Marek Jakubowski

Publications of Marek Jakubowski

• Biological monitoring versus air monitoring strategies in assessing environmental-occupational exposure.

  Authors: Marek Jakubowski

  Journal of environmental monitoring : JEM. 12/2011; 14(2):348-52.

  Assessment of environmental and occupational exposure to chemicals can be performed with environmental monitoring (EM) and biological monitoring (BM). Biological monitoring was for a long timeAssessment of environmental and occupational exposure to chemicals can be performed with environmental monitoring (EM) and biological monitoring (BM). Biological monitoring was for a long time considered as a method complementary to environmental monitoring. At present this attitude is changing and in certain areas biological monitoring is applied as the method of choice for exposure and health-risk assessment. This paper examines advantages and disadvantages of those two approaches. In occupational settings environmental monitoring of exposure to VOCs seems to be superior to biological monitoring (possibility of simultaneous determination of components of mixtures, simple interpretation, possibility of evaluation of short-term exposure to local irritants). In the case of this group of compounds BM can be useful in selected cases such as evaluation of dermal absorption or efficiency of protective measures. In the case of metals both forms of monitoring can be used depending on the available methods for interpretation of results. BM of exposure may be considered as superior for evaluating the effects of exposure to lead, cadmium and mercury. However, quantitative evaluation of cancer risk after exposure to arsenic or chromium is possible only on the basis of determination in the air and the use of unit risk values. Both environmental and biological monitoring are useful for evaluation of occupational and environmental exposure to polycyclic aromatic hydrocarbons (PAHs). In certain areas such as evaluation of exposure to external tobacco smoking, cytostatic drugs, and pesticides, biological monitoring is the method of choice used for individual exposure assessment or tracing the trends of environmental exposure.

• Evaluation of the TRA ECETOC model for inhalation workplace exposure to different organic solvents for selected process categories.

  Authors: Małgorzata Kupczewska-Dobecka, Sławomir Czerczak, Marek Jakubowski

  International journal of occupational medicine and environmental health. 06/2011; 24(2):208-17.

  The aim of this work is to describe the operation principle of the TRA ECETOC model developed using the descriptor system, and the utilization of that model for assessment of inhalation exposures toThe aim of this work is to describe the operation principle of the TRA ECETOC model developed using the descriptor system, and the utilization of that model for assessment of inhalation exposures to different organic solvents for selected process categories identifying a given application. Measurement results were available for toluene, ethyl acetate and acetone in workplace atmosphere in Poland. The following process categories have been postulated: (1) Paints and lacquers factory: use in closed, continuous process with occasional controlled exposure; (2) Shoe factory: roller or brush application of glues; (3) Refinery: use in closed process, no likelihood of exposure. The next step was to calculate the workplace concentration at chosen process categories by applying the TRA ECETOC model. The selected categories do not precisely describe the studied applications. Very high concentration values of acetone were measured in the shoe factory, mean 443 ppm. The concentration obtained with the aid of the model is underestimated, ranging from 25.47 to 254.7 ppm, for the case with and without activation of the local exhaust ventilation (LEV), respectively. Estimated concentration at a level corresponding to that of the measured concentration would be possible if the process category involving spraying, e.g., PROC 7 was considered. For toluene and ethyl acetate, the measured concentrations are within the predicted ranges determined with the use of the model when we assume the concentration predicted with active ventilation for the beginning, and the concentration predicted with inactive ventilation for the end of the range. Model TRA ECETOC can be easily used to assess inhalation exposure at workplace. It has numerous advantages, its structure is clear, requires few data, is available free of charge. Selection of appropriate process categories related to the uses identified is guarantee of successful exposure assessment.

• Low-level environmental lead exposure and intellectual impairment in children--the current concepts of risk assessment.

  Authors: Marek Jakubowski

  International journal of occupational medicine and environmental health. 03/2011; 24(1):1-7.

  Lead is an environmental contaminant. The majority of epidemiological research on the health effects of lead has been focused on children, because they are more vulnerable to lead than adults. InLead is an environmental contaminant. The majority of epidemiological research on the health effects of lead has been focused on children, because they are more vulnerable to lead than adults. In children, an elevated blood lead (B-Pb) is associated with reduced Intelligence Quotient (IQ) score. This paper summarizes the current opinions on the assessment of the health risk connected with the children's environmental exposure to lead. The B-Pb level of concern of 100 μg/l proposed by the US Centers of Disease Control in 1991 was for a long time accepted as the guideline value. In the meantime there has been a significant worldwide decrease of B-Pb levels in children and present geometric mean values in the European countries range from 20 to 30 μg/l. The recent analyses of the association of intelligence test scores and B-Pb levels have revealed that the steepest declines in IQ occur at blood levels < 100 μg/l and that no threshold below which lead does not cause neurodevelopmental toxicity can be defended. European Food Safety Authority (EFSA) concluded in 2010, on the basis of results of Benchmark Dose (BMD) analysis, that an increase in B-Pb of 12 μg/l (BMDL₀₁) could decrease the IQ score by one point. It seems that this value can be used as a "unit risk" to calculate the possible decrease of IQ and, consequently, influence of the low-level exposure to lead (< 100 μg/l) on the health and socioeconomic status of the exposed population.

