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A Aitio

Publications and source records attributed to A Aitio.

At least 19 recordsLinked to original sources
PubMed1995

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↗
PubMed1995

Quality assurance in biomarker measurement.

Quality assurance (QA) concerns the validity of all the analytical processes (from collection of the samples to interpretation of the results). It is not an abstract concept but must be adapted to the different situations such as the different exposure levels, the different analytical methods, and the context of use (risk assessment procedures, research, routine determinations). The main requirements in QA programmes regard the control of all the known sources of preanalytical and analytical variations, while the instruments with which adequate QA can be implemented are the certified materials and the quality control programmes (quality manual, internal and external quality controls). Another important concept in QA is that measurements must be placed a different metrological levels: at the highest there are the methods (definitive, reference) to be used for assessing accuracy of routine methods. QA programmes should enable a grading of biomarkers (from experimental only to full evaluated) and of the laboratories in order to identify the significance of the test and to assess the level at which a laboratory could operate.

Biomarkers↗
PubMed1994

Biological monitoring today and tomorrow.

Biological monitoring is important in the assessment of both occupational exposure to chemical agents and the health risks involved. For some chemicals data from biological monitoring can be reliably translated into health risks, while for the majority it only indicates uptake. Several workplace chemicals can be analyzed from biological specimens, but no interpretation of health risk or exposure is possible. For such chemicals, comparing the results to data from similar industries may help to determine whether smaller levels of exposure are possible. The biggest problem with most biological monitoring is that no good interpretation is immediately available. This statement is equally true for classical specific analytical chemical analyses, nonspecific assays of exposure, and almost all effect monitoring. Health-based interpretation of biological monitoring will never become possible unless biological monitoring is performed (even in the absence of immediate interpretation) and the results are stored for future analysis in a retrievable and usable form.

DNA Damage↗
PubMed1994

Reference limits in occupational toxicology.

Two categories of reference limits can be discerned in biological monitoring: The first category identifies individuals who have been exposed to a toxic agent at work, and is based on the distribution of the concentration of the agent or its metabolite in the population that has not been exposed to the agent at work. The second category, for which the term biological action level (BAL) is proposed, provides a guideline on the level of exposure that is acceptable. These levels may be either directly health-based or derived from good working practices. Thus BAL is a biological equivalent for the generic term occupational exposure limit. BAL should be independent of legal overtones, and implies that workers' exposure should be reduced.

Environmental Monitoring↗
PubMed1993

Normal concentrations of chromium in serum and urine--a TRACY project.

The validity of "normal" concentrations for total chromium in serum and urine (S-Cr and U-Cr, respectively) in papers published mainly in the last decade were evaluated and graded by two investigators according to TRACY criteria. The results were in close agreement. Because of possible contamination during sampling from stainless steel needles, the description of the sample collection method was considered important. Documentation of analytical quality control was emphasized. The chromium concentrations were categorized according to nonoccupational conditions that could influence the levels. Eighty-seven publications reporting chromium concentrations in blood and 58 on U-Cr were evaluated, 53 dealing with S-Cr and 41 with U-Cr being found suitable for the TRACY project. In selected publications the arithmetic mean values presented for S-Cr and U-Cr in individuals with no known exposure were within the following ranges: 1-3 nmol.1-1 for S-Cr and 2-10 nmol.1-1 or 0.2-1 mumol.mol creatinine-1 for U-Cr.

Chromium↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

In vivo measurements of lead in bone at four anatomical sites: long term occupational and consequent endogenous exposure.

Measurements of bone lead concentrations in the tibia, wrist, sternum, and calcaneus were performed in vivo by x ray fluorescence on active and retired lead workers from two acid battery factories, office personnel in the two factories under study, and control subjects. Altogether 171 persons were included. Lead concentrations in the tibia and ulna (representative of cortical bone) appeared to behave similarly with respect to time but the ulnar measurement was much less precise. In an analogous fashion, lead in the calcaneus and sternum (representative of trabecular bone) behaved in the same way, but sternal measurement was less precise. Groups occupationally exposed to lead were well separated from the office workers and the controls on the basis of calculated skeletal lead burdens, whereas the differences in blood lead concentrations were not as great, suggesting that the use of concentrations of lead in blood might seriously underestimate lead body burden. The exposures encountered in the study were modest, however. The mean blood lead value among active lead workers was 1.45 mumol l-1 and the mean tibial lead concentration 21.1 micrograms (g bone mineral)-1. The kinetics of lead in the tibia appeared to be noticeably different from that in the calcaneus. Tibial lead concentration increased consistently both as a function of intensity of exposure and of duration of exposure. Calcaneal lead concentration, by contrast, was strongly dependent on the intensity rather than duration of exposure. This indicated that the biological half life of lead in calcaneus was less than the seven to eight year periods into which the duration of exposure was split. Findings for retired workers clearly showed that endogenous exposure to lead arising from skeletal burdens accumulated over a working lifetime can easily produce the dominant contribution to systemic lead concentrations once occupational exposure has ceased.

