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H Kivistö

Publications and source records attributed to H Kivistö.

18 recordsLinked to original sources

TTCA measurements in biomonitoring of low-level exposure to carbon disulphide.

OBJECTIVES: The biomonitoring of carbon disulphide exposure is currently performed by measuring the concentration of 2-thiothiazolidine-4-carboxylic acid (TTCA) in the urine of exposed workers. METHODS: In this study the effect of TTCA, which is found in some vegetables, on the biomonitoring of low-level carbon disulphide exposure was evaluated. In addition the upper reference limit (URL) of TTCA in the non-exposed Finnish population was estimated by analysing TTCA in urine samples from 116 people. The samples were collected at health centres all over Finland from people in employment and in the age group 24-64 years. The analytical measurements were made using a modern column-switching technique and the results were compared with those from the same samples using the extraction method generally in use and, until now, recommended for the determination of TTCA in urine. RESULTS: The results obtained with the two analytical methods correlated very well with each other (r = 0.9). The liquid-liquid extraction method gave results constantly about 3.5 micromol/l higher than the column-switching method. The results of this study also confirmed that many cruciferous vegetables (Cruciferae) contain endogenous TTCA (0.6-5.0 mg/kg), which is excreted unchanged in the urine. After a normal meal which included these vegetables, the TTCA concentration did not rise above the biomonitoring action level even if this was as low as 2 mmol/mol creatinine, but was easily above the URL of TTCA in the non-exposed population. The URL, calculated as the 95th percentile, was 0.3 mmol/mol creatinine. CONCLUSION: The results showed that the extraction method was not sufficiently specific or sensitive when the TTCA concentrations were lower than 10 micromol/l. In contrast, the column-switching method seemed to give reliable results even at these low levels, which are the levels of interest in current practice.

Adult↗

Results of biomonitoring analyses in Biomonitoring Laboratory, Helsinki, Finland in 1997.

In 1997 a total of 4848 results of 47 different analytes from blood or urine specimens, were performed in the Finnish Institute of Occupational Health, Biomonitoring Laboratory, Helsinki, Finland. The results of these service analyses were registered in a database with additional information concerning the worker and the work place. The biomonitoring register, containing one or more results of about 30,000 workers, enables the follow-up of chemical exposure on individual or working group levels. In general, the levels of chemicals or their metabolites in biological specimens have been slowly but continuously declined in Finland during the last decade. In 1997 the decrease in the levels of heavy metals was particularly important. The most problematic organic solvent in Finland is styrene. Styrene exposures have remained in unacceptable levels in work places and still in 1997 more than a third of the workers analysed had very high concentrations of styrene metabolites in their urine. In most major analyte groups studied, there were workers whose exposure level exceeded the Finnish biomonitoring action level (BAL), and in about half of the specimens the level exceeded the upper reference limits (URL), of the non-exposed persons.

Air Pollutants, Occupational↗

Biological monitoring of exposure to benzene in the production of benzene and in a cokery.

The purpose of this study was to compare different biological methods in current use to assess benzene exposure. The methods involved in the study were: benzene in blood, urine and exhaled air, and the urinary metabolites t,t-muconic acid (MA) and S-phenylmercapturic acid (S-PMA). Blood, urine and exhaled air samples were collected from workers in a benzene plant (pure benzene exposure) and cokery (mixed exposure, e.g. polycyclic aromatic hydrocarbons--PAHs) in an Estonian shale oil petrochemical plant. The benzene in these samples was analysed with a head-space gas chromatograph, and the metabolites MA and S-PMA with a liquid chromatograph using methods developed from published procedures. Some of the values measured in the Estonian shale oil area were high in comparison with those published during the last few years, whereas the values measured in the control group did not show any exposure to benzene except in the smokers group. The highest median exposure was in the benzene factory, 0.9 cm3/m3 TWA (2.9 mg/m3) and the highest individual value was 15 cm3/m3 TWA (49 mg/m3). All biological measurements in this study gave the same assessment about exposure to benzene and correlated highly significantly with each other and with the air measurements (r = 0.8 or more). In the benzene factory the correlation was good even when calculated from samples with air concentration < 1 cm3/m3 (3.2 mg/m3) in the case of blood benzene and urinary MA. However, for S-PMA it was weak (r = 0.4) and for benzene in urine and exhaled air it did not exist any more. In the cokery, with mixed exposure, the correlation at low levels was weaker even for blood benzene and urinary MA (r = 0.6). According to the results in the benzene factory the exposure to pure benzene at the level 1 cm3/m3 (3.25 mg/m3) TWA gave: the blood benzene value about 110 nmol/l (8.6 micrograms/l), MA 23 mumol/l (3.3 micrograms/l) or 2.0 mg/g creatinine, S-PMA 58 micrograms/g creatinine or 0.4 mumol/l (95.7 micrograms/l), benzene in urine 499 nmol/l (39 micrograms/l), and benzene in the exhaled air 2.8 nmol/l (0.2 microgram/l). In general, the measurement of benzene in blood and in exhaled air, as well as benzene and its metabolites MA and S-PMA in urine, all gave similar results. However, at low exposure level (< 1 cm3/m3) the most reliable analyses were MA in urine and benzene in blood.

