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The contribution of the Clinica del Lavoro of Milan to the development of industrial hygiene and toxicology in the twentieth century
Abstract
In 1910, the founder of the Clinica del Lavoro of Milan, Luigi Devoto established a chemistry laboratory in the new institute, sustaining its importance in the study of occupational diseases. In 1948, the new director of the Clinica, Enrico C. Vigliani established the first laboratory of industrial hygiene in Italy, in the years of the economic boom. In 1960s, this laboratory, directed by Nicola Zurlo, significantly contributed to the research in the field. In 1980s and 1990s, the laboratory of the Clinica started to explore the field of environmental toxicology, studying the effects of benzene and other traffic pollutants on the general population. The analysis of history of the Clinica del Lavoro of Milan may represent a valuable tool for studying the origin and the development of industrial hygiene, occupational and environmental toxicology in the twentieth century.
... introduzione La Clinica del Lavoro di Milano è sempre stata all'avanguardia in numerosi campi di ricerca, incluso quello dell'igiene industriale e della tossicologia occupazionale. Gli importanti contributi offerti in quest'ambito dall'istituto milanese nel corso del Novecento sono stati di recente descritti nel dettaglio in una pubblicazione dedicata (58). Secondo gli autori di questo lavoro, l'esperienza condotta in quegli anni nei laboratori milanesi può essere considerata esemplificativa del percorso storico fatto dall'igiene industriale e dalla tossicologia occupazionale a livello mondiale nello stesso periodo (58). ...
... Gli importanti contributi offerti in quest'ambito dall'istituto milanese nel corso del Novecento sono stati di recente descritti nel dettaglio in una pubblicazione dedicata (58). Secondo gli autori di questo lavoro, l'esperienza condotta in quegli anni nei laboratori milanesi può essere considerata esemplificativa del percorso storico fatto dall'igiene industriale e dalla tossicologia occupazionale a livello mondiale nello stesso periodo (58). Infatti, così come è accaduto nei più importanti centri internazionali, anche i ricercatori della Clinica si sono inizialmente concentrati sullo studio delle classiche intossicazioni di origine professionale (saturnismo, fosforismo, solfocarbonismo) per poi occuparsi della misurazione delle concentrazioni delle sostanze nei luoghi di lavoro e dell'individuazione dei loro valori limite, arrivando infine a trattare tematiche più ampie di tossicologia ambientale (58). ...
... Secondo gli autori di questo lavoro, l'esperienza condotta in quegli anni nei laboratori milanesi può essere considerata esemplificativa del percorso storico fatto dall'igiene industriale e dalla tossicologia occupazionale a livello mondiale nello stesso periodo (58). Infatti, così come è accaduto nei più importanti centri internazionali, anche i ricercatori della Clinica si sono inizialmente concentrati sullo studio delle classiche intossicazioni di origine professionale (saturnismo, fosforismo, solfocarbonismo) per poi occuparsi della misurazione delle concentrazioni delle sostanze nei luoghi di lavoro e dell'individuazione dei loro valori limite, arrivando infine a trattare tematiche più ampie di tossicologia ambientale (58). ...
Background:
The Clinica del Lavoro of Milan provided several contributions to industrial hygiene and occupational toxicology during the twentieth century.
Objectives:
Describe the first years of the laboratory of industrial hygiene of Milan through three figures who played a leading role: Enrico Carlo Vigliani, Nicola Zurlo and Gianmario Cavagna.
Methods:
Scientific literature of the period 1948-1970 was investigated, also interviewing first-hand witnesses of that period.
Results:
Enrico Vigliani was the first European scholar to understand the importance of a laboratory of industrial hygiene within his institution. Thanks to the support of private (Montecatini) and public (INAIL) institutions he succeeded in creating a laboratory in 1948. Nicola Zurlo, who directed this structure in the first thirty years, conducted innovative studies on chronic mercury intoxication, lead intoxication and silicosis, designing and creating instruments for capturing and analyzing atmospheric dust and protection devices. He conducted analysis of the health effects of organophosphorus insecticides and started to study the air pollution. Zurlo also provided an epistemological and methodological content to the discipline. Gianmario Cavagna, one of the first Italian toxicologists, contributed to the discovery of the origin of fevers caused by the inhalation of metal fumes and to the studies on the pathogenesis of byssinosis, hypothesizing a role of bacterial endotoxins in the genesis of this disease.
Conclusions:
The contributions provided by these three protagonists to industrial hygiene and occupational toxicology were relevant and made in those years the Clinica del Lavoro of Milan as a landmark, not only in Italy but also abroad.
... Inoltre avevo una discreta pratica chirurgica, in quanto mi guadagnavo la vita come ferrista in camera operatoria di una clinica privata milanese. Vigliani mi propose di continuare la formazione e ricerca verso il malato (con Gianmario Cavagna), ma mi illustrò le prospettive ulteriori che avrei avuto in Clinica, dove erano attivi laboratori di immunologia (Benvenuto Pernis), di biochimica clinica (Raul Grisler) ed igiene industriale (Nicola Zurlo) (13). Mi pose però una condizione più o meno bonaria: la tendenza che voleva sviluppare nell'Istituto era quella di una ricerca senza ostacoli economici, ma effettuata tramite una attività in squadra (team work), multicollaborativa a seconda delle finalità. ...
... Negli ultimi anni Sessanta del secolo scorso la Clinica del Lavoro intitolata a Luigi Devoto era pronta per un balzo in avanti della ricerca in autonomia, pur conservando la sua missione di formazione medica al letto del malato sulle malattie professionali. Vi era infatti un grosso laboratorio di biochimica clinica, una dotazione completa di animali di laboratorio su cui sperimentare, un attrezzato laboratorio di igiene industriale (13), un nascente laboratorio di immunologia. Tutte queste strutture furono indotte ad uscire dall'isolamento di una operatività brillante, ma tendenzialmente chiusa in se stessa. ...
