Biomedical subjects

David L Ashley

Publications and source records attributed to David L Ashley.

31 records · Page 2Linked to original sources

PubMed2003

Tobacco-specific nitrosamines in tobacco from U.S. brand and non-U.S. brand cigarettes.

Tobacco-specific nitrosamines (TSNAs) are one of the major classes of carcinogens found in tobacco products. As part of collaborative efforts to reduce tobacco use and resulting disease, the U.S. Centers for Disease Control and Prevention (CDC) carried out a two-phase investigation into the worldwide variation of the levels of TSNAs in cigarette tobacco. In the first phase, representatives of the World Health Organization (WHO) purchased cigarettes; scientists from the CDC subsequently measured the levels of TSNAs in tobacco from 21 different countries. Although the data collected from this initial survey suggested that globally marketed U.S.-brand cigarettes typically had higher TSNA levels than locally popular non-U.S. cigarettes in many countries, the number of samples limited the statistical power of the study. To improve statistical power and to ensure adequate sampling, the CDC conducted a second survey of 14 countries. In addition to the United States, the CDC selected the world's 10 most populous countries and three additional countries, so that at least two countries from each of the six WHO regions were represented. For each country, the CDC compared 15 packs of Marlboro cigarettes, which is the world's most popular brand of cigarettes, with 15 packs of a locally popular non-U.S. brand in the study country. Marlboro cigarettes purchased in 11/13 foreign countries had significantly higher tobacco TSNA levels than the locally popular non-U.S. brands purchased in the same country. The findings suggest that TSNA levels in tobacco can be substantially reduced in some cigarettes.

Carcinogens↗

PubMed2003

Determination of tar, nicotine, and carbon monoxide yields in the smoke of bidi cigarettes.

A survey of the nicotine, tar, and carbon monoxide (CO) levels in mainstream smoke from 21 brands of bidi cigarettes and five brands of traditional cigarettes was conducted using a variation of the Federal Trade Commission (FTC) standardized cigarette smoking machine method. The primary difference between this method and the FTC method was a reduction of the 60-s puff interval to 15 s. The shorter puff interval was required to prevent the bidi cigarettes from self-extinguishing and may represent a closer approximation to human usage. The goal of this study was to evaluate the smoke-delivery potential for tar, nicotine, and CO in mainstream smoke from bidi cigarettes compared with traditional domestic cigarettes smoked under identical conditions. Approximately half of the bidi brands examined were marketed as filtered varieties. Unlike traditional cigarettes, the filtered and unfiltered bidi brands yielded comparable smoke deliveries. Thus, a filtered bidi cigarette brand does not provide any harm-reduction benefit that might result from a reduction in levels of tar, nicotine, and CO compared with an unfiltered variety. Our findings indicate that bidi cigarettes can deliver high levels of tar (77.9+/-9.5 mg/bidi), nicotine (2.7+/-.4 mg/bidi), and CO (39.2+/-5.7 mg/bidi). In comparison, traditional cigarettes smoked using the bidi cigarette protocol have lower tar and CO yields, but have nicotine deliveries comparable with bidi cigarettes.

Carbon Monoxide↗

PubMed2003

Urinary levels of trichloroacetic acid, a disinfection by-product in chlorinated drinking water, in a human reference population.

Trichloroacetic acid (TCAA), a known mouse liver carcinogen and a possible human carcinogen, is found in chlorinated drinking water. We measured TCAA in archived urine samples from a reference population of 402 adults using isotope-dilution high-performance liquid chromatography-tandem mass spectrometry. TCAA was detected in 76% of the samples examined at concentrations ranging from < 0.5 micro g TCAA/L to more than 25 micro g/L; the 90th percentile concentration was 23 micro g/L (22 micro g TCAA/g creatinine); and the geometric mean and median concentrations were 2.9 micro g/L (2.6 micro g/g creatinine) and 3.3 micro g/L (3.2 micro g/g creatinine), respectively. The frequency of detection of TCAA in urban areas was higher than in rural areas (p = 0.00007), and sex and place of residence (i.e., urban vs. rural) were found to have a significant interaction in modulating the levels of TCAA (p = 0.012). Urban residents had higher mean levels of TCAA (men, 5.3 micro g/L, 3.8 micro g/g creatinine; women, 2.9 micro g/L, 2.8 micro g/g creatinine) than did rural residents (men, 2.2 micro g/L, 1.7 micro g/g creatinine; women, 2.6 micro g/L, 2.7 micro g/g creatinine). The higher frequency of detection of TCAA in urban than in rural areas and higher levels of TCAA among urban than among rural residents may reflect the fact that urban residents use primarily chlorinated water from public water supplies, whereas those in rural areas are more likely to obtain water from private wells, which typically are not chlorinated.