Adult↗
PubMed1991

Urinary excretion of chlorinated phenols in saw-mill workers.

The excretion and conjugation of chlorophenols were studied in workers exposed to 2,4,6-tri-, 2,3,4,6-tetra-, and pentachlorophenolates, the main components of the chlorophenolate product manufactured by direct chlorination of phenol. The workers were exposed in two different saw mills in which sodium chlorophenolate was used for treatment of lumber during the warm season. Urine specimens were collected at the end of the treatment season as well as at the start of a new treatment period in the spring. Serum specimens were collected towards the end of the treatment period. Total and unconjugated chlorophenols were analyzed with a gas chromatographic method. The maximal concentrations of urinary 2,4,6-tri-, 2,3,4,6-tetra- and pentachlorophenol at the end of the lumber-treatment period were 1-11.8, 3.4-17.3, and 0.2-0.9 mumol/l, respectively, and the average apparent half-times calculated using a one-compartment model were 18 h, 4.3 days and 16 days, respectively. For 2,3,4,6-tetrachlorophenol, the data of some subjects showed a better fit with a two-compartment model; the corresponding half-times were 5.3 and 26 days. During the continuous-exposure period the average serum levels of tetra- and pentachlorophenol were rather similar before and after the working day: 2.79 +/- 1.78 mumol/l for tetrachlorophenol and 0.85 +/- 0.4 mumol/l for pentachlorophenol. Renal clearance values for tetra- and pentachlorophenol were related to urine flow and indicated tubular reabsorption. At low concentrations, sulfate conjugation was dominant. With increasing chlorophenol concentrations the proportion of glucuronide conjugation was increased, especially for pentachlorophenol.

Chlorophenols↗
PubMed1991

Assessment of exposure to polychlorinated biphenyls: analysis of selected isomers in blood and adipose tissue.

Concentrations of 12 selected polychlorinated biphenyl (PCB) congeners and isomers in human serum and adipose tissue after environmental and short- and long-term occupational exposures were determined. The individual congener concentrations in adipose tissue varied between less than 0.01 and 420 micrograms/kg (tri-, tetra-, penta-, hexa-, and heptachlorobiphenyls); the dominating isomers were 2,2',4,4',5,5'- and 2,2',3,4,4',5'-hexaCB, which represented approximately 90% of all PCBs in adipose tissue. Those isomers were also the most abundant in serum specimens after environmental exposure, their contribution together with the 2,2',3,4,4',5',6-heptaCB was approximately 90%. After short-term as well as long-term occupational exposure, the most remarkable changes were observed in the concentrations of the tri- and tetrachlorobiphenyls. In long-term occupational exposure 2,4,4'-triCB (mean 3.15 micrograms/liter) and 2,4,4',5-tetraCB (mean, 9.4 micrograms/liter) showed the highest concentrations, whereas after short-term exposure 2,2',5-tri- (mean 2.04 micrograms/liter) and 2,3',4,4'-tetraCB (mean 1.5 micrograms/liter) were most abundant. In people with only environmental exposure, the concentrations in adipose tissue of some PCB isomers were interrelated. The concentrations of the isomers 2,4,4'5-tetraCB (IUPAC 74), 2,2',4,4',5,5'-hexaCB (IUPAC 153), 2,2',3,4,4'5'-hexaCB (IUPAC 138), 2,3,3',4,4',5-hexaCB (IUPAC 156), 2,2',3,4,4',5',6-heptaCB (IUPAC 183), and 2,2',3,3',4,4',5-heptaCB (IUPAC 171) showed close correlation, the coefficients varied from 0.42 to 0.98. The correlation between the concentrations of individual PCB isomers in adipose tissue was highest for 2,4-substituted highly chlorinated isomers, i.e., isomers with longest half-times in the body.

Adipose Tissue↗
PubMed1991

Cytochrome P-450 isozyme pattern is related to individual susceptibility to diethylnitrosamine-induced liver cancer in rats.