Viene riportata una esperienza personale di inserimento e attività presso la Clinica del Lavoro “Luigi Devoto” dell’Università di Milano negli anni 1965-1975. L’attenzione è focalizzata sulla metodologia di lavoro in squadra introdotta nell’attività di ricerca dal direttore Enrico C. Vigliani. Una squadra di ricerca veniva formata con persone di differenti abilità, con il presupposto di multidisciplinarità e di libertà nel perseguire un obiettivo comune. L’autore descrive il proprio contributo nella squadra di Immunologia e Allergologia, con gli studi sperimentali sulla ipersensibilità al berillio cellulo-mediata. Successivamente nella squadra di tossicologia sperimentale, con gli studi emodinamici nel coniglio sugli effetti circolatori renali e periferici di piombo, cadmio, zinco e mercurio. Infine nella squadra per lo studio della patologia asmatica da diisocianati, con la quale fu messo a punto per la prima volta in Italia il test di esposizione controllata professionale a toluene diisocianato (TDI). Per tutti questi studi fornirono supporto il laboratorio di igiene industriale e il laboratorio di biochimica. I mutamenti culturali dopo il 1968 determinarono il cessare della ricerca sperimentale e l’orientamento della Clinica verso le indagini globali per la salute in fabbrica, delle quali vengono citati due esempi. La metodologia di squadra fu stabilmente adottata fin dai primi interventi sul campo, evolvendo verso la collaborazione paritaria fra medico del lavoro e igienista industriale. Quando l’autore lasciò la Clinica per iniziare l’esperienza lombarda della medicina del lavoro di territorio, la metodologia di squadra trapassò a Lecco, nella prima delle Unità Operative Ospedaliere di Medicina del Lavoro (UOOML), dotata di un efficiente laboratorio di igiene industriale; da qui divenne parte della cultura dei servizi di prevenzione periferici, venendo utilizzata come procedura di buona norma.
... In 1906, to celebrate the opening of the Simplon Tunnel, an extraordinary work of civil engineering, which brought Italy closer to Europe, the city of Milan hosted the "International Exhibition of Simplon". 7,8 On 26 September of the same year, the inauguration of the Obstetric-Gynaecological Institute, located in the street "via della Commenda" was held in Milan: it was a place of hospitalisation and care for the female population, but also of specialisation for doctors, as well as headquarters of the Midwifery' School for the training of "Certified Midwives". 1 The building, majestic both in its external appearance and in the attention to details, had a comb shape, often adopted at the time for the most modern hospitals, and contributed to making Milan a "Health Capital". 9,10 Three arms branched off from the longer front, of which, the one closest to via della ...
The history of the modern Italian gynaecology is closely related to the figure of an enlightened clinician and passionate master, Luigi Mangiagalli (1850-1928), who, with good reason, can be considered one of the fathers of this discipline. In 1906, Mangiagalli founded the Obstetric-Gynaecological Institute in Milan, directing this structure until 1925. The aim of this paper is to describe some aspects of Italian gynaecology at the beginnings of the twentieth century through the analysis of 250 original medical records, dating back to the years 1906-1912, fragments of real life of women, midwives and doctors in a pioneering era of obstetrics and gynaecology.
Keywords
Italian gynecology, midwifery, medical records, history, archives
... dai primi anni del secolo scorso [Riva et al. 2019] con la istituzione della Clinica del lavoro di Milano. Attività di rilevazione in campo degli inquinanti fra cui polveri e silice in particolare, erano effettuate per definire la esposizione professionale. ...
To date, the Certification scheme applied by ICFP complies with UNI CEI EN ISO / IEC 17024 and UNI 11711 Standards in their current revisions; guarantees an assessment of knowledge, skills and competences based on objective criteria; provides for the management of conflicts of interest to guarantee the impartiality and objectivity of issuing the Certifications.
La necessità di qualificare l'attività dell'igiene industriale, così come la necessità di certificare la figura dell'igienista industriale che abbia acquisito specifica formazione hanno trovato il proprio sbocco con la fondazione, nel dicembre 1986, dell'Istituto per la Certificazione degli Igienisti Industriali (ICII). Nel 2004, con la costituzione dell'Istituto per la Certificazione delle Figure della Prevenzione (ICFP), si compie un ulteriore passo verso la certificazione di parte terza della figura professionale dell'Igienista Industriale, fissando anche i campi di competenza e un codice deontologico aggiornato. Nel gennaio del 2009 è stata superata l'ultima fase del percorso di accreditamento previsto dalla ISO 17024 per il riconoscimento da parte di SINCERT (oggi ACCREDIA) che ha valore per tutto il territorio europeo. Nel frattempo, il percorso professionale stabilito da ICFP per la certificazione ha trovato riconoscimento a livello interna-zionale da parte del National Accreditation Recognition Committee (NAR) dell'International Occupational Hygiene Association. Ad oggi lo schema di Certificazione applicato da ICFP, è conforme alle Norme UNI CEI EN ISO/IEC 17024 e UNI 11711 nelle loro revisioni correnti; garantisce una valutazione delle conoscenze, abilità e competenze basata su criteri oggettivi; prevede la gestione dei conflitti di interesse a garanzia dell'imparzialità e obiettività di rila-scio delle Certificazioni. Introduzione La disciplina dell'Igiene Industriale è da sempre integra-ta con le discipline che si occupano di prevenzione nel mondo del lavoro e dell'ambiente e in particolare, stori-camente, più strettamente interconnessa con la Medicina del Lavoro, a sottolineare la complementarietà e sinergia tra la componente di valutazione dell'esposizione profes-sionale e la componente clinica. Ciò costituisce un in-dubbio valore aggiunto non solo in tema di prevenzione, ma anche come strumento di formazione e crescita cul-turale. Nel contesto italiano la disciplina della Medicina del Lavoro si era già ben strutturata e sviluppata a partire LA CULTURA DELLA PREVENZIONE 50 anni di Igiene Occupazionale in Italia
... In conclusione, anche se il primo moderno laboratorio di igiene industriale della Clinica del Lavoro di Milano venne istituito da Enrico C. Vigliani (1907Vigliani ( -1992 nel 1948 (32), è possibile trovare alcuni esempi pioneristici di applicazione di tecniche chimiche allo studio delle malattie professionali già nei primi anni di vita dell'istituto milanese (26). Luigi Devoto fu tra i primi studiosi italiani a comprendere l'importanza del ruolo del laboratorio di chimica nella ricerca biomedica e, in particolare, a conferire alla chimica la stessa dignità delle diverse branche cliniche. ...
