A Forni

University of Milan, Milano, Lombardy, Italy

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Publications (30)38.06 Total impact

  • Article: The influence of cytochrome P450 1A1 and glutathione S-transferase M1 genotypes on biomarker levels in coke-oven workers.
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    ABSTRACT: The present study has the aim of evaluating gene-environment interaction on the levels of different biomarkers in coke-oven workers exposed to PAH. In order to assess whether the levels of some biomarkers (PAH-DNA adducts, nitro-PAH adducts to Hb and MN frequency) could be modulated by the genetic metabolic polymorphisms for CYP1A1 and GSTM1, we analysed in 76 coke-oven workers and 18 controls the CYP1A1 (MspI and Ile/Val sites) and the GSTM1 genotypes by a PCR assay. In individuals with shared setup of CYP1A1 or GSTM1 genotypes, we analysed how the specified biomarkers correlated with total PAH exposure (urinary levels of 1-hydroxypyrene) both by a stratified analysis and logistic regression modelling. Statistically significant (P = 0.03 and P = 0.01) higher percentages of the more susceptible GSTM1- subjects compared to the GSTM1+ subjects and of the more susceptible CYP1A1 Ile/Val individuals compared to the CYP1A1 Ile/Ile individuals were detected for high levels of PAH-DNA adducts in the high exposure group (namely high levels of 1-OHP). A statistically significant association was observed between increased PAH-DNA adduct levels and the more susceptible GSTM1- genotype (P.O.R. = 4.18, P = 0.03) in a logistic regression modelling and a significant interaction between PAH exposure and GSTM1-genotype was found for PAH-DNA adducts. No effect of these metabolic genotypes was observed for MN frequency and nitro-PAH adducts to Hb. In conclusion, a gene-environment interaction between PAH exposure and two metabolic genotypes involved in activation (CYP1A1) and detoxification (GSTM1) of PAHs, respectively, has been identified.
    Archive für Toxikologie 12/1999; 73(8-9):431-9. · 4.67 Impact Factor
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    Article: Benzene-induced chromosome aberrations: a follow-up study.
    A Forni
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    ABSTRACT: To study the evolution of cytogenetic damage from past exposure to high concentrations of benzene and its health significance, chromosome aberrations (CA) in lymphocytes were reinvestigated after approximately 20 years in four subjects with past severe hemopathy and in seven controls studied in the late 1960s. Increased chromosome-type aberrations were still present up to 30 years after benzene toxicity, but blood counts were normal. The vital status at the end of 1993 was ascertained for 32 subjects with a history of benzene toxicity and for 31 controls studied for CA from 1965 to 1970, who differed significantly for CA rates. Of the 32 benzene-exposed subjects, 1 was lost to follow-up, 20 were still alive, and 11 had died at ages 36 to 83, between 1 and 20 years after the last CA study. Five deaths were from neoplasia (acute erythroleukemia, brain tumor, cancer of lung, paranasal cavity, esophagus). The decreased subjects had significantly higher rates of chromosome-type aberrations than those alive, and those who died of neoplasia had the highest rates of these aberrations in the last study before death or diagnosis of cancer. Out of the 31 controls, 12 had died from 4 to 23 years after the CA study. Three deaths were from neoplasia (two lung cancer, one brain tumor). Even if this is a small sample, the results suggest a higher risk of cancer for the benzene-exposed cohort, who had persistently high CA rates in lymphocytes.