• Calculating the dermal flux of chemicals with OELs based on their molecular structure: An attempt to assign the skin notation.

  Authors: Małgorzata Kupczewska-Dobecka, Marek Jakubowski, Sławomir Czerczak

  Environmental toxicology and pharmacology. 09/2010; 30(2):95-102.

  Our objectives included calculating the permeability coefficient and dermal penetration rates (flux value) for 112 chemicals with occupational exposure limits (OELs) according to the LFER (linearOur objectives included calculating the permeability coefficient and dermal penetration rates (flux value) for 112 chemicals with occupational exposure limits (OELs) according to the LFER (linear free-energy relationship) model developed using published methods. We also attempted to assign skin notations based on each chemical's molecular structure. There are many studies available where formulae for coefficients of permeability from saturated aqueous solutions (K(p)) have been related to physicochemical characteristics of chemicals. The LFER model is based on the solvation equation, which contains five main descriptors predicted from chemical structure: solute excess molar refractivity, dipolarity/polarisability, summation hydrogen bond acidity and basicity, and the McGowan characteristic volume. Descriptor values, available for about 5000 compounds in the Pharma Algorithms Database were used to calculate permeability coefficients. Dermal penetration rate was estimated as a ratio of permeability coefficient and concentration of chemical in saturated aqueous solution. Finally, estimated dermal penetration rates were used to assign the skin notation to chemicals. Defined critical fluxes defined from the literature were recommended as reference values for skin notation. The application of Abraham descriptors predicted from chemical structure and LFER analysis in calculation of permeability coefficients and flux values for chemicals with OELs was successful. Comparison of calculated K(p) values with data obtained earlier from other models showed that LFER predictions were comparable to those obtained by some previously published models, but the differences were much more significant for others. It seems reasonable to conclude that skin should not be characterised as a simple lipophilic barrier alone. Both lipophilic and polar pathways of permeation exist across the stratum corneum. It is feasible to predict skin notation on the basis of the LFER and other published models; from among 112 chemicals 94 (84%) should have the skin notation in the OEL list based on the LFER calculations. The skin notation had been estimated by other published models for almost 94% of the chemicals. Twenty-nine (25.8%) chemicals were identified to have significant absorption and 65 (58%) the potential for dermal toxicity. We found major differences between alternative published analytical models and their ability to determine whether particular chemicals were potentially dermotoxic.

• A proposal for calculating occupational exposure limits for volatile organic compounds acting as sensory irritants on the basis of their physicochemical properties.

  Authors: Marek Jakubowski, Sławomir Czerczak

  Journal of occupational and environmental hygiene. 07/2010; 7(7):429-34.

  A common biological effect of exposure to workplace chemicals is sensory irritation. The ACGIH(R) threshold limit values (TLVs(R)) are developed based on data derived from industrial settings as wellA common biological effect of exposure to workplace chemicals is sensory irritation. The ACGIH(R) threshold limit values (TLVs(R)) are developed based on data derived from industrial settings as well as experimental human and animal studies. Considering the limited amount of human data and the tendency to reduce the volume of animal testing, there is a need for an alternative method to assess sensory irritation. Nasal pungency involves transfer of a compound through the mucosa into the receptor area. This environment is inhomogeneous, being partly a hydrophobic lipid-like and hydrophilic aqueous-like area. A general equation has been developed that seems satisfactory for explaining the transfer of volatile organic compounds (VOCs) from the gaseous phase to biophases, making it possible to calculate the nasal pungency threshold (NPT). The obtained correlation between log 1/NPT and log TLV for 71 VOCs, which is based exclusively on their irritant properties, indicates that for the compounds that act through a nonreactive mechanism (alcohols, ketones, esters, ethers, aromatic and aliphatic hydrocarbons, amides) the relationship between these values differs from that calculated for compounds that act through a reactive mechanism (aldehydes, allyl compounds, aliphatic amines, benzyl halides, carboxylic acids, acrylates, and mercaptans). The correlation coefficient for nonreactive VOCs is very high (n = 46, r = 0.89), and it appears that the regression equation (log TLV = -0.422 log 1/NPT + 0.309) could be used to predict occupational exposure limits (OELs) for this group of compounds. Regarding reactive VOCs, the correlation coefficient is considerably lower (n = 25, r = 0.32), which implies that some kind of correction for their reactivity would have to be applied to calculate the OEL values.

