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The Position Paper (PP) on asbestos of the Italian Society of Occupational Medicine (SIML) aims at providing a tool to the occupational physician to address current diagnostic criteria and results of epidemiological studies, and their consequences in terms of preventive and evaluation actions for insurance, compensation and litigation. The PP was based on an extensive review of the scientific literature and was compiled by a Working Group comprising researchers who have contributed to the international literature on asbestos-related diseases, as well as occupational physicians with extensive experience in the evaluation of risks and the medical surveillance of workers currently and formerly exposed to asbestos. The PP was drafted and reviewed between 2017 and 2018; its final version was prepared according to the guidelines of AGREE Reporting Checklist. All the members of the Working Group subscribed to the document, which was eventually approved by SIML’s Executive Committee. The first section addresses industrial hygiene issues, such as methods for environmental monitoring, advantages and limitations of different microscopy techniques, the potential role of microfibers and approaches for retrospective assessment of exposure, in particular in epidemiological studies. The second section reviews the biological effects of asbestos with particular attention to the diagnostic aspects of asbestosis, pleural changes, mesothelioma and lung cancer. In the following section the criteria of causal attribution are discussed, together with different hypotheses on the form of the risk functions, with a comparison of the opinions prevalent in the literature. In particular, the models of the risk function for mesothelioma were examined, in the light of the hypothesis of an acceleration or anticipation of the events in relation to the dose. The last section discusses topics of immediate relevance for the occupational physician, such as health surveillance of former exposed and of workers currently exposed in remediation activities.

Il Position Paper SIML dedicato all’asbesto si propone di offrire uno strumento che consenta al Medico Competente un rapido orientamento sui criteri diagnostici attuali e sui risultati della ricerca epidemiologica con le conseguenti indicazioni per l’azione preventiva e di valutazione in contesti previdenziali, assicurativi e medico-legali. Par- tendo da una ampia revisione della letteratura scientifica in argomento e, nel corso delle riunioni del Gruppo di lavoro, costituito sia da ricercatori che hanno fornito un apporto di livello internazionale sul tema delle patologie asbesto-correlate sia da Medici del Lavoro con ampia esperienza nella valutazione del rischio e nella sorveglianza sanitaria di esposti ed ex-esposti ad amianto, sono stati discussi tra il 2017 ed il 2018 i diversi argomenti trattati con ampie e ripetute revisioni del testo. La versione definitiva è stata sottoposta alla valutazione abituale per le Linee Guida secondo lo standard metodologico AGREE. Il documento, su cui si è registrato l’unanime consenso del Gruppo di Lavoro ed è stato successivamente approvato dal Direttivo Nazionale della Società, si articola in alcune principali sezioni. La prima riguarda gli argomenti propri dell’Igiene Industriale quali le metodiche per il monitoraggio ambientale, i vantaggi e i limiti delle tecniche microscopiche disponibili, il potenziale ruolo delle mi- crofibre e gli approcci per la valutazione retrospettiva dell’esposizione, specialmente a fini epidemiologici. La secon- da gli effetti biologici da amianto con particolare attenzione agli aspetti diagnostici dell’asbestosi, delle alterazioni pleuriche, del mesotelioma e del tumore del polmone. La terza i criteri di attribuzione causale e discusse le diverse ipotesi sulla forma delle funzioni di rischio, vengono confrontate le principali posizioni al riguardo disponibili in letteratura. In particolare sono stati approfonditi i modelli della funzione di rischio per il mesotelioma ed affron- tato il tema dell’ipotesi di un effetto acceleratore e anticipazione della frequenza degli eventi in relazione alla dose. Infine sono stati trattati gli argomenti di attualità applicativa per il Medico Competente quali la sorveglianza sanitaria degli ex esposti ad amianto e di quella degli operatori attualmente esposti in attività di bonifica.

