Effect of occupational mercury exposure on plasma lysosomal hydrolases

Summary The activities of three plasma lysosomal hydrolases, -galactosidase, -glucuronidase and -N-acetylglucosaminidase, were studied in 20 workers exposed to metallic mercury vapor in a chlorine alkali plant and in 10 nonexposed referents. The urinary excretion and blood levels of mercury were determined on the day of study, and the history of mercury exposure was reviewed from the records of mercury concentrations in urine and blood over periods of up to 133 months. The average levels of -N-acetylglucosaminidase and -glucuronidase were higher in the plasma of exposed workers, but the difference was not significant. No significant positive correlation was seen between lyosomal enzyme activities and cumulative long-term exposure to mercury. It is concluded that measurement of plasma lysosomal hydrolase-activities is not of great value in the biological monitoring of workers exposed to low concentrations of metallic mercury vapor.In line with published data, the concentration of mercury showed a clearcut diurnal variation in nonexposed persons, persons currently exposed and persons with a history of past exposure. The excretion rate of mercury remained constant throughout the day.     

Different effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on glucuronide conjugation of various aglycones. Studies in Wistar and Gunn rats.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) (20 μg/kg) was administered to homozygous Gunn and Wistar as well as heterozygous rats, and the activity of UDP-glucuronosyltransferase determined in the liver and kidney toward o-aminophenol, p-nitrophenol, 4-methylumbelliferone, and bilirubin. Diethylnitrosamine was used to activate the enzyme in vitro. TCDD did not enhance UDP-glucuronosyltransferase (UDPGT) activity in the Gunn rat, either in the liver or in the kidney. In the Wistar rat, the UDPGT activity toward methylumbelliferone was enhanced eightfold in the liver and twofold in the kidney. TCDD did not affect UDPGT activity toward bilirubin. Diethylnitrosamine activated o-aminophenol and p-nitrophenol glucuronidation in vitro in the liver only. No activation in vitro due to diethylnitrosamine treatment could be seen in the liver of the TCDD-treated Wistar rat.     

Effects of tetraethyl lead on the activities of drug metabolizing enzymes in different tissues of the rat.

The present study describes the effects of tetraethyl lead on various drug metabolizing enzymes in different tissues of the rat. Tetraethyl lead was administered intraperitoneally to rats (250 mumol/kg) on two consecutive days. The animals were killed on day 3. Tetraethyl lead-treatment decreased the concentration of hepatic cytochrome P-450 (to 45 per cent of the control), the hepatic activity of aryl hydrocarbon hydroxylase (to 41 per cent of the control) and ethoxycoumarin deethylase (to 45 per cent of the control). Epoxide hydratase activity was enhanced in the liver (1.3-fold), kidney (3.3-fold), and small intestinal mucosa (4.7-fold). The activity of glutathione S-transferase decreased in the liver (to 69 per cent of the control) but increased in the kidney (1.5-fold) and small intestinal mucosa (1.7-fold). The glucuronidation of o-aminophenol was enhanced (2.2-fold) in the kidney of tetraethyl lead treated rats. It is concluded that exposure to tetraethyl lead brings about widespread changes in the ability of mammals to detoxify foreign compounds.     

Exceptional pharmacokinetics of trivalent chromium during occupational exposure to chromium lignosulfonate dust

The excretion of chromium in the urine of workers exposed to chromium lignosulfonate was studied. The chromium in the dust was in the trivalent (III) oxidation state, and 30% of the particles were less than 5 micron in diameter. Chromium (III) lignosulfonate dust was rapidly absorbed, and a peak of urinary excretion was seen immediately after exposure. No appreciable accumulation of chromium occurred over 3 d, as evaluated by comparison with preshift urinary chromium concentrations. The addition of ethylenediaminetetra-acetate to the urine of exposed persons greatly enhanced the capacity of chromium to traverse a dialysis membrane; the same effect was seen with chromium (III) chloride. It is concluded that chromium (III) lignosulfonate yields chromium (III), which acts pharmacokinetically like water-soluble hexavalent chromium compounds.     