• Unmetabolized VOCs in urine as biomarkers of low level occupational exposure.

  Authors: Beata Janasik, Marek Jakubowski, Wiktor Wesołowski, Małgorzata Kucharska

  International journal of occupational medicine and environmental health. 01/2010; 23(1):21-6.

  To compare the usefulness of determining unchanged forms of volatile organic compounds (VOCs), namely toluene (TOL), ethylbenzene (EB) and xylene (XYL), in urine with the effectiveness of the alreadyTo compare the usefulness of determining unchanged forms of volatile organic compounds (VOCs), namely toluene (TOL), ethylbenzene (EB) and xylene (XYL), in urine with the effectiveness of the already used biomarkers of occupational exposure. Surveys were conducted in two workplaces (paint factory and footwear factory). In total, 65 subjects participated in the study. Air samples were collected using individual samplers during work shift. Urine and blood samples were collected at the end of work shift. Urine samples were analyzed for unchanged compounds and selected metabolites, while blood samples were tested for unchanged compounds. VOCs in blood and urine were determined by solid phase microextraction gas chromatography (SPME-GC-MS). In the paint factory, the geometric mean (GM) concentrations of VOCs in the air ranged as follows: 0.2-4.7 mg/m(3) for TOL, 0.4-40.9 mg/m(3) for EB and 0.1-122.6 mg/m(3) for XYL. In the footwear factory, the GM concentration of TOL in the air amounted to 105.4 mg/m(3). A significant correlation (p < 0.05) was observed between VOCs in blood, urine and air. The regression analyses performed for paint factory workers showed that TOL-U and TOL-B were better biomarkers of exposure (r = 0.72 and r = 0.81) than benzoic acid (r = 0.12) or o-cresol (r = 0.55). The findings of the study point out that the concentration of unchanged VOCs in urine can be a reliable biological indicator of low level occupational exposure to these compounds.

• [Application of predictive model to estimate concentrations of chemical substances in the work environment].

  Authors: Małgorzata Kupczewska-Dobecka, Sławomir Czerczak, Marek Jakubowski, Piotr Maciaszek, Beata Janasik

  Medycyna pracy. 01/2010; 61(3):307-14.

  Based on the Estimation and Assessment of Substance Exposure (EASE) predictive model implemented into the European Union System for the Evaluation of Substances (EUSES 2.1.), the exposure to threeBased on the Estimation and Assessment of Substance Exposure (EASE) predictive model implemented into the European Union System for the Evaluation of Substances (EUSES 2.1.), the exposure to three chosen organic solvents: toluene, ethyl acetate and acetone was estimated and compared with the results of measurements in workplaces. Prior to validation, the EASE model was pretested using three exposure scenarios. The scenarios differed in the decision tree of pattern of use. Five substances were chosen for the test: 1,4-dioxane tert-methyl-butyl ether, diethylamine, 1,1,1-trichloroethane and bisphenol A. After testing the EASE model, the next step was the validation by estimating the exposure level and comparing it with the results of measurements in the workplace. We used the results of measurements of toluene, ethyl acetate and acetone concentrations in the work environment of a paint and lacquer factory, a shoe factory and a refinery. Three types of exposure scenarios, adaptable to the description of working conditions were chosen to estimate inhalation exposure. Comparison of calculated exposure to toluene, ethyl acetate and acetone with measurements in workplaces showed that model predictions are comparable with the measurement results. Only for low concentration ranges, the measured concentrations were higher than those predicted. EASE is a clear, consistent system, which can be successfully used as an additional component of inhalation exposure estimation. If the measurement data are available, they should be preferred to values estimated from models. In addition to inhalation exposure estimation, the EASE model makes it possible not only to assess exposure-related risk but also to predict workers' dermal exposure.

• Calculating the retention of volatile organic compounds in the lung on the basis of their physicochemical properties.

  Authors: Marek Jakubowski, Sławomir Czerczak

  Environmental toxicology and pharmacology. 09/2009; 28(2):311-5.

