The opinion of the Italian Society of Occupational Medicine and Industrial Hygiene (SIMLII) on silica-exposure and lung cancer risk.

BACKGROUND: The Italian Society of Occupational Medicine and Industrial Hygiene (SIMLII) began a thorough overview of the silica-silicosis-lung cancer question starting in 2005. METHODS AND RESULTS: The body of informa tion obtained from a number of epidemiological studies, meta-analyses and reviews following the decision of the IARC to classify Respirable Crystalline Silica (RCS) as a human carcinogen (Group 1) led to different conclusions, which can be summarized as follows: basically an increased risk of developing lung cancer is demonstrated and generally accepted for silicotics; the association of lung cancer and exposure to silica per se is controversial, with some studies in favour of an association and some leading to contrary conclusions. Due to methodological problems affecting most studies and the difficulty in identifying the mechanism of action, we agree that the silica-lung cancer association is still unclear. The UE approach is more practical than scientific, in that it recommended the use of "good practices" subject to an agreement with the social partners, without any need to classify RCS as a human carcinogen. However, in 2008 the UE asked the Institute of Occupational Medicine (IOM) in Edinburgh to assess, as a primary objective, the impact of introducing a system for setting Occupational Exposure Limits (OELs) based on objective risk criteria. CONCLUSION: In the present state of the art SIMLII's conclusions are: a) There is no need to label RCS with phrase H350i (ex R.49); b) It is of utmost importance to enforce compliance with current OELs; c) Future guidelines specific for silicosis risk should include adequate health surveillance; d) For legal medicine purposes, only lung cancer cases with an unquestionable diagnosis of silicosis should be recognised as an occupational disease.

Occupational silica exposure and lung cancer risk: a review of epidemiological studies 1996-2005.

BACKGROUND: In 1997, a Monograph from the International Agency for Research on Cancer (IARC) classified occupational exposure to crystalline silica as carcinogenic to humans. Large amounts of epidemiological data have been published subsequently. METHODS: We conducted a systematic review of epidemiological investigations on silica exposure and lung cancer risk published after the IARC Monograph, including 28 cohort, 15 case-control and two proportionate mortality ratio (PMR) studies. These were identified in the available literature. RESULTS: The pooled RR of lung cancer, calculated using random effects models, from all cohort studies considering occupational exposure to silica was 1.34. The RRs were 1.69 in cohort studies of silicotics only, 1.25 in studies where silicosis status was undefined and 1.19 among non silicotic subjects. The pooled RR was 1.41 for all case-control studies. The RRs were 3.27 in case-control studies of silicotics only, 1.41 in studies where silicosis status was undefined and 0.97 among non silicotic subjects. The RR was 1.24 for PMR studies. CONCLUSIONS: In this re-analysis, the association with lung cancer was consistent for silicotics, but the data were limited for non silicotic subjects and not easily explained for undefined silicosis status workers. This leaves open the issue of dose-risk relation and pathogenic mechanisms and supports the conclusion that the carcinogenic role of silica per se in absence of silicosis is still unclear.

Factors related to the development of sensitization to green coffee and castor bean allergens among coffee workers.

BACKGROUND: Occupational allergic respiratory symptoms in coffee workers have been frequently reported, but the ultimate cause of sensitization is still debated, castor bean being considered besides green coffee beans. Atopy and cigarette smoking have been suggested as promoting factors of sensitization for several occupational allergens. OBJECTIVE: This study was carried out to assess the prevalence of allergic respiratory symptoms and of sensitization to both green coffee beans and castor bean in the whole workforce of a coffee manufacturing plant. Furthermore we wanted to ascertain both the presence of castor bean antigens in the settled dust of the green coffee beans warehouse and the possible crossreactivity between the two beans. Meanwhile, the effect of smoking and atopy was considered. METHOD: Two-hundred and eleven workers were examined. A questionnaire on oculorhinitis and asthma was administered and skin-prick tests for green coffee beans, castor bean and 15 common inhalant allergens were carried out. Isoelectric focusing, isoelectric focusing immunoblot and radioallergosorbent assay (RAST) inhibition were performed on samples of settled environmental dust from the green coffee area, as well as on castor bean and green coffee beans. RESULTS: Ten per cent of the workers complained of oculorhinitis alone and 16% of asthma (nearly always associated with oculorhinitis). The overall prevalence of skin-sensitization was: 15% for green coffee beans, 22% for castor bean, 22% for common allergens. Evidence of sensitization to occupational allergens was more common in smokers, with a more than twofold increase in relative risk. The strong association between skin positivity to common and occupational allergens suggests that atopy acts as an enhancing host factor towards occupational sensitization. The analysis of the dust confirmed the presence of castor bean antigens. CONCLUSION: Our findings indicate that castor bean is the major cause of occupational sensitization among coffee workers, whereas smoking and atopy act as enhancing factors.

