Biomedical subjects

D L Ashley

Publications and source records attributed to D L Ashley.

58 records · Page 4Linked to original sources

PubMedDate not supplied

A rapid, sensitive method for the quantitation of N-acetyl-S-(2-hydroxyethyl)-L-cysteine in human urine using isotope-dilution HPLC-MS-MS.

Because of increasing concern about exposure to carcinogens and other toxicants, reliable methods for biological monitoring of potentially exposed populations must be developed. For biological monitoring to be useful, appropriate biomarkers of exposures to xenobiotics must be identified, and sensitive, specific methods for quantifying the targeted biomarker must be developed. We have developed a sensitive and selective method for the analysis of N-acetyl-S-(2-hydroxyethyl)-L-cysteine (HEMA), urinary metabolite of at least three different known human carcinogens (vinyl chloride, ethylene oxide, and ethylene dibromide). The method uses strong anion-exchange solid-phase extraction and isotope-dilution high-performance liquid chromatography-tandem mass spectrometry. Our method is simple and is not labor intensive; the preparation time per sample is less than 10 min. Because urine samples vary in both their concentration and ion strength, intersample variability in HEMA recovery during the extraction is large. To overcome this inherent limitation, we use the isotope-dilution technique, which allows a complete correction for the extraction recovery for each sample. The limit of detection of the method is 0.68 microgram/L in a 1-mL urine sample with a coefficient of variation of 22% (determined by replicate analyses at both 4 and 11 micrograms/L) and an accuracy indistinguishable from 100%. Preliminary analyses of urine from a population with no known overt exposure to the parent toxicants show a frequency of detection of approximately 75%, which indicates that this method has the sensitivity to detect urinary HEMA derived from environmental exposure. We are currently using this method to establish a reference range of background exposure to these toxicants in the U.S. population.

Acetylcysteine↗

PubMedDate not supplied

Strategies for biological monitoring of exposure for contemporary-use pesticides.

Pesticides are used on a massive scale in the United States. The widespread use of these pesticides has made it virtually impossible for the average person to avoid exposure at some level. Generally, it is believed that low-level exposure to these pesticides does not produce acute toxic effects; however, various cancers and other noncancer health endpoints have been associated with chronic exposure to several groups of pesticides. Therefore, it is imperative that well-designed studies investigate the potential relationship between contemporary pesticide exposure and health effects. For these studies to be accurate, reliable methods for determining individual exposure must be used. Biological monitoring is a useful tool for assessing exposure to some contemporary pesticides. As with any analytical method, biological monitoring entails many difficulties, but, in many instances, they can be overcome by the logical use of available information and information acquired in carefully designed studies. At the Centers for Disease Control and Prevention (CDC), we have acquired extensive experience in the development and application of specific techniques for biological monitoring of a variety of toxicants, including many of the contemporary-use pesticides. We have used these methods to measure the internal dose of pesticides received by people in acute and chronic incidents resulting from both environmental and industrial exposure. Additionally, we have established normative values, or reference ranges, of several pesticides based on measurements of their metabolites in the urine of randomly selected adults in the US population. These data have been successfully used to distinguish overt exposures from 'background' exposure. In this paper, we present several examples of the usefulness of biological monitoring in urine and blood and describe the difficulties involved with developing methods in these matrices. We also present a general strategy, considerations, and recommendations for developing biological monitoring techniques for measuring the internal dose of contemporary-use pesticides.

Adult↗

PubMedDate not supplied

Application of analytical standards in method development: selected chlorinated phenols and herbicides.

Pure analytical standards are key components in the successful development of accurate analytical methods. When such compounds are unavailable commercially, a laboratory synthesis activity can provide such materials for use in method development. An example of such an approach is the synthesis of ethyl ethers of chlorinated phenols and ethyl esters of several phenoxy herbicides. Individual synthesis steps and the characterization of such materials are described. The use of such analytical standards in method development is vital for defining method characteristics. In addition, such materials are helpful in diagnosing chromatographic and mass spectral problems in the course of this work. Key mass spectral information including parent and daughter scans obtained from these analytical standards by using tandem mass spectrometry provide the basis for a new analytical method with increased sensitivity and specificity.

Chemical Phenomena↗

PubMedDate not supplied

Volatile organic compound testing of a population living near a hazardous waste site.

Accurate measures of individual exposure are critical in reducing misclassification and establishing scientifically valid associations between health outcomes and exposures to environmental contaminants. As part of a community health study, the Agency for Toxic Substances and Disease Registry conducted exposure testing for volatile organic compounds (VOCs) in the blood of people residing near an industrial complex. The purposes of the study were to assess recent exposures to VOCs in this community and to assess the utility of conducting blood VOC testing on populations near hazardous waste sites. One hundred blood specimens from the target area and 106 blood specimens from the control area were collected for analysis. The blood VOC levels in the target-area participants were compared to those in the control area and to a national reference population. Of the 31 separate VOCs for which testing was done, only acetone was statistically significantly (p < 0.05) higher in target-area participants (1,636 parts per billion [ppb]) than in control-area participants (1,353 ppb). 1,1,1-Trichloroethane was found at higher geometric mean levels in the control group (0.169 ppb) than in the target group (0.115 ppb) (p = 0.01). Median blood levels of 2-butanone and 1,4-dichlorobenzene were slightly higher in both target- and control-area groups than in the national reference population, but neither area was statistically significantly higher than the national reference population for any contaminant measured. Overall, there appeared to be no association between residing in the target area and elevated blood VOC levels. Based on the results of this study, blood VOC testing should be limited to populations living near sites where environmental testing has shown recent, elevated VOC exposure, or where unusual circumstances of illness may be attributed to VOC exposure.

Acetone↗