Introduction:
The Clinica del Lavoro, the first clinic for occupational diseases of the world, was inaugurated in Milan on 20 March 1910; its first director was Luigi Devoto, who was in charge until 1935. The purpose of this work is to review the activities of industrial hygiene and toxicology carried out at the Clinica del Lavoro under the guidance of Devoto.
Methods:
Documents published by the Istituti Clinici di Perfezionamento, a group of clinics of which the Clinica del Lavoro was part, record the birth and organization of this structure and the presence of a laboratory of chemistry; documents by Devoto and other authors were also retrieved to extrapolate specific information on activities of industrial hygiene and toxicology.
Results:
The Clinica del Lavoro, at the time of its inauguration, included four laboratories: of chemistry, clinical physics, histopathology and bacteriology. The chemistry lab was located on the first floor and was composed of 6 well-lit rooms, modernly equipped with work benches that could accommodate 12 people. In Devoto's view, the chemistry laboratory, supported by that of clinical physics, had to assess the toxicological properties of chemicals commonly found in the workplace and to reveal the mechanisms of induction of damage to humans. In the first 30 years of activity, the Clinica del Lavoro investigated various diseases deriving from exposure to chemical agents, including saturnism, or lead intoxication, mercurialism, phosphorism, benzolism, sulfocarbonism, dust diseases. Several assays were developed and applied to measure toxicants in different biological and environmental mean as evidenced by scientific publications starting from 1920.
Conclusion:
In Devoto's view, industrial hygiene and toxicology were essential tools for the research and prevention of occupational diseases since the first years of activity of the Clinica del Lavoro.
Operas may provide valuable information on the society of that time. In particular, they could unexpectedly give information on the evolution of meaning of the work, on the workers’ health conditions and on the progressive acknowledgment of work-related diseases in medical and popular opinion. Most of the Italian greatest opera composers had studied and worked in Milan. Hence, they had certainly been influenced by the frenetic and industrial activities of that city, one of the world major financial and business centres and the industrial capital of Italy. So, sounds and noises from the occupational environment could be surprisingly found in the melodies and music of their compositions. In this chapter, a selected anthology of five tracks from Italian operas is presented, testifying working conditions in the nineteenth and early twentieth centuries and disclosing some classical occupational diseases. The ‘Anvil Chorus’ in ‘Il Trovatore’ by Giuseppe Verdi (1813–1901) allows us to analyse the relationship between singing, music and work. The final scene of Act 1 of ‘Il Barbiere di Siviglia’ by Gioachino Rossini (1792–1868) musically depicts the noisy work at the forge. ‘Cavalleria Rusticana’ by Pietro Mascagni (1863–1945) contains praises of work, allowing us to reflect on the meaning of work in the nineteenth century. ‘La Fanciulla del West’ by Giacomo Puccini (1858–1924) refers to some health problems among gold miners. At the beginnings of the twentieth century, occupational physicians started to study silicosis and ancylostomiasis in these workers. Homesickness is also reported in the opera by Puccini. Finally, ‘Pagliacci’ by Ruggero Leoncavallo (1857–1919) addresses the issue of psychological problems in professional performers on the stage.
Background:
Benzene is a highly flammable, highly volatile liquid aromatic hydrocarbon. It has been used in many industrial processes as a solvent or a starting material. At the beginning of the twentieth century, it was very widely used in the workplace, especially in printing and in the shoe manufacturing and rubber industries. Although benzene was first recognized to cause aplastic anemia, its association with leukemia has been investigated only since the 1930s. In 1963, Italy was one of the first countries in the world to adopt a law to ban benzene as a solvent in work activities.
Objectives:
This study analyzed the contribution of the Clinica del Lavoro in Milan, Italy, to studies of the relationship between exposure to benzene and leukemia.
Methods:
Scientific literature and historical sources on benzene and leukemia in the twentieth century were reviewed, and interviews with a first-hand witness of that period were conducted.
Results:
By 1928, several scholars had reported anecdotal cases of leukemia among workers exposed to benzene. Enrico Vigliani was the first to collect all of these cases and to try to conduct statistical analysis on these data, in order to support the association between benzene and leukemia. In the 1960s, Vigliani and Alessandra Forni showed that benzene could cause chromosome aberrations in the bone marrow that could produce leukemic clones.
Conclusions:
As a result of these studies and the subsequent regulations which banned benzene, exposure conditions changed in the workplace in the last few decades. The resulting low concentrations have prompted researchers to investigate new exposure biomarkers and to study any related health problems.
scientific association with the primary purpose of promoting the development, deepening and dissemination of Industrial Hygiene, the scientific discipline aimed at identifying, assessing and controlling chemical, physical and biological risk factors (as well as transversal risks) either inside or outside the workplace, which can alter the health and well-being status of workers and/or the general population, for the purpose of effective prevention and protection of human health. Over the decades, the activities of AIDII have evolved to meet some of the current needs and challenges, while remaining consistent with the basics set by the founders. riassunto L'Associazione Italiani degli Igienisti Industriali (AIDII) è stata fondata nel 1969, da esperti accademici del settore operanti presso la Clinica del Lavoro di Milano, una delle più antiche e scientificamente e culturalmente prolifiche istituzioni di Medicina del Lavoro e Igiene Industriale a livello mondiale. AIDII nasce come associazione scientifica avente lo scopo primo di promuovere lo sviluppo, l'approfondimento e la divulgazione dell'igiene industriale, ovvero di quella disciplina scientifica volta ad individuare, valutare e controllare i fattori di rischio chimico, fisico e biologico, nonché fattori di rischio trasversali, presenti all'interno e all'esterno degli ambienti di lavoro, in grado di alterare lo stato di salute e di benessere dei lavoratori e/o della popolazione generale, ai fini di una efficace prevenzione, protezio-ne e tutela della salute umana. Nel corso dei decenni, le attività di AIDII si sono evolute per rispondere alle esigenze e alle sfide poste dall' evoluzione del mondo del lavoro, rimanendo però coerenti agli insegnamenti di base posti dai maestri della disciplina, che hanno contribuito allo sviluppo della Clinica del Lavoro di Milano e, contestualmente, dell'Associazione stessa.
