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[Biological monitoring of chronic hemodialysis].

Patients suffering from acute renal failure must undergo dialysis to substitute for the kidney's excretory function. Dialysis is a means of exchange between two solutions: blood and a liquid known as dialysate, across a semi-permeable membrane. This membrane permits the passage of water and aqueous solutions of low molecular weight but not that of the aqueous solutions of high molecular weight such as proteins. Dialysed patients are biologically monitored to prevent the various complications arising from blood dialysis, to check the efficacy of the treatment as well as to reduce the risk of morbidity and mortality. Because of the multiple and complex nature of renal functions, biological monitoring of a dialysis patients presents many, often inter-related facets. In addition to the complications inherent in dialysis itself, the dialysed patient is exposed to other causes of mortality or morbidity such as nutritional, hematologic, cardiovascular and infectious problems. Clinicians is confronted by other complications, albeit less common and easier to control, in the form of osteoarticular troubles or even aluminium poisoning. Lastly, biological assessment of the efficacy of purifying processing depends principally on calculating the dose of dialysate and the ureic index of subtraction which, in turn, requires the measurement of uremia.

Acid-Base Equilibrium↗

Analytical methods for biological monitoring of exposure to pesticides: a review.

Synthetic pesticides have been used since in the early to mid twentieth century. In the US alone, over 800 pesticide active ingredients are formulated in about 21,000 different commercial products. Although many public health benefits have been realized by the use of pesticides, their potential impact on the environment and public health is substantial. For risk assessment studies, exposure assessment is an integral component, which has unfortunately, often been weak or missing. In the past several decades, researchers have proposed to fill these missing data gaps using biological monitoring of specific markers related to exposures. In this paper, we present a review of existing analytical methodology for the biological monitoring of exposure to pesticides. We also present a critical assessment of the existing methodology and explore areas in which more research is needed.

Environmental Monitoring↗

Biological monitoring of occupational exposure to electrophilic compound during rubber industry.

Electrophilic compounds are widely used in industry. Rubber processing is the famous example of sites where workers are exposed to electrophilic compounds. Besides their immediate effect on different body systems, electrophilic compounds include most mutagenic and carcinogenic substances. The present study was carried out to elucidate the possibility of using non selective assays in the biological monitoring of occupational exposure to electrophilic compounds. The study included a total number of 40 workers exposed to chemicals during rubber industry (n=25 exposed) and comparison group (n=15). The biochemical tests carried out on each subject included: (1) Estimation of thioether levels in urine as a biological indices of electrophilic compounds. (2) Non selective assays as urinary RNase and alpha esterase, glutathione-S-transferase and aryl sulphatase. Their determination is recommended in the biological monitoring of workers exposed to such agents beside the medical surveillance of workers exposed to such chemicals. The study finding showed significant increase in the levels of thioether and all the non-selective assays among exposed workers rather than the comparison group.

Air Pollutants, Occupational↗

Biological monitoring of occupational exposure to electrophilic compounds.

Electrophilic compounds are widely used in industry. Plastic and dyeing industries are foremost examples of sites where workers are exposed to electrophilic compounds. Besides their immediate effect on different body systems, electrophilic compounds include most mutagenic and carcinogenic substances. The present study was carried out to elucidate the possibility of using nonselective assays in the biological monitoring of occupational exposure to electrophilic compounds. The study included a total number of 225 workers selected from the Plastic and Battery Company where workers are exposed to styrene (n = 70), and the Kafr El Dawar chemical and Dyeing Company where workers are exposed to aniline (n = 60) and benzidine (n = 25). Workers exposed to diesel engine exhaust were selected from a bus garage in Smoha (n = 70). A comparison group consisting of 141 subjects was selected from the administrative departments of the selected factories. The biochemical tests carried out on each subject included: (1) estimation of the biological indices of exposure: urinary mandelic acid and benzidine, blood methemoglobin, and carboxyhemoglobin, (2) liver and kidney function tests; and (3) nonselective biochemical parameters of early detection of carcinogenic and mutagenic risk: urinary thioether levels, urinary RNase and alpha esterase activities. The study revealed that two out of three nonselective assays have been affected by occupational exposure to electrophilic compounds. These were the urinary thioethers and RNase levels. Their determination is recommended in the biological monitoring of workers exposed to such agents especially in developing countries.

Adult↗

Aspects of biological monitoring of exposure to glycol ethers.

