Beverly S. Cohen

Ultrafine Particle Deposition in a Human Tracheobronchial Cast

The deposition of 0.20, 0.15, and 0.04 μm diameter particles was measured in a human central airway cast using a variable larynx with cyclic inspiratory flow. Data were compared with theoretical predictions for deposition from laminar flow for the first seven airway generations. With the exception of tracheal deposition, which on average exceeded predictions by a factor of 9, the measured deposition was about twice that predicted. The enhanced deposition is attributable to secondary swirling flows. Less enhancement is observed at higher inspiratory flow rates as turbulence increases. The surface density of particles deposited at bifurcations was approximately 20% greater than along the airway lengths. This increased deposition at bifurcations should be considered when calculating tissue dose for particles which act before the initial deposit is removed by clearance processes.

Validation of biomarkers in humans exposed to benzene: urine metabolites.

BACKGROUND The present study was conducted among Chinese workers employed in glue- and shoe-making factories who had an average daily personal benzene exposure of 31+/-26 ppm (mean+/-SD). The metabolites monitored were S-phenylmercapturic acid (S-PMA), trans, trans-muconic acid (t,t-MA), hydroquinone (HQ), catechol (CAT), 1,2, 4-trihydroxybenzene (benzene triol, BT), and phenol. METHODS S-PMA, t,t-MA, HQ, CAT, and BT were quantified by HPLC-tandem mass spectrometry. Phenol was measured by GC-MS. RESULTS Levels of benzene metabolites (except BT) measured in urine samples collected from exposed workers at the end of workshift were significantly higher than those measured in unexposed subjects (P < 0.0001). The large increases in urinary metabolites from before to after work strongly correlated with benzene exposure. Concentrations of these metabolites in urine samples collected from exposed workers before work were also significantly higher than those from unexposed subjects. The half-lives of S-PMA, t,t-MA, HQ, CAT, and phenol were estimated from a time course study to be 12.8, 13.7, 12.7, 15.0, and 16.3 h, respectively. CONCLUSIONS All metabolites, except BT, are good markers for benzene exposure at the observed levels; however, due to their high background, HQ, CAT, and phenol may not distinguish unexposed subjects from workers exposed to benzene at low ambient levels. S-PMA and t,t-MA are the most sensitive markers for low level benzene exposure.

Deposition of Charged Particles on Lung Airways

The effect of a single electric charge on the efficiency with which ultrafine particles deposit in human airways has been investigated. When inhaled short-lived radon progeny are attached to electrically neutral particles their deposition efficiency is controlled by diffusion. But most ambient particles carry one, or a few, charges. We measured and compared the deposition (DE) of singly charged, charge-neutralized, and zero-charge 20-nm and 125-nm particles in hollow-cast models of human airways. These particle sizes were selected because they are about where modal peaks occur for the activity of the short-lived radon progeny in indoor air. For singly charged 20-nm particles deposition (+/- standard error) in the casts was 3.4 +/- 0.3 times that for charge neutralized aerosols and 5.3 +/- 0.3 times the amount deposited for zero-charged particles. Corresponding ratios for the 125-nm particles were 2.3 +/- 0.3 and 6.2 +/- 0.7. Since most ambient particles are charged this effect must be considered when models are used to predict dose from inhaled ultrafine particles.

Deposition of ultrafine particles in the upper airways: An empirical analysis

Abstract Deposition efficiencies measured in replicate casts of the upper bronchial airways of the human respiratory tract were compared with values predicted for deposition by diffusion and impaction for particles with mean diameters from 0.04 μm to 0.2 μm. In addition, mass deposition fractions were calculated for polydisperse particles ( σ g =1.3) to compare with predictions for monodisperse aerosols ( σ g =1). Utilizing the experimental flow rates and particle sizes it was found that the deposition efficiency by impaction was much smaller than that by diffusion, except for the case of a 0.2 μm diameter particle at a high inspiratory flow rate. An empirical expression for the diffusional deposition efficiency of particles in the upper airways was obtained based on the experimental data. In the uppermost airways of the lung the deposition predicted using this expression was about twice the value obtained using Inghams equation for particle deposition by diffusion from parabolic flow. The predictions converged as penetration increased to deeper branching levels. The behavior was analogous with predicted deposition of diffusive particles in developing flows. Detailed knowledge of deposition efficiency for these particles is required for evaluation of the risk from exposure to ambient short-lived radon decay products.