Nel contesto legislativo attuale si colloca l'iniziativa della SIML che cerca, attraverso l'istituzione di un gruppo di lavoro specifico, di mettere a fuoco ed aggiornare i molteplici aspetti (diagnostici, medico-legali, previdenziali) coinvolti nel problema delle malattie lavoro-correlate

The technological advancements, the occurrence of new emerging occupational risks and diseases, and the changes in the regulatory framework for occupational health and safety induce a constant evolution of occupational medicine. Consequently, the skills and training needs of the occupational physicians should be periodically revalued and upgraded in order to identify technical and operational issues and problems of this discipline. In this context, the aim of this national survey, carried out using a self-administered questionnaire submitted to a sample of 1,237 occupational physicians, has been to gain helpful information to ensure a continuous improvement of the quality and effectiveness of measures aimed at protecting the health and safety of workers. The questionnaire, that consists of 43 questions divided into 5 different areas (personal and professional information, training and updating needs of occupational physicians, professional activities and relationships with the corporate prevention system, relationships with the supervisory board of the Local Health Authority, relationships with the National Health Service), allowed to obtain personal and professional data, to assess the training needs and demands of occupational physicians and to evaluate their relationships with the other stakeholders of the Italian prevention system and with the National Health Service. The preliminary results of this survey appear extremely important. In fact, this findings, highlighting the current problems of occupational physician, constitute the starting point to identify, develop and implement management methodologies, operative procedures and training programs that are effective and modern.

Aim. To study the validity of urinary benzene as a biomarker of low and very low exposure to this toxicant, as compared with t,t-muconic acid (t,t-MA) and S-phenylmercapturic acid (SPMA), also taking into account the influence of cigarette smoking and co-exposure to toluene on the urinary excretion of benzene. MATERIALS AND METHODS: The results obtained in two different studies were compared: in the first, workers occupationally exposed to low concentrations of benzene (18 fuel tanker drivers and 23 filling station attendants) were compared with 31 controls and in the second, workers exposed to very low concentrations of benzene (the same 23 filling station attendants) were compared with the 31 controls. Exposure to airborne benzene and toluene was monitored with passive personal samplers (Radiello). Then the urine collected at the end of the work shift was analyzed for t,t-MA, SPMA and urinary benzene. All participants also filled out a questionnaire about their lifestyle habits. RESULTS: There were no differences among the three groups in terms of age and smoking habit. Occupational exposure to benzene and toluene and the urinary concentrations of t,t-MA, SPMA and urinary benzene were higher in the fuel tanker drivers than the filling station attendants and higher in the latter than in the controls. Cigarette smoking was found to be associated with urinary excretion of t,t-MA, SPMA and urinary benzene at both low and very low exposure to benzene. The biomarkers t,t-MA, SPMA and urinary benzene were almost always correlated, for both low and very low exposure to benzene. Notably, for low exposure to benzene a dependency relation was found with the levels of t,t-MA, SPMA and urinary benzene on both cigarette smoking and airborne benzene, whereas for very low exposure to benzene there was a dependency relation of SPMA on cigarette smoking and airborne benzene, of urinary benzene only on cigarette smoking and of t,t-MA on none of the variables considered. CONCLUSIONS: For occupational exposure to low concentrations of benzene, urinary benzene and SPMA showed a comparable validity, while for exposure to very low concentrations of this toxicant the validity of SPMA was confirmed while urinary benzene was found to be less useful. Cigarette smoking was the main factor conditioning the excretion of all the biomarkers of benzene in conditions of both low and very low exposure to the toxicant, so for the analysis of occupational exposure to benzene it is best to recommend abstention from smoking at least in the hours immediately before urine collection.

