Monitoring of occupational exposure to tetrachloroethene by analysis for unmetabolized tetrachloroethene in blood and urine in comparison with urinalysis for trichloroacetic acid.

OBJECTIVE: The present study was initiated to examine a quantitative relationship between tetrachloroethene (TETRA) in blood and urine with TETRA in air, and to compare TETRA in blood or urine with trichloroacetic acid (TCA) in urine as exposure markers. METHODS: In total, 44 workers (exposed to TETRA during automated, continuous cloth-degreasing operations), and ten non-exposed subjects volunteered to participate in the study. The exposure to vapor was monitored by diffusive sampling. The amounts of TETRA and TCA in end-of-shift blood and urine samples were measured by either head-space gas chromatography (HS-GC) or automated methylation followed by HS-GC. The correlation was examined by regression analysis. RESULTS: The maximum time-weighted average (TWA) concentration for TETRA-exposure was 46 ppm. Regression analysis for correlation of TETRA in blood, TETRA in urine and TCA in urine, with TETRA in air, showed that the coefficient was largest for the correlation between TETRA in air and TETRA in blood. The TETRA in blood, in urine and in air correlated mutually, whereas TCA in urine correlated more closely with TETRA in blood than with TETRA in urine. The TCA values determined by colorimetry and by the GC method were very similar. The biological marker levels at a hypothetical exposure of 25 ppm TETRA were substantially higher in the present study than were the levels reported in the literature. Possible reasons are discussed. CONCLUSIONS: Blood TETRA is the best marker of occupational exposure to TETRA, being superior to the traditional marker, urinary TCA.

Biological monitoring of hexachloroethane.

A small group (n = 12) of military white smoke munition workers provided blood plasma during a production break (S I) and after five weeks' production (S II) of a hexachloroethane (HCE)/titanium dioxide formula. Plasma was also obtained from a sex and age matched control group (n = 12) and a group (n = 13) of previously HCE-exposed workers, respectively. HCE in plasma (P-HCE) was determined with gas chromatography and electron capture detection. No HCE was found in the plasma samples from the two control groups. In the HCE exposed group the mean (+/- SD) P-HCE level increased almost two orders of magnitude from S I (0.08 +/- 0.14 microgram/l) to S II (7.30 +/- 6.04 micrograms/l) despite efforts to minimize the internal dose. Biological monitoring of HCE could be useful in occupational hygiene.

Are ethane and pentane evolution and thiobarbituric acid reactivity specific for lipid peroxidation in erythrocyte membranes?

Peroxidation of human erythrocyte membranes was followed in vitro with head space analysis of ethane and pentane and a thiobarbituric acid assay in a standardized system liberating free oxygen radicals. Simultaneously, the decrease of the membrane palmitic, linoleic, arachidonic and docosahexaenoic acid was monitored. The recoveries of the peroxidation products of the red cell ghost preparations were compared with those obtained by peroxidation of pure fatty acids. Experiments using purified fatty acids revealed that ethane was preferentially produced from docosahexaenoic and linolenic, and pentane from linoleic and arachidonic acids. Thiobarbituric acid-reactive material (TBAR) was produced from each unsaturated fatty acid tested, but the amount was dependent on the number of carbon chain double bonds. During peroxidation of the erythrocyte ghosts, 72% of ethane and 51% pentane were produced during the first 12 h of incubation, whereas TBAR was produced at a constant rate throughout the 36-h test period. Hydrocarbon and TBAR production were similarly inhibited by desferoxamine (at p less than 0.005 and p less than 0.0001, respectively). The total recoveries of ethane, pentane and TBAR exceeded the amount expected by 7.8-, 1.4- and 5.5-fold, respectively. It was concluded that measurement of pentane is a reliable method to monitor lipid peroxidation during oxidative damage of the erythrocyte membrane.

An in vitro gas equilibration method for determination of chemical partition coefficients in fish.

1. A gas equilibration method for the determination of in vitro chemical partition coefficients in mammals was adapted for use with fish. 2. In vitro blood: water and tissue: blood partition coefficients were determined for three chlorinated ethanes in rainbow trout (Oncorhynchus mykiss). 3. In vitro partition coefficients accurately predicted chemical concentrations in tissues of exposed trout.

Physiologically based toxicokinetic modeling of three waterborne chloroethanes in rainbow trout (Oncorhynchus mykiss).

A physiologically based toxicokinetic model for fish was used to simulate the uptake and disposition of three waterborne chloroethanes in rainbow trout (Oncorhynchus mykiss). Trout were exposed to 1,1,2,2-tetrachloroethane, pentachloroethane, and hexachloroethane in fish respirometer-metabolism chambers to assess the kinetics of chemical accumulation in arterial blood and chemical extraction efficiency from inspired water. Chemical residues in tissues were measured at the end of each experiment. Trout exposed to tetrachloroethane were close to steady-state in 48 hr. Fish exposed to pentachloroethane were near steady-state in 264 hr. Extraction efficiency data showed that systemic (extrabranchial) elimination of both chemicals was small. Hexachloroethane continued to accumulate in fish exposed for 600 hr. Parameterized with chemical partitioning data obtained in vitro, the model accurately simulated the uptake of all three chloroethanes in blood and tissues and their extraction from inspired water. These results provide support for the basic model structure and the accuracy of physiological input parameters.