Since the end of the 19th century, X-rays have been used to detect lung diseases. In Italy, 207,096 miniature chest radiographs were taken from 1941 to 1948. Traditional radiographs gave better results, but miniature chest radiographs were useful for screening. Indeed, the development of mobile miniature chest radiography units resulted in an improvement in mass X-rays screening for the detection of penumoconiosis. These mobile miniature units were mounted on a bus chassis, a solution that allowed to easily reach workers. The authors analyze some models of X-ray wagon units used by the "Clinica del Lavoro" in Milan in the 1950s. From the point of view of medical museology, the preservation of these devices requires appropriate spaces.
Background: One of the last century's greatest personalities in Occupational Medicine was Enrico Carlo Vigliani (1907-1992), director of the "Clinica del Lavoro" in Milan (1942-1977), editor-in-chief of "La Medicina del Lavoro" (1942-1991), Secretary-Treasurer and then President of the "Permanent Commission and International Association on Occupational Health" (1957-1981), the original nucleus of the ICOH. Objectives: The 20th anniversary of his death provides us with the opportunity to discuss the role of this brilliant scholar in the international development of Occupational Medicine and Industrial Hygiene. Methods: A comprehensive analysis of Vigliani's scientific works was conducted. In addition, his close collaborators and pupils were interviewed. Results: In the 1930s, as a young doctor, Vigliani, first in the world, demonstrated the effect of lead on porphyrin metabolism. Afterwards he conducted pioneering studies on occupational oncology (benzene-induced leukaemia, bladder cancer due to aromatic amines, asbestos-related tumours), pathogenesis of silicosis, encephalopathy in carbon disulfide poisoning, byssinosis and metal fume fever, so influencing international research and the implementation of preventive measures against these conditions. Vigliani's scientific authority was widely recognized internationally, as confirmed by his role in ICOH. During his period of active service, the Commission developed from an academic institution to a more open association, substantially increasing its membership. Furthermore, he contributed to establishing subcommittees devoted to specific topics (now called "scientific committees"), one of the strengths of the present Commission. Conclusions: Vigliani's contribution to the development of Occupational Health may be considered as an expression of his genial eclecticism which ranged from clinical medicine to the environment.
Academic journals in a specialist field provide an interesting historical record of its development and progression over time. This article describes the evolution of some major international journals of occupational medicine, including some historical background on their editorial board. As North America, the United Kingdom, and Northern Europe are known to have the highest contribution to scientific production, it was considered appropriate to investigate the main occupational medicine periodicals in these regions. Given the remarkable improvements in Japanese occupational health following the Second World War, it was also considered worthwhile to investigate the two English-language journals of occupational medicine from this country.
A biomonitoring study was conducted to simultaneously measure individual benzo(a)pyrene (BaP) exposure in 50 office employees, not occupationally exposed to polycyclic aromatic hydrocarbons (PAH), using personal samplers and the formation of (+) r-7, t-8-dihyroxy-t-9,t-10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE) adducts to haemoglobin (BPDE-Hb) and serum albumin (BPDE-SA). The population enrolled was exposed to an average of 0.58 ± 0.46 ng BaP m(-3) (mean ± SD). The concentration of BaP collected from smokers' samples was double that from non-smokers (P = 0.007). BPDE adducts to Hb and SA were quantified as BaP tetrols released from hydrolysis of macromolecules and measured by high-resolution gas chromatography-negative ion chemical ionization-mass spectrometry. BPDE-Hb adducts were detected in 16% of the population and BPDE-SA adducts in 28%. Smoking did not affect adduct formation. When BaP personal monitoring data were used as the criterion of exposure, no correlation was found with the presence and the levels of BPDE-Hb and BPDE-SA adducts. Undetected sources of PAH, such as the diet, might markedly alter the exposure profile depicted by individual air sampling and affect the frequency and levels of protein biomarkers. This is the first comparative analysis of BPDE-Hb and BPDE-SA adducts, providing reference values for these biomarkers in a general urban population. However it is difficult to establish which biomarkers would be the more relevant in assessing low BaP exposure, due to undetectable factors such as dietary PAHs, that might have influenced the results to some degree.
Cavagna, G., Foá V., and Vigliani, E. C. (1969)
Brit. J. industr. Med.,
26,
314-321.
Effects in man and rabbits of inhalation of cotton dust or extracts and purified endotoxins
The incidence of byssinosis in workers in a cotton card-room, where the airborne concentration of bacterial endotoxins was 7·2 μg./m.³, was 32%; and 47% in a hemp card-room where the endotoxin concentration was 8·7 μg./m.³; no cases were observed among workers exposed to only traces of endotoxins. The effect of the inhalation by aerosol of purified Escherichia coli endotoxin on F.E.V.1·0 and F.V.C. was studied in normal subjects and in patients with chronic bronchitis. A significant reduction in F.E.V.1·0 lasting more than 6 hours was observed in two out of eight normal subjects, in one out of three subjects with chronic bronchitis inhaling 80 μg. endotoxin, and in one out of four subjects with chronic bronchitis inhaling 40 μg. endotoxin. These results show that the inhalation of bacterial endotoxin can produce, in some individuals, changes in F.E.V.1·0 similar to those experienced on Mondays by some card-room workers.
A study of the mechanism of pathogenesis of inhaled bacterial endotoxins was carried out on rabbits subjected for 20 weeks to aerosols of purified E. coli endotoxin (20 μg./day) and cotton extract (2 mg./day). This treatment produced patterns of bronchitis: i.e., a increase in the respiratory tract fluid with increased protein content and characteristic histopathological changes. The bronchitis occurred after the appearance of cross-reacting circulating antibodies against E. coli endotoxin and cotton extract. These antibodies were detected with the haemagglutination tests after the first three weeks of treatment, and in subsequent weeks reached progressively higher titres, up to a maximum of 1:512.