  In the workplace, deliberate or accidental exposure to volatile organic compounds (VOCs) may occur by ingestion, but more usually through inhalation or dermal contact. The basic model of occupationalIn the workplace, deliberate or accidental exposure to volatile organic compounds (VOCs) may occur by ingestion, but more usually through inhalation or dermal contact. The basic model of occupational exposure assumes repeated inhalation exposure during long periods of time, such as 8-h daily, 40-h per working week. Evaluation of the systemic health effects of industrial chemicals can be based on biological levels or internal doses absorbed in dermal or inhalation exposures. The lungs are the primary route of absorption in exposure to gases, vapors, and aerosols. In inhalation exposure, the dose absorbed can be calculated using the following equation: [formula in text] where C, concentration in the air; T, duration of exposure; V, lung ventilation; R, lung retention expressed as % of intake. As lung retention of VOCs has been studied on human volunteers in costly and time-consuming chamber-type experiments, available data are limited. To calculate dosage for the purpose of risk assessment, the default value of 100% is used. As the lung retention of VOCs in lungs can vary from less than 20 to more than 90%, a possibility of predicting the retention values on the basis of blood/air partition coefficients (K(B)) has been investigated. Lung retention data for 36 compounds were obtained from the existing scientific literature. These values derive from human volunteer studies lasting at least 2h. The K(B) values were either the already published experimental data or were calculated based on their physicochemical properties using a published solvation equation. The compounds under study were divided arbitrarily into two groups: water soluble (>10 g/l) and slightly soluble in water (<10 g/l) compounds. For water soluble compounds, the correlation between K(B) and lung retention was high (r=0.75 and 0.73 respectively); this referred both to K(B) values obtained experimentally or calculated in this report. For the compounds slightly soluble in water, the respective values amounted to 0.79 and 0.82. The obtained results indicate that VOC retention in the lung can be calculated solely on the basis of the partition coefficient K(B). As the descriptors used in the solvation equation can be predicted from chemical structure, this finding indicates that it is possible to assess lung retention for any chemical structure of VOC. The model described in the present report can be a practical alternative to the necessity costly and long-lasting chamber-type experiments which are also questionable on ethical grounds.

• Excretion of unchanged volatile organic compounds (toluene, ethylbenzene, xylene and mesitylene) in urine as result of experimental human volunteer exposure.

  Authors: Beata Janasik, Marek Jakubowski, Piotr Jałowiecki

  International archives of occupational and environmental health. 03/2008; 81(4):443-9.

  OBJECTIVES: To investigate elimination of unchanged volatile organic compounds (VOC's) through urine and the use of respective data for occupational exposure assessment, six volunteers were exposedOBJECTIVES: To investigate elimination of unchanged volatile organic compounds (VOC's) through urine and the use of respective data for occupational exposure assessment, six volunteers were exposed under controlled conditions to toluene (TOL), ethylbenzene (EB), xylene (XYL) and mesitylene (MES) at concentrations ranging from 20 to 200 mg/m(3). The study was to elicit the toxicokinetic data and compare the precision of VOC's exposure assessment based on determining unchanged compounds in blood, urine and their metabolites in urine. METHODS: During and after exposure blood and urine samples were analysed by gas chromatography using the headspace and SPME headspace technique RESULTS: The kinetics of VOC's elimination in urine complied with an open two-compartment model. The (half-time) T (1/2 )values varied from 0.45 to 0.88 h for phase I and from 6.7 to 19.2 h for phase II. The precision of the method for unchanged VOC's was similar to that based on unchanged compounds in blood and better than their main metabolites in urine. CONCLUSION: The obtained result indicate that determining unchanged VOC's in urine can be used as an exposure test even in the ranges of VOC's in the air that are much lower than the current TWA for occupational exposure.

• Renal and neurologic effects of cadmium, lead, mercury, and arsenic in children: evidence of early effects and multiple interactions at environmental exposure levels.

  Authors: Claire de Burbure, Jean-Pierre Buchet, Ariane Leroyer, Catherine Nisse, Jean-Marie Haguenoer, Antonio Mutti, Zdenek Smerhovsky, Miroslav Cikrt, Malgorzata Trzcinka-Ochocka, Grazyna Razniewska, Marek Jakubowski, Alfred Bernard

  Environmental health perspectives. 05/2006; 114(4):584-90.