Adult↗

PubMed2002

Determination of nicotine and other minor alkaloids in international cigarettes by solid-phase microextraction and gas chromatography/mass spectrometry.

Nicotine, nornicotine, anabasine, and anatabine are the most abundant alkaloids in tobacco. Along with the addictiveness of nicotine, other properties, including their occurrence in tobacco at relatively high concentrations, and as the primary precursors for the highly carcinogenic tobacco-specific nitrosoamines, make these chemicals important from a public health standpoint Therefore, developing a fast and accurate quantitative method to screen large numbers of cigarette samples for these alkaloids was important. This report describes the first use of headspace analysis using solid-phase microextraction combined with gas chromatography/mass spectrometry for the unambiguous detection of tobacco alkaloids. Detection and confirmation of each analyte isestablished by both chromatographic retention times and the ratio of reconstructed ion chromatogram peak areas from characteristic quantitation ion and confirmation ion. Twenty-eight cigarette brands from 14 countries were analyzed. Surprisingly, the minor alkaloids' response factors varied considerably among different styles of cigarettes. Accurate quantification was achieved using a three-point standard addition protocol. The standard addition approach was essential to obtain accurate measurements by minimizing matrix effects that would otherwise have contributed to quantitation bias. Significant differences in the alkaloid profiles were measured in the different cigarette brands. These results strongly suggest that such differences reflect variations associated with blend compositions, tobacco quality, and manufacturing practices.

Alkaloids↗

PubMed2002

Quantitation of 2-chlorovinylarsonous acid in human urine by automated solid-phase microextraction--gas chromatography--mass spectrometry.

Lewisite [dichloro(2-chlorovinyl)arsine] is a highly toxic chemical warfare agent with vesicant properties. The accidental exposure to lewisite or its intentional use as a chemical terrorism weapon are a public health threat and warrant investigations for the development of analytical methods to detect biomarkers of exposure to lewisite. Under aqueous conditions, lewisite rapidly hydrolyzes to the non-volatile 2-chlorovinylarsonous acid (CVAA). We have developed a sensitive, simple, and automated method for measuring CVAA in human urine. The assay is based on the use of solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) after derivatization of the CVAA with 1,3-propanedithiol (PDT). The volatile CVAA-PDT is adsorbed onto a SPME fiber and analyzed by GC-MS. The assay was validated on human urine samples spiked with CVAA to determine the accuracy, precision, and limit of detection (LOD). The LOD was 7.4 pg in 1 ml of urine.

Arsenicals↗

PubMed2002

Quantitative detection of trichloroacetic acid in human urine using isotope dilution high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.

The chemical disinfection of drinking water to control microbial contaminants results in the formation of disinfection byproducts (DBPs). The volatile trihalomethanes and the nonvolatile haloacetic acids (HAAs) are the most prevalent DBPs. It is important to monitor human exposure to HAAs because of their potential adversehealth effects, such as cancer. Among the HAAs, urinary trichloroacetic acid (TCAA) is a potential valid biomarker for assessing chronic ingestion exposure to HAAs from drinking water. We have developed a rugged, high-throughput, sensitive, accurate, and precise assay for the measurement of trace levels of TCAA in human urine using a simple solid-phase extraction (SPE) cleanup followed by isotope dilution high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). TCAA is extracted from the urine using SPE, separated from other extract components by reversed-phase HPLC, and analyzed by negative ion electrospray ionization-isotope dilution-MS/MS using a multiple reaction monitoring experiment. The method is simple and fast and is not labor intensive (sample preparation and analysis can be performed in approximately 15 min) with a limit of detection of 0.5 ng/mL in 1 mL of urine.