A challenging aerosol of 0·1 mg. E. coli endotoxin in two rabbits and 10 mg. cotton extract in another two of the rabbits treated as above produced a marked increase in pulmonary resistance lasting more than two hours. In control rabbits a challenging aerosol of 1 mg. endotoxin or 100 mg. cotton extract caused only a moderate increase in pulmonary resistance, which returned to normal in less than one hour.
It may be concluded that the repeated inhalation of endotoxins induces in rabbits a state of hypersensitivity and at the same time the appearance of inflammatory reactions in the bronchi and alterations in the mechanical properties of the lung. These changes may be significant in the pathogenesis of byssinosis.
Urinary porphyrin excretion was investigated in 67 workers occupationally exposed to commercial mixtures of polychlorinated biphenyls (PCBs) by determining the concentration of uro-, hepta-, hexa-, penta-, and coproporphyrin homologues. The workers had a mean blood PCB concentration of 386 ± 257 ppb (mean ± SD; range 162–1319 ppb). These values are at least ten-fold higher than that expected in a population not occupationally exposed to PCBs. No qualitative alterations of the urinary porphyrin excretion were found and the uroporphyrin: coproporphyrin ratio remained normal. There was a definite increase in the excretion of all the porphyrinic homologues, so that the average concentration of total porphyrins in urine was 94.5 μg 1−1 in the exposed group versus 48.3 μg 1−1 in the control group. This excretory pattern of porphyrins corresponds to that usually observed in the first stage of chemical porphyria induced by polyhalogenated aromatic hydrocarbons. In accordance with current knowledge, this should be interpreted as a consequence of the specific inductive properties of PCBs on liver microsomal enzymes. The results of this investigation show that, as already observed in experimental animals, commercial mixtures of PCBs have a porphyrinogenic activity in man, as well.
The relationship between FEP and the indicators of an internal dose of lead (PbB, PbU, PbU-EDTA) was considered in a group of adult male subjects with varying lead exposure, whose PbB values ranged from 15 – 150 μg/100 ml; a highly significant correlation was found between FEP and PbB, PbU, and PbU-EDTA (r = 0.904; r = 0.889; r = 0.894, respectively).
The regression curves representing the relationship between the erythrocyte metabolite and the indicators of internal dose are uniform and are of nonlinear (logistic) type. In the first stage, within the range of normal values (up to 46 μg/100 ml RBC), FEP increases moderately with the rise of internal dose; subsequently it increases exponentially and tends finally to an asymptotic value in the range 250 – 300 μg/100 ml RBC.
The data obtained in our investigation suggest that FEP is a useful test to assess metabolic damage in adult subjects arising from an “abnormal” lead absorption and to evaluate the amount of “active deposit” of the metal present in the body.
Validity analysis showed that the erythrocyte metabolite can reliably be used as a screening test for monitoring occupationally exposed subjects and can also be applied in general population studies, since FEP has a good validity in the PbB range of 40 – 70 μg/100 and in the PbU-EDTA range of 500 – 2000 μg/24 h.
A cohort mortality study of 5000 vinyl chloride manufacturers is ongoing in 9 Italian plants. They represent the entire workforce of those ever employed in the production of the monomer and its polymerization.The objectives of the study are to investigate the mortality of the exposed population and to clear up the carcinogenic spectrum of vinyl chloride. This article gives the results for 3 out of 9 plants, Rosignano, Ferrara and Ravenna, which represent about 25% of the total cohort.The expected deaths have been calculated using the mortality rates of the Italian population. For the deceased persons information from the death certificates were used in the analysis of mortality; additional clinical and pathological data were collected (best pathological evidence, b.p.e.).In Ferrara a statistically significant excess for all malignant tumors and lung cancer was detected. In Rosignano and Ravenna the number of observed deaths were small and therefore no comments can be made on cancer mortality. The cohort study is ongoing in the 6 remaining cohorts and the future analysis will consider duration and level of exposure and latency.
Lead is determined in urine by atomic absorption spectrophotometry after separation by coprecipitation with thorium, in the presence of copper(II) ; concentration of lead and removal of interferences are achieved simultaneously. Fresh urine or samples acidified with hydrochloric acid must be used. Precipitation is quantitative from the urine of subjects excreting coproporphyrins or treated with chelating agents, as the added copper liberates the chelated lead. The precision of the method is ±0.005 p.p.m. of lead.RésuméLe plomb dans l'urine peut être dosé par spectrophotométrie par absorption atomique après séparation par coprécipitation, à l'aide de thorium, en présence de cuivre(II). La concentration du plomb et l'élimination des interférences se font simultanément. On doit utiliser de l'urine fraîche ou des échantillons acidifiés par l'acide chlorhydrique. La précipitation est quantitative dans les urines de sujets excrétant des coproporphyrines ou traitées par des agents chélatants : le couvre ajouté libère le plomb complexé. La précision de la méthode est ±0.005 p.p.m. de plomb.ZusammenfassungEs wird die Bestimmung von Blei in Urin mit der Atomabsorptionsspektroskopie beschrieben. Das Blei wird durch Mitfällung mit Thorium in Gegenwart von Kupfer(II) konzentriert; dadurch werden gleichzeitig Störungen vermieden. Dazu müssen frische, mit Salzsäure versetzte Proben verwendet werden. Die Fällung ist quantitativ in solchen Proben, die gleichzeitig Coproporphyrin enthalten oder mit Chelatbildnern versetzt wurden, da das hinzugegebene Kupfer das komplexgebundene Blei freimacht. Die Genauigkeit der Methode beträgt 0.005 p.p.m. Pb.
Carlo Moreschi (1876-1921) was founding co-editor of the journal "Il Lavoro" (now known as "La Medicina del Lavoro"), together with Luigi Devoto in 1901. Despite this fact, many of his pioneering contributions to 20th century scientific debate are not well known outside Italy. Objectives: The aim of this paper therefore was to recall Moreschi' achievements and the groundbreaking work of this remarkable Italian physician.
A comprehensive analysis was conducted on scientific papers written by Carlo Moreschi between 1901 and 1920, extending the investigation to his original manuscripts and private correspondence with family and colleagues.
