Chlorinated derivatives of dibenzo-p-dioxin and related compounds for use as reference compounds in method development and environmental toxicology.
Explore the source record for details and available documents.
Dioxins↗
Biomedical subjects
D L Ashley
Publications and source records attributed to D L Ashley.
Assessment of a scheme for prioritizing inorganic toxicants by using signs-and-symptoms analysis.
In cases of exposure to unknown substances, analyzing environmental or biological samples for elevated levels of toxicants can be extremely complex. We assessed a method for prioritizing toxic substances according to the agreement between toxic-specific and incident-reported signs and symptoms by analyzing 25 reported case histories of exposure to inorganic toxicants. In all but one case, this analysis scheme successfully prioritized toxicants for subsequent analysis. Despite its limitations, the scheme is a substantial improvement over other available methods.
Diagnosis, Differential↗
In vitro erythrocyte water transport in Duchenne muscular dystrophy: an NMR investigation.
Previous nuclear magnetic resonance (NMR) studies of erythrocyte water transport in Duchenne muscular dystrophy (DMD) have been extended to include mothers, as well as a larger patient group. The results, reported as values of the mean residence time, tau a, of intracellular water, reveals an experimentally significant decrease in permeability to water in most of the patients and one-half of the mothers examined. It was found that all mothers of patients with normal tau a values also show normal results. This finding suggests that Duchenne muscular dystrophy may exhibit genetic heterogeneity.
Biological Transport↗
Nuclear magnetic resonance analyses of the cold cataract: whole lens studies.
Pulse nuclear magnetic resonance (NMR) magnetization decay studies were performed on normal and cold cataractous rat lenses. Computer analyses of the decay curves have been interpreted to reflect two types of water within the lens that do not exchange rapidly. Upon lowering the temperature in the presence and absence of 5% acrylamide (a known agent that prevents the cold cataract phenomenon), significant differences in the relaxation rates of one water fraction were noted. 2H (NMR) spectra on young rabbit and human lenses showed temperature-related linewidth changes, which are significantly diminished in lenses incubated in acrylamide. 31P spectra also showed similar inorganic phosphate linewidth changes and also reflected progressive alterations in the metabolic state of these lenses. These studies demonstrate the potential of NMR methods for monitoring physicochemical parameters in the normal and cataractous mammalian lens.
Acrylamide↗
Nuclear magnetic resonance evidence for abnormal water transport in Duchenne muscular dystrophy erythrocytes.
Explore the source record for details and available documents.
Biological Transport↗
Time dependence of the effect of p-chloromercuribenzoate on erythrocyte water permeability: a pulsed nuclear magnetic resonance study.
Pulsed nuclear magnetic resonance spectroscopy is employed to determine the time dependence of the change in erythrocyte water permeability following exposure to p-chloromercuribenzoate (PCMB) or p-chloromercuribenzene sulfonic acid (PCMBS). pH variation was used to examine the environment of the sulfhydryl groups reactive to these drugs. PCMB reacted with at least two sulfhydryl groups which affect water permeability. This was shown by the double exponential character of the change in erythrocyte diffusional permeability with time after PCMB addition. However, only one inhibition rate process could be distinguished following PCMBS exposure, suggesting that one site bound by PCMB is not accessible to PCMBS. This site is postulated to be located in a hydrophobic region of the membrane, whereas the site reached by both drugs is located in the normal anion permeation channel. The effect of pH on the degree of inhibition due to each component and the inhibition rates is explained in terms of its effect on solubility of the reagents in the membrane and variation of the dissociated-to-undissociated ratio of PCMB.
4-Chloromercuribenzenesulfonate↗
The application of dextran-magnetite as a relaxation agent in the measurement of erythrocyte water exchange using pulsed nuclear magnetic resonance spectroscopy.
Explore the source record for details and available documents.
Adult↗
Pulse nuclear magnetic resonance measurements of water exchange across the erythrocyte membrane employing a low Mn concentration.