Acetylcysteine↗

Effect of cytochrome P450 isozyme induction and glutathione depletion on the metabolism of CS2 to TTCA in rats.

Analysis of 2-thiothiazolidine-4-carboxylic acid (TTCA), a metabolite of carbon disulfide (CS2), is used in the biological monitoring exposure to CS2 at work. In order to clarify the metabolic reasons for individual variation in the urinary excretion of TTCA, the latter was studied in rats pretreated with model cytochrome P450 (CYP) enzyme inducers or glutathione (GSH) depletors. Ethanol, phenobarbital (PB) or 3-methylcholanthrene (MC) did not increase 24-h TTCA output following CS2 inhalation (50 or 500 ppm, 6h). After oral dosing (10 mg/rat), PB had an inhibiting effect on the excretion rate of TTCA. Tissue GSH depletors phorone, L-buthionine-(RS)-sulfoximine (BSO) and diethylmaleate (DEM) decreased TTCA excretion in rats given an oral dose (10 mg/rat) of CS2. The initial inhibition by phorone and DEM was reversed after 6 h and from 12 h onward the TTCA in urine exceeded the control level, an effect not seen with BSO. The proportion of CS2 excreted in urine as TTCA within 24 h was 1.7% in control rats and 1% after BSO treatment, 1.3% after PB, 1.7% after acetone, 1.8% after MC, 2.0% after phorone and 2.5% after DEM treatment. The amount of TTCA in urine increased with the CS2 dose in a non-linear fashion: 1.6 mumol (50 ppm/6 h) vs. 4.9 mumol (500 ppm/6 h), and 0.2 mumol (1 mg/kg) versus 3.6 mumol (100 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Analysis and stability of phenylglyoxylic and mandelic acids in the urine of styrene-exposed people.

In this work a high-performance liquid chromatographic method is described that is reliable and practical for use in routine biological monitoring of exposure to styrene. The method uses a modern diode array detection technique by which mandelic and phenylglyoxylic acids can be measured simultaneously using different wavelengths. The liquid chromatographic method was compared to a gas chromatographic method developed for the analysis of mandelic, phenylglyoxylic and para-hydroxymandelic acids. The methods gave results consistent with each other. These two methods were then used to check the stability of the main metabolites of styrene, especially of phenylglyoxylic acid, in urine samples stored at +6 degrees C or at -18 degrees C for periods up to 70 days. None of the frozen samples showed any significant decrease in the phenylglyoxylic acid concentration, whereas at 6 degrees C one of the samples showed a reduction of 46% after 1 month.

Chromatography, Gas↗

Assessment of exposure to carbon disulfide in viscose production workers from urinary 2-thiothiazolidine-4-carboxylic acid determinations.

