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Exhaled breath condensate (EBC) is a non-invasive biological matrix that allows easy access to the lung epithelial lining fluid. It can provide, for instance, useful biochemical information in workers following inhalatory exposure. Recently, nuclear magnetic resonance (NMR)-based metabolomics has been applied to EBC profiling to identify metabolic phenotypes ("metabotypes") of relevance in respiratory medicine. We aimed at verifying if NMR-based metabolomics of EBC, combined with statistical analysis, could find differences in metabolomic profiles between groups of subjects occupationally exposed to levels of airborne inhalable dust, phenol, formaldehyde and volatile organic compounds (VOCs) below regulatory limits. Samples were collected from 20 blue-collar workers without wearing a mask (therefore "exposed" to ambient air) and after wearing a mask ("not exposed"). This procedure was only allowed after the standard air quality tests had shown levels of airborne xenobiotics below the occupational exposure limit or even below the LOD. Ten white-collar controls were also included. After partial least squares discriminant analysis, the exposed to the controlled plant environment and the not exposed groups were clearly separated, and discrimination was due to alteration of fatty acids and alcohols, whose statistical significance was also evaluated. Our results show that NMR-based metabolomics of EBC is a useful tool that has the potential to be successfully used in occupational health to distinguish between subjects exposed and non-exposed to very low airborne levels of chemicals., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The aim of the study was to investigate the effect of various factors that modulate the metabolism of benzene, including smoking habits, metabolic genotype of GST and co-exposure to toluene, on the levels of three biomarkers, i.e. urinary benzene (UB), S-phenylmercapturic acid (SPMA) and t,t-muconic acid (t,t-MA), in 146 refinery workers exposed to low levels of air benzene (AB) in the range <1.5-529.2 μg/m 3 (mean value 32.6 μg/m 3 ). The study confirmed the validity of SPMA as a good biomarker of benzene exposure even at low levels of exposure. It was also confirmed that cigarette smoking is the main confounding factor when assessing biological monitoring data of occupational exposure to AB. Our data indicate that the GSTT1, but not the GSTM1 genotype, significantly increases the urinary levels of SPMA, even at low levels of exposure. It is not known, though, whether subjects with a GSTT1 "null" genotype may be more susceptible to the effects of benzene. Finally, environmental toluene appears to inhibit the metabolism of benzene to SPMA even at low concentrations, also resulting in an underestimation by SPMA levels of the actual exposure of workers to benzene., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This paper deals with the environmental characterization of a large and densely populated area, with a poor reputation for contamination, considering the contribution of environmental features (air, soil, soil hydraulic and groundwater) and the potential effects on human health. The use of Geographic Information System (GIS) has made possible a georeferenced inventory and, by overlaying environmental information, an operational synthesis of comprehensive environmental conditions. The cumulative effects on environmental features were evaluated, taking into account superposition effects, by means of the Spatial MultiCriteria Decision Analysis (S-MCDA). The application of the S-MCDA for converging the combination of heterogeneous factors, related to soil, land and water, deeply studied by heterogeneous groups of experts, constitutes the novelty of the paper. The results confirmed an overall higher potential of exposure to contaminants in the environment and higher mortality rates in the study area for some tumours, but hospital admissions for tumours were generally similar to the regional trend. Besides, mortality data may be strictly dependent on the poor socioeconomic conditions, quality of therapy and a lack of welfare in the area relative to the rest of Italy. Finally, as regards the possible relationship between presence of contaminants in the environment and health conditions of the population no definite conclusions can be drawn, although the present study encourages the use of the new proposed methods, that increase the possibilities for studying the combined effect of more environmental factors., Competing Interests: The authors declare no conflict of interest.