A simple, precise, and rapid pulse nuclear magnetic resonance technique for measuring the rate of water exchange across the erythrocyte membrane is presented. The technique is based upon the nonlinear fit of Carr-Purcell-Meiboom-Gill (CPMG) transverse relaxation time data of blood doped with 1.7 mM MnCl2 to the general two-compartment exchange condition. Previous approaches using CPMG data required high MnCl2 concentrations (25-53 nM), shown in this work to induce systematic errors ranging from 35 to 45%. At 23 degrees C the average residence time of a water molecule inside the erythrocyte (tau a) is 21.0 +/- 0.6 ms (SE). The Arrhenius plot for water exchange is linear over the range of 3 degrees - 37 degrees C and th Arrhenius activation energy is 4.79 +/- 0.03 kcal (SE). This value does not differ significantly from the energy required for bulk water flow. Results are compared with previous determinations, and sources of systematic error in tau a and the activation energy are evaluated.
Body Water↗
Reference range concentrations of N-acetyl-S-(2-hydroxyethyl)-L-cysteine, a common metabolite of several volatile organic compounds, in the urine of adults in the United States.
N-acetyl-S-(2-hydroxyethyl)-L-cysteine (2-hydroxyethyl mercapturic acid, HEMA) is a urinary metabolite of several hazardous chemicals, including vinyl chloride (VC), ethylene oxide (EO), and ethylene dibromide (EDB). Information about the levels of HEMA in the general population is useful for assessing human exposures to HEMA parent compounds, including VC, EO, and EDB. To establish reference range concentrations for HEMA, we analyzed urine samples from 412 adult participants in the Third National Health and Nutrition Examination Survey (NHANES II) by using isotope-dilution high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). HEMA was detected in 71% of the samples examined. Creatinine-corrected concentrations ranged from less than 0.68 microg/g creatinine to 58.7 microg/g creatinine; the 95th percentile concentration was 11.2 microg/g creatinine; and the geometric mean and median creatinine-corrected concentrations were both 1.6 microg/g creatinine. We observed a statistically significant difference (P=0.0001) in the creatinine-corrected geometric mean concentration values of HEMA between smokers (2.8 microg/g creatinine) and nonsmokers (1.1 microg/g creatinine). The high levels of HEMA seen among smokers likely originated from HEMA-producing chemicals known to be present in tobacco smoke.
Acetylcysteine↗
Household exposures to drinking water disinfection by-products: whole blood trihalomethane levels.
Exposure to drinking water disinfection by-products (DBPs), such as trihalomethanes (THMs), has been associated with bladder and colorectal cancer in humans. Exposure to DBPs has typically been determined by examining historical water treatment records and reconstructing study participants' water consumption histories. However, other exposure routes, such as dermal absorption and inhalation, may be important components of an individual's total exposure to drinking water DBPs. In this study, we examined individuals' exposure to THMs through drinking, showering, or bathing in tap water. Thirty-one adult volunteers showered with tap water for 10 min (n = 11), bathed for 10 min in a bathtub filled with tap water (n = 10), or drank 1 l of tap water during a 10 min time period (n = 10). Participants provided three 10 ml blood samples: one sample immediately before the exposure; one sample 10 min after the exposure ended; and one sample 30 min (for shower and tub exposure) or 1 h ( for ingestion) after the exposure ended. A sample of the water (from the tap, from the bath, or from the shower) was collected for each participant. We analyzed water samples and whole blood for THMs (bromoform, bromodichloromethane, dibromochloromethane, and chloroform) using a purge-and-trap/gas chromatography/mass spectrometry method with detection limits in the parts-per-quadrillion range. The highest levels of THMs were found in the blood samples from people who took 10 min showers, whereas the lowest levels were found in the blood samples from people who drank 1 l of water in 10 min. The results from this study indicate that household activities such as bathing and showering are important routes for human exposure to THMs.
Adult↗
Recent chemical exposures and blood volatile organic compound levels in a large population-based sample.
Little is known about factors that influence blood levels of volatile organic compounds in nonoccupationally exposed populations. The authors examined the possible relationship between recent self-reported chemical exposures and elevated blood volatile organic compound levels among 982 adult participants in theThird National Health and Nutrition Examination Survey. A strong dose-response effect was indicated (p < .001) for increasing lifetime pack-years of cigarettes smoked for elevated levels of toluene, styrene, and benzene. A positive dose-response effect was indicated for daily alcohol consumption with respect to elevated blood levels of 2-butanone and acetone. For volatile organic compounds typically found in 10-75% of the population, the establishment of a link with specific environmental exposures is relatively easy because there is less effect of confounding in this group. Some volatile organic compounds, however, are seen in less than 10% of the general population; finding these compounds at any level may warrant a search for a particular exposure.