Glycol ethers are frequently used as solvents, detergents, and emulsifiers alone or as components in industrial and consumer products. The monomethyl and monoethyl ethers of ethylene glycol, and their acetate esters, are teratogenic and embryotoxic and cause testicular damage in laboratory animals, while the monobutyl ether causes hemolysis of the red blood cells. The adverse effects are attributed to the acid metabolites methoxy-, ethoxy- and butoxyacetic acid, respectively. The glycol ethers may readily enter the body by inhalation as well as dermal uptake. Biological monitoring of exposure to glycol ethers has therefore been suggested. This paper reviews physical properties, occurrence, analysis, toxicity, and toxicokinetics of the most common glycol ethers and then discusses toxicokinetic aspects of biological monitoring. The effect of physical exercise and the relative importance of respiratory and percutaneous absorption on the internal exposure to glycol ethers are illustrated. Monitoring the acid metabolite in urine is suggested as the best index of exposure. Intra- and inter-individual variability, dose-dependent toxicokinetics, and metabolic induction and inhibition are examples of possible sources of error in the estimation of internal exposure from the urinary excretion of acid metabolite.

Adult↗

Timing of sample collection for biological monitoring of occupational exposure.

The timing of sample collections for the biological monitoring of occupational exposure profoundly affects the resulting data. Sampling time with respect to the day in the working week and the end of exposure is crucial for measurements of rapidly excreted indicators of exposure. Owing to the cumulation of slowly excreted exposure indicators, timing of sample collection with respect to the duration of employment is essential. The steady state is established within a week, if the exposure indicator is excreted rapidly (with a half-life shorter than 45 h), or within months or years, if it is excreted slowly. In this study, exposure indicators are characterized by the elimination half-life. A monocompartmental model is used to calculate the biological levels at steady state and the duration of occupational exposure needed to reach the apparent steady state.

Half-Life↗

Determination of benzene and its metabolites: application in biological monitoring of environmental and occupational exposure to benzene.

Methods for the biological monitoring of benzene and its metabolites in exhaled air, blood and urine are reviewed. Analysis of benzene in breath can be carried out by using an exhaled-air collection tube and direct analysis by GC or GC-MS; however, this technique is less reliable when compared to analysis using blood or urine. For the determination of non-metabolized benzene in blood and urine, GC head-space analysis is recommended. Phenol, the major metabolite of benzene can be monitored by either HPLC or GC methods. However, urinary phenol has proved to be a poor biomarker for low-level benzene exposure. Recent studies have shown that trans,trans-muconic acid, a minor metabolite of benzene can be determined using HPLC with UV detection. This biomarker can be used for detection of low-level benzene exposure. Urinary S-phenylmercapturic acid is another sensitive biomarker for benzene, but it can be detected only by GC-MS. Hydroquinone, catechol and 1,2,4-benzenetriol can be measured using HPLC with either ultraviolet or fluorimetric detection. Nevertheless, their use for low-level assessment requires further studies. Eventually, for the assessment of health risks caused by benzene, biological-exposure reference values need to be established before they can be widely used in a field setting.

Animals↗

Biological monitoring of occupational exposure to enflurane (ethrane) in operating room personnel.

Biological monitoring of occupational exposure to enflurane (ethrane) can be achieved by measuring concentrations of inorganic fluorides in the blood and urine and of enflurane in alveolar air and venous blood. Measurement of these concentrations, however, has limitations. Another method for monitoring exposure to enflurane is to measure its concentration in urine throughout the period of exposure. In this study, we measured the environmental and urinary concentrations of enflurane. Enflurane in the ambient atmosphere was determined in 18 operating theaters of eight hospitals in Italy. Ambient air concentrations exceeded the National Institute for Occupational Safety and Health-recommended time-weighted average exposure level of 1 ppm (median: 1.31 ppm). Enflurane was detected in urine of 159 exposed subjects (anesthetists, surgeons, and nurses). A significant correlation was found between enflurane concentration in urine produced during the shift and environmental concentration (r = 0.77, p = .0001). The results showed that urinary enflurane concentration can be used as an appropriate biological exposure index. The biological values proposed are 153 micrograms/l, corresponding to 75 ppm of environmental exposure; 22 micrograms/l, corresponding to 10 ppm of environmental exposure; and 3.5 micrograms/l, corresponding to 1 ppm of environmental exposure. The proposed values can be regarded as time-weighted average samples, reflecting exposure for a 4-h period.