  Lead, cadmium, mercury, and arsenic are common environmental pollutants in industrialized countries, but their combined impact on children's health is little known. We studied their effects on twoLead, cadmium, mercury, and arsenic are common environmental pollutants in industrialized countries, but their combined impact on children's health is little known. We studied their effects on two main targets, the renal and dopaminergic systems, in > 800 children during a cross-sectional European survey. Control and exposed children were recruited from those living around historical nonferrous smelters in France, the Czech Republic, and Poland. Children provided blood and urine samples for the determination of the metals and sensitive renal or neurologic biomarkers. Serum concentrations of creatinine, cystatin C, and beta2-microglobulin were negatively correlated with blood lead levels (PbB), suggesting an early renal hyperfiltration that averaged 7% in the upper quartile of PbB levels (> 55 microg/L; mean, 78.4 microg/L). The urinary excretion of retinol-binding protein, Clara cell protein, and N-acetyl-beta-d-glucosaminidase was associated mainly with cadmium levels in blood or urine and with urinary mercury. All four metals influenced the dopaminergic markers serum prolactin and urinary homovanillic acid, with complex interactions brought to light. Heavy metals polluting the environment can cause subtle effects on children's renal and dopaminergic systems without clear evidence of a threshold, which reinforces the need to control and regulate potential sources of contamination by heavy metals. Key words: arsenic, biomarkers, cadmium, dopaminergic, heavy metals, interactions, lead, mercury, renal.

• [Effectiveness of preventive actions for lead exposed workers: an assessment based on biological monitoring]

  Authors: Małgorzata Trzcinka-Ochocka, Marek Jakubowski, Urszula Nowak

  Medycyna pracy. 02/2006; 57(6):537-42.

  Biological monitoring plays a significant part in the assessment of occupational exposure to lead. The method basically comprises determinations of blood lead concentration and of one of earlyBiological monitoring plays a significant part in the assessment of occupational exposure to lead. The method basically comprises determinations of blood lead concentration and of one of early toxic-effect biomarkers: the level of either zincprotoporphyrin (ZnPP) in blood or deltaaminolevulinic acid (ALA) in urine. However, biological monitoring is conducted only in 25% of all industrial plants, where the employed technological processes are the source of occupational lead exposure. The project that has been implemented by the Nofer Institute of Occupational Medicine, Lódź, Poland and Outpatient Clinic for Occupational Health, Poznań, Poland, since 1997 made it possible to assess the dynamics of lead exposure in one of the largest battery plants in Western Poland. Based on the analysis of blood lead determinations in lead-exposed workers, the authors could trace the effectiveness of the project aimed at reducing lead exposure in the plant. The findings revealed that the preventive measures applied over the years 1997-2005 resulted in a considerably decreased percentage of blood lead concentrations exceeding the relevant BEI (biological exposure index) value of 500 microg/l: from 19% in 1997 to 1% in 2005. Such a high effectiveness of the project can be mostly attributed to a successful cooperation between the occupational physician, in-plant occupational health services, and the employer. They were all actively involved in a wide-range of activities for workers' health protection and workplace health promotion.

• Influence of occupational exposure to organic solvents on kidney function.

  Authors: Marek Jakubowski

  International journal of occupational medicine and environmental health. 02/2005; 18(1):5-14.

  Exposure to nephrotoxic substances may cause renal tubular and glomerular dysfunction. The aim of the paper was to evaluate, based on literature reports, whether occupational exposure to organicExposure to nephrotoxic substances may cause renal tubular and glomerular dysfunction. The aim of the paper was to evaluate, based on literature reports, whether occupational exposure to organic solvents entails a risk of renal dysfunction. The results of the studies performed over the last twenty years are contradictory. In workers occupationally exposed to organic solvents, tubular, glomerular, or no effects were found. The lack of association between the renal effects and the intensity or duration of exposure was reported in most of the studies. It has been suggested that this can be attributed to an individual susceptibility. Available information points to a possibility of mild renal effects, but not to a serious influence on the kidney function at the current levels of occupational exposure to organic solvents. Biological monitoring of early effects can help identify individuals susceptible to nephrotoxicity of this group of chemicals.

• [Asessment of occupational exposure to lead in Poland]

  Authors: Małgorzata Trzcinka-Ochocka, Marek Jakubowski, Grazyna Raźniewska

  Medycyna pracy. 02/2005; 56(5):395-404.