Careful examination of Moreschi's work reveals several studies in the field of social medicine, epidemiology of infectious diseases, general pathology and oncology. In particular, his main interest in haematology and immunology enabled Moreschi to be one of the first to understand the mechanisms of complement fixation and the formation pathways ofantiglobulin sera. In this manner, Moreschi significantly contributed to the work of Wassermann regarding the diagnosis of syphilis, as well as contributing to the discovery of the "antiglobulin test", first described by Coombs in 1945. Furthermore, Moreschi co-founded "Il Lavoro" and "Haematologica", the oldest journals in their respective fields.
According to Devoto, Moreschi can be remembered as the archetype modern researcher and clinician. His role in the 20th century scientific debate and his pioneering work in the field of immunology and haematology, that are often forgotten due to his premature death, deserve to be reconsidered and re-assessed by the Italian and international scientific community.
Chelatable lead (PbU-EDTA) is the best indicator of lead concentration at the critical organ level (indicator of dose). However, since this test is not easily applicable for the biological monitoring of lead-exposed subjects, the current practice is to determine lead in blood (PbB) and/or in urine (PbU). But these tests are indicators of exposure and not of dose. To analyze the reliability of PbB and PbU in estimating lead dose, the relationships between PbU-EDTA and PbB and between PbU-EDTA and PbU were studied in two groups of male lead workers: 48 currently exposed and 45 with past exposure to lead.
In currently exposed workers the correlation between PbU-EDTA and PbB and between PbU-EDTA and PbU was very close (r = 0.85, r = 0.74, respectively); in past exposed workers the correlation with PbU-EDTA was decidedly lower for PbB (r = 0.54) and not significant for PbU (r = 0.29). In both cases the relationship between the variables was linear. In the previously exposed men, PbB displayed lower values than those found in currently exposed men.
These results indicate that both PbB and PbU allow an indirect estimation to be made of the internal dose in currently exposed subjects, whereas the tests cannot be used for this purpose in subjects who have long since ceased to be exposed. In these cases chelatable lead must be determined.
The relationship between FEP and the indicators of dose (PbB, PbU, PbU-EDTA) was examined in a group of male subjects who had left lead-exposing jobs more than 12 months previously. In these subjects, FEP and PbB and FEP and PbU were correlated to a distinctly lower degree compared to previous findings in currently exposed subjects, although the correlations were still statistically significant. In the previously exposed subjects the erythrocyte metabolite displayed definitely higher values than those found in currently exposed subjects at the same PbB or PbU levels. A very close correlation was found between FEP and PbU-EDTA, as was found in exposed subjects. The regression curve assumed an identical profile in the two situations. From these results it may be concluded that FEP persists at high levels for a long time after cessation of exposure due to a direct inhibition of heme synthetase caused by lead released from the tissue deposits. It should be noted that FEP proved to be a valid test for predicting the amount of lead storage, even a long time after cessation of exposure.
In previous research we established that FEP is a suitable and valid test for evaluating the metabolic damage caused by lead absorption. In this study, in the same sample consisting of adult male subjects with PbB levels ranging from 15 to 150 μg/100 ml, we examined the relationship existing between PbB and the other indicators of effect so as to compare their behavior with that of FEP and establish whether there is a field of application where the erythrocyte metabolite is to be preferred. FEP and ALAD displayed a very much better correlation with PbB than the urinary tests (ALAU and CPU). The decrease in ALAD values is already clear at PbB levels which do not cause an elevation of FEP; on the other hand, when the enzyme is markedly inhibited, the erythrocyte metabolite is elevated further with the increase in the internal lead load. FEP increases earlier compared to ALAU and CPU; nevertheless, the urinary metabolites undergo increasing elevations at PbB levels higher than 90 μg/100 ml when the FEP values have become stable. We confirmed that FEP possesses good predictive validity at PbB levels of 60 and 70 μg/100 ml; for such PbB levels, also ALAD, measured with the European Standardized Method, displayed high validity. Validity of the urinary metabolites was rather modest. FEP was, moreover, well correlated also with other indicators, suggesting that the erythrocyte metabolite may be used to predict both dose and effect.
In a population of workers (81 subjects) exposed to inorganic mercury vapors in a chlorine alkali plant (airborne mercury concentration between 0.06 and 0.3 mg/m3) and in a group (104 subjects) of people never exposed to mercury the plasma level of -galactosidase, -glucuronidase, -N-acetylglucosaminidase, and -glucosidase was determined.The results are as follows:1.
The plasma level of the four acid lysosomal hydrolases are higher in the group of workers exposed to mercury than in the control group. The difference is significant at the P < 0.001="" level="" for="" all="" studied="" enzymatic="" activities.="">2.
There is a significant correlation between the increase of the plasma levels of these enzymatic activities and the degree of exposure.
These results suggest the use of this procedure for detecting an undue mercury absorption in workers exposed to the metal before any clinical signs.RBC and plasma cholinesterase activities were not affected. The results of the study of urinary proteins were not useful for detecting an early impairment of the kidney function. However, in some cases we observed a marked glomerular proteinuria without any clinical explanation: this fact makes one very cautious about denying the existence of a kidney impairment in workers exposed to the metal before any clinical sign is present.
The International Centre for Pesticide Safety (ICPS) was inaugurated in March 1990. Coordinated by the World Health Organization (WHO) and in collaboration with research and university institutions, the Centre operates in the following areas of activity: information and documentation on pesticide toxicity; epidemiological, toxicological and clinical research; training and education; laboratory research. ICPS is also a centre of meetings and courses on permanent education. This paper reports on the activities carried out so far and on the future programmes of ICPS.
A definition is first of all made of the fractions of airborne dust that can deposit in the various regions of the respiratory apparatus, according to the aerodynamic size of the particles. Since the "respirable" fraction is the most important fraction from a medical point of view, instruments have always been developed that were designed to sample this portion of dust. The author describes the evolution of the criteria for sampling the "respirable" dust fraction and the contribution to research in this field made by the group of industrial hygienists of Milan, under the leadership of Prof. Zurlo, in particular with the development of the aeolian classifier. The results are reported of a comparison made between the four respirable dust selectors most widely used in European Community countries, that was carried out in a pyrite mine in Tuscany. The mean values obtained were practically identical, thus demonstrating that sampling techniques have now achieved proven homogeneity.