Adult↗

Japanese experience in biological monitoring.

In Japan, industrial health control is accomplished by control of the working environment, work practice management and health care. Periodical biomonitoring of workers exposed to lead and 8 popular organic solvents, including mixed solvents, became mandatory as of October 1, 1989, with an ordinance issued by the Ministry of Labor. This ordinance states that the results of measurements of lead and the 8 solvents in each work place must be classified into 3 categories, named distributions 1, 2 and 3 based on the biological level of the determinant, and then must be reported to the Labor Standards Inspection Office. Distribution 3 encompasses workers having concentration levels above the BEIs of ACGIH except for the concentration of lead in the blood. The National Federation of Industrial Health Organizations surveyed the state of biological monitoring in Japan by a questionnaire to the laboratories. The total number of cases examined in the fiscal year 1990 was about 110,000 for the biomonitoring of lead, and about 520,000 for the monitoring of urinary metabolites of the 8 organic solvents. The ratio of the number of workers in distribution 3 to that of the total workers examined was 0.4% for urinary delta aminolevulinic acid and 0.2-3.5% for the urinary metabolites of each organic solvent. Similar results were obtained from 7 major laboratories. To achieve large-scale biological monitoring in future, a method is necessary for evaluating the exposure or health risks of workers exposed to mixed organic solvents by estimating their urinary metabolites.

Air Pollutants, Occupational↗

Environmental and biological monitoring of endocrine disrupting chemicals.

Trends toward an increase of adverse health effects on reproductive organs have been reviewed. An urgent need has been recognised to establish validated in vivo and in vitro screening assays to test for hormonal activities of chemicals. Relevant existing OECD guidelines have been reviewed and enhancements of some of these have been identified, mainly to test for estrogenic and androgenic activity of chemicals. The problems connected to monitoring activities are outlined, particularly for ambient and biological monitoring. Indeed, the problem of assessing human exposure to endocrine disrupting chemicals through environmental chemical analysis tends to a very high level of complexity. This has been illustrated through the example of one single subclass of endocrine disrupting compounds (EDCs), the organohalogen compounds. Valid biological markers are also needed to be effectively used in epidemiological studies and risk assessment. A multidisciplinary approach and the collaboration among experts in the field of clinical biochemistry, toxicology, and epidemiology is required.

Animals↗

Biological monitoring of hospital pharmacy personnel occupationally exposed to cytostatic drugs: urinary excretion and cytogenetics studies.

For evaluation of the risk borne by hospital pharmacy personnel exposed to antineoplastic agents, the incorporation of cyclophosphamide, ifosfamide, and platinum-containing drugs was quantified by the determination of urinary concentrations. In addition, the induction of micronuclei (MN) and sister-chromatid-exchange (SCE) rates in peripheral blood lymphocytes were studied for correlation with the urinary excretion of cytostatic drugs. Cyclophosphamide and ifosfamide were determined in 24-h urine samples using gas chromatography with electron capture (detection limit 2.5 micrograms/l). Voltammetric analysis enabled the determination of platinum concentrations of 4 ng/l. Heparinized blood (20 ml) was drawn and lymphocytes were cultured for MN and SCE studies. In all, 13 hospital pharmacists and pharmacy technicians regularly involved in the preparation of cytostatic drugs participated in this investigation (7 persons represent a follow-up group). All subjects applied standard safety precautions, including the use of a vertical laminar air-flow hood, protective gowns, and latex gloves. On the day of urine sampling an average of 4,870 mg cyclophosphamide, 5,580 mg ifosfamide, and 504 mg platinum-containing drugs were handled. The excretion of 5 and 9 micrograms cyclophosphamide/l urine was measured in two samples, respectively. An elevated level of urinary platinum was found in one pharmacist (22.3 ng/g creatinine) in comparison with a nonexposed control group. Mean frequencies of MN and SCE did not differ significantly between the drug exposed group and control group. The employees who had incorporated chemotherapeutic agents were part of the follow-up group and, thus, particularly cautious and sensitive to a possible hazard. The results emphasize the necessity of improving personal protection of hospital pharmacy personnel occupationally exposed to cytostatic drugs and support the importance of biological monitoring. In an ongoing project in our department the sources of contamination are being investigated parallel to biological monitoring so as to determine critical situations and improve personal protection.

Adult↗

Biological monitoring results for cadmium exposed workers.