  The aim of the study was to assess the current occupational exposure to lead in Poland and to evaluate the competence of laboratories responsible for biological monitoring and analysis of healthThe aim of the study was to assess the current occupational exposure to lead in Poland and to evaluate the competence of laboratories responsible for biological monitoring and analysis of health risks in workers exposed to lead. According to the current data, 26,500 workers are employed in 517 factories, including 1895 persons working under condition of exposure exceeding the Polish MAC level of 0.050 mg/m3. The biological monitoring analysis includes measurements of blood lead (Pb-B). Levels and concentrations of one of the markers of early health effect are carried out only in 22% (112) of plants, covering only 76% (20,300) of all workers. Of the 18 laboratories performing this kind of determinations, only 2 are granted the analytical laboratory accreditation certificate. The obtained data indicate that occupational exposure to lead is still a problem in Polish industry. The proportion (76%) of the workers covered with biological monitoring analysis show that neither the recommendations laid down in the decree of 1996 issued by the Minister of Health and Social Welfare, and reinforced by the Minister of Health in 2004, nor the EU directive (98/24/EC) is universally observed. Both these documents provide for that Pb-B determinations in employees occupationally exposed to lead are compulsory. The competences of the majority of analytical laboratories are not sufficient to evaluate biological monitoring analysis in workers occupationally exposed to lead. They have not yet adopted the obligatory Polish versions of European standards of the quality assurance set in PN-EN ISO/IEC 17025. The Minister of Health issued another decree, dated 20 April 2005, according to which from 1 January 2008 every analytical laboratory will have to possess accreditation.

• Biological monitoring of exposure: trends and key developments.

  Authors: Marek Jakubowski, Malgorzata Trzcinka-Ochocka

  Journal of occupational health. 02/2005; 47(1):22-48.

  The concept of biological monitoring (BM) has gained the special interest of individual scientists and international organizations. Today, when analytical problems have almost ceased due to newThe concept of biological monitoring (BM) has gained the special interest of individual scientists and international organizations. Today, when analytical problems have almost ceased due to new laboratory techniques and quality assurance systems, the methods for interpretation of results have become the most important issue. There are important discrepancies regarding the role of biological monitoring of occupational exposure between Europe and the United States. BM has been an important tool of medical health surveillance in the European countries. In the United States it belongs rather to the field of occupational hygiene. It seems that both the approaches can be accepted. More attention should be paid to the development of the truly health-based biomarkers of exposure based on the dose-effect and dose-response relationships. New areas of application of BM of occupational exposure include determination of DNA and protein adducts, unchanged volatile organic compounds in urine, monitoring of exposure to pesticides, antineoplastic drugs, hard metals, and polycyclic aromatic hydrocarbons. In the general environment BM is the most valuable tool for acquiring knowledge of current levels of internal exposure to xenobiotics, identifying the hot spots and developments in trends of exposure. BM can provide policy makers with more accurate information on the control measures undertaken. At present, the main areas include heavy metals, persistent organic pollutants and pesticides. BM of chemical exposure has become increasingly important in the assessment of the health risk in occupational and environmental medicine. Therefore it would be worthwhile to include BM in the curricula for the training of occupational hygienists.

• Influence of long-term occupational exposure to cadmium on lung function tests results.

  Authors: Marek Jakubowski, Alina Abramowska-Guzik, Wiesław Szymczak, Małgorzata Trzcinka-Ochocka

  International journal of occupational medicine and environmental health. 02/2004; 17(3):361-8.

  OBJECTIVES: The study aimed at assessing the lung function in workers exposed to cadmium (Cd). MATERIALS AND METHODS: Pulmonary ventilatory function was assessed in 79 workers (mean age, 50.4+/-8.9OBJECTIVES: The study aimed at assessing the lung function in workers exposed to cadmium (Cd). MATERIALS AND METHODS: Pulmonary ventilatory function was assessed in 79 workers (mean age, 50.4+/-8.9 years, 44% of male workers) previously exposed to cadmium in a cadmium battery plant. The group, not occupationally exposed to cadmium (n = 159, mean age, 48.4+/-4.2 years, 56% of males) was selected from the inhabitants of the same town. All the subjects were examined at the same out-patient-clinic. In cadmium battery workers measurements of blood cadmium concentrations have been performed since 1983 by the Nofer Institute of Occupational Medicine in Lódź, Poland. The data on cadmium concentrations in the air were obtained from the plant's files covering the period of 1981-1999. All subjects were divided into four groups according to their cumulative cadmium exposure indexes: Cd-B x t (Cd in blood in microg/l x years of exposure ) ( index 1) or Cd-A x t (Cd in air mg/m3 years of exposure) (index 2). The ranges of Cd-B x t amounted to <25; 25-500; >500-1000 and > 1000 and Cd-A x t to <0.01; 0.01-1.5; >1.5-4.0 and >4.0. Statistical analysis of the results was performed by means of one-way analysis of variance with multiple comparison tests and Fisher's exact test. RESULTS: The analysis of index 1 showed that only the group with the highest exposure level (>1000 microg Cd-B x years ) had a significantly decreased values for forced expiratory volume in one second (FEV1) peak expiratory flow rate (PEF) maximum midexpiratory flow (MEF) at 25%, 50%, and 75% compared to the group with the lowest exposure (<25 microg/l x years). As revealed by the analysis of index 2, the highest exposure group (>4 mg Cd-A x t) showed a significantly decreased MEF at 50% and not quite significantly decreased FEV1. CONCLUSIONS: Exposure to high cadmium concentrations in the cadmium battery plant resulted in the deterioration of some lung functions in the workers, suggesting a mild airway obstruction.