Differences in susceptibility to chemical carcinogenesis between rodent strains and species have been linked to variations in genetically-determined mixed function oxidase activities. In order to verify whether such variations also determine the susceptibility of individual animals of the same strain to a chemical carcinogen, outbred male Wistar rats were administered diethylnitrosamine (DEN) (1, 2, or 3 mg/kg) five times a week for 20 weeks. The relationship was examined between the outcome (i.e., presence or absence of liver tumors, and latency period) and the hepatic activities of mixed function oxidases and conjugating enzymes, as well as of O6-methylguanine-DNA-methyltransferase, measured before the carcinogen treatment. In addition, the metabolic profiles of two model drugs, antipyrine and disopyramide, in the urine were analyzed and correlated with the carcinogen susceptibility. The length of the latency period of hepatocellular tumors in individual rats was negatively related to the activities of hepatic dimethylnitrosamine N-demethylase, aryl hydrocarbon hydroxylase and epoxide hydrolase and positively related to the amount of microsomal protein. Consistent relationships between the other 10 measured parameters and the susceptibility to DEN-induced carcinogenesis were not detected. Long-term treatment with DEN slightly decreased the proportion of metabolism of antipyrine into norantipyrine, and increased the share of 4-hydroxyantipyrine; a decrease in the metabolism of disopyramide to N-deisopropyldisopyramide was also detected. It is concluded that the pattern of cytochrome P-450 isoenzymes is related to differences in individual susceptibility to nitrosamine-induced carcinogenesis. The relationship was most marked at low dose levels, which are the levels at which nitrosamine exposures of humans are known to occur.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1990

Pulmonary toxicity of inhaled styrene in acetone-, phenobarbital- and 3-methylcholanthrene-treated rats.

Pulmonary changes in glutathione (GSH) indicated by the concentration of non-protein sulphydryls showed a decrease of 43% in rats exposed for 5 h per day three times to 500 cm3/m3 (2100 mg/m3) styrene vapour. In these rats, only a marginal decrease was observed in the pulmonary cytochrome P450 oxidative metabolism. Following a single 24-h inhalation exposure to 500 cm3/m3 styrene, the decreases in GSH were 66% in lung but only 16% in liver. On the other hand, a multifold increase in the disposition of thioether compounds was found in urine. Pulmonary cytochrome P450-dependent metabolism was decreased, shown by low residual activities of 7-ethoxyresorufin (less than 20%), 7-ethoxycoumarin (53%) and 7-pentoxyresorufin O-dealkylases (76%). Epoxide hydrolase and GSH S-transferase enzyme activities which catalyze styrene detoxification were not decreased. Styrene exposure (24 h) of acetone-, phenobarbital- or 3-methylcholanthrene-pretreated rats resulted in pulmonary effects different from each other and from those of styrene alone. Acetone potentiated the lung effect and elevated 1.5-fold urine thioether output. Inducer pretreatment seemed to be a factor aggravating styrene toxicity; in effect this was clearest in acetone-induced rats. In general, GSH depletion accompanied by inhibition of cytochrome P450-dependent oxidative drug metabolism were the earliest biochemical lesions manifested in styrene-exposed lung.

Acetone↗
PubMed1989

Simultaneous determination of benzene and toluene in the blood using head-space gas chromatography.

A head-space method for the simultaneous determination of benzene and toluene in blood using a gas chromatograph equipped with a photoionization detector was developed. Internal standards for benzene and toluene were fluorobenzene and o-xylene, respectively, and the detection limit was 5 nmol/l for both solvents. This method is sensitive enough for needs of biological monitoring of benzene and toluene in exposed workers. With automation it offers a possibility for routine measurements. An application of the method in monitoring exposed workers in the industry is presented.

Benzene↗
PubMed1989

Human carcinogens so far identified.

The massive exploitation of natural resources, of which tobacco and asbestos are two conspicuous, though very different examples, and the synthesis of industrial chemicals have generated new hazards and new carcinogens which have been added to older ones. The majority of the over 50 agents that have been firmly identified so far as being human carcinogens belong to the relatively new hazards, that is environmental chemicals or chemical mixtures to which humans have been exposed only during the last century and a half. They are of more importance for cancer occurring in men than in women, and there is no evidence so far that they are related to cancers occurring at some of the most common target sites in either sex. It would be mistaken to believe that complete cancer prevention could be achieved solely by controlling these new, or relatively new, carcinogenic agents, but it would be similarly wrong to deny the importance of trying to control them and of continuing to do so. The experimental approach for the identification of carcinogens has an irreplaceable role to play in preventing the dispersal into our environment of new hazards and in identifying among the chemicals already in use, those that are carcinogenic. That a closer integration between the epidemiological and the experimental approaches may succeed in substantially reducing the size of the unknown region within the spectrum of cancer-causing factors, is today's hope that awaits confirmation. At the same time, advances in the understanding of the mechanisms underlying the different steps of the process leading to the clinical manifestation of cancer may help in the uncovering of agents and risk factors that the approaches used, at least in the way they have been used until now, may not have been apt to identify.