Carbon Isotopes↗

PubMed2002

Comparison of trihalomethanes in tap water and blood.

Trihalomethane (THM) concentrations in blood and tap water were measured for 50 women living in two locations with different bromide concentrations and disinfectant types. Blood samples were taken from each woman early in the morning prior to any major water-use activity and again immediately after showering. Each residence was sampled for THMs in tap water prior to the woman's shower. Cobb County, GA, tap water exhibited high THM concentrations composed primarily of chloroform. Corpus Christi, TX, tap water exhibited lower THM concentrations with significant proportions of brominated THMs. THMs in tap water and blood were compared using mole fraction speciation, extent of bromine incorporation, and correlation analysis. Results indicated that THMs in the blood rose significantly as a result of showering, that showering shifted the THM distribution in the blood toward that found in the corresponding tap water, and that THMs measured in the blood of women living in the two locations reflected species and concentration differences in their respective tap waters. In general, blood concentrations were not significantly correlated with tap water concentrations. This finding suggests that other factors, in addition to tap water concentrations, may be important in determining THM concentrations in the blood.

Adult↗

PubMed2002

Treatment of high risk or recurrent meningiomas with hydroxyurea.

Recurrent, irresectable meningioma constitutes an uncommon but significant problem. Many systemic therapies have been tested without clear evidence of efficacy. More recently, two reports have suggested that hydroxyurea has activity in this context. This study examined the efficacy and toxicity of hydroxyurea in the treatment of 15 patients with high risk meningioma, residual meningioma post resection and progressive meningioma. Hydroxyurea was well tolerated although two patients ceased therapy because of skin rashes. There were no objective responses. Eleven patients achieved stable disease including eight patients who had documented progression prior to commencing hydroxyurea. These results are consistent with previous reports. In conclusion, hydroxyurea may provide some clinical benefit in patients with progressive meningioma by delaying progression of disease.

Adult↗

PubMed2002

Assessing exposure in epidemiologic studies to disinfection by-products in drinking water: report from an international workshop.

The inability to accurately assess exposure has been one of the major shortcomings of epidemiologic studies of disinfection by-products (DBPs) in drinking water. A number of contributing factors include a) limited information on the identity, occurrence, toxicity, and pharmacokinetics of the many DBPs that can be formed from chlorine, chloramine, ozone, and chlorine dioxide disinfection; b) the complex chemical interrelationships between DBPs and other parameters within a municipal water distribution system; and c) difficulties obtaining accurate and reliable information on personal activity and water consumption patterns. In May 2000, an international workshop was held to bring together various disciplines to develop better approaches for measuring DBP exposure for epidemiologic studies. The workshop reached consensus about the clear need to involve relevant disciplines (e.g., chemists, engineers, toxicologists, biostatisticians and epidemiologists) as partners in developing epidemiologic studies of DBPs in drinking water. The workshop concluded that greater collaboration of epidemiologists with water utilities and regulators should be encouraged in order to make regulatory monitoring data more useful for epidemiologic studies. Similarly, exposure classification categories in epidemiologic studies should be chosen to make results useful for regulatory or policy decision making.

Acetates↗

PubMedDate not supplied

The development and testing of a dermal exposure system for pharmacokinetic studies of administered and ambient water contaminants.

INTRODUCTION: In order to investigate the pharmacokinetics of water-borne chemicals while eliminating exposures by other routes, a dermal exposure system was developed to expose the hand and forearm of human subjects. METHODS: The goal was, primarily, to study the dermal pharmacokinetics of methyl tertiary butyl ether (MTBE), a water contaminant, and, secondarily, the ambient disinfection byproducts (DBPs). MTBE is used as a fuel oxygenate and DBPs result from chlorination of drinking water. The DBPs measured in the water and blood of the subjects were chloroform, bromodichloromethane, and dibromochloromethane. The dermal exposure system was constructed of inert and impervious materials. The interface between the glass and Teflon exposure tank and the subject was custom-made of clear Tedlar (polyvinylfluoride) so that the depth of the arm in the media could be monitored. RESULTS: Sampling of the water concentration of the test chemical, MTBE, demonstrated stability over the duration of the exposure. A temperature loss of about 1.5 degrees C occurred over the course of the 1-h exposure. Blood concentrations taken from 14 human subjects before, during, and after the 1-h exposure demonstrated that measurable MTBE and DBPs were absorbed. DISCUSSION: This system has the advantages of maintaining contaminant concentration and exposing an anatomically distinct body region, and the convenience of blood sampling.