• [Biological monitoring of chemical exposure]

  Authors: Marek Jakubowski

  Medycyna pracy. 02/2004; 55(1):13-8.

  The concept of biological monitoring (BM) has evoked a lot of interest among individual scientists and international organizations. Biological monitoring of exposure has thus far been applied toThe concept of biological monitoring (BM) has evoked a lot of interest among individual scientists and international organizations. Biological monitoring of exposure has thus far been applied to environmental and occupational toxicology or epidemiological studies. At present, BM plays no more than complementary role in industrial hygiene. Moreover, it is not clear whether BM belongs to occupational hygiene or to occupational medicine. Consequently, BM recommendations are not regarded as legal standards in most countries. Nowadays, when analytical problems have almost ceased to exist due to new laboratory techniques and quality assurance systems, the methods for interpreting the results have become a major issue. New, promising areas of BM application include determination of pesticides, antineoplastic drugs, hard metals, and unchanged volatile organic compounds in urine. The identification of new possible health-based biomarkers of exposure and the development of more sensitive methods due to decreasing occupational exposure limits seem to be one of the most important issues.

• Assessment of biotransformation of the arene moiety of styrene in volunteers and occupationally exposed workers.

  Authors: Paola Manini, Luca Buzio, Roberta Andreoli, Matteo Goldoni, Enrico Bergamaschi, Marek Jakubowski, Pavel Vodicka, Ari Hirvonen, Antonio Mutti

  Toxicology and applied pharmacology. 07/2003; 189(3):160-9.

  Styrene is a chemical widely used in the plastic industry. The main pathway of styrene metabolism in humans occurs via the oxidation to styrene-7,8-oxide (7,8-SO). The aim of this study was theStyrene is a chemical widely used in the plastic industry. The main pathway of styrene metabolism in humans occurs via the oxidation to styrene-7,8-oxide (7,8-SO). The aim of this study was the investigation of a minor metabolic route, involving the oxidation of the arene moiety of styrene, by means of the characterization of the conjugated urinary metabolites of 4-vinylphenol (4-VP). 4-vinylphenol-glucuronide (4-VP-G) and -sulfate (4-VP-S), were measured by liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS) from 174 workers belonging to three cohorts recruited in European countries and from 26 volunteers exposed to 50 mg/m(3) (11.8 ppm) of styrene for 8 h. The 4-VP conjugates represented about 0.5-1% of the total excretion of styrene metabolites. Both 4-VP-G and 4-VP-S are eliminated with a monophasic kinetic, the glucuronide being excreted faster (half-time, 2.2 +/- 0.2 h) than the sulfate (half-time 9.7 +/- 1.7 h). The urinary 4-VP was found to be significantly correlated both with airborne styrene (r = 0.607, p < 0.001) and the sum of MA and PGA (r = 0.903, p < 0.001 in "end-of-shift" samples). Apart from 7,8-SO, 4-VP is the only styrene metabolite not shared with ethylbenzene and therefore thought to be a highly specific marker of styrene exposure. However, a measurable background excretion of 4-VP was also found in all urine samples from controls not occupationally exposed to styrene. This background appears to be highly correlated to smoking (p < 0.001) and possibly also to the dietary intake of styrene or 4-VP. Consequently, the use of 4-VP as a biomarker of styrene exposure is recommended for exposures exceeding 1 ppm.

• Interest of genotyping and phenotyping of drug-metabolizing enzymes for the interpretation of biological monitoring of exposure to styrene.

  Authors: Vincent Haufroid, Marek Jakubowski, Beata Janasik, Danuta Ligocka, Jean-Pierre Buchet, Enrico Bergamaschi, Paola Manini, Antonio Mutti, Sergio Ghittori, Michael Arand, Nina Hangen, Franz Oesch, Ari Hirvonen, Dominique Lison

  Pharmacogenetics. 01/2003; 12(9):691-702.

