Patrick L. Kinney

A Sensitivity Analysis of Mortality/Pm-10 Associations in Los Angeles

AbstractSeveral recent studies have reported statistically significant and quantitatively similar associations between daily mortality and PM-10 or total suspended particulates (TSP). These results have raised questions of biological plausibility, as well as questions regarding the statistical methods employed, which are relatively new and not widely understood. This article evaluates the sensitivity of mortality/PM-10 results to a range of statistical methods in a newly developed data set from Los Angeles county for the period 1985–1990. Data reported here include total daily deaths (excluding accidents and suicides), 24-h average PM-10, daily 1-h maximum 03 and carbon monoxide, maximum daily temperature, and mean daily relative humidity. Analyses were limited to the subset of days on which PM-10 data were available (every sixth day). Several alternative methods for addressing each of four issues were explored in this data set. These four issues were cyclic data variations, weather influences, other air ...

Variations in PM-10 Concentrations Within two Metropolitan Areas and Their Implications for Health Effects Analyses

AbstractTemporal variations of PM-10 levels at multiple sites between 1985 and 1990 in two maJor metropolitan areas, Cook County, IL, and Los Angeles County, CA, were characterized, and sensitivity of mortality-PM-10 associations to the choice of alternate sites was examined. In both cities, the correlation of PM-10 levels among multiple sites decreased as their distance increased. While averaging PM-10 concentrations over multiple sites generally improved the significance of PM-10-mortality associations, the highest PM-10-mortaiity association in Cook County was found for an individual site. In Cook County, the magnitude of the mortality association for the average of 6 PM-10 sites, as expressed as “relative risk” per 100 μg/m3 PM-10, was similar (RR = 7.06, 95% CI 1.01–1.10) to those reported in other PM-10 studies with similar model specifications. However, the significance of regression coefficients for individual PM-10 sites varied considerably (t ratios range -0.62 to 3.30). Furthermore, every-6-day...

Distribution of chromium within cells of the blood

Although a number of investigators have examined the uptake of chromium in red blood cells (RBC) or whole blood, little is known about chromium uptake in white blood cells (WBC). Radiolabeled chromium (51Cr) was used to determine chromium uptake and distribution. Isolated RBC and enriched WBC populations were exposed in vitro to potassium chromate (Cr+6) and uptake was determined over a 2-hr time period. Exposure of either rat or human blood cells to 50 microM K2CrO4 for 2 hr resulted in greater accumulation of chromium within WBC than RBC. Uptake by rat WBC was significantly greater than that of human; whereas, uptake by human RBC was greater than that of the rat. Exposure of human whole blood to 50 microM K2CrO4, prior to isolation of WBC, also resulted in an increased uptake of chromium by WBC. Fisher 344 rats were exposed either orally or intravenously to a single dose of K2CrO4 and the distribution of chromium within blood cells was determined 1 hr, 24 hr, or 7 days following exposure. Regardless of the route or time following exposure, WBC chromium levels were consistently greater than those of RBC. However, the absolute levels of chromium did change with time. A comparison of chromium distribution 24 hr following a single oral exposure (1 ppm Cr+6) to the distribution 7 days following exposure demonstrated a reduction in chromium levels for RBC (10-fold) and for WBC (approximately 2.5-fold). In contrast, intravenous administration of chromate resulted in no significant decrease in RBC chromium levels when compared 1 hr, 24 hr, and 7 days following exposure. Although no difference in WBC chromium content was observed at 1 and 24 hr after exposure, an approximate 1.7-fold decrease in chromium content was detected at Day 7 for WBC. Intravenous administration of chromic chloride (Cr+3) resulted in a low level of chromium associated with RBC following 1 hr, and chromium was undetected in the WBC. These data demonstrate that WBC accumulate hexavalent chromium following both in vitro and in vivo exposure. In addition, white blood cells accumulate chromium to a greater extent than red blood cells. Since WBC accumulate chromium, their use as a target for the development of biomarkers of chromium exposure may be warranted.