    Environmental Health Perspectives 01/1997; 104 Suppl 6:1309-12. · 7.04 Impact Factor
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    Article: Prevention of Risks from Occupational Exposures to Antineoplastic Drugs: Consensus Document
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    ABSTRACT: Ever-increasing numbers of cancer patients have been treated with antineoplastic drugs in the past few years. Among patients treated with these drugs, an increased risk of a "second neoplasm" has been observed, mainly as a function of increased life expectancy. On the basis of this observation, the International Agency for Research on Cancer has classified a number of antineoplastic drugs as carcinogenic or probably carcinogenic for humans. Various categories of workers are at risk for exposure to antineoplastic drugs, absorbing these substances mainly through inhalation or dermal contact. Although the absorbed doses are notably lower than those administered to patients, review of the literature reveals increased risks of spontaneous abortions and chromosomal aberrations in subjects who have worked without adequate protection. A working group, Prevention of Occupational Risks Due to Handling Antineoplastic Drugs in Health Care, was established by the Italian Institute of Prevention and Safety at Work (Istituto Superiore per la Prevenzione e Sicurezza sul Lavoro-ISPESL) in February 1995. This group reviewed the epidemiologic studies and research on cytogenetic indicators of genotoxicity in occupationally exposed subjects. In addition, the group made recommendations for environmental and biological monitoring of exposure and health surveillance, and developed guidelines for primary and secondary prevention. The group's recommendations are summarized in a consensus document, but cannot be considered definitive, since work practices continue to evolve and will have to be examined further in the future. Thus, more research is needed to achieve answers to the questions raised by the working group. The main topics to be addressed are indicated in the consensus document. In particular, it will be necessary to evaluate working conditions nationwide, using standardized protocols for risk assessment, to achieve precise estimates of workers' exposures.
    Int J Occup Environ Health. 01/1997; 3:84.
  • Article: Cytogenetic studies in coke oven workers.
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    ABSTRACT: Chromosome aberrations, micronuclei, and sister chromatid exchanges (SCE) were evaluated in cultured lymphocytes of coke oven workers of an Italian steel industry plant, occupationally exposed to polycyclic aromatic hydrocarbons, and in a group of unexposed controls from a non-oven plant in the same area. No differences were found between exposed and controls for rates of total abnormal metaphases (including and excluding gaps), chromatid-type and chromosome-type aberrations, cells with 2 or more breaks, and for micronuclei. On the contrary, SCE were significantly increased in the exposed versus the controls, but, when smoking habits were considered, the increase was significant only for smokers.
    Toxicology Letters 12/1996; 88(1-3):185-9. · 3.23 Impact Factor
  • Article: Prevention of risks from occupational exposure to antineoplastic drugs. Consensus document.
    La Medicina del lavoro 01/1996; 87(3):201-206. · 0.32 Impact Factor
  • Article: Bronchoalveolar lavage in the diagnosis of hard metal disease.
    A Forni
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    ABSTRACT: Bronchoalveolar lavage (BAL) a technique which is not very invasive and which permits investigations of deep lung reactions from various causes, has been demonstrated to be also useful in the diagnosis of lung disorders from hard metals (HM) and/or cobalt, thus overcoming, in most cases, a need for open lung biopsies. Cases with HM interstitial disease show at BAL the signs of a high-intensity alveolitis, characterized by increased total cells with bizarre multinucleated giant cells and increased inflammatory cells. These findings correspond well to the histological pattern of desquamative giant cell interstitial pneumonitis. The persistence of alveolitis and especially high numbers of eosinophils at following BALs, despite cessation of exposure and steroid treatment, has an ominous prognostic significance. The few reported cases of cobalt asthma studied by BAL present either normal findings or increased T lymphocytes with inverted helper/suppressor ratio. This last finding has also been described in some asymptomatic exposed subjects, which indicates a subclinical (or preclinical?) lung reaction. Determination by neutron activation analysis of trace metals (cobalt, tungsten, tantalum) in BAL and other biological specimens may be important in documenting recent or past exposures, but is not discriminant for diagnosis, since no relationship has been found between levels of any metal and the occurrence of the disease.
    Science of The Total Environment 07/1994; 150(1-3):69-76. · 3.29 Impact Factor
  • Article: Comparison of chromosome aberrations and micronuclei in testing genotoxicity in humans.