  In the field of occupational and/or environmental toxicology, the measurement of specific metabolites in urine may serve to assess exposure to the parent compounds (biological monitoring ofIn the field of occupational and/or environmental toxicology, the measurement of specific metabolites in urine may serve to assess exposure to the parent compounds (biological monitoring of exposure). Styrene is one of the chemicals for which biological monitoring programs have been validated and implemented in environmental and occupational medicine. However, inter-individual differences in the urinary excretion exist both for the main end-products (mandelic acid and phenylglyoxylic acid) and for its specific mercapturic acids (phenylhydroxyethylmercapturic acids, PHEMA). This limits to a certain extent the use of these metabolites for an accurate assessment of styrene exposure. In a group of 26 volunteers selected with relevant genotypes, and exposed to styrene vapours (50 mg/m3, 8 h) in an inhalation chamber, we evaluated whether genotyping or phenotyping relevant drug-metabolizing enzymes (CYP2E1, EPHX1, GSTM1, GSTT1 and GSTP1) may help to explain the observed inter-individual variability in the urinary metabolite excretion. Peripheral blood lymphocytes were used for genotyping and as reporter cells for the phenotyping of CYP2E1 and EPHX1. The GSTM1 genotype was clearly the most significant parameter explaining the variance in urinary PHEMA excretion (6-fold lower in GSTM1 null subjects; P < 0.0001) so that systematic GSTM1 genotyping should be recommended routinely for a correct interpretation of PHEMA urinary levels. Variant alleles CYP2E1*6 (7632T>A) and His113EPHX1 were associated with a significant reduction of, respectively, the expression (P = 0.047) and activity (P = 0.022) of the enzyme in peripheral blood lymphocytes. In combination with GSTM1 genotyping, the phenotyping approach also contributed to improve the interpretation of urinary results, as illustrated by the combined effect of CYP2E1 expression and GSTM1 allelic status that explained 77% of the variance in PHEMA excretion and allows the recommendation of mercapturates as specific and reliable biomarkers of exposure to styrene.

• Integrated indexes of occupational exposure as predictors of kidney dysfunction.

  Authors: Marek Jakubowski, Małgorzata Trzcinka-Ochocka, Tadeusz Hałatek, Grazyna Raźniewska, Wiesław Szymczak

  International journal of occupational medicine and environmental health. 02/2002; 15(4):393-9.

  The aim of the study was to evaluate the dose-effect and dose-response relationships between the integrated indexes Cd-A x t (mg/m3 x years of exposure) and Cd-B x t (microg/l x years of exposure),The aim of the study was to evaluate the dose-effect and dose-response relationships between the integrated indexes Cd-A x t (mg/m3 x years of exposure) and Cd-B x t (microg/l x years of exposure), and the increase in retinol binding protein excretion in urine (RBP-U) and beta2-microglobulin concentration in serum (beta2M-S). The study was carried out in the nickel-cadmium battery factory in 1998-1999. Exposure to cadmium was formerly very high. The study group consisted of 116 persons for whom the results of determinations of Cd-B were available during two former observation periods (1983 and 1986-1988). The mean age of the group was 49 years and the mean period of exposure was 17 years. The dose-effect relationship between Cd-B x t and RBP-U or beta2M-S was much better (r = 0.642 and 0.513) than between Cd-A x t and RBP-U or beta2M-S (r = 0.173 and 0.127). There was also correlation between Cd-U (microg/g creatinine), measured in 1998-1999, and RBP-U or beta2M-S (r = 0.343 and 0.198). Urinary cadmium should, however, be used with caution as a dose estimate because its excretion may increase as a result of renal damage. According to the dose-response relationship, an increase in RBP excretion above 300 microg/g creatinine can be expected in 10% of subjects at the integrated exposure index (Cd-B x t) of about 450 microg/l x years, and an increase in beta2M-S above the accepted cut-off point of 2.4 mg/l can be expected in 10 % of subjects at Cd-B x t of about 190 microg/l x years. The data obtained confirmed the validity of the recommended at present health-based limit for occupational exposure of 5 microg/l of blood, as well as the superiority of the biological monitoring of exposure to cadmium over the environmental monitoring.

• Occupational health in Poland.

  Authors: Lech Dawydzik, Konrad Rydzyñski, Marek Jakubowski

  Occupational medicine (Philadelphia, Pa.). 17(3):479-90, v.

  Globalization and Poland's pending membership in the European Union have created a need for reappraisal of the country's occupational health and safety (OHS) programs. The current trend of industrialGlobalization and Poland's pending membership in the European Union have created a need for reappraisal of the country's occupational health and safety (OHS) programs. The current trend of industrial growth is likely to follow observed historical patterns in other parts of the world: the manufacturing sector will shrink, and the service sector will increasingly play a dominant role. Poland's OHS structure must be tailored accordingly. This article outlines the current state of OHS in Poland and indicates priorities for future research and special attention.