GSTT1, and myeloperoxidase (MPO), were identified and did not show significant effects on the formation of metabolites, except GSTT1 on S-PMA. The production rate of S-PMA from benzene in exposed workers with GSTT1 null alleles (24.72+/-32.48mug/g creatinine/ppm benzene) was significantly lower than that in subjects with the wild type of GSTT1 (59.84+/-47.66mug/g creatinine/ppm benzene, p<0.0001). Further regression analysis of S-PMA production rate on GSTT1 genotype with adjustment of sex, age, benzene exposure, and cotinine levels indicated that the genotype of GSTT1 plays a critical role in determining the inter-individual variations of S-PMA formation from benzene exposure. Therefore, the individual genotype of GSTT1 needs to be identified and considered while using S-PMA as a marker to estimate the personal exposure levels of benzene in future population studies

This field evaluation study was conducted to assess new technology designed to measure number concentrations of strongly acidic ultrafine particles. Interest in these particles derives from their potential to cause adverse health effects. Current methods for counting and sizing airborne ultrafine particles cannot isolate those particles that are acidic. We hypothesized that the size-resolved number concentration of such particles to which people are exposed could be measured by newly developed iron nanofilm detectors on which sulfuric acid (H2SO4*) droplets produce distinctive ringed reaction sites visible by atomic force microscopy (AFM). We carried out field measurements using an array of samplers, with and without the iron nanofilm detectors, that allowed indirect comparison of particle number concentrations and size-resolved measures of acidity. The iron nanofilm detectors are silicon chips (5 mm x 5 mm x 0.6 mm) that are coated with iron by vapor deposition. The iron layer was 21.5 or 26 nm thick for the two batches used in these experiments. After exposure the detector surface was scanned topographically by AFM to view and enumerate the ringed acid reaction sites and deposited nonacidic particles. The number of reaction sites and particles per scan can be counted directly on the image displayed by AFM. Sizes can also be measured, but for this research we did not size particles collected in the field. The integrity of the surface of iron nanofilm detectors was monitored by laboratory analysis and by deploying blank detectors and detectors that had previously been exposed to H2SO4 calibration aerosols. The work established that the detectors could be used with confidence in temperate climates. Under extreme high humidity and high temperature, the surface film was liable to detach from the support, but remaining portions of the film still produced reliable data. Exposure to ambient gases in a filtered air canister during the field tests did not affect the film quality. Sampling sessions to obtain particle measurements were scheduled for two 1-week periods in each of the four seasons at a rural site in Tuxedo, New York. This schedule was selected to test outdoor performance of the iron nanofilm detectors under a variety of weather conditions. To seek possible artifacts caused by local source differences, we also sampled outdoors for two 1-week sessions during the winter in New York City. Indoor tests were conducted in the cafeteria at the Nelson Institute of Environmental Medicine (NIEM) in Tuxedo and in a residence in Newburgh, New York. For the outdoor tests we simultaneously deployed several particle samplers to obtain several measures: --the number concentration of acidic and total particles that penetrated the 100-nm cut size of a microorifice impactor (MOI) and were electrically precipitated in an electrostatic aerosol sampler (EAS) onto the iron nanofilm detectors; --the number concentrations of acidic and total particles estimated from detectors placed in a simple ultrafine diffusion monitor (UDM); --the size-fractionated mass concentration of strong acids in samples from the submicrometer collection stages of the MOI and from a polycarbonate filter, parallel to the EAS, that also collected particles penetrating the MOI's 100-nm cut size; and --the number concentration of all ambient particles with diameters of 300 nm or smaller, determined using a scanning mobility particle sizer (SMPS). In the results from these samplers, the mean number concentration of acidic particles ranged from about 100 to 1800/cm3, representing 10% to 88% of all ambient ultrafine particles for the different seasons and sites. The number concentration did not correlate with the acidic