The "Clinica del Lavoro" had already begun work on dust pollution in the working environment in the mid-1930's but was only able to study the problem more in depth at the beginning of the 1950's when the Industrial Hygiene Laboratory was established under the fortunate direction of Professor Nicola Zurlo. The first research studies in that period were aimed at the correct choice of the most suitable sampling equipment and analytical methods for assessment of the extent of such types of pollution. The results achieved in these initial studies, the experience acquired in the field and further, more detailed research enabled Professor Zurlo to develop and perfect new types of sampling instruments that were more appropriate to the goals it was desired to achieve and these instruments are still widely used to-day. The paper also considers the evolution of analytical methods using the optical microscope for determination of the concentration of particles and fibres, most of which were developed and perfected in our Laboratory, up to the present time. It is stressed that phase contrast microscopy is still indispensable for dust analysis and still offers ample scope for research in the field of artificial fibres that have recently been put on the market, even though the electron microscope is now the only acceptable solution for research in living environments.
Largely produced and used as a 'universal biocide', pentachlorophenol (PCP) is under investigation as possible carcinogenic agent for man, after Scandinavian studies have shown that human exposure to chlorophenols might be associated with cancer and leukaemia. PCP is used mainly in the wood and tanning industries. Technical grade PCP may be contaminated by variable amounts of impurities, including chlorinated dioxins and furans. This makes it uncertain whether the acute and chronic effects observed in experimental animals can be ascribed to PCP itself or to its contaminants. The acute toxic effects of PCP are due to uncoupling of oxidative phosphorylation. The porphyrogenic and acnigenic activity shown by the commercial products appears to be related to the presence of contaminants. Both pure and technical grade PCP induce toxic damage to the liver and changes in the immunological system. Analytical grade PCP has been found to be teratogenic in animals. Analogous effects have also been caused by hexachlorodibenzodioxin, one of the main contaminants of PCP. So far, the carcinogenic activity of PCP has not been sufficiently studied. Experimental investigations in animals are few and of questionable value. Human epidemiological data address multiple exposure situations, where the significance of PCP exposure cannot be easily singled out. Therefore the question is still open and further research is needed. Absorption of PCP in humans may occur through inhalation, skin penetration and via the digestive system. PCP is metabolized in the organism only to a limited extent and is mostly excreted unchanged with the urine. Human exposure is not confined to work settings. Although environmental persistence of PCP is rather short, minimal amounts of PCP can be traced almost everywhere in the environment and in human tissues. PCP may dissipate in the environment from waste disposal, treated wood or other sources. Release of PCP from treated wood may be of importance as a source of human exposure for countries where log homes are popular. PCP can be detected in environmental samples using sensitive and specific analytical methods; these methods can also be adapted for use in human biological monitoring by measuring the PCP concentration in blood and urine. The relationship between environmental exposure and PCP levels in body fluids is rather uncertain. Urinary PCP concentrations can be used for biological monitoring of exposed subjects. Health surveillance of workers exposed to PCP should be addressed mainly to the evaluation of skin disorders, liver function changes and nervous system alterations.
The paper discusses the analytical features and presents the results of biological variability of a standardised European method to determine cholinesterase activity in plasma (PChE) and in erythrocytes (AChE), based on a modified version of Ellman's method. The method, which determines the activity in whole blood and in plasma, with the activity of the RBC's derived from the difference, uses blood and in plasma, with the activity of the RBC's derived from the difference, uses propionilthiocoline as a substrate; instruments and operation are relatively simple. The method was found to be accurate, especially in relation to the wide biological variability. The mean activity of AChE was 4.01 ± 0.65 Ul/ml of blood in 48 male subjects and 3.45 ± 0.61 Ul/ml of blood in 47 females. This difference disappears when the activity is expressed in Ul/ml of erythrocytes. The mean activity of PChE was 3.03 ± 0.66 Ul/ml blood in males and 2.77 ± 0.68 Ul/ml blood in females. If the activity is expressed in Ul/ml plasma, the difference between males and females is further accentuated. The intra-individual variability of the PChE and AChE activity was much lower than the inter-individual variability, the former having men CV's of 11% and 7% respectively for PChE and AChE. For a correct biological monitoring of subjects exposed to anticholinesterasic agents, it is indispensable to determine the base value of each subject before exposure and refer subsequent determinations made after the beginning of exposure to this value. Otherwise, the high biological variability may make it impossible to detect an inhibition of AChE or PChE below or equal to the maximum level recommended by Biological Limits for Working Environments.
Urinary creatinine is used as an adjustment factor of the concentration of metabolites excreted in urinary random samples. The usefulness of this practice is longtime disputed. The aim of this study, made in 94 workers, is to estimate if the creatinine-adjustment of V and Ni urinary concentrations brings a true advantage in his capacity to predict the amount of metal excreted in 24 hours. The results shown this practice is pointless and that also in case of urinary samples at anomalous dilution. A greater accuracy in expression of analytical results of V and Ni excretion may be obtained collecting the urinary samples with a known amount, that is to say more representative of the daily diuresis.
The recent Health and Safety Act devolves the management of workers' health protection to new local authorities named "Local Sanitary Units." The specific program is framed in the existing state regulations and is in agreement with European community politics regarding health risks arising from the industrial use of particular substances like lead, asbestos, benzene, PCBs and others. The rapid industrial growth during recent years put into evidence completely new and numerous risks with the result of both qualitative and quantitative modifications of occupational diseases which existed in the years preceding the second world war. This rapid and remarkable change required a general adjustment in the country, which involved universities, government and industry. At the same time, the need of new relationships between occupational risks and insurance management rose. Beginning in the seventies, the Italian Industrial Hygiene Association [Associazione Italiana Degli Igienisti Industriali (A.I.D.I.I.)] promoted the progress of industrial hygiene in Italy through national and international conferences, continuous educational activities and participation with government standard-setting committees. The trend in A.I.D.I.I. future activities embraces the development of standard evaluation and control procedures and the improvement of research following European guidelines in strict cooperation with correlated European and American organizations.