    A Forni
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    ABSTRACT: Chromosome-type aberrations (CsA) and micronuclei (Mn) rates were compared in conventional 2-day lymphocyte cultures. In 67 healthy controls the mean rate of CsA was 0.54%, and that of Mn 2.38/1000 (median 1.66/1000). Mn were significantly correlated with age. The rate of Mn was higher in the 30 individuals with CsA > or = 1% than in the 37 subjects with no CsA. However, in 40 cadmium (Cd) workers, contrary to that found for CsA, the rates of Mn did not differ from those of the controls matched for age and smoking habits, not even in the subgroup with the highest Cd cumulative exposure index, while an age effect was evident both in the exposed and in the controls.
    Toxicology Letters 07/1994; 72(1-3):185-90. · 3.23 Impact Factor
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    Article: Biological monitoring of cadmium exposure--an Italian experience.
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    ABSTRACT: Studies carried out over the last 12 years in northern Italy on a case list of 105 cadmium (Cd) workers showed that blood levels (B-Cd) were influenced not only by current exposure but also by body burden, while urinary levels (U-Cd) were influenced predominantly by body burden. Moreover, no advantages were gained by adjusting U-Cd for creatinine or specific gravity. The urinary beta 2-microglobulin levels were within the reference values when B-Cd and U-Cd were below the current threshold values. However, some indicators of early renal effect appeared to be altered. An increase in chromosome-type aberrations in lymphocytes occurred in workers with a heavy cadmium burden. Studies carried out on more than 600 subjects from the general population showed higher B-Cd levels in smokers than in nonsmokers. B-Cd levels were higher in men and in higher age groups. Identifying reference values for B-Cd through meta-analysis studies seems useful.
    Scandinavian journal of work, environment & health 02/1993; 19 Suppl 1:27-33. · 3.12 Impact Factor
  • Article: Reference values for chromosome aberrations in human lymphocytes as indicators of genotoxic effects.
    A Forni
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    ABSTRACT: Increased chromosome aberrations (CA) in human cultured lymphocytes are an accepted indicator of early biological effects of exposure to genotoxic agents, which has also been investigated, with conflicting results, in several groups of subjects occupationally exposed to metals known or suspected to be carcinogenic. One of the problems with this indicator is the lack of universally accepted reference values. Difficulty in establishing absolute reference values for CA depends on individual variability in the reference groups (due to several environmental and genetic confounding factors) and on methodological variants at the different stages of the test (culture methods, scoring, classification and reporting of CA). Therefore, at present, CA studies in exposed groups should include proper 'control' groups, matched for the known confounders, investigated in the same laboratory, with the same methods in order to minimize factors of variation. The results of the studies should be statistically compared and evaluated mainly on a group basis.
    Science of The Total Environment 07/1992; 120(1-2):149-53. · 3.29 Impact Factor
  • Article: Chromosomal effects of cadmium exposure in humans.
    A Forni
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    ABSTRACT: Cytogenetic studies on subjects occupationally or environmentally exposed to cadmium are reviewed and discussed. After a first report of increased chromosome aberrations in lymphocytes of itai-itai patients from Japan, several studies on workers occupationally exposed to cadmium gave conflicting results. These differences may perhaps be explained by the action of co-factors (e.g., nutritional deficiencies in itai-itai patients; concomitant exposure to other metals in some occupational groups), or by different levels of exposure. In a study on cadmium workers with a wide range of cumulative exposure, as compared with matched controls, an increase in chromosome-type aberrations in lymphocytes, an indicator of cumulative damage, was found only because of the increased rates in the subgroup with the highest cumulative exposure and cadmium burden. As far as environmental exposure is concerned, of two recent reports, one from China is positive for chromosome aberrations and the other, from Japan, is negative for sister chromatid exchanges.
    IARC scientific publications 02/1992;
  • Article: [Proposal of environmental and biological monitoring and health surveillance of the exposed to inhalation anesthetics. Consensus. A Study Group on Occupational Exposure to Inhalation Anesthetics].