Lung adenocarcinoma and indicators of asbestos exposure.

A case-control study was carried out on 145 male lung-cancer patients diagnosed at autopsy and 178 controls, in order to investigate the relationship between asbestos exposure and the cell type of pulmonary carcinoma. Adenocarcinomas (AD) were individually matched with other cell types and with controls. The relative risk (RR) of developing AD in relation with lung asbestos body (AB) content as the exposure indicator was calculated by using logistic-regression analysis for matched sets. Two cutoff levels, 1,000 and 10,000 asbestos bodies per gram dry weight (AB/gdw), were used in the analysis. In addition, AB counts were treated as a continuous variable (log AB+I). A significant association was found between AD and asbestos exposure, using levels and logarithmic transformation. However, an association of asbestos exposure with cell types other than AD could not be ruled out.

[The use and utility of multistage models of carcinogenesis in cohort studies]. / L'uso e l'utilità dei modelli multistage di cancerogenesi negli studi di coorte.

Multistage models have been widely employed in recent years and are thought to be useful for the interpretation of biological bases of epidemiological results. We have employed two general models, both interpretable under the multistage theory, using GLIM package for the simultaneous analysis of the effect on mortality of several factors, including age at first exposure, duration of exposure, time interval since exposure ended. In the multiplicative model (relative risk, RR) each variable is supposed to act multiplicatively on the number of expected cases. In the additive model (absolute risk, AR; excess of risk, ER) each variable is thought to act multiplicatively on the excess risk; the result is then added to the expected number of cases. These models were applied to data regarding exposure to aromatic amines and bladder cancer mortality. The results suggested that aromatic amines act on more than one stage of the carcinogenic process, most probably on both early and late stages. In addition, hints for prevention measures were obtained. In fact, the effect on late stages implies a decreasing risk after cessation of exposure, and in this case discontinuing exposure can be useful; an effect on early stages, instead, indicates the necessity of intensive medical surveillance even after cessation of exposure. However, it seems that the possibility of obtaining results interpretable under the multistage theory is at present confined to the rare cases in which there is a substantial excess mortality from specific cancers.

The prediction of recommended energy expenditure for an 8 h work-day using an air-purifying respirator.

Thirty railway workers executed maximal, or near maximal, stress tests with and without the use of a half mask air-purifying respirator (Spasciani 85 A1 P1) fitted with two combined filters for simultaneous protection from organic vapours and particulate matter. The pressure-flow characteristics of inspiratory and expiratory resistance at airflows in the range 0-90 l.min-1 were established by a continuous flow method on one test mask. Significant differences were found by paired t-test between the two exercises (with and without use of mask), showing reduced values with use of the mask, for breath frequency, ventilation rate, oxygen uptake, carbon dioxide production, maximal oxygen uptake, percentage of maximal voluntary ventilation used at the maximal exercise ventilation. No significant differences were found for tidal volume, respiratory quotient, heart rate, systolic blood pressure, oxygen uptake at anaerobic threshold, and duration of exercise. The predicted energy expenditure recommended for an 8 h work shift, corresponding to 40% of maximal oxygen uptake, is found to be reduced working with respirator and is significantly different from that observed during stress test without mask. The average ventilation rate at this workload is below 25 l.min-1, with predicted inspiratory mouth pressure equal to, or less than, 20 mm H2O. This maximal inspiratory mouth pressure is proposed as a safety limit for prolonged work using a respirator, with a recommended energy expenditure close to 40% of maximal oxygen uptake.

Tentative reference values for gold, silver and platinum: literature data analysis.