As part of a settlement agreement with the Occupational Safety and Health Administration (OSHA) involving exposure to cadmium (Cd), a battery production facility provided medical surveillance data to OSHA for review. Measurements of cadmium in blood, cadmium in urine, and beta 2-microglobulin in urine were obtained for more than 100 workers over an 18-month period. Some airborne Cd exposure data were also made available. Two subpopulations of this cohort were of primary interest in evaluating compliance with the medical surveillance provisions of the Cadmium Standard. These were a group of 16 workers medically removed from cadmium exposure due to elevations in some biological parameter, and a group of platemakers. Platemaking had presented a particularly high exposure opportunity and had recently undergone engineering interventions to minimize exposure. The effect on three biological monitoring parameters of medical removal protection in the first group and engineering controls in platemakers is reported. Results reveal that both medical removal from cadmium exposures and exposure abatement through the use of engineering and work practice controls generally result in declines in biological monitoring parameters of exposed workers. Implications for the success of interventions are discussed.

Air Pollutants, Occupational↗

Biological monitoring of bisphenol a in a Korean population.

To conduct proper biological monitoring of environmental exposure to bisphenol A (BPA), the variation in host susceptibility need to be investigated. For this purpose, we studied effects of genetic polymorphism in sulfotransferase (SULT) 1A1 on urinary BPA, a biomarker for BPA exposure, in 73 Koreans (male, 34; female, 39; age, 48.9 +/- 11.9 yrs). We used reverse phase-HPLC/FD for analysis of urinary BPA and obtained information from each subject on lifestyle, environment, and potential exposure to BPA via food. The HPLC/FD method showed good reproducibility (CVs < 0.1) and a relatively sensitive detection limit of 0.012 microg/L. These methods yielded a geometric mean of urinary BPA as 9.54 microg/L (8.91 microg/g creatinine), with a geometric standard deviation of 8.32 microg/L. Among potential routes for BPA exposure, only "vinyl wrapping of microwave heating" indicated a borderline positive association with urinary BPA level (p = 0.1). After PCR-RFLP, we found the allele frequencies of SULT1A1*1 and SULT1A1*2 were 0.89 and 0.11, respectively within the subjects. As the SULT1A1*1 allele of SULT1A1 is known to be a rapid sulfonylation-allele, the presence of SULT1A1*1 is suspected to rapidly dispose of environmental BPA. However resultant, urinary BPA levels were not significantly different between the SULT1A1*1/*1 identified subjects and the SULT1A1*1/*2 subjects. Therefore, to clarify host variability in urinary BPA level, different genetic polymorphisms in BPA metabolic enzymes other than SULT1A1 should be further studied.

Arylsulfotransferase↗

Biological monitoring of bidi industry workers occupationally exposed to tobacco.

Ambient and biological monitoring was undertaken among tobacco processors who are chronically exposed to tobacco particulates via nasopharyngeal and cutaneous routes. Ambient monitoring revealed that the inspirable dust concentration was 150-fold higher in the tobacco factory than in the control environment, and was associated with chronic bronchitis in workers. Increased systemic exposure to tobacco constituents was evident from the high levels of cotinine, thioethers, promutagens and direct acting mutagens in workers' urine. The mean glutathione level and glutathione S-transferase activity were significantly lower in the peripheral blood lymphocytes of workers; however, the frequency of the GSTM1 null allele was similar to that in controls. A significant increase in chromosomal damage was noted in target and non-target cells of tobacco processors. In view of the association between tobacco use and several non-communicable diseases, the findings of the present study indicate an urgent need to minimize tobacco exposure among the processors.

Adolescent↗

Biological monitoring of diazinon exposure using saliva in an animal model.

Alternative biological monitoring methods are currently being pursued to better quantify pesticide exposures. In this study, the feasibility of using saliva as a tool for measuring diazinon exposure was determined in an animal model. Male Spraque-Dawley rats were dosed with 1 or 10 mg/kg diazinon by bolus intravenous injection. Time-matched saliva and arterial blood samples were collected from 10 to 250 min post administration. Diazinon was distributed and eliminated rapidly in rats following intravenous (iv) bolus injection, according to a two-compartmental pharmacokinetic analysis. Salivary concentration of diazinon showed a strong correlation with plasma concentration of diazinon. The saliva/plasma (S/P) concentration ratio of diazinon was not affected by administered dose, sampling time, or salivary flow rate, suggesting that salivary excretion of diazinon in rats is fairly constant. Diazinon concentrations in saliva were consistently lower than those in arterial plasma. The mean S/P concentration ratios of diazinon were 0.16 and 0.13 for 1 and 10 mg/kg iv bolus doses, respectively. It is most likely that the incomplete transfer of diazinon from plasma to saliva is due to protein binding of diazinon in plasma. If the protein-unbound fraction of diazinon in plasma is used to calculate the S/P ratio, the S/P concentration ratio of diazinon is close to unity. The results from this study support the conclusion that diazinon salivary concentrations not only can be used to predict the plasma levels of diazinon in rats, but also reflect the unbound fraction of diazinon in plasma.