Adult↗
Methyl tertiary butyl ether in human blood after exposure to oxygenated fuel in Fairbanks, Alaska.
Residents of Fairbanks, Alaska reported health complaints when 15%, by volume, methyl tertiary butyl ether (MTBE) was added to gasoline during an oxygenated fuel program. We conducted an exposure survey to investigate the effect of the program on human exposure to MTBE. We studied 18 workers in December 1992 during the program and 28 workers in February 1993 after the program was suspended. All workers were heavily exposed to motor vehicle exhaust or gasoline fumes. In December, the median post-shift blood concentration of MTBE in the workers was 1.8 micrograms/l (range, 0.2-37.0 micrograms/l), and in February the median post-shift blood concentration of MTBE in the 28 workers was 0.24 micrograms/l (range, 0.05-1.44 micrograms/l; p = .0001). Blood MTBE levels were measurably higher during the oxygenated fuel program in Fairbanks than after the program was suspended.
Adult↗
p-Dichlorobenzene exposure among 1,000 adults in the United States.
p-Dichlorobenzene is used widely in the United States as a room deodorizer, a moth repellent, and a precursor for a polymer. In a previous study of selected children in Arkansas, we found that 96% of the children had detectable urinary concentrations of 2,5-dichlorophenol, the metabolite of p-dichlorobenzene. In the current study, we found that, in a sample of 1,000 adults who lived throughout the United States, 98% had detectable levels of 2,5-dichlorophenol in their urine, and 96% had detectable levels of p-dichlorobenzene in their blood. Urinary 2,5-dichlorophenol concentrations ranged up to 8,700 micrograms/l (median and mean concentrations of 30 micrograms/l and 200 micrograms/l, respectively). p-Dichlorobenzene blood concentrations ranged up to 49 micrograms/l, with median and mean concentrations of 0.33 micrograms/l and 2.1 micrograms/l, respectively. The Pearson correlation coefficient for 2,5-dichlorophenol in urine and p-dichlorobenzene in blood was .82 (p < .0001), thus demonstrating a strong association between these exposure measurements. Neither age nor gender was related to urinary 2,5-dichlorophenol or blood p-dichlorobenzene concentrations (p > .40). When these results are viewed with data from other studies, the collective data show that p-dichlorobenzene is a common, worldwide contaminant. The high prevalence of exposure to p-dichlorobenzene, coupled with its potential for adverse health effects, indicate the need for more detailed studies, including studies of long-term health effects on exposed populations.
Adult↗
Exposure to methyl tertiary-butyl ether from oxygenated gasoline in Stamford, Connecticut.
In 1993, state health officials in Connecticut invited the Centers for Disease Control and Prevention (CDC) to assist in an investigation of exposure to methyl tertiary-butyl ether in oxygenated gasoline in Stamford, Connecticut. Venous blood samples were collected from 14 commuters and from 30 other persons who worked in the vicinity of traffic or automobiles, and the samples were analyzed for methyl tertiary-butyl ether, tertiary-butyl alcohol, benzene, m-/p-xylene, o-xylene, and toluene. The highest levels of methyl tertiary-butyl ether in blood were measured among gasoline service station attendants (median = 15 micrograms/l, range = 7.6-28.9 micrograms/l). Blood levels of methyl tertiary-butyl ether were highly variable among persons who worked in car-repair shops (median = 1.73 micrograms/l, range = 0.17-36.7 micrograms/l) and were generally lowest among commuters (median = 0.11 micrograms/l, range = < 0.05-2.60 micrograms/l). Blood levels of methyl tertiary-butyl ether were correlated strongly with personal-breathing-zone samples of methyl tertiary-butyl ether and blood levels of other volatile organic compounds. This exposure information should prove useful to a future risk analysis of this high-volume chemical.
Air Pollutants↗
Time dependence of blood concentrations during and after exposure to a mixture of volatile organic compounds.