Lyophilized and natural urine specimens in the quality control of analyses of toxic metals

A quality control program of analyses of toxic metals in urine has been carried out in the Nordic countries since 1978. In connection with these programs, the advantages and disadvantages of lyophilized compared to natural urine specimens as control materials have been investigated in three successive similar studies. Three parallel lyophilized and natural specimens were distributed to 12 participating laboratories. Two of the three specimen pools were spiked with known amounts of As, Cd, Cr, Hg, Ni, and Pb standard solutions. The data indicate no clear differences in the mean concentrations, coefficients of variation, or mean recoveries for the various metals between the two control materials used with the various types of analytes. However, rather wide random variations were observed, emphasizing the analytical difficulty of these analyses and the need for routine quality control.     

Exposure and effect monitoring: a critical appraisal of their practical application.

The prerequisite for the use of biomarkers of exposure as indicators of health risk is that the relationship between the biomarker and the health effects and the representation in time of the biomarker level are known. Some exposure biomarkers may be applied for the quantitative assessment of the amount of exposure. In this task, the half-time of the parameter measured is crucial, since it determines what length of time of exposure the result reflects. For reliable assessment of the exposure the species (e.g. metal, oxide or salt) has to be known. For some chemicals the estimation of exposure from biomonitoring is based on several studies with uniform results and is quite reliable, while for others the uncertainty is wide. Exposure biomarkers have been successfully used in the identification of exposed individuals and follow-up of exposure. For example, macromolecule adducts and mutagenicity in urine have been successfully applied to the identification of workers exposed to carcinogens and as indicators of changes of exposure. Biomarkers of renal effects of cadmium, lead effects on haemoglobin synthesis and organophosphate effects on cholinesterase activities have been well validated and are widely used in routine monitoring activities. However, effect markers for lead and cadmium offer little advantage over the analysis of the chemical itself and where accurate metal analysis is readily available, they have a limited use today. For the analysis of chromosomal aberrations, limited data are available suggesting that elevated frequencies may indicate a carcinogenic risk. In several instances, genotoxic effect monitoring has been used to identify groups of people exposed to hazardous chemicals and in the follow-up of improvements in industrial hygiene.     

Cytosolic glutathione S-transferases in various rat tissues differ in stereoselectivity with polycyclic arene and alkene oxide substrates

The stereoselectivity of cytosolic glutathione S-transferases (GS-T) in rat tissues was determined using (+/-)-benzo(a)pyrene 4,5-oxide (BPO), (+/-)-benz(a)anthracene 5,6-oxide (BAO), pyrene 4,5-oxide (PO), and (+/-)-styrene 7,8-oxide (SO) as substrates. An HPLC system is described which separates the four diastereomeric glutathione (GSH) adducts of BPO. Liver, lung, testis, and heart cytosol were found to be highly selective for catalysis of the reaction of the GSH sulfur atom with R-configured oxirane carbon atoms of BPO; heart was the most stereoselective of these tissues with 93% of the products arising from thiol attack at the R-configured carbons. These same tissues showed identical but lower stereoselectivity with PO or BAO as substrate. With SO as substrate, GSH attack was primarily at the benzylic carbon atom of the R-configured enantiomer in all tissues. In contrast, kidney and spleen cytosol were highly stereoselective for reaction of GSH with S-configured oxirane carbon atoms of all three polycyclic arene oxides (R/S ratio = 0.2-0.3) and showed a greater amount of attack at the terminal carbon atom of (7R)-SO. Enantioselectivity of GS-T from these tissues with BPO as substrate varied substantially; liver, kidney, spleen, and intestine preferentially catalyzed reaction with (4R,5S)-BPO (2.8- to 5.1-fold), but testis, lung, and heart showed little or no enantioselectivity [(4R,5S)-BPO/(4S,5R)-BPO = 1.3, 1.3, and 0.96, respectively]. In general, the differences in stereoselectivity between different rat tissues correlate with known tissue differences in isozyme composition and demonstrate that some rat GS-T isozymes may have markedly different stereo- and enantioselectivities with chiral epoxide substrates.     