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    ABSTRACT: The Study Group on Occupational Exposure to Inhalation Anaesthetics of the Lombardy Association of Occupational Health and Industrial Hygiene prepared a document that was discussed during the Congress "Occupational Risks due to Inhalation Anaesthetics", held in Brescia, Italy, on May 12, 1992. The same document was then approved by the Directory Council of the Lombardy Association of Occupational Health and Industrial Hygiene. Data on environmental concentrations of Nitrous Oxide collected from 1989 to 1991 in 269 operating rooms of 47 hospitals in Lombardy are reported. The measured levels are considerably lower than those collected from the same Study Group from 1985 to 1987 in 111 operating rooms. The methodologies for exposure control are discussed, regarding both environmental and biological monitoring. These two techniques are complementary and can be used with standardized methods. The review of the literature on the early effects showed, even with some uncertainty at the current exposure levels, effects on liver and Central Nervous System. Still controversial are the data regarding the reproductive toxicity. Health surveillance programs have been organized in the last 5 years in 18 Lombardy hospitals and they indicate no cases of pathologies due to inhalation anesthetics on 1498 subjects. Operative proposals are suggested on the methodology and the frequency of environmental/biological monitoring and health surveillance. The "technical limit values" reported in the document from the Italian Ministry of Health are also discussed. Finally, research topics are suggested in order to assess the early effects of exposure.
    Giornale italiano di medicina del lavoro 01/1992; 14(1-6):101-4.
  • Article: Alveolar and lung fibre levels in non-occupationally exposed subjects.
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    ABSTRACT: Mineral fibre concentrations and characteristics were evaluated by the same electron microscope methods in 15 bronchoalveolar lavage samples and in 40 surgical lung tissue samples of subjects with no occupational exposure to asbestos. Both fibre alveolar load and lung burden evaluated by transmission electron microscopy were higher in the groups of industrial workers with no specific asbestos exposure than in the groups of individuals exposed only to general environmental pollution. In both types of samples, the fibre burden consisted of extremely small fibres (mean length less than 2 microns, mean diameter less than 0.1 micron), with a trend towards a further reduction in mean length in the lung tissue as compared with the alveolar load. These data suggest that there is a need for a critical reconsideration of the methods of evaluating environmental fibre pollution and of those for assessing exposure-effect relationships.
    IARC scientific publications 02/1989;
  • Article: [Talcosis-asbestosis: an unusual risk in a food industry].
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    ABSTRACT: In a 37 years-old female worker, who had undergone surgical excision of a segment of the right lower lobe for a chronic aspecific pleuropneumonitis, the histological examination of the excised lung tissue showed asbestos alveolitis with diffuse interstitial fibrosis, and multiple granulomata containing talc particles. An investigation at the work site showed that the worker had been engaged for 22 years in dusting salami with a mixture of rice flour and talc contaminated with chrysotile asbestos. Thirteen work-mates engaged in the same job were studied. In two of them, with chest X-rays negative for pneumoconiosis, a functional ventilatory impairment, restrictive in type, associated with a reduced pulmonary diffusion of gases, was demonstrated. In these two cases, bronchoalveolar lavage showed signs of severe exposure to asbestos (which at TEM evaluation resulted to be amphibolic) talc and other fibres, with presence of iron-laden macrophages, indicators of haemorrhagic alveolitis. Moreover, in one of them, a severe macrophagic-lymphocytic alveolitis, with inverted T helper/T suppressor ratio, was presented, possible expression of a hypersensitivity pulmonary reaction. Taking into consideration the length and modality of work, with exposure to talc powder contaminated with asbestos, for the three cases the diagnosis of "pre-radiologic talcosis-asbestosis" was made. Since the occupational risk was not known in this industry, no ambient and personal preventive and protective measures had been taken; anyway, such type of work has now been stopped. The exposed workers shall be kept under control in the future for surveillance directed towards early diagnosis of possible further asbestos effects.
    Giornale italiano di medicina del lavoro 06/1988; 10(3):111-3.
  • Article: Alveolar fiber load in asbestos workers and in subjects with no occupational asbestos exposure: an electron microscopy study.