Personal exposure to different levels of benzene and its relationships to the urinary metabolites S-phenylmercapturic acid and trans,trans-muconic acid

This report is part of an extensive study to verify the validity, specificity, and sensitivity of biomarkers of benzene at low exposures and assess their relationships with personal exposure and genetic damage. The study population was selected from benzene-exposed workers in Tianjin, China, based on historical exposure data. The recruitment of 130 exposed workers from glue-making or shoe-making plants and 51 unexposed subjects from nearby food factories was based on personal exposure measurements conducted for 3-4 weeks prior to collection of biological samples. In this report we investigated correlation of urinary benzene metabolites, S-phenylmercapturic acid (S-PMA) and trans,trans-muconic acid (t,t-MA) with personal exposure levels on the day of urine collection and studied the effect of dose on the biotransformation of benzene to these key metabolites. Urinary S-PMA and t,t-MA were determined simultaneously by liquid chromatography-tandem mass spectrometry analyses. Both S-PMA and t,t-MA, but specifically the former, correlated well with personal benzene exposure over a broad range of exposure (0.06-122 ppm). There was good correlation in the subgroup that had been exposed to <1 ppm benzene with both metabolites (P-trend <0.0001 for S-PMA and 0.006 for t,t-MA). Furthermore, the levels of S-PMA were significantly higher in the subgroup exposed to <0.25 ppm than that in unexposed subjects (n=17; P=0.001). There is inter-individual variation in the rate of conversion of benzene into urinary metabolites. The percentage of biotransformation of benzene to urinary S-PMA ranged from 0.005 to 0.3% and that to urinary t,t-MA ranged from 0.6 to approximately 20%. The percentage of benzene biotransformed into S-PMA and t,t-MA decreased with increasing concentration of benzene, especially conversion of benzene into t,t-MA. It appears that women excreted more metabolites than men for the same levels of benzene exposures. Our data suggest that S-PMA is superior to t,t-MA as a biomarker for low levels of benzene exposure.

Asbestos Fiber Deposition in a Human Tracheobronchial Cast. I. Experimental

AbstractHollow replicate casts of a human tracheobronchial (TB) tree were used to evaluate the conditions and mechanisms affecting fiber deposition. These casts were exposed to an aerodynamically classified crocidolite asbestos aerosol at cyclic inspiratory flow rates of 15 and 60 l/min. The deposited fibers were washed from the interior surfaces, and their dimensions were measured by scanning electron microscopy. Deposition efficiency was found to increase with fiber length and flow rate, and deposition densities were greater at the bifurcations than along the airway walls. Deposition densities were also high at two tracheal “hot spots”: the upper dorsal section and the lower ventral section.

Alpha radioactivity in cigarette smoke

The ..cap alpha.. activity of cigarette smoke tar deposited onto membrane filters was found to be associated with the relatively insoluble fraction. Perfusion of the tar with physiological saline resulted in no change in the mean measured activity, but there was more variability in the measured values for the perfused tar than for the initial tar samples. Analysis of cigarette smoke condensate shows that radium and thorium are present, but over 99% of the ..cap alpha.. activity results from /sup 210/Po. Repeat measurements after a time lapse of 2 1/2 years indicate that the initial /sup 210/Pb content of the tar is roughly 30 to 40% of the original /sup 210/Po content for both unprocessed and perfused samples. An increase in the ..cap alpha.. activity concentration of smoke deposited in lung tissue may result from the lack of solubility of the radioactive material compared with other smoke constituents.

Deposition of inhaled charged ultrafine particles in a simple tracheal model

The deposition of ultrafine (d [le] 200 nm) particles on airway surfaces is an important determinant of the radiation dose that results from inhalation of radon progeny. The activity median diameter of particles to which radon daughters attach is small (10--140 nm). In the absence of charge, deposition in the upper airways of the respiratory system occurs by impaction for large particles and diffusion for small particles. Sedimentation is negligible due to the high flow rates in these airways. Experiments conducted in hollow casts and in vivo in humans have all shown an increase in deposition due to the particle charge. In vivo experimental results showed that there exists a threshold value of charge on the particle (q[sub c]) above which the electrostatic charge enhances deposition. These experiments were performed for particles for which deposition by diffusion is small (d [le] 300 nm). Deposition of ultrafine particles in the airways may occur by a combined mechanism of diffusion and electrostatic charge.

Asbestos Fiber Deposition in a Human Tracheobronchial Cast. Ii. Empirical Model

AbstractExperimental data on asbestos fiber deposition in hollow replicate casts of a human tracheobronchial tree were used to derive a generic empirical model for the deposition of fibrous aerosols in lung airways. The mechanisms primarily responsible for deposition under the experimental conditions used were inertial impaction and interception. The initial empirical model developed on the basis of these two deposition mechanisms and turbulent flow fit the data reasonably well for fibers less than 10 μm in length. The addition of a term to account for the influence of partial turbulence on interception efficiency improved the fit of the data for the longer fibers to the model.

Sensitive biomarker of polycyclic aromatic hydrocarbons (PAHs): urinary 1-hydroxyprene glucuronide in relation to smoking and low ambient levels of exposure

Abstract 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 µg m−3, respectively. The corresponding levels in residents were 0.050, 0.034 and 0.025 µg m−3; and those in gardeners were 0.011, 0.020 and 0.008 µg 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 µg 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.