Exposure to chemicals released during urban waste disposal and treatment is increasingly regarded as a potential occupational health issue. Indeed, several toxic metals emitted by an incinerator, including As, Be, Cd, Cr, Pb, Mn, Hg, Ni and V, have potentially toxic properties and their exposure, therefore, may be of concern for the health of the workers involved. The levels of exposure should therefore be carefully measured. Environmental monitoring, however, may be unable, alone, to assess true exposure, due to its intrinsic limitations mainly concerning its inability to assess oral and dermal absorption. In these cases biological monitoring may represent a fundamental supplementary tool for the definition of the workers' true occupational exposure and for the prevention of the related health effects. There is, therefore, an increasing interest in developing and using, in these workers, sensitive and specific biomarkers for health risk assessment, particularly at low or even very low levels of exposure. Despite the large number of original and review articles present in the literature on the biomonitoring of workers exposed to metals, the data on subjects employed in waste treatment activities are scattered and results are sometimes inconsistent. This is the first systematic review, performed according to PRISMA methodology, of the major studies investigating the levels of different toxic metals measured in the main biological matrices (blood, urine, hair) of incinerator workers. The results show that the levels of metals measured in incinerators' workers are generally low, with some notable exceptions for Cd and Pb. These results, though, can be affected by several confounders related either to non-occupational exposure, including diet, area of residence and others, and/or by a number of methodological limitations, as we found in the reported studies. Future work should focus on an integrated approach, using ideally both biological and environmental monitoring. A particular emphasis should be given to the measurement of the different granulometric fractions of the dust containing metals, i.e. inhalable, thoracic, respirable and ultrafine fractions. Moreover, an accurate description of the work tasks and the characteristics and levels of non-occupational exposure should always be provided., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: The main aim of this study was to investigate the cobalt (Co) concentrations in urine along 4 months and their relationship with Co concentrations in blood and haemoglobin (adducts) in 34 workers from a hard metal manufacturing plant where metallic Co and Co oxide were used. Furthermore, the excretion kinetics of Co was investigated and the half-lives of Co in blood, plasma and urine were calculated along 18 days of non-exposure in the same workers., Methods: Co was analysed, in all biological samples, by ICP/MS., Results: Wide fluctuations in the urinary Co concentration were observed throughout the work shift and during the work week. A highly significant linear correlation was found between Co concentration (geometrical mean) in urine samples provided each Thursday (end shift) during 16 subsequent weeks and levels of Co-haemoglobin adducts or blood Co concentrations at the end of the same period. The Co elimination kinetics in globin calculated along 18 days without Co exposure was slow, being related to the physiological metabolism of haemoglobin, while in blood, plasma and urine Co half-lives were 12.3, 9.1 and 5.3 days, respectively., Conclusion: Co concentrations in haemoglobin or blood are highly related to the geometrical mean concentration of urinary Co when samples are collected weekly for several subsequent weeks. The biological monitoring of occupational exposure to Co in hard metal facilities provides reliable results by using the Co concentrations in haemoglobin or in whole blood. The urinary findings, though, do not show the same reliability because of their wide daily and weekly fluctuations.

This study aimed to correlate environmental sevoflurane levels with urinary concentrations of sevoflurane (Sev-U) or its metabolite hexafluoroisopropanol (HFIP) in order to assess and discuss the main issues relating to which biomarker of sevoflurane exposure is best, and possibly suggest the corresponding biological equivalent exposure limit values. Individual sevoflurane exposure was measured in 100 healthcare operators at five hospitals in north-east Italy using the passive air sampling device Radiello(®), and assaying Sev-U and HFIP concentrations in their urine collected at the end of the operating room session. All analyses were performed by gas chromatography-mass spectrometry. Environmental sevoflurane levels in the operating rooms were also monitored continuously using an infrared photoacoustic analyzer. Our results showed very low individual sevoflurane exposure levels, generally below 0.5 ppm (mean 0.116 ppm; range 0.007-0.940 ppm). Sev-U and HFIP concentrations were in the range of 0.1-17.28 μg/L and 5-550 μg/L, respectively. Both biomarkers showed a statistically significant correlation with the environmental exposure levels (Sev-U, r=0.49; HFIP, r=0.52), albeit showing fairly scattered values. Sev-U values seem to be influenced by peaks of exposure, especially at the end of the operating-room session, whereas HFIP levels by exposure on the previous day, the data being consistent with the biomarkers' very different half-lives (2.8 and 19 h, respectively). According to our results, both Sev-U and HFIP are appropriate biomarkers for assessing sevoflurane exposure at low levels, although with some differences in times/patterns of exposure. More work is needed to identify the best biomarker of sevoflurane exposure and the corresponding biological equivalent exposure limit values., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Biological monitoring, i.e., the use of biomarkers for the measurement of systemic human exposure, effects and susceptibility to chemicals has increased considerably in recent years. Biomonitoring techniques, originally limited to a few metals and other chemicals in the workplace, are currently applied to a large number of exposure situations and have become a useful tool for occupational and environmental health risk assessment. Almost any biomonitoring program, however, entails a number of relevant ethical issues, which concern all the phases of the entire process, from the selection of the biomarker to the study design, from the collection, storage and analysis of the biological sample to the interpretation, communication and management of the results, from the (truly?) informed consent of the worker to the independence and autonomy of the occupational health professional. These issues require a balanced assessment of the interests and responsibilities of all the parties, the worker primarily, but also the employer, the occupational health professional, the health authorities and, for research studies on new biomarkers, also the scientists involved. Ideally, decisions of ethical relevance concerning biomarkers should be based on, and respectful of the best scientific, legal and ethical evidence available. When, however, a conflict should arise, before any decision is taken a thorough risk-benefit analysis should be done, at the beginning of the process and after listening to the workers and the management involved, by the occupational physician or scientist, based on his/her professional experience, independent judgement and individual responsibility., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Current levels of occupational exposure to benzene, a genotoxic human carcinogen, in Western countries are reduced by two-three orders of magnitude (from ppm to ppb) as compared to the past. However, as benzene toxicity is strongly dependent on biotransformation and recent evidence underlines a higher efficiency of bio-activation pathways at lower levels of exposure, toxic effects at low doses could be higher than expected, particularly in susceptible individuals. Currently, biological monitoring can allow accurate exposure assessment, relying on sensitive and specific enough biomarkers of internal dose. The availability of similarly reliable biomarkers of early effect or susceptibility could greatly improve the risk assessment process to such an extent that risk could even be assessed at the individual level. As to susceptibility biomarkers, functional genetic polymorphisms of relevant biotransformation enzymes may modulate the risk of adverse effects (NQO1) and the levels of biomarkers of internal dose, in particular S-phenylmercapturic acid (GSTM1, GSTT1, GSTA1). Among biomarkers of early effect, genotoxicity indicators, although sensitive in some cases, are too aspecific for routine use in occupational health surveillance programmes. Currently only the periodical blood cell count seems suitable enough to be applied in the longitudinal monitoring of effects from benzene exposure. Novel biomarkers of early effect are expected from higher collaboration among toxicologists and clinicians, also using advanced "omics" techniques., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Risk assessment (RA) represents the first step to ensure the protection of the workers' health in all work sectors, production and services included. For this reason RA has become a legal duty for the occupational physician in his/her professional activity. The basic concepts of RA have been developed as a formal procedure for the management of chemical risks but they are currently applied to protect human health against all types of occupational and environmental risk factors. In the construction industry, in particular, chemical risk assessment is specially difficult due to the complexity of the working condition, and the variability and multiplicity of exposure. The critical aspects of RA in the construction industry will be discussed here, in the attempt to highlight how the occupational physician, making use of traditional and new tools, including biological monitoring, can address and partly overcome them.