Assessment of toxicologic interactions resulting from acute inhalation exposure to sulfuric acid and ozone mixtures

Studies examining effects of air pollutants often use single compounds, while real world exposures are to more than one chemical. Thus, it is necessary to assess responses following inhalation of chemical mixtures. Rabbits were exposed for 3 hr to sulfuric acid aerosol at 0, 50, 75, or 125 micrograms/m3 in conjunction with ozone at 0, 0.1, 0.3, or 0.6 ppm, following which broncho-pulmonary lavage was performed. Various pulmonary response endpoints related to general cytotoxicity and macrophage function were examined. In addition, a goal of the study was to define an improved approach to the analysis of data sets involving binary pollutant mixtures. Results were evaluated using analysis of variance with multiple linear contrasts to determine the significance of any effect in the pollutant-exposed groups compared to sham control animals and to assess the type, and extent, of any toxicological interaction between acid and ozone. Interaction was considered to occur when the effects of combined exposure were either significantly greater or less than additive. Pollutant exposures had no effect on lavage fluid levels of lactate dehydrogenase, prostaglandins E2 and F2 alpha, nor on the numbers, viability, or types of immune cells recovered by lavage. Phagocytic activity of macrophages was depressed at the two highest acid levels and at all levels of ozone. Exposure to all mixtures showed significant antagonism. Superoxide production by stimulated macrophages was depressed by acid exposure at the two highest concentrations, while ozone alone had no effect. Significant antagonistic interaction was observed following exposure to mixtures of 75 or 125 micrograms/m3 acid with 0.1 or 0.3 ppm ozone. The activity of tumor necrosis factor elicited from stimulated macrophages was depressed by acid at 75 and 125 micrograms/m3 while ozone had no effect. Exposure to mixtures of 125 micrograms/m3 acid with 0.3 or 0.6 ppm ozone resulted in synergistic interaction. This study provided additional evidence for antagonism between two common air pollutants and demonstrated that the type of interaction between sulfuric acid and ozone depended upon the endpoint but that the magnitude of any interaction was not always related to the exposure concentrations of the constituent pollutants.

Increased DNA-protein crosslinks in lymphocytes of residents living in chromium-contaminated areas.

It has been known for a number of years that chromium-containing mine slags were used as landfill in residential areas of Hudson County, New Jersey. Since one of the major lesions induced in intact cells by chromate is the DNA-Protein crosslink, we have used this lesion as a biomarker of biological effect of chromium (Cr) exposure. We have previously developed a sensitive and easy-to-perform assay to detect DNA-Protein crosslinks, based on the selective K SDS precipitation of DNA associated with protein. We examined the levels of DNA-Protein crosslinks in peripheral blood mononuclear cells of 33 individuals determined to be at risk for chromium exposure by virtue of their residence in Hudson County and their urinary Cr levels. These data were compared to the levels of DNA-Protein crosslinks among 49 controls who resided in noncontaminated areas. A complete clinical examination and urine analysis did not show any Cr-related abnormalities among the exposed population. The mean DNA-Protein crosslink level in the lymphocytes of the exposed group was 1.3±0.5% (SD), whereas the unexposed group had 0.8±0.4% (p<0.001), after adjustment for age, gender, race, smoking, and weight. Further studies in this population are needed to confirm the possible association between the high levels of DNA-Protein crosslink and Cr exposure.

Long-Term Intermittent Exposure to Sulfuric Acid Aerosol, Ozone, and Their Combination: Alterations in Tracheobronchial Mucociliary Clearance and Epithelial Secretory Cells

Understanding the effects from long-term exposure to individual ambient air pollutants and mixtures of pollutants is necessary for adequate assessment of health risk. This study examined quantitative and temporal alterations in tracheobronchial mucociliary clearance function and bronchial epithelial secretory cells in rabbits exposed to sulfuric acid (125 micrograms/m3), ozone (0.1 ppm), and their combination for 2 h/d, 5 d/wk for up to 1 yr; some animals were allowed a 6-month post-exposure period. Clearance times were altered during exposure to sulfuric acid or to the mixture, and became progressively slower following the end of exposures to each of the pollutant atmospheres. There was no indication of any interaction in terms of clearance response between the acid and ozone in the group exposed to the mixture. Histological examination of intrapulmonary conducting airways was performed after 4, 8, or 12 months of exposure, and after the post-exposure period. Sulfuric acid resulted in an increase in the number of secretory cells in small airways by 12 months of exposure. Ozone and the mixture resulted in an increase in secretory cell number by 4 months, but the response became attenuated with continued exposure. There was evidence for synergistic interaction between ozone and acid at 4 months, and antagonistic interaction at subsequent times. No inflammation or other biologically significant histological effects were found in any of the animals.