Role of molecular diffusion in conventional and high frequency ventilation.

The influence of molecular diffusion on gas-mixing during conventional mechanical ventilation (CMV) and high frequency ventilation (HFV) was studied by observing the wash-in of six poorly soluble, inert gases in arterial blood. Anesthetized dogs were ventilated either with CMV or HFV. Following a step change in inspired gas composition, the increase in arterial concentrations of hydrogen, helium, methane, ethane, isobutane, and sulfur hexafluoride was determined by gas chromatography. The relative gas diffusivities encompassed a range of almost one order of magnitude. Propane, present in inspired gas during both the control and wash-in phases, served as an internal reference for calculation of blood tracer concentrations. The wash-in of all six inert gases followed a single exponential time course during both CMV and HFV. The rate of wash-in of each gas decreased with increasing molecular weight (MW). The relationship of rate constants to a measure of relative diffusivity (MW-0.5) was significantly different than zero for both types of ventilation. The slope of this relationship was three times larger for CMV than HFV, indicating that molecular diffusion has a greater role in gas mixing during ventilation with large tidal volumes. Diffusion has a minor role in gas mixing during high frequency ventilation with small tidal volumes. Demonstration of the presence of gas separation secondary to molecular diffusion during HFV is enhanced by measuring wash-in, rather than wash-out, of inert gases because gas separation is likely to be obscured as exhaled gases pass through the well-mixed central airways during gas wash-out.

Radiation-induced volatile hydrocarbon production in platelets.

Generation of volatile hydrocarbons (ethane, pentane) as a measure of lipid peroxidation was followed in preparations from platelet-rich plasma irradiated in vitro. The hydrocarbons in the headspace of sealed vials containing irradiated and nonirradiated washed platelets, platelet-rich plasma, or platelet-poor plasma increased with time. The major hydrocarbon, pentane, increased linearly and significantly with increasing log radiation dose, suggesting that reactive oxygen species induced by ionizing radiation result in lipid peroxidation. Measurements of lipid peroxidation products may give an indication of suboptimal quality of stored and/or irradiated platelets.

Thiols and hepatic coma.

The plasma concentrations of methane and ethane thiols have been determined during the course of acute liver failure by a gas-chromatographic technique, and a prognostic evaluation is possible using this analysis. Further, the effects of some therapeutic measures, notably hemoperfusion, on the thiol levels have been investigated. It is concluded that these toxins, which are to a large extent covalently protein-bound, are extremely difficult to remove in an extracorporeal liver support system. Since the cause of the pathological thiol concentrations is probably the elevated plasma methionine levels associated with severe liver disease, it is suggested that the most hopeful course of action against the accumulation of thiols in the body might be a preventative therapy involving the normalization of methionine at an early stage of the disease.

Pulmonary shunt: a comparison between oxygen and inert gas infusion methods.

Pulmonary shunt measurement was compared using the standard oxygen (Berggren) technique and a new multiple inert gas infusion (Wagner et al.) technique in 11 mongrel dogs with either regional atelectasis or diffuse pulmonary edema. Relative retentions of sulfur hexafluoride, ethane, cyclopropane, halothane, diethyl ether, and acetone were used to calculate intrapulmonary shunt. Relative dilution of oxygen (Berggren method) was used to calculate total right to left shunt. The two methods gave similar results in the range of 20-80%. At low shunts the oxygen method measured higher values. This is because of the greater relative importance of fixed extrapulmonary shunts at this level and, as well, error in the measurement of PO2. Both techniques are suitable for normal clinical use.

Continuous distributions of ventilation-perfusion ratios in normal subjects breathing air and 100 per cent O2.

A new method has been developed for measuring virtually continuous distributions of ventilation-perfusion ratios (V(A)/Q) based on the steadystate elimination of six gases of different solubilities. The method is applied here to 12 normal subjects, aged 21-60. In nine, the distributions were compared breathing air and 100% oxygen, while in the remaining three, effects of changes in posture were examined. In four young semirecumbent subjects (ages 21-24) the distributions of blood flow and ventilation with respect to V(A)/Q were virtually log-normal with little dispersion (mean log standard deviations 0.43 and 0.35, respectively). The 95.5% range of both blood flow and ventilation was from V(A)/Q ratios of 0.3-2.1, and there was no intrapulmonary shunt (V(A)/Q of 0). On breathing oxygen, a shunt developed in three of these subjects, the mean value being 0.5% of the cardiac output. The five older subjects (ages 39-60) had broader distributions (mean log standard deviations, 0.76 and 0.44) containing areas with V(A)/Q ratios in the range 0.01-0.1 in three subjects. As for the young subjects, there was no shunt breathing air, but all five developed a shunt breathing oxygen (mean value 3.2%), and in one the value was 10.7%. Postural changes were generally those expected from the known effects of gravity, with more ventilation to high V(A)/Q areas when the subjects were erect than supine. Measurements of the shunt while breathing oxygen, the Bohr CO(2) dead space, and the alveolar-arterial oxygen difference were all consistent with the observed distributions. Since the method involves only a short infusion of dissolved inert gases, sampling of arterial blood and expired gas, and measurement of cardiac output and minute ventilation, we conclude that it is well suited to the investigation of pulmonary gas exchange in man.