RIASSUNTO. INTRODUZIONE. Studiare il contributo che tradizionali (acido t,t-muconico - t,t-MA ed S-fenilmercapturico - SPMA) e nuovi (benzene urinario) biomarcatori urinari di dose interna possono fornire per escludere l’origine occupazionale di esposizioni a concentrazioni molto molto basse di benzene, considerando altresì l’influenza che fonti di esposizione non occupazionale ad esso, quali fumo di sigaretta ed inquinamento delle aree urbane, possono avere sui livelli di questi indicatori. MATERIALI E METODI. Sono stati esaminati 6 lavoratori che operavano presso un impianto di depurazione di acqua di falda contaminata da benzene (esposti) e 6 impiegati amministrativi che lavoravano presso la stessa azienda (controlli); entrambi i gruppi comprendevano fumatori e non fumatori. Il monitoraggio ambientale (campionamenti fissi e personali della durata di 8 ore) ed il monitoraggio biologico (determinazione di t,t-MA, SPMA, benzene urinario, creatinina urinaria per la correzione dei biomarcatori) sono stati effettuati negli esposti per 10 giorni consecutivi, comprendenti anche i giorni di riposo (ambienti di vita), e nei controlli una sola volta. RISULTATI. L’esposizione ambientale a benzene è risultata sempre inferiore al limite di rilevabilità della metodica analitica in tutti i campionamenti, sia fissi che personali, eseguiti su esposti e controlli durante i giorni di lavoro, mentre le misurazioni personali effettuate sugli esposti durante i giorni di riposo hanno mostrato concentrazioni di benzene anche superiori a 5 μg/m3, che rappresenta il valore limite di qualità dell’aria degli ambienti di vita. Le concentrazioni di t,t-MA, SPMA e benzene urinario non hanno mostrato differenze tra esposti, indipendentemente se considerati nei giorni di lavoro o di riposo, e controlli e sono apparse sostanzialmente comprese nel range dei valori di riferimento per la popolazione italiana. Per tutti gli indicatori di dose interna studiati sono stati osservati valori significativamente più alti nei fumatori rispetto ai non fumatori. In questi ultimi, l’SPMA è risultato sempre inferiore al limite di rilevabilità mentre il benzene urinario è risultato dosabile nel 60.0% delle determinazioni effettuate nei giorni di lavoro e nell’87.5% di quelle effettuate nei giorni di riposo. CONCLUSIONI. In condizioni di esposizione occupazionale molto molto bassa o assente a benzene, per escludere l’esposizione occupazionale si rende indispensabile applicare un approccio integrato monitoraggio ambientale - monitoraggio biologico con determinazione di SPMA e/o benzene urinario, insieme ad un’attenta valutazione dei fattori che possono aver determinato un’esposizione non occupazionale al tossico. In queste particolari situazioni di esposizione occupazionale a benzene l’interpretazione dei risultati del monitoraggio ambientale e di quello biologico non deve tenere conto soltanto dei TLV o degli IBE, ma anche dei valori limite di qualità dell’aria degli ambienti di vita e rispettivamente dei valori di riferimento della popolazione generale, considerata la possibilità di comparsa degli effetti cancerogeni genotossici del benzene anche a concentrazioni di esposizione molto molto basse.

Risultati di uno studio di monitoraggio ambientale e biologico in soggetti esposti a basse dosi di benzene.

Biological monitoring of subjects exposed to carcinogen agents can be efficiently realized trough the quantification of the hemoglobin adducts. This procedure requires the development of selectively purification methods of the alkylated hemoglobin fraction in order to achieve high accuracy. To this end, in the present paper a digestion with calpain has been realized, preliminary results showed a different reactivity of the enzyme with respect to normal and alkylated hemoglobin: normal fraction was digested only, with a consequent concentration of the alkylated one Nell’ambito del monitoraggio biologico di soggetti esposti ad agenti cancerogeni uno strumento di analisi molto efficace è rappresentato dalla quantificazione degli addotti emoglobinici, che richiede, al fine di ottenere risultati accurati, lo sviluppo di metodiche di purificazione selettiva della frazione emoglobinica alchilata. A tal fine, nel presente lavoro è stata realizzata una digestione con calpaina, i risultati preliminari hanno evidenziato una diversa reattività dell’enzima nei confronti di emoglobina nativa ed alchilata con epicloridrina: viene digerita solo l’emoglobina normale, con un conseguente arricchimento della frazione alchilata.