Biological monitoring (BM) represents one of the most dynamic areas of research in occupational health today. From a few tens of articles published yearly in the 70s and 80s, there are now several thousand papers published in the peer review literature each year and the trend is still growing. BM was originally used to assess exposure, effects and susceptibility to occupational agents, but it has been now extended to environmental chemical risk assessment, as well as to several other biomedical sciences, such as epidemiology, tumor science, molecular biology, to mention just a few. The aim of the present paper is to consider new experiences in the use of BM at the international level and to discuss the contribution that these approaches may provide to develop new diagnostic and preventive tools in occupational and environmental health.

Biological monitoring (BM or biomonitoring) deals with the assessment of individual human exposure, effect and susceptibility to occupational risk factors. It is a fundamental tool in occupational health risk assessment (OHRA) and occupational health practice (OHP) and it has become one of the most, if not the most active area in occupational health (OH) research today. From the few hundred BM papers published in the 80s, there are now several tens of thousand papers published in the peer review literature each year, and the trend is still rising exponentially. As a result, BM has become a priority for the Scientific Committee on Occupational Toxicology (SCOT) of the International Commission on Occupational Health (ICOH). Moreover, there has been a long-term interest in biological monitoring by other SCs of ICOH such as the Scientific Committees on Toxicology of Metals (SCTM) and on Rural Health (SCRH). Despite its current popularity, though, BM is not always correctly used or interpreted by those involved in OHRA or OHP. The present review has been prepared to fill this gap and to help preventing misuse and misinterpretation of data. Although the document is meant to be a reference primarily for those involved in OH research and/or practice, it might become of interest for a wider audience within and outside ICOH, including scientists, occupational physicians, industrial hygienists and occupational or public health professionals in general, involved in chemical risk assessment for occupational health. The mission of SCOT and also of other SCs of ICOH, such as SCTM and SCRH, is indeed to promote the advancement and diffusion of knowledge on biological monitoring and other relevant occupational toxicology aspects and to make them available and useful to the entire OH scientific community. All articles retrieved as of 3 January, 2007 as "Review" with the combined key words "biological monitoring" in PubMed from 2000 to 2007 have been scanned individually. This yielded a total of 1400 articles from a grand total of 2486 (excluding limitation on year of publication). When the title was related to human occupational biological monitoring, the abstract was read and its content was included. Articles outside the 2000-2007 time frame or that are not classified as "Review" in PubMed have also been included, when relevant. The review is in four parts: (a) the introduction, containing the basic principles and definitions of BM and the different types of biomarkers (BMK), their toxicological significance, practical use and limitations, (b) the methodological and analytical aspects of BM in exposed workers, (c) the interpretation and management of BM data, including a number of recommendations to be considered when planning, performing and interpreting BM results and, finally, (d) the ethical aspects of BM. A list of key references to relevant papers or documents has been included. The BM of specific chemicals or groups of chemicals is outside the purpose of the review. The document is aimed to represent the state of the art on biological monitoring in occupational risk assessment. We expect that reference to its content will be made, whenever appropriate, by those involved in occupational health practice and research when dealing with BM issues. The document is not meant, though, to represent a rigid nor a permanent set of rules and it will be periodically updated according to new developments and any significant advance in BM science. Any part of the document, therefore, is open to suggestions by scientifically qualified persons or institutions officially involved in BM and comments should be sent directly to the authors. A preliminary draft of the document has been presented at the 7th International Symposium on Biological Monitoring, Beijing, 10-12 September, 2007., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