Air Pollution Epidemiology: Considerations in Time-Series Modeling

AbstractRecent epidemiological studies have indicated that ambient air pollution, including PM-10, is associated with excess mortality and morbidity. These studies have included both cross-sectional comparisons across communities and time-series analyses over time in single communities. Time-series analysis offers certain advantages, primarily in that the study population is the same over time, so that it acts as its own “control.” However, modeling such data is complicated by the fact that other environmental factors and other causes of illness can confound the results unless they are adequately addressed. For example, wintertime influenza epidemics cause long-wave peaks in respiratory mortality, and variations in emissions, dispersion, and atmospheric chemistry can cause seasonal cycles in pollution. Such superimposed long-wave variations in both health outcomes and pollutant concentrations can undermine the statistical validity of time-series models by inducing autocorrelation, and can create long-wave...

Effects of nickel ions on polymerase activity and fidelity during DNA replication in vitro

Nickel is a genotoxic carcinogen. However, the mechanisms of nickel-induced genotoxicity are not well understood. We have investigated the effects of Ni2+ ions on DNA polymerase activity and the fidelity of DNA replication in vitro. The effect of Ni2+ on different DNA polymerases is quite variable. The amount of enzyme inhibition and degree of alteration in replication fidelity induced by Ni2+ are dependent both on the polymerase and its associated 3-5 exonuclease activity. Some polymerases, such as E. coli DNA polymerase I, AMV reverse transcriptase and human DNA polymerase alpha, can utilize Ni2+ as a weak substitute for Mg2+ during DNA replication. Other polymerases are very sensitive to inhibition by Ni2+ and the IC50 can vary by an order of magnitude. T4 polymerase is relatively insensitive to inhibition by Ni2+, although the sensitivity is enhanced in the absence of added Mg2+, and Ni preferentially inhibits the 3-5 exonuclease function of T7 DNA polymerase. The fidelity and processivity of DNA polymerases may be either increased or decreased by Ni ions in a polymerase dependent manner. The inhibition DNA polymerase activity and altered replication fidelity may contribute significantly to Ni-induced mutagenesis and genotoxicity in vivo.

Field Evaluation of Instrument Performance: Statistical Considerations

Abstract Evaluation of the performance of air sampling instruments in field situations is a complex problem involving many components. These include aspects of the engineering design of the sampler, the physical properties of the environment being sampled, and methods for controlling and measuring instrument bias and imprecision. The broad range of air sampling designs and environments of possible interest precludes the development of a single set of field evaluation methods that could be uniformly applied in all situations. However, there are several basic underlying principles that must be considered in any field evaluation problem. This article discusses these principles and summarizes appropriate statistical methods available to assess them. An example of the application of these methods in practice is presented, based on the recent field implementation of an ambient acid aerosol monitor by New York University Medical Center. Kinney, P.L.; Thurston, G.D.: Field Evaluation of Instrument Performance: St...

Airborne Fiber Levels During Asbestos Operations and Maintenance Work in a Large Office Building

Abstract While there is growing interest in the management of asbestos-containing materials (ACM) in buildings using operations and maintenance (O&M) programs, very little data are yet available on the effectiveness of such programs in reducing airborne fiber exposures of workers and other building occupants. This article presents and analyzes air sampling data collected in conjunction with O&M work over a 5-year period in a large Washington, DC, office building. ACM present in the building included pipe insulation, air handling unit insulation, acoustical ceiling plaster, and air supply ductwork. The database included 916 phase contrast microscopy (PCM) and 163 transmission electron microscopy (TEM) area samples. Seventy-six samples were analyzed by both methods. Overall, TEM and PCM concentrations averaged 0.0109 structures/ml (s/ml) for fibers longer than 5 μm (0.0035 s/ml after excluding two outliers) and 0.0059 fibers/ml, respectively. We examined fiber concentrations in several work activity categor...