Data available on biologic fluid content of therapeutic metals are uneven for silver, gold and platinum respectively. Tentative reference values may be proposed on the basis of the most representative studies for silver and gold. For silver it is suggested that the variability in normal subjects could range up to 10 micrograms/l in whole blood and up to 1 microgram/l in urine. For gold 0.5 microgram/l can be considered the upper limit for both whole blood and urine. For platinum there is no indication that concentration in either blood or urine could reach detectable amounts in normal subjects.

Airborne fibrous and non-fibrous particles in a silicon carbide manufacturing plant.

Silicon carbide (SiC) fibre generation is reported to occur during commercial SiC crystal production. Dust levels and fibre concentrations were measured by static sampling in an Italian plant operating 24 Acheson furnaces. X-ray Diffraction (XRD) was used to assess the quartz content in the dust collected. Optical microscopy (OM) and scanning electron microscopy (SEM) were used for fibre counting and identification of fibres. Only alpha-quartz was identified, but airborne concentrations were found to be higher than the concentration of crystalline silica reported in other similar studies. Two types of fibre, coarse and fine, were identified by OM and SEM: for both, only the peak of silicon (Si) was evident at energy dispersive X-ray analysis (EDXA). Coarse fibres are irregular in shape, with a diameter greater than 5 microns. Fine (respirable) fibres are straight, regular in shape, with a typical diameter between 1 and 2 microns. Fine fibre concentration does not appear to be related either to total dust or to total fibre concentration. It cannot therefore be predicted from the nature of the various processes involved.

Autopsy indicators of exposure to asbestos and lung cancer.

In many instances, only post-mortem examination can provide probative data about (i) the presence of lung cancer and (ii) its relationship to exposure to asbestos. Moreover, the results of an autopsy may suggest that a thorough investigation of occupational history should be carried out, since such information is rarely recorded in clinical records. We considered pathological indicators for selecting subjects who had a high likelihood of previous occupational exposure to asbestos. The positive predictive value of pleural plaques ranged from 20 to 75%, depending on their size and on the concentrations of asbestos bodies and uncoated mineral fibres in the lung. The probability of no exposure was greater than 90% if neither asbestos bodies nor uncoated mineral fibres were found. Another purpose of our work on lung cancer and exposure to asbestos was to investigate the relationships between exposure and the occurrence of specific cell types of lung cancer in an autopsied population. Both work history and asbestos body count were considered. The matched analysis showed some tendency towards an association between the occurrence of adenocarcinoma and the presence of indicators of exposure to asbestos.

An update of cancer mortality among chrysotile asbestos miners in Balangero, northern Italy.

The mortality experience of a cohort of chrysotile miners employed since 1946 in Balangero, northern Italy was updated to the end of 1987 giving a total of 427 deaths out of 27,010 man-years at risk. A substantial excess mortality for all causes (standardised mortality ratio (SMR) = 149) was found, mainly because of high rates for some alcohol related deaths (hepatic cirrhosis, accidents). For mortality from cancer, however, the number of observed deaths (82) was close to that expected (76.2). The SMR was raised for oral cancer (SMR 231 based on six deaths), cancer of the larynx (SMR 267 based on eight deaths), and pleura (SMR 667 based on two deaths), although the excess only reached statistical significance for cancer of the larynx. Rates were not increased for lung, stomach, or any other type of cancer. No consistent association was seen with duration or cumulative dust exposure (fibre-years) for oral cancer, but the greatest risks for laryngeal and pleural cancer were in the highest category of duration and degree of exposure to fibres. Although part of the excess mortality from laryngeal cancer is probably attributable to high alcohol consumption in this group of workers, the data suggest that exposure to chrysotile asbestos (or to the fibre balangeroite that accounts for 0.2-0.5% of total mass in the mine) is associated with some, however moderate, excess risk of laryngeal cancer and pleural mesothelioma. The absence of excess mortality from lung cancer in this cohort is difficult to interpret.

Asbestos exposure and histologic cell types of lung cancer in surgical and autopsy series.

A case-control study was carried out on 41 surgical and 106 autopsy histological tissue samples of lung cancer in men, in order to investigate the relationships between asbestos exposure and cell type of pulmonary carcinoma. Both occupational history (obtained by interviews of surgical patients or of the next-of-kin for deceased subjects) and lung asbestos body content (determined by optical count after hypochlorite digestion and membrane filtration of lung tissues) were considered as asbestos exposure indicators. No significant relationships were found in the surgical series after adjustment for smoking. The autopsy series showed a trend towards an association between lung adenocarcinoma and asbestos exposure indicators and a markedly higher agreement between the 2 kinds of indicators than that observed in the surgical series.