mass (hydrogen ion, or H+, content) for particles smaller than 100 nm in diameter. This was not surprising because a single 100-nm particle may contain the same acid volume as many smaller particles if they are pure acid droplets. The ambient concentrations of H+, sulfate (SO4(2-)), and ammonium (NH4+), collected on polycarbonate filters and measured as a function of particle size, were highest for particles with diameters between 280 and 530 nm, but the size distributions also suggested that a small peak of these ions existed in the particle size range below 88 nm. The H+ / SO4(2-) ratio was somewhat higher for particles below 88 nm, suggesting greater excess acidity for these small particles. Our continuous monitoring showed that airborne concentrations of ultrafine particles varied substantially with time. The iron nanofilm detectors provided a time-integrated number concentration over several days or weeks. The counts on the detectors were relatively low for some of the sampling sessions, resulting in high statistical errors in calculations. Nonetheless, agreement of the mean values was remarkably good for some of the measurements. In future tests, longer collection times and new technologies, such as improved particle-charging methods for electrical precipitation samplers, could provide more efficient collection of particles onto the detectors, higher counts, and lower count-associated uncertainties. In general, concentrations of ultrafine particles determined by AFM analysis of the detectors in the MOI-EAS and UDM appeared to underestimate the total number concentration as determined by comparison samplers. The ability to monitor airborne acidic particles provided by these iron nanofilm detectors enlarges the array of air quality variables that can be measured. This may help to resolve some of the outstanding questions related to causal relations between demonstrated health effects of ambient particles and particulate matter (PM) components

Documentation of the airborne fine and ultrafine particles produced by the terrorist attack on the World Trade Center (WTC), particularly while fires were burning, was essential for evaluating the risk of adverse health effects in people who live and work in this area. We collected airborne particles for 3 months at a site about 400 m east of the former WTC. Ultrafine particles were collected by deposition onto small detector chips for morphometric analysis by atomic force microscopy. Some chips were coated with an iron nanofilm for detection of strong acids. A condensation nucleus counter and two impactors measured particle number concentrations and size distributions. Collected particles exhibited a variety of globular forms, and most appeared to be agglomerates. No ultrafine acid particles were detected. Particle number concentrations ranged from below 1 x 10(4) cm(-3) to about 5 x 10(4) cm(-3). Occasional peaks reached values over 7 x 10(4) cm(-3). The average total mass concentration was about 17 mug/m(3) in mid-October, about half that value in November, and as low as 5 mug/m(3) in mid-December. Particle size distributions were mostly bimodal. The mass concentration of very fine particles (0.1 mum to 0.29 mum) ranged from 4.3 mug/m(3) to 0.7 mug/m(3), and the ultrafine (d < 0.1 μm) ranged from 1.46 μg/m(3) to nondetectable after 5 November 2001. Some backup filters from the October sampling sessions were analyzed for organic and elemental carbon (OC/EC) and polyaromatic hydrocarbons (PAH). About 70% of the total carbon was organic. The PAIR levels ranged from 10 to 1500 ng m(-3). Overall, our data for particle mass and number concentrations did not differ substantially from data we had collected in Manhattan the previous year. The dominant organic compounds found in these samples are those most common in urban environments. These data do not suggest, but cannot rule out, an unusual risk of adverse health effects from the number, or mass, of the fine ambient particles