The follow-up of environmental carbon disulfide (CS2) exposure and urinary excretion of 2-thiothiazolidine-4-carboxylic acid (TTCA) among 20 operatives over a 4-day working week in two viscose producing factories confirmed earlier observations that TTCA is a sensitive and reliable indicator of exposure to CS2. Exposure to as low as 0.5-1.0 ppm (1.6-3.2 mg/m3) of CS2 (8-hour time-weighted average [TWA]) was associated with detectable amounts of TTCA in end-of-shift urine. Moreover, the excretion of TTCA, relative to estimated CS2 uptake, appeared surprisingly constant in the studied work force. Approximately 3% (range 2-6.5%) of absorbed CS2 was detected in urine as TTCA. The proportional TTCA excretion did not show dose dependency in the estimated CS2 dose range which varied by about 20-fold. TTCA elimination exhibited both a fast (T 1/2 6 hour) and a slow (T 1/2 68 hour) phase. The slow elimination is compatible with a high lipid solubility and reversible protein binding of CS2. Consequently, urinary excretion of TTCA, relative to CS2 exposure, increased by about a third during the workweek. Urinary TTCA concentration of 4.5 mmol/mol creatinine in a postshift sample corresponded to a TWA exposure to 10 ppm CS2 towards the end of the working week.

Adult↗

Urinary and blood manganese in occupationally nonexposed populations and in manual metal arc welders of mild steel.

To obtain reference values for blood and serum manganese levels, blood specimens were collected from 29 men and 36 women. Mn in blood showed a normal distribution; its upper 97.5% limit in blood was 0.38 mumol/l. Mn in serum showed a skewed distribution, which did not differ from the normal one after logarithmic transformation. The respective reference limit was 19 nmol/l. In both specimens, the levels of Mn were significantly lower in men than in women. To obtain reference values for Mn in urine, midday urine specimens were collected from 58 men and 96 women. Mn in urine also showed a skewed distribution, and the upper 97.5% limit was 38 nmol/l. The levels of Mn in blood and urine were statistically significantly higher in manual metal arc (MMA) welders of mild steel (MS) than in the reference populations. Five MMA/MS welders were subjected to a further study in which the ambient intramask Mn levels and urinary Mn excretion were monitored throughout a full working week. For two welders the correlation of Mn in urine specimens voided in the afternoon was good with the before noon Mn concentrations in the hygienic measurements; for the rest the correlation was minimal. Mn in diurnal urine specimens collected in six portions showed fluctuation if specific gravity or creatinine in urine was used to standardize for the urinary flow, but it was less evident for urinary Mn excretion rate. Our results seem to indicate that the measurement of Mn in urine or blood may be used for monitoring Mn exposure in MMA/MS welders only at the group level.

Adolescent↗

Serum angiotensin-converting enzyme and lysosomal enzymes in tobacco workers.

The activities of angiotensin-converting enzyme (ACE) in people with extrinsic allergic alveolitis (EAA) have been both increased and decreased. These observations suggest that pulmonary macrophages or endothelial cells participate in the disease process. Exposure to molds in the tobacco industry has recently been suspected to be associated with chronic extrinsic allergic alveolitis. In the present study, we analyzed the serum activities of ACE and two lysosomal enzymes, beta-N-acetylglycosaminidase (NAG) and beta-glucuronidase (GLU), among 57 tobacco workers. The tobacco workers not exposed had serum ACE levels similar to those of the reference population workers not occupationally exposed to dust (N = 127). The tobacco workers' serum levels of NAG (16.0 +/- 2.0 units/L and GLU (2.4 +/- 0.7 units/L) were higher than among the referents (NAG, 9.1 +/- 2.0 units/L; GLU, 1.0 +/- 0.6 units/L; p less than 0.01). Fifteen tobacco workers with respiratory symptoms compatible with pulmonary diseases caused by organic dust had a trend toward increased ACE, NAG, and GLU levels. The mean level of ACE in serum was higher among the workers with (25.8 +/- 4.5 units/L) than among those without pulmonary fibrosis (20.7 +/- 7.5 units/L; p less than 0.025). The mean ACE level was also higher among workers with the highest exposure to molds (24.6 +/- 7.1 units/L) compared to those with the mildest exposure (18.3 +/- 5.7 units/L; p less than 0.05). Tobacco workers with or without antibodies against one or more microbes had similar mean levels of ACE, NAG, and GLU. All of these findings indicate that raw tobacco dust and its contaminants may cause allergic or toxic reactions or both, reflected by the serum levels of ACE, NAG, and GLU.