Short-term respiratory changes in polyurethane foam workers exposed to low MDI concentration.

Our study included 27 polyurethane foam workers exposed to MDI only at low concentrations (ranging from 0.0005 to 0.001 ppm) and 27 clerks from the same factory matched by age. Respiratory function tests were performed on a Monday and Friday of the same week at shift onset, 4 h later and at shift end. The subjects under study were asymptomatic for asthma. The two groups had quite similar spirometric values with minimal functional impairment. A statistical analysis was carried out by Student's t-test for matched pairs and two-way analysis of variance (ANOVA), in order to take into account both occupational exposure and smoking habits. No significant differences between the two groups were observed with paired t-tests in the respiratory parameter trend during both the Monday and Friday work shift. Nor were differences observed within the two groups when Friday's and Monday's results were compared. No significant differences between the two groups were found in paired comparisons between Friday and Monday for respiratory parameters. ANOVA demonstrated that the FEV1 and FEF25-75 reduction present on Friday, when compared to Monday, was related to smoking and not to occupational exposure. In conclusion our findings showed no short-term respiratory changes in subjects exposed to low MDI concentration.

[Effects of long-term use of inhaled steroids (beclomethasone dipropionate) in patients with occupational asthma no longer exposed]. / Effetti dell'uso a lungo termine di steroidi inalatori (beclometasone dipropionato) in asmatici professionali non più esposti.

Ten subjects with occupational asthma who, were either no longer exposed or had minimal exposure, were controlled every three months after cessation of exposure. All subjects showed airway responsiveness to metacholine, complained of mild symptoms and had minor lung function abnormalities. The subjects underwent inhalation therapy with beclomethasone dipropionate (2000 micrograms/day) for 3 to 12 months. Although pulmonary function values and symptoms did not change significantly during treatment, PD20 FEV1 improved markedly after 3 months and further improved after the longest period of treatment. PD20 FEV1 after treatment was significantly correlated with the base PD20 FEV1 value and not with the FEV1 increase. Good therapeutic results were obtained in 6 subjects. In the remaining 4 subjects who did not respond to treatment, the base PD20 FEV1 value was below 200 micrograms. In 4 of the 6 subjects who responded to treatment PD20 FEV1 was lower than during treatment but higher than before treatment.

Cancer mortality in a northern Italian cohort of rubber workers.

An analysis of the mortality of a cohort of 6629 workers employed from 1906 to 1981 in a rubber tyre factory in northern Italy (978 deaths and over 133,000 man-years at risk) showed that the all cause mortality ratio was slightly lower than expected (0.91). Overall cancer mortality was close to expected (275 v 259.4) but there were significant excess rates for two cancer sites: pleura (9 observed v 0.8 expected, which may be due to the use of fibre containing talc) and bladder (16 observed v 8.8 expected). Death rates were not raised for other sites previously associated with employment in the rubber industry, such as cancers of the lung and brain, leukaemias, or lymphomas. The substantially reduced relative risk of pleural cancer among workers first employed after 1940 (RR = 0.05 compared with before 1940) probably reflected improvements in working conditions over more recent periods. For cancer of the bladder, the relative risk was also lower for workers first engaged after 1940. Thus no appreciable risk for any disease was apparent for workers employed over the past four decades. Analysis for each of the 27 job categories showed a substantial excess for cancer of the pleura in the mechanical maintenance workers (4 observed v 0.17 expected); an excess of cancer of the lung (21 v 13.48) was also present in this job category.

[Respiratory impairment and metal exposure in a group of 68 industrial welders]. / Compromissione respiratoria ed esposizione a metalli in un gruppo di 68 saldatori al lavoro.