If a society aims at preserving its socio-ethical values, practices concerning the planning, assessment and management of biomonitoring tests in occupational health surveillance and research should not conflict with these values. Protecting both health and employment of every candidate or employee must be the aim of the occupational health physician. For assessing ethical acceptability of occupational health surveillance practices, their accuracy, relevance, need or necessity, and consequences must first be analysed. This analysis must constitute the basis for any societal democratic decision making process, which cannot be substituted for simply by individual informed consent. A physician trained in occupational health is the professionalism required for doing the testing and assuring the protection of the confidentiality of medical data, in accordance with strict legal and deontological rules. In biological monitoring studies and, in general, in any occupational health research settings, however, the principle of individual, really informed consent must be used, whenever possible. This may also considerably contribute to the committment of study subjects to the research goals. On the other hand, this committment would also contribute to promoting impartial research which is needed to improve the knowledge in occupational health and to increase health protection and prevention.

Biological monitoring or, simply, biomonitoring (BM), refers to the periodic measurement of biological markers, or biomarkers (BMKs), in human fluids and tissues to assess the interaction (absorption, early health effects, susceptibility) between physical, chemical or biological agents and the human organism. The primary aim of BM in the workplace is to integrate environmental monitoring data and detect early, reversible biochemical or functional changes in workers exposed to chemicals before they become clinically relevant. BM also contributes to the assessment of chemical risk to workers, as individuals or as a group. Biomarkers are generally divided into three main types: biomarkers of exposure (BME), response/effect (BMR), and susceptibility (BMS). Other, more specific types of biomarkers are those of internal dose (BID), those of biologically effective dose (BED) and early biomarkers of disease (EBD). It is not always easy, however, to allocate a given BMK--such as the measurement of cytochrome P450 phenotype in subjects exposed to organic solvents--to one or the other type. Biomonitoring provides several advantages over environmental monitoring or health surveillance. For example, it allows an estimate of inter- and intra-individual variability in the absorption, distribution and excretion of chemicals. It also allows the detection of reversible changes before the appearance of a clinically relevant occupational impairment or disease. For these reasons, BM has become a routine procedure in occupational health practice throughout the world. Even the widely acknowledged, recently updated Code of Ethics for Occupational Health Professionals, a milestone in occupational health practice, only provides the basic ethical principles associated with biological monitoring. The aim of the present paper is to survey the various types of BMK available today with two main objectives: to discuss their toxicological significance and highlight the substantial differences that exist between their use in the practice of occupational health and in medical research. The development of new, more valid and reliable BMKs is strongly dependent on the understanding not only of the toxicokinetic and toxicodinamic mechanisms of chemicals, but also of the various susceptibility factors involved, whether genetic or environmental. It is hoped that the concurrent use of BMKs of different types may improve chemical risk assessment in workers, both individually and as a group.

Biotransformation is an important step in the investigation of occupational toxic chemicals. This is because the knowledge of the metabolic pathways and the enzymes involved in the activation and/or detoxication of xenobiotics may help in understanding the mechanism of toxicity and to rationalize the biological monitoring of exposed subjects. The largest enzymatic system involved in the biotransformation of industrial chemicals is cytochrome P-450, a family of haemoproteins capable of metabolizing a vast number of lipophilic, structurally different compounds. The study of the various metabolic reactions of this peculiar group of enzymes has greatly contributed to a) the clarification of the mode of action of several classes of occupational toxic and/or carcinogenic compounds, such as aromatic amines, polycyclic aromatic hydrocarbons, halogenated alkanes, benzene compounds and others, and b) the improvement of risk assessment in the biological monitoring of the exposed subjects, by allowing the toxicological significance (activation/detoxication) of single metabolites to be better understood.