Acetylglucosaminidase↗

Passive and active exposure to cigarette smoke in a smoking experiment.

Six volunteer female habitual smokers were exposed during a 2-wk experimental period to cigarette smoke, both actively and passively, in an exposure chamber (volume 10 m3, average air exchange rate 6.8 times/h), where the ambient carbon monoxide, particle, and aldehyde concentrations were monitored. Three of the six subjects were smoking at the time, 2 cigarettes (filtered, self-burning low tar brand) per person per hour, 30 cigarettes altogether during each of the 5-h experimental days in the chamber. Samples of blood and urine were taken from each subject after 3 nonsmoking days and after each day of active or passive smoking. Among the parameters tested, blood carboxyhemoglobin, plasma cotinine, and urinary mutagenicity were higher in samples taken after active smoking than after nonsmoking periods. Although the exposure conditions were similar for all subjects, the parameters measured showed quite high interindividual variation. Thioethers and thiocyanates were not significantly elevated in the active smoking samples; neither were there any differences during this short experimental period in the sister chromatid exchange frequencies. The only parameters showing an increasing trend after passive exposure, as compared with nonsmoking samples, were urinary mutagenicity and plasma cotinine, the main metabolite of nicotine.

Adult↗

Tumor markers and neurological signs in asbestosis patients.

Ninety asbestosis patients were examined clinically with special emphasis on the function of the peripheral and the central nervous system. Serum specimens were analyzed for carcinoembryonic antigen(s) (CEA), ferritin, and beta 2-microglobulin (beta 2m) content. The patients were classified into four subgroups: (1) those with peripheral neuropathy, (2) those with involvement of central nervous system, (3) those with both types of neurological signs, and (4) those with normal neurological status. The levels of serum CEA, ferritin, and beta 2m were elevated in all four subgroups. No statistically significant differences were found between the groups in the prevalence of elevated values of the three tumor markers (equal or above the following limits: CEA, 5 micrograms/liter; ferritin, 400 micrograms/liter, and beta 2m, 3 mg/liter). The patients currently smoking had a higher level of serum CEA than nonsmokers or exsmokers, but the differences were not statistically significant. In the subgroup that comprised those asbestosis patients in whom the disease could be considered progressive according to the ILO 1980 classification of the chest radiographs, the mean level of CEA in serum was higher than that of the patient group without such progression of the disease (p less than 0.05, Student's t test). Although the prevalence of abnormal neurological signs was high in these asbestosis patients, no obvious correlation was found between the neurological findings and the tumor markers studied.

Adult↗

Effects of methyl methacrylate on non-protein thiols and drug metabolizing enzymes in rat liver and kidneys.

Male Wistar rats received methyl methacrylate monomer (MMA) i.p. in olive oil 1.0 g/kg body weight on 3 successive days. The weight of the livers and kidneys, and the body weights did not differ from their controls. On the fifth day after treatment, hepatic NADPH-cytochrome c reductase, 7-ethoxycoumarin 0-deethylase and the 2,5-diphenyloxazole hydroxylase exhibited maximal decreases in activity (25%, 58%, 36%, respectively) without any coincident effect on the total amount of cytochrome P-450 hemoprotein itself. One week later these activities had returned to control levels. The enzymatic changes in the kidneys were smaller in magnitude, and they were also reversed sooner. A single i.p. dose of MMA (2 g/kg body weight) caused elevation of serum alanine aminotransferase activity. A tenfold increase of the excretion rate of urinary thioethers was also discovered. The hepatic reduced glutathione (GSH) was depleted in 3 h to 20% and the GSSG to half of the value in controls. In kidneys, the GSH was decreased to 48% in 3 h before an apparent phase of overrecovery. At the end of the 24 h observation period, cytochrome P-450 concentrations were somewhat decreased in the liver. The GSH contents showed dose and time-dependent reversible decreases in isolated hepatocytes when incubated for 2 h in a medium containing MMA at the nominal concentrations of 0, 2, 5, or 10 mM. None of the treatments affected either the content of cytochrome P-450 or the viability of the liver cells.