A group of 68 currently employed welders were examined who were exposed to welding fumes either for the whole or for at least half the working day and who used at least two welding processes, which were mainly manual metal arc welding and metal active gas welding, but also metal and tungsten inert gas welding, or oxyacetylene welding. The welders were classified into 3 groups according to the class of materials used, i.e.: 1) only mild and stainless steel; 2) mild and stainless steel and other metals; 3) only other metals. Chronic bronchitis symptoms were observed in 22% of the subjects; signs of suspected radiological fibrosis were present in 18%, initial signs of radiological fibrosis in 4%. Small airway disease was prevalent in the smokers (28 smokers versus 2 nonsmokers); one worker had an obstructive syndrome and another a restrictive syndrome (both were smokers). There was a good correlation between years of exposure and: 1) MEF25 in non-smokers; 2) urinary cobalt in the whole group. There was also a correlation between smoking and FEV1, MEF50, MEF25, PaO2 and urinary cadmium. Serum copper was higher in workers exposed full time than in those exposed part time. Urinary chromium and cobalt and serum copper were high in steel welders, lower in welders using steel and other metals and low in welders using other metals. Urinary chromium was similar in smokers and non-smokers. Serum zinc was found to be of little use for biological monitoring of welders. Urinary chromium was studied for one week in 10 full-time exposed steel welders. The difference between the chromium values at the end of the workshift and those at the beginning was small (low current exposure); the chromium values at the end of the workshift were not uniform in the whole group (different past exposure levels).

[Various air pollutants in Torino]. / Studio su alcuni inquinanti nell'aria di Torino.

The trend of concentrations of some pollutants (total particulate, polycyclic aromatic hydrocarbons (PAH), benzo(a)pyrene (BaP), chromium, nickel, lead, vanadium) in the urban air of Turin for the years 1986-87-88 was studied. The air was sampled daily by glass fiber's filters; a ponderal determination of total particulate was made; PAH was dosed by gas-chromatography and by mass spectrometry, metals was determined by atomic absorption spectrometry. These are the values of the three years mean concentration: total particulate 156.3 micrograms/mc, PAH 27.2 ng/mc, B(a)P 2.16 ng/mc, Cr 28.6 ng/mc, Ni 40.5 ng/mc, Pb 1.37 micrograms/mc, V 55.2 ng/mc. Finally, we try to calculate the conjectural carcinogenic effect of the B(a)P for the residents of Turin.

Skin notation in the context of workplace exposure standards.

In the establishment of workplace exposure standards, the potential for cutaneous absorption is taken into consideration through the addition of "skin notation" to the relevant substance. In the TLVs Documentation (ACGIH, 1986) dermal lethal dose to 50% (LD50) or human data are the bases for the assignment of "skin notation" to 91 of 168 substances. For the other substances, the "skin" attribution seems to be based on undocumented statements in 24 (14.5%), skin effects in 13 (8%), and analogy in 7 (4%), while in the remaining 33 (20%) any reference is lacking as to the basis for notation of the cutaneous route of entry. Furthermore, since the established "cut-off" value of 2 g/kg is sometimes bypassed when a notation is added or omitted, the use of dermal LD50 is perplexing. Given the relevance of the skin notation for the validation of threshold limit values (TLVs) in the workplace, a full examination and citation of all available scientific data are recommended when establishing the TLV of substances absorbable through the skin.

Bladder cancer mortality of workers exposed to aromatic amines: analysis of models of carcinogenesis.

The effects of various factors were evaluated on both relative risk (multiplicative model), and absolute excess risk (additive model) of bladder cancer among 664 workers of a dyestuff factory in Northern Italy. These workers were exposed to aromatic amines in fairly constant working conditions from 1922 to 1970, and were employed for at least one year. They were followed up till the end of 1981 for a total of 12,302 man-years at risk. Under both models, the risk was greater for workers directly involved in aromatic amine manufacture than for those with only intermittent exposure. There was no marked effect of age at first exposure on the absolute excess risk of bladder cancer, but the relative risk was strongly and negatively related to age at first exposure. Under the multistage theory of carcinogenesis, this pattern of risk indicates an early stage effect. Absolute excess risk increased sharply during exposure, and continued to rise, although less sharply, after exposure had ceased. Relative risk, however, decreased after cessation of exposure, indicating a possible late stage effect. Thus, the results derived from both additive and multiplicative models are not in contrast when interpreted in terms of the multistage theory of carcinogenesis, though they are not totally consistent with a single-stage effect, either early or late. Aromatic amines may act on a stage somewhere between the first and penultimate, or on more than one stage of the process of carcinogenesis. Alternatively, it is possible that imprecision in the job classification or other observational problems may obscure the trends, or produce fictitious trends in the effects of variables such as age at first exposure and time since last exposure. Finally, such a pattern of trends could emerge if there were only two stages and the first and penultimate stage were the same.