This article reports an extensive program to monitor individual personal exposures of subjects recruited for a study conducted in a Chinese occupational population to determine whether selected biological markers of exposure to benzene are reliable and sensitive enough to detect low-level benzene exposure in people. The monitoring program reported here was to assure an appropriate range of exposure for subject selection as well as to provide data for the exposure response assessment. The overall study resulted in correlation of the measured exposures with the measured concentrations of two minor urinary benzene metabolites, trans,trans-muconic acid and S-phenylmercapturic acid. The study design and evaluation of biological end points are presented in separate publications. Recruitment of 130 exposed subjects was based on personal exposure measurements collected with passive organic vapor monitors at weekly intervals for 3 to 4 weeks prior to collection of biological samples. Two monitors, side by side, were used for all of the personal monitoring in the first year of the study and about 10 percent of subsequent monitoring. One of each pair was analyzed immediately in Beijing at the Institute of Occupational Medicine, and the other was shipped to the United States and analyzed at the New York University Institute of Environmental Medicine. Exposure concentrations measured over 4-5 weeks were reasonably stable with average coefficients of variation of 0.58, 0.59, and 0.46 for benzene, toluene, and xylene, respectively. Benzene exposure averaged 10 +/- 13 ppm benzene with a median of 3.8 ppm for the recruited exposed workers. Excellent correlation was obtained between samples analyzed for benzene at the two laboratories. The extensive effort to document exposures was important to the exposure-response relationship demonstrated in the full study, which concluded that S-phenylmercapturic acid appears to be a good biomarker for detecting and evaluating benzene exposure at concentrations less than 0.25 ppm

This study was conducted to validate biomarkers for early detection of benzene exposure and effect in 2 phases. The main purpose of phase 1 was to determine whether these biomarkers could reliably detect differences between workers with high exposure levels and unexposed subjects, which is the minimal screening criterion for a biomarker assay. Phase 2 of the study mainly focused on evaluating the exposure-response relation, confounding factors, and sensitivities of biomarkers for low benzene exposures. The Chinese occupational population studied had a broad range of benzene exposures. On the day of biological sample collection, exposures ranged from 0.06 to 122 ppm with a median exposure of 3.2 ppm. The median of the 4-week mean benzene exposures was 3.8 ppm, and the median lifetime cumulative exposure was 51.1 ppm-years. Compared with benzene levels in collected samples, toluene levels were relatively high, with a median of 12.6 ppm (mean, 26.3 ppm), but xylene levels were low, with a median of 0.30 ppm (mean, 0.40 ppm). The biomarkers evaluated were urinary metabolites S-phenylmercapturic acid (S-PMA*), trans,trans-muconic acid (t,t-MA), hydroquinone (HQ), catechol (CAT), and phenol; albumin adducts of benzene oxide and 1,4-benzoquinone (BO-Alb and 1,4-BQ-Alb, respectively) in blood; blood cell counts; and chromosomal aberrations. Blood cell counts in this population, including red blood cells (RBCs), white blood cells (WBCs), and neutrophils, decreased significantly with increased exposures but remained in normal ranges. Chromosomal aberration data showed significant increases of chromatid breaks and total chromosomal aberrations in exposed subjects compared with unexposed subjects. Among the urinary metabolites, the levels of S-PMA and t,t-MA were significantly elevated after benzene exposures. Both markers showed significant exposure-response trends even over the exposure range from 0 to 1 ppm. However, HQ, CAT, and phenol showed significant increases only for benzene exposure levels above 5 ppm. Multiple regression analyses of these urinary metabolites on benzene exposure indicated that toluene exposure, smoking status, and cotinine levels had no significant effects on urinary metabolite levels. A time-course study estimated the half-lives of S-PMA, t,t-MA, HQ, CAT, and phenol to be 12.8, 13.7, 12.7, 15.0, and 16.3 hours, respectively. Both BO-Alb and 1,4-BQ-Alb showed strong exposure-response associations with benzene. Regression analyses showed that after adjustment for potential confounding by smoking, there was still a strong association between benzene exposure and these markers. Furthermore, the analyses for correlations among biomarkers revealed that the urinary metabolites correlated substantially with each other. The albumin adducts also correlated well with the urinary biomarkers, especially with S-PMA. BO-Alb and 1,4-BQ adducts also correlated well with each other (r = 0.74). For benzene exposure monitoring, both S-PMA and t,t-MA were judged to be good and sensitive markers, which detected benzene exposures at around 0.1 ppm and 1 ppm, respectively. But S-PMA was clearly superior to t,t-MA as a biomarker for low levels of benzene exposure