Animals↗

Effect of occupational mercury exposure on plasma lysosomal hydrolases.

The activities of three plasma lysosomal hydrolases, beta-galactosidase, beta-glucuronidase and beta-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 beta-N-acetylglucosaminidase and beta-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 clear-cut 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.

Acetylglucosaminidase↗

A multi-centre evaluation of the FP-900 analyzing system.

The performance of the FP-900 Analyzing system manufactured by Labsystems Oy, Helsinki, Finland, was evaluated in a multi-centre study according to the principle outlined in the 1st Draft of the Standard for Instrument Testing produced by the European Committee for Clinical Laboratory Standards (ECCLS). The FP-900 System comprises a photometer for simultaneous measurement of the absorbance in a nine-compartment cuvette block, and the accessories for handling samples (sampler, simultaneous dispensing of 9 reagent charges, incubator with thermostat and shaker, and centrifuge); the photometer function, printout of results and data processing are programmable with a microprocessor. The performance specifications given by the manufacturer were checked when appropriate. As examples of typical methodologies cholesterol was selected as an end-point absorbance method, creatinine as a fixed-time (two-point) kinetic and aspartate aminotransferase as multi-point, continuous method. The within- and between-laboratory imprecision, deviation from assigned values of commercial control sera, and carry-over were determined. The performance was compared with other analytical systems: Mark I Autoanalyzer and Hitachi 705. The cost, speed and capacity was estimated from the results of the present study. The performance of the analyser and results of applying the ECCLS Draft to actual instrument testing are discussed.

Aspartate Aminotransferases↗

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.

Absorption↗

Dose-related effects of dichloromethane on rat brain in short-term inhalation exposure.

Male Wistar rats were exposed to 500, 1000 or 100 ppm as time-weighted average (t.w.a.) concentrations of dichloromethane vapour. The 1000 (t.w.a.) ppm exposure consisted of two 1-h peak concentrations (2800 ppm) on a basal exposure of 100 ppm. All exposures lasted for 6 h, 5 days weekly and for 2 weeks. The solvent burdens were analyzed in the perirenal fat samples which showed a relation to the dose with the highest values in the 1000 (t.w.a.) ppm exposures. The solvent concentrations increased in the perirenal fat between the two weeks of exposure. Blood carbon monoxide concentrations did not accurately reflect the body solvent burdens. Neurochemical effects also displayed a dose relationship, and included decreased succinate dehydrogenase activity in the cerebellum at the two higher doses and increased acid proteinase activity at 1000 ppm in the cerebrum. Withdrawal of the animals for 7 days from the 2-week exposure showed that the biochemical changes were largely abolished with the exception of decreased succinate dehydrogenase activity at 1000 ppm (t.w.a.).

Adipose Tissue↗

Dichloromethane and carbon monoxide inhalation: carboxyhemoglobin addition, and drug metabolizing enzymes in rat.

Male Wistar rats were exposed for 3 h to 100 ppm Co, 1,000 ppm dichloromethane, or to their combination. Exposure to dichloromethane alone or in combination with CO double the ethoxycoumarin O-deethylase activity in the kidney microsomes but not in the liver. An additive effect on blood COHb concentration by simultaneous exposure to CO and dichloromethane was observed. The mechanism of the additive effect is discussed.

7-Alkoxycoumarin O-Dealkylase↗

Biochemical effects of carbon monoxide poisoning in rat brain with special reference to blood carboxyhemoglobin and cerebral cytochrome oxidase activity.

Male Wistar rats exposed to 1000 ppm carbon monoxide for 3 h showed a rapid removal of carbon monoxide from the blood, and a cerebral cytochrome oxidase activity within the control range immediately after the end of the exposure. The cytochrome oxidase activity decreased while carboxyhemoglobin concentration diminished during the reoxygenation period. The effect might have been caused through a loss of mitochondria by increased lipid peroxidation as cerebral glutathione concentration decreased and lysosomal acid proteinase activity increased in glial cell fractions. The present results seem to indicate that the cerebral cytochrome oxidase may not be specifically inhibited in non-lethal carbon monoxide poisoning despite its proven interactions in vitro.

Animals↗