This paper describes the position of the Joint Working Group of the Italian Association of Industrial Hygienists (AIDII), the Italian Society of Occupational Health and Industrial Hygiene (SIMLII) and the Italian Society of Toxicology (SITOX) on "Analysis of Parliamentary Act D.Lgs 25/02 and role of the Scientific Societies in the definition of Limit Values". The positive aspects of the new law which implements the European Directive 98/24 are discussed, including the abolition of the rigid periodicity of medical examinations as stated by the old rule D.P.R. 303/56. The Authors also address various parts of the law which appear to be unclear and controversial and highlight the expected difficulties arising for the employers and the safety and health professionals during the application of this new piece of legislation. Moreover, a number of discrepancies are noted between the new Italian law and the original Directive or other current Italian rules such as i. the translation of the term "slight risk", as from the original Directive, into "moderate risk", and the resulting non compulsoriness of health surveillance and biological monitoring of the workers in presence of a "moderate risk", ii. the concurrent exclusion, under the same circumstances, of the occupational physician from risk assessment procedures and iii. the upward modification of the previously established (D.Lgs 277/91) occupational exposure limits for lead. Moreover, the Authors examine and criticize--both in semantic and in toxicological terms--a recent proposal for the definition of "moderate risk" made by an ad hoc Consulting Committee of the Labour Ministry, in which the term "moderate" has been interpreted either as "low" or as "irrelevant for health effects", clearly two very different meanings. Besides, it would be inappropriate to define the conditions of a moderate risk based only on the level of exposure to the chemical (expressed as a fraction of the corresponding limit value), without considering the two other components of risk assessment for that chemical (hazard and susceptibility). Even worse would be the use of simplified models based on "algorithms", which might be useful in a preliminary phase of risk assessment, but easily could lead to an under- or over-estimation of risk, particularly when used by non professionals. In conclusion, the Working Group recommend that the new law be amended in order to clarify its most controversial aspects, whose misinterpretation could severely jeopardize the protection of the workers' safety and health at work.

To study how traditional (t,t-muconic acid--t,t-MA and S-phenylmercapturic--SPMA) and new (urinary benzene) urinary biomarkers of internal dose can contribute to exclude an occupational source of exposure to extremely low concentrations of benzene, also analyzing the influence that non-occupational sources of exposure, such as cigarette smoking and urban pollution, can have on the levels of these biomarkers.Assessment was made of 6 workers employed at a groundwater purification plant polluted by benzene (exposed) and 6 administrative clerks employed at the same plant (controls); both groups included smokers and non-smokers. Environmental monitoring (fixed and personal samplings lasting 8 hours) and biological monitoring (determinations of t,t-MA, SPMA, urinary benzene, and urinary creatinine so as to apply suitable adjustments) were performed in exposed workers on 10 successive days, including also rest days (background exposure), and in controls only once.Airborne benzene always resulted lower than the limit of detection of the analytical method in both fixed and personal samplings done on exposed workers and controls during working days, while personal samplings done on exposed workers during rest days showed benzene concentrations even higher than 5 microg/m3, that is the limit value for ambient air quality. Concentrations of t,t-MA, SPMA and urinary benzene did not show differences between exposed workers, regardless of whether they were studied on working or rest days, and controls and appeared to be largely within the reference value range for the Italian population. All biomarkers of internal dose examined in the study showed significantly higher values in smokers than non-smokers. In the latter, SPMA was always below the limit of detection, while urinary benzene resulted higher than the limit of detection in 60.0% and 87.5% of the determinations done on working and on rest days, respectively.In situations of occupational exposure to extremely low doses of benzene or of absence of exposure, the application of an integrated environmental--biological monitoring approach, involving the determination of SPMA and/or urinary benzene, together with a careful evaluation of those factors determining non-occupational exposure to the toxicant, seems indispensable in order to be able to exclude the presence of occupational exposure. In these particular situations of occupational exposure to benzene, the interpretation of the results of environmental and biological monitoring should not only consider the TLV or BEI, but also the limit value for ambient air quality and the reference value for the general population, since benzene is able to determine genotoxic carcinogenic effects even at exposure to extremely low concentrations of the toxicant.