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    ABSTRACT: The alveolar fiber load was evaluated by bronchoalveolar lavage and by scanning and transmission electron microscopy (SEM and TEM) in 50 subjects with or without occupational exposure to asbestos. The concentration of asbestos fibers in bronchoalveolar lavage was significantly higher in the groups of people currently and formerly occupationally exposed, compared to the concentration found in people only exposed environmentally, despite wide interindividual variation within the groups. Nonasbestos inorganic fibers were present in all groups, but the concentrations did not differ significantly. Both in people occupationally exposed and in those only environmentally exposed, the alveolar load consisted mainly of ultrashort and ultrathin fibers, which can be studied only with TEM. In fact, the percentage of fibers greater than 5 micron long was only around 15% in the occupationally exposed and was minimal in those only environmentally exposed. The geometric mean diameters of asbestos fibers retained in the alveoli ranged from 0.05 micron for chrysotile to 0.15 micron for amphiboles.
    American Journal of Industrial Medicine 02/1988; 14(1):37-46. · 1.63 Impact Factor
  • Article: Benzene and its biologic effects in humans. Discussion paper.
    A Forni
    Annals of the New York Academy of Sciences 02/1988; 534:493-5. · 3.15 Impact Factor
  • Article: Epidemiology in protection and prevention against environmental mutagens/carcinogens. Examples from occupational medicine.
    A Forni, P A Bertazzi
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    ABSTRACT: Subjects occupationally exposed to potential mutagens/carcinogens represent the most suitable groups for epidemiological studies aimed at assessing the risk for the individual or the offspring. Several cancer risks to humans have been detected by epidemiological studies performed in occupational settings. Cancer epidemiology studies have been able (a) to identify specific occupations or agents associated with the risk; (b) to verify the results of experimental studies; (c) to test the effectiveness of changes in production or preventive measures in decreasing risks. Reproductive epidemiology has suggested a risk of spontaneous abortions or of malformation in the offspring of workers exposed to some chemicals or occupations, but data are often conflicting due to methodological problems. With the aim of early assessment of risk in mind, the epidemiological use of indicators of exposure or of the early effect of exposure to genotoxic agents is increasingly applied to occupational groups. Cytological monitoring of subjects at risk of occupational cancer of lung or bladder is carried out mainly to diagnose precancerous lesions of target tissues. Cytogenetic methods (chromosome aberrations, SCE, micronuclei) in somatic cells provide a means for detecting early effects of occupational exposure to known or potential mutagens/carcinogens in selected groups of individuals, but their significance is widely debated. Monitoring of urinary mutagenicity, as applied in nurses handling cytostatic drugs, is an example of how an indicator of exposure to genotoxins can be used to evaluate the impact of preventive measures. Among the perspectives, biochemical epidemiology seems to be promising in detecting individuals genetically susceptible to cancer.
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 01/1988; 181(2):289-97. · 2.85 Impact Factor
  • Article: [New diagnostic methods in occupational lung diseases: bronchoalveolar lavage. Experience at the Institute of Occupational Medicine, University of Milan].
    La Medicina del lavoro 76(1):11-6. · 0.32 Impact Factor
  • Article: [An unusual exposure to asbestosis risk in a bag manufacturing plant: observations on 22 cases].
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    ABSTRACT: Although the risks connected with occupational exposure to asbestos and its numerous industrial uses are widely known, it still happens that instances of exposure with high potential risk are discovered. A detailed study of a worker suffering from silicosis and asbestosis who had worked for many years in a firm dealing with the recovery and re-use of used jute sacks also containing asbestos, revealed the existence of a real asbestosis risk in the firm, with the result that other workers in the same firm were studied. A total of 22 subjects were studied, 17 of whom also underwent bronchoalveolar lavage (BAL) and determination of the cellular composition of the recovery liquid in order to establish the presence of asbestous alveolitis. The age of the subjects ranged between 39 and 75 years (x = 56.36), length of service in the firm ranged between 2 and 18 years (x = 9.27), time between start of exposure and clinical examination varied between 29 and 50 years (x = 40.27). The 22 subjects were divided into 3 groups on the basis of the radiological examinations: 1) 8 cases were negative (36.36%); 2) 8 cases had pleural alterations only (36.36%); 3) 6 cases had interstitial lung disease (with and without pleural lesions) (27.27%). Of the 17 subjects who underwent BAL, 7 were in the first group, 7 in the second and 3 in the third. Among these 17 subjects BAL showed absence of alveolitis in all subjects of the first group, diagnosis of alveolitis in only some of the second group, and in all of the third group.(ABSTRACT TRUNCATED AT 250 WORDS)
    La Medicina del lavoro 81(4):290-5. · 0.32 Impact Factor
  • Article: [Markers of fibrogenesis in bronchoalveolar lavage and in serum of workers exposed to asbestos].