Animals↗

[Data quality and the interpretation of biological monitoring results].

Quality assurance criteria are not uniformly applied to routine biological determination, in particular with regard to the biomonitoring of exposure to organic solvents. Quality assurance is not an abstract concept but rather a flexible tool which can be adapted to different situations, such as the measurement of different exposure levels or the use of different analytical methods, for a range of purposes (routine determination, risk assessment procedures, research). The occupational health physician should be actively involved in the definition of quality objectives, as well as in checking that they have been implemented. This paper deals with some general issues regarding quality assurance, and in particular with certain requirements of analytical quality (analytical uncertainty, imprecision, bias) and its implementation (quality control, reference materials, standardization, reference values), contextualized to the biological monitoring of organic compounds and the relative metabolites.

Environmental Monitoring↗

A study on biological monitoring of n-hexane exposure.

n-Hexane is one of the solvents widely used in industry and well known to be neurotoxic. Recently it was clearly revealed that n-hexane is metabolized in vivo and its metabolites are excreted in the urine. However, the relationship between the exposed dose of n-hexane and the metabolites in the urine has not yet been substantially determined. Therefore, in this investigation we intended to clarify the above relationship in order to establish its usefulness for biological monitoring of n-hexane exposure. The exposed dose was measured by means of a personal monitoring badge worn by workers in seven factories manufacturing vinyl sandals. The time-weighted average (TWA) concentration of n-hexane was 0.2-47.4 ppm. The n-hexane metabolites in the urine of 22 workers were measured with modified Perbellini's method [12] in the early morning (6:00-7:00 hrs) and at 17:00 hrs. 2,5-Dimethylfuran, 2,5-hexanedione and gamma-valerolactone were identified by gas chromatography and mass spectrometory. At 17:00 hrs the means +/- SD of the metabolites were 0.21 +/- 0.11 mg/l for 2,5-dimethylfuran, 1.13 +/- 0.71 mg/l for 2,5-hexanedione, and 2.04 +/- 2.31 mg/l for gamma-valerolactone. The metabolites were also found in the urine in the early morning. 2-Hexanol was not detected in the urine of any worker examined. A strong correlation between TWA concentration of n-hexane and 2,5-hexanedione in the urine was found at 17:00 hrs (r = 0.895, P less than 0.001). The results suggest that the urinary metabolites of n-hexane, especially 2,5-hexanedione, could be useful indicators for biological monitoring of n-hexane exposure. Furthermore the present study offers the advantage of a better estimate of n-hexane TWA.

Adolescent↗

[Trends of the biological monitoring measurements from 1991 to 1995].

Partial amendments to the Japanese Regulation on the Prevention of Lead Poisoning and that of Organic Solvent Poisoning were made in 1989. As a result, the measurement of blood lead and urinary delta-aminolevulinic acid (delta-ALA) became indispensable items of the occupational health examination for workers who handle lead. Also, the measurement of urinary metabolites of workers who handle eight kinds of organic solvents (xylene, N,N-dimethylformamide, styrene, tetrachloroethylene, 1,1,1-trichloroethane, trichloroethylene, toluene, and normal-hexane) became mandatory. The results of the biological monitoring mentioned above are classified into one of three categories, that is, distribution 1, 2 and 3, according to the concentration of the determinants. In this paper, the incidence of distribution 1, 2 and 3 of each determinant is reported and its change from 1991 to 1995 is discussed. The incidence of distribution 3 was 0.1-5.0% in each determinant. Although the ratio of distribution 1, 2 and 3 seems to have been almost the same for 5 years some determinants decreased their percentage of distribution 3. It is important to utilize the biological monitoring results for the improvement of working environments and working styles, and health management.

Aminolevulinic Acid↗