Volatile organic compounds constitute a group of important environmental pollutants that have been associated with the constellation of symptoms known as sick building syndrome. An understanding of the kinetics of uptake and elimination of volatile organic compounds is important for the proper interpretation of the internal dose concentrations of people exposed to these compounds. Blood concentrations measured before, during, and after exposure of five individuals to a mixture of volatile organic compounds in a controlled chamber are described. Blood concentrations were related directly to air exposure concentrations and appeared to be a function of the blood/air partition coefficient. The half-lives of the internal dose of the volatile organic compounds measured were less than 1/2 h, but the elimination time courses were multiexponential. The complexity of the elimination curve suggested the existence of multiple storage sites within the body. The presence of a long-term exponential in the blood elimination curve suggested that, with repeated exposure, bioaccumulation may occur in humans.
Adult↗
Laboratory investigation of a poisoning epidemic in Sierra Leone.
In June 1986, an epidemic of poisoning occurred in Sierra Leone, West Africa; it involved 49 persons--with 14 deaths. Our laboratory's approach and investigation of this incident is described. Using positive chemical ionization mass spectrometry and nuclear magnetic resonance spectroscopy, the toxicant was identified as parathion, a highly toxic organophosphorus pesticide. Analysis of various items supported the epidemiologic hypothesis that bread was made from contaminated flour and that the flour became contaminated with parathion during a truck shipment. Modern analytical instruments played a major role in this laboratory investigation and effected the identification of the unknown toxicant within hours of receiving the initial bread sample. Close cooperation and clear communication between the epidemiologic and laboratory teams were important in this investigation.
Bread↗
Measurement of methyl tert-butyl ether and tert-butyl alcohol in human blood by purge-and-trap gas chromatography-mass spectrometry using an isotope-dilution method.
We developed an isotope-dilution method for measuring methyl tert-butyl ether (MTBE) and tert-butyl alcohol (TBA) in whole human blood using a purge-and-trap gas chromatographic-mass spectrometric method. The labeled analogues for MTBE and TBA were [2H12]methyl tert-butyl ether and [2H9]-tert-butyl alcohol, respectively. Volatiles were removed from the blood by direct helium purging of the liquid; were trapped on a Tenax trap; and were desorbed, cryofocused, and chromatographed on a DB-624 capillary column that was connected directly to the ion source of a mass spectrometer. Detection was by mass analysis using a double-focusing magnetic-sector mass spectrometer operating in the full-scan mode at the medium mass resolution of 3000. For the isotope-dilution method, the minimum detection limits in blood (5-10 mL) are 0.01 microgram/L for MTBE and 0.06 microgram/L for TBA. The isotope-dilution method proved to be a big improvement in recovery, reproducibility, and sensitivity over our previous analytical method, which used the labeled ketone, [4-2H3]-2-butanone, as the internal standard for both MTBE and TBA. The isotope-dilution method has sufficient sensitivity for monitoring blood levels of MTBE and TBA in populations exposed to oxygenated fuels containing MTBE.
Butanols↗
An improved analysis for chlorinated pesticides and polychlorinated biphenyls (PCBs) in human and bovine sera using solid-phase extraction.
Chlorinated pesticides and polychlorinated biphenyls (PCBs) remain public health concerns because of their unresolved health impact and their persistence in humans. Current epidemiological studies of cancer, non-Hodgkins lymphoma, and endocrine disruption in National Center for Environmental Health (NCEH) laboratories require exposure assessment of many analytes in thousands of people. Previous methods of analyzing pesticides and PCBs in serum have proven inadequate for timely processing of the number of samples required for epidemiological studies. A new method that involves solid-phase extraction (SPE) and cleanup followed by dual-column gas chromatographic separation and electron capture detection has been developed. Nine surrogate compounds were added to the serum prior to sample workup to provide quality assurance for the SPE steps. These surrogates mimic the chemistry of the analytes in the extraction, cleanup, and gas chromatographic analysis steps. To increase selectivity, extracts were injected onto two gas chromatographs with different capillary columns, a DB-1701 and a DB-5. Recoveries of 17 pesticides, 28 PCB congeners, and one polybrominated biphenyl congener ranged from 40 to 80%. Recoveries from this procedure were found to be similar to those from the previously used liquid-liquid extraction method. Correlation of analyte and surrogate recoveries were compared to examine the ruggedness of the technique. The SPE method was found to provide improved sample throughput by a factor of 15.
Animals↗