Toxicokinetics of methyl tert-butyl ether (MTBE) and tert-amyl methyl ether (TAME) in humans, and implications to their biological monitoring

Healthy male volunteers were exposed via inhalation to gasoline oxygenates methyl tert-butyl ether (MTBE) or tert-amyl methyl ether (TAME). The 4-hr exposures were carried out in a dynamic chamber at 25 and 75 ppm for MTBE and at 15 and 50 ppm for TAME. The overall mean pulmonary retention of MTBE was 43 +/- 2.6%; the corresponding mean for TAME was 51 +/- 3.9%. Approximately 52% of the absorbed dose of MTBE was exhaled within 44 hr following the exposure; for TAME, the corresponding figure was 30%. MTBE and TAME in blood and exhaled air reached their highest concentrations at the end of exposure, whereas the concentrations of the metabolites tert-butanol (TBA) and tert-amyl alcohol (TAA) concentrations were highest 0.5-1 hr after the exposure and then declined slowly. Two consecutive half-times were observed for the disappearance of MTBE and TAME from blood and exhaled air. The half-times for MTBE in blood were about 1.7 and 3.8 hr and those for TAME 1.2 and 4.9 hr. For TAA, a single half-time of about 6 hr best described the disappearance from blood and exhaled air; for TBA, the disappearance was slow and seemed to follow zero-order kinetics for 24 hr. In urine, maximal concentrations of MTBE and TAME were observed toward the end of exposure or slightly (< or = 1 hr) after the exposure and showed half-times of about 4 hr and 8 hr, respectively. Urinary concentrations of TAA followed first-order kinetics with a half-time of about 8 hr, whereas the disappearance of TBA was slower and showed zero-order kinetics at concentrations above approx. 10 micro mol/L. Approximately 0.2% of the inhaled dose of MTBE and 0.1% of the dose of TAME was excreted unchanged in urine, whereas the urinary excretion of free TBA and TAA was 1.2% and 0.3% within 48 hr. The blood/air and oil/blood partition coefficients, determined in vitro, were 20 and 14 for MTBE and 20 and 37 for TAME. By intrapolation from the two experimental exposure concentrations, biomonitoring action limits corresponding to an 8-hr time-weighted average (TWA) exposure of 50 ppm was estimated to be 20 micro mol/L for post-shift urinary MTBE, 1 mu mol/L for exhaled air MTBE in a post-shift sample, and 30 micro mol/L for urinary TBA in a next-morning specimen. For TAME and TAA, concentrations corresponding to an 8-hr TWA exposure at 20 ppm were estimated to be 6 micro mol/L (TAME in post-shift urine), 0.2 micro mol/L (TAME in post-shift exhaled air), and 3 micro mol/L (TAA in next morning urine).     

Effects of low level exposure to lead on neurophysiological functions among lead battery workers.

OBJECTIVES: Assessment of neurophysiological functions in workers with low level exposure to lead and evaluation of the efficacy of bone lead measurements in the prediction of effects of lead. METHODS: Exposure to lead of 60 workers from a lead battery battery factory was estimated from historical blood lead measurements and analysis of lead in the tibial and calcaneal bones with x ray fluorescence. Peripheral and central nervous system functions were assessed by measuring conduction velocities, sensory distal latencies, sensory amplitudes, and vibration thresholds as well as by quantitative measurement of the absolute and relative powers and mean frequencies of different electroencephalograph (EEG) channels. RESULTS: Sensory amplitudes, and to a smaller degree sensory or motor conduction velocities, showed a negative correlation with long term exposure to lead, most clearly with integrated blood lead concentration and exposure time. Vibration thresholds measured in the arm were related to recent exposure to lead, those measured in the leg to long term exposure. The alpha and beta activities of the EEG were more abundant in subjects with higher long term exposure to lead. Calcaneal lead content reflected short term exposure, tibial lead content reflected long term exposure. Blood lead history showed a closer relation with effects of lead than the tibial or calcaneal lead concentrations. CONCLUSIONS: Vibratory thresholds, quantitative EEG, and to a smaller extent the sensory amplitude, provide sensitive measures of effects of lead in occupationally exposed adults. Most accurate estimates of health risks induced by lead can be obtained from a good history of blood lead measurements. If such a history of blood lead concentrations is not available, analysis of bone lead may be used for the assessment of health risks.