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    ABSTRACT: The N-terminal peptide of type III procollagen (PIIIP) and fibronectin (FBN), two markers possibly implicated in the pathogenesis of pulmonary fibrosis, were determined in bronchoalveolar lavage fluid (BAL) and in serum of 27 subjects with a history of occupational exposure to asbestos, in 10 sarcoidosis patients and in 7 healthy controls. At the same time, the study of the cell populations and asbestos bodies count in BAL were also performed. In BAL of sarcoidosis patients the mean concentration of PI-IIIP was higher compared to that of the other two groups, and the difference was significant compared with the healthy controls. Among the group of asbestos workers, both PIIIP and FBN were significantly higher in subjects with radiological signs of pulmonary asbestosis compared with those with no signs of asbestosis. On the basis of BAL cytology, the asbestos-exposed were divided into two subgroups, with or without signs of alveolitis: the mean concentrations of BAL PIIIP was significantly higher in the subgroup with alveolitis. Moreover, in this subgroup there was a positive correlation between total number of cells and PIIIP, and between the number of asbestos bodies and PIIIP in BAL. Serum PIIIP values did not differ significantly among the various groups, with the exception of higher values in sarcoidosis patients. The results of this study seem to confirm the usefulness of PIIIP and FBN determinations in BAL, as indicators of the activity of the fibrotic process which, in particular cases, might also assume a prognostic significance.
    La Medicina del lavoro 82(3):238-47. · 0.32 Impact Factor
  • Article: [The toxicology and prevention of the risks of occupational exposure to aromatic polycyclic hydrocarbons. III. The effects: epidemiological evidence, early effects. Individual hypersusceptibility. Health surveillance].
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    ABSTRACT: Adverse effects following occupational exposure to polycyclic aromatic hydrocarbons (PAH) are mainly carcinogenic. The available epidemiological data suggest that some substances and industrial processes, in which PAH exposure is frequent, are classified as carcinogenic to humans: primary aluminium industry, cola gasification, coke production, iron and steel foundry, coal tar, pitch, creosote, untreated mineral oils, asphalt, soot. The target organs are mainly lung, bladder, skin. Other relevant effects are skin lesions such as folliculitis. The studies on early biological effects (chromosomal aberrations, sister chromatid exchanges, micronuclei) have shown contradictory results, mainly because of differences in exposure intensity. The metabolic polymorphism may account for a higher susceptibility to lung and bladder cancer following exposure to risk factors; the role of PAH occupational exposure is however to be examined, and the use of indicators of genetic susceptibility is currently limited to research programs. Health surveillance for PAH exposed workers is funded on the Italian laws (DPR 303/56 and D.Lgs. 626/94) and it is mainly dedicated to prevention of carcinogenic effects. Preventive examinations should consider PAH target organs (skin, lung, bladder, larynx) and look for early signs and symptoms. Particular attention will be paid to life habits such as tobacco smoking or diseases which could represent condition of susceptibility. Periodical examinations (every six months) will similarly evaluate PAH target organs. Health surveillance is also programmed for formerly exposed workers and the institution of exposure and cancer registries is mandatory. On the basis of the current scientific data, it is not advisable the use of tumor markers or cytogenetic tests at the individual level as well as the screening of asymptomatic PAH exposed workers for early diagnosis of lung or bladder cancer. Information and formation activities will be part of medical examinations and will be included in specific programs in cooperation with other company functions.
    Giornale italiano di medicina del lavoro ed ergonomia 19(4):152-63.