Ferro-chromium production is based on the use of chromium oxide (III) and it is generally accepted that chromium in this form is not able to cross biological barriers. However, the data on the toxic and carcinogenic effects of hexavalent chromium in man are now firmly established. Some studies have questioned these data, calling for a clarification as to whether exposure to trivalent chromium can also produce human effects, perhaps with different latency time. A study was carried out on the exposure conditions (type and degree) in a ferro-chromium foundry that had been in operation since 1972. The absorption levels in the working population of the foundry, and the possible toxic effects on the kidney have been investigated. A total of 236 workers (142 employed in production departments, 33 office workers and 61 sub-contractor employees) were examined with measurement of the indicators of dose (urinary-chromium) and of effect on the kidney (albumin, retinol binding protein, and renal tubular epithelium antigens in the urine). Environmental hygiene measurements showed relatively low values of total chromium in the air (always less than 0.160 mg/m3). Hexavalent chromium was absent or, if present, at levels below the sensitivity of the analytical method used (0.001 mg/m3). The values of urinary chromium measured at the beginning and at the end of the working day and at the end of the work shift were always less than 5 micrograms/g creatinine, which has been proposed as a biological limit in chromium exposure. However, differences were observed between groups of subjects employed on different jobs, which is indicative of an absorption process varying according to the degree of exposure. The indicators of effect did not reveal any renal impairment, even early, that could be attributed to the toxic action of chromium.
Cadmium in blood (CdB), cadmium in urine (CdU) and beta 2-microglobulins (beta 2MU) were determined in 83 male workers exposed to cadmium fumes. CdU was measured both on 24-h urine samples and on spot samples. The behaviour of the biological indicators of cadmium was assessed in relation to degree of current exposure, length of exposure and cumulative exposure (computed as concentration of cadmium at the workplace multiplied by duration of exposure). CdB values were significantly higher in the subgroups of subjects with higher current cadmium exposure and in the subgroups of subjects with greater cumulative exposure, but the test levels were not influenced by duration of exposure. CdU levels were significantly higher in the subgroup of subjects with greater cumulative exposure, but were less influenced by current exposure or duration of exposure. Considering the entire population, a rather close correlation (r = 0.69) was observed between CdB and CdU. When the population was divided according to level of current exposure, a close relationship was observed between the two indicators in all subgroups; nevertheless, for identical CdU values, the CdB values were higher in the subjects with heavier current exposure. Even if in all Cd workers the beta 2MU levels were in the range of reference values, the highest beta 2MU levels were found in the subjects with CdU greater than 10 micrograms/l. The data confirm that CdU is prevalently influenced by the body burden of metal, but they also suggest that the CdB levels are not influenced solely by the intensity of current exposure but also depend to a considerable degree on the body burden.
The present investigation is an attempt to determine the amount of lead in urine and blood of the adult population living in Milan, in its suburbs, and in its neighboring towns. Lead in blood was measured by the titrimetic dithizone method. Lead in urine was measured by atomic absorption spectrophotometry. The arithmetical mean of lead in urine was 38.3 µg/1 for males, and 28.7 µg/1 for females; in blood it was 30 µg per 100 ml for males and 23.7 µg per 100 ml for females.
Plasma and red cell cholinesterase activities were determined in 250 male and 100 female healthy adults by a continuous pH-stat automatic titration method. A study of plasma and red cell chollnesterases was then carried out in sick adults and children and in healthy pregnant women admitted to hospital wards disinsected with “Vapona Strips.” A moderate decrease in plasma cholinesterases was observed only in subjects exposed for 24 hours per day to DDVP airborne concentrations above 0.1 mg/cu m and in patients with liver insufficiency. In all subjects examined, even in those whose plasma cholinesterase dropped, the red cell cholinesterase was unaffected. The use of garments kept in cupboards disinsected with Vapona Strips did not produce changes in either plasma or red cell cholinesterases.
The aim of this presentation is to comment on the epidemiology byssmosis describe the clinical aspects and relate them to the presence of particular agents in the environment. Other pulmonary diseases related to Gram- negative bacteria and endotoxin will also be discussed.
Both in animals and in man the inhalation of CS2 vapor induces a chronic polyneuropathy with primary lesions in the axons of peripheral nerves. Since it was reported in several studies that the administration of gangliosides improves nerve regeneration and the functional recovery of nerves damaged by section as well as cryodegeneration, a study was undertaken to evaluate the effects of bovine-brain gangliosides administration on the experimental CS2 neuropathy in the rat. One hundred and fifty male rats were intoxicated with CS2 by a discontinuous inhalation exposure to 700 ppm for 12 weeks until a clear neuropathy developed. Thereafter the animals were subdivided at random into five groups and treated in different ways: 10 mg/kg BW gangliosides, 0.5 mg/kg gangliosides, 0.5 mg/kg vitamin B1, and 1 mg/kg vitamin B6, physiological solution, and controls without any treatment. The recovery from neuropathy was controlled for 18 weeks of treatment and assessed periodically by means of clinical, electromyographic, and morphological examination. The results of morphological studies showed more pronounced regeneration activity in the rats treated with the high dose of gangliosides than in all others, while no differences among the groups could be observed as far as clinical and neurophysiological parameters are concerned. The mechanism supporting this ganglioside-induced effect has so far not been ascertained, and further studies on this subject are in progress.
A clinical laboratory examines some part of the living patient—his excreta or blood or secretions—to help the physicians reach a diagnosis or provide a better treatment. The oldest example of this, going far back into antiquity, is uroscopy. As the name indicates, in this examination the physician did not manipulate the urine but merely looked at it. Certain appearances allegedly correlated with certain clinical states.
The principle involved—that the characteristics of the urine provided a sign of what was going on within the body—was sound, even though the coefficient of error was enormous. For centuries, physicians studied the urine with various methods, attempting to draw conclusions that would remain valid. Hermann Boerhaave (1668-1738) for example, early in the 18th century, tried to determine whether urine contained "blood serum." He collected a cask of urine whose weight, he said, he reduced by evaporation from 100 lb to 1 lb. But, he