Administration, Cutaneous↗

PubMedDate not supplied

Quantitative determination of the hydrolysis products of nitrogen mustards in human urine by liquid chromatography-electrospray ionization tandem mass spectrometry.

Nitrogen mustards are a public health concern because of their extreme vesicant properties and the possible exposure of workers during the destruction of chemical stockpiles. A sensitive, rapid, accurate, and precise analysis for the quantitation of ultratrace levels of N-ethyldiethanolamine (EDEA) and N-methyldiethanolamine (MDEA) in human urine as a means of assessing recent exposure to the nitrogen mustards bis(2-chloroethyl)ethylamine and bis(2-chloroethyl)methylamine, respectively, was developed. The method was based on solid-phase extraction, followed by analysis of the urine extract using isotope-dilution high-performance liquid chromatography-mass spectrometry with TurbolonSpray ionization and multiple-reaction monitoring. The method limits of detection were 0.41 ng/mL for EDEA and 0.96 ng/mL for MDEA in 1 mL of urine with coefficients of variation < 10% for both compounds.

Chemical Warfare Agents↗

PubMedDate not supplied

Quantitation of biomarkers of exposure to nitrogen mustards in urine from rats dosed with nitrogen mustards and from an unexposed human population.

The nitrogen mustards bis(2-chloroethyl)ethylamine (HN1), bis(2-chloroethyl)methylamine (HN2), and tris(2-chloroethyl)amine (HN3) have the potential to be used as chemical terrorism agents because of their extreme vesicant properties. We modified a previously reported method to incorporate automated solid-phase extraction, improve chromatography, and include the urinary metabolite for HN3. The improved method was used to measure levels of the urinary metabolites N-ethyldiethanolamine (EDEA), N-methyldiethanolamine (MDEA), and triethanolamine (TEA) in rats dosed with HN1, HN2, and HN3, respectively, and to establish background levels of EDEA, MDEA, and TEA in human urine samples from a population with no known exposure to nitrogen mustards. Rat dosing experiments confirmed that EDEA, MDEA, and TEA could be detected in urine for at least 48 h after exposure to HN1, HN2, and HN3, respectively. Substantial amounts of EDEA (89 ng/mL), MDEA (170 ng/mL), and TEA (1105 ng/mL) were measured in the urine of rats exposed to 10 mg HN1, HN2, and HN3, respectively, 48 h after exposure. The background concentrations for TEA in the human population ranged from below the limit of detection (LOD 3 ng/mL) to approximately 6500 ng/mL. Neither EDEA (LOD 0.4 ng/mL) nor MDEA (LOD 0.8 ng/mL) was detected above the LOD in the human samples.

Administration, Cutaneous↗

PubMedDate not supplied

Changes in blood trihalomethane concentrations resulting from differences in water quality and water use activities.

Water disinfection is extremely important for the protection of public health; however, it also forms by-products, including trihalomethanes (THMs). Previous studies of health effects from disinfection by-products have lacked accurate methods to quantify exposure over time. As a first step in establishing a better system for exposure assessment, the authors investigated which household water use activities cause a significant increase in internal dose concentrations of THMs. In this study, 7 subjects in 2 different cities carried out 12 common activities that involved water use. In 3 of these activities-bathing, showering, and washing dishes by hand-the blood concentrations of THMs increased substantially. Further analysis of the data suggested that tap water concentrations primarily controlled the blood concentrations from bathing exposure, whereas tap water concentrations and ambient air concentrations resulting from water use affected the blood concentrations from showering exposure. Further studies will focus on variables in these activities that can alter exposure.

Adult↗