Animals↗
PubMed1989

Metabolism of antipyrine and m-xylene in rats after prolonged pretreatment with xylene alone or xylene with ethanol, phenobarbital or 3-methylcholanthrene.

1. The metabolic disposition of antipyrine (AP) and m-xylene (XYL) has been studied in rats pretreated for a prolonged period with XYL, dosed alone or in combination with ethanol, phenobarbital (PB), or 3-methylcholanthrene (MC). 2. XYL inhalation exposure at 300 ppm in air (7 h/day, 4 days/week, for 1 or 4 weeks) did not alter the total 24-h recovery of AP and its major metabolites in urine, but the excretion profile changed compared with controls: 3-hydroxymethylantipyrine (3-HMA) increased (less than or equal to 14%, P less than 0.001), norantipyrine (NORA) (less than or equal to 23%, P less than 0.01) and AP (less than or equal to 53%, P less than 0.01) decreased. 4-Hydroxyantipyrine (4-OHA) was unchanged. 3. Oral dosage of XYL at 800 mg/kg per day (5 days/week, for 12 days) altered the metabolic disposition of AP similarly to inhalation. 4. XYL + ethanol did not alter the xylene-type effect on AP metabolism. This was at variance with the changes following XYL + PB and, to a greater extent, XYL + MC pretreatments: 4-OHA increased (53-74%, P less than 0.01), 3-HMA (11-42%, P less than 0.05) and AP (greater than or equal to 50%, P less than 0.05) decreased. The effect on NORA was less clear. 5. XYL pretreatment accelerated metabolic disposition of its major urinary metabolite, methylhippuric acid (MHA) and formation of thioethers. 6. Thioether excretion in 24 h urine was enhanced about 10-fold after XYL inhalation and 20-fold after oral administration. Only XYL + PB treatment enhanced further the excretion of xylene-derived thioethers (P less than 0.05). 7. Drug-metabolizing activity (phase I and II reactions) in liver, lung and kidney showed that the treatments resulted in marked and differential biochemical alterations. 8. In conclusion, m-xylene enhanced the rate of its own metabolism and induced differential changes on urinary AP metabolite profile depending on the pretreatment.

Administration, Inhalation↗
PubMed1988

Long-lasting effects of tobacco smoking on pulmonary drug-metabolizing enzymes: a case-control study on lung cancer patients.

Lung tissue specimens were taken during surgery from middle-aged men with either lung cancer (LC, n = 54) or a nonneoplastic lung disease (n = 20). Aryl hydrocarbon hydroxylase (AHH), 7-ethoxycoumarin O-deethylase (ECDE), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronosyltransferase (UDPGT) activities and glutathione and malondialdehyde contents were determined in 12,000 X g supernatant fractions from nontumorous parenchymal tissues. Interindividual differences in enzyme activities ranged from 11- to 440-fold, and glutathione content varied by 17-fold; the values showed unimodal distributions. AHH, ECDE, EH, and UDPGT activities were significantly and positively correlated to each other; a significant negative correlation was found between GST and the other enzymes. A relationship between enzyme activity and number of cigarettes smoked (pack-years) was found only for GST. Ignoring detailed smoking histories in the 6-month period preceding surgery, no difference was found in enzyme activities or glutathione content between LC and nonneoplastic lung disease patients or between smokers and nonsmokers. However, when the number of days since stopping smoking was considered, in smokers a significant increase was found for AHH, EH, and UDPGT activities and a significant decrease was found for GST activity, as compared to nonsmokers. LC patients who had smoked until the day before surgery had higher activities of AHH, ECDE, EH, and UDPGT than nonsmokers, while GST activity was reduced by one-third. The activities of these enzymes returned to the basal level found in nonsmokers within 59 (AHH), 108 (EH), 67 (UDPGT), and 40 (GST) days. LC patients who were recent smokers (within 30 days prior to surgery) had significantly induced AHH and ECDE activities when compared with smoking nonneoplastic lung disease patients. These results show that pulmonary drug metabolism can be altered by tobacco smoking and that these effects can last 40 to 108 days after cessation of smoking. These new findings should be considered in studies on the role of carcinogen-metabolizing enzymes in determining susceptibility to lung cancer.

7-Alkoxycoumarin O-Dealkylase↗