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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.

Several recent meta-analyses, although some inconsistencies between studies, provide evidence for subtle deficits in neurobehavioural tests being associated with average blood levels (PbB) between 350 and 600 microg/l and for significant correlations between impairments in some test results and increasing indices present andlor cumulative exposure to inorganic lead. In this study we assessed the relationship between blood lead level (PbB) and results of some neurobehavioural tests derived from the SPES battery and from the WAIS-R among a sample of 94 lead smelter workers (median PbB: 302 microg/l; range: 60-690 microg/l). The stepwise multiple regression analysis shows that, even after adjusting for age, education level, score in the vocabulary test and for alcohol and cigarette consumption, the rise of PbB above 300 microg/l was significantly associated with the rise in the number of errors and in the response time of the Symbol Digit test. No significant relationship between PbB and results of the other tests was observed after adjusting for the main confounding factors. Despite the small size of this study and the few number of neurobehavioural tests applied, our results are suggestive for suble potential neurotoxic effects of inorganic lead even at the present exposure levels found in the studied sample of smelter workers and support the ACGIH BEI and the SCOEL recommendation for a biological limit of 300 microg/l of PbB.

The delta-aminolevulinate dehydrase (ALAD) genetic polymorphism was investigated along with biomarkers of lead exposure and effect on 333 male workers, occupationally exposed to lead, with blood lead levels (PbB) higher than 100 microg/l. ALAD genotype frequencies were distributed as expected among Caucasians. Workers bearing at least one ALAD-2 allele showed PbB values slightly higher than those from ALAD-1-1 subjects, who also exhibited higher urinary delta-aminolevulinic acid (ALAU) and blood zinc protoporphyrin (ZPP) levels. The plasmatic lead (PbP)/PbB ratio was similar in both groups. Exposure and effect biomarkers were significantly each other correlated among ALAD-1-1 subjects only, who showed also a significant inverse relationship between ALAD activity and ZPP values. Results confirm previous studies, supporting the hypothesis that ALAD polymorphism may interfere with toxico-kinetic and toxico-dynamic parameters of occupational exposure to Pb.

It is here presented the project sustained by the Ministry of Public Instruction, University and Research "Environmental and Occupational Exposure to Inorganic Lead: assessment of human health effects due to current doses and preventive measures" ruled out between 2001 and 2003. The aim of the study was to investigate about the toxic effects related to current occupational exposures to inorganic lead (particularly those effects concerning blood pressure, carcinogenic risk, nervous and immunological systems), to identify hypersusceptibility conditions, particularly the ALAD genetic polymorphism and to evaluate the role of traditional biomarker and the possibility of introducing new ones. In the present article the procedures followed during the project lasting and the contribution of each Unit are described. The results of the research, presented in detail in the current issue, do confirm the inadequacy of the biological exposure index nowadays ruled by Lex 25/2002.

In the present study the role of the traditional biomarkers of exposure and effect on haeme system during lead exposure was analysed: the opportunity of introducing new biomarkers such as lead and delta-aminolevulinic acid in plasma was also evaluated, especially by considering the current levels of exposure. The population in study was constituted by 371 males owning to different production fields and selected by five national units. The results suggest caution in the use of lead in plasma as a biomarker of lead exposure in the biological monitoring procedures, mainly in reason of its great variability affecting in particular the sampling time and the pre-analytical treatment of the sample. The other biomarkers were well correlated between them and with the exposure biomarkers for lead in blood >300 microg/L, suggesting the BEI to which the protection of workers exposed to lead would be guaranteed (instead the actual of 600 microg/L).

Evidence, even if not univocal, of increase of systolic and diastolic blood pressure for Pb doses lower than 30 microg/dl stimulated studies in the last years and opened a discussion on a possible relapse in morbility and mortality, since hypertension is an important factor of cardiovascular risk. In this study, it was possible to investigate the relationship between lead and blood pressure of 303 subjects occupationally exposed to this metal with blood-Pb between 10 and 80 microg/dl and 206 subjects belonging to the general population with blood-Pb between 0.5 and 9 microg/dl. In both groups it resulted a positive and statistically significant correlation between blood-Pb values and systolic and diastolic blood pressure values, in detail in hypertensive subjects, belonging to the not-occupationally exposed group, this effect is proportionally higher. The effect of lead on blood pressure appears therefore proved, as confirmed by previous literature, but taking into consideration three specific information. It presents itself in a large range of doses, it is quantitatively very modest, it appears more evident at low doses, thus we could hypothesize different mechanisms for different doses.

A latent variable model was applied to the results of an Italian multicenter nation-wide cross-sectional study to assess the earliest health effects due to mercury (Hg) exposure caused by occupation, dental amalgams (DENTAM) and fish eating (FISH). The studied population included subjects recruited from four different geographical areas. A total number of 122 workers from chloroalkali plants and production of thermometers and neon lamps formed the occupationally exposed group, whereas 196 subjects, recruited from the same areas and not occupationally exposed to mercury, formed the control group. Neuropsychological functions were assessed with neurobehavioral testing including vigilance, motor and cognitive function, tremor measurements, and with symptoms concerning neuropsychological and mood assessment. Neuroendocrine function was examined with the measurement of prolactin (PRL) level. Parameters of immunological and renal function were also measured. The target population was characterized by the number and surface of dental amalgams and consumption of fish. In the exposed workers the average urinary mercury (U-Hg) was 10.4+/-6.9 (geometric mean 8.3, range 0.2-35.2) microg/g creatinine, whereas in the control group it was 1.9+/-2.8 (geometric mean 1.2, range 0.1-33.2) microg/g creatinine. The preliminary results indicated that finger tapping (FT) and the Branches alternate movement task (BAMT) coordination test were associated with the occupational exposure (OCCEXP). PRL was significantly decreased among the exposed workers, and inversely related to U-Hg. Among the immunological and renal parameters, cytokine serum interleuchin-8 (sIL8) and beta(2) micro globulin (beta(2)MG) were lower in the exposed group and negatively correlated to U-Hg. Small-size fish consumption was associated to a beneficial effect on symptoms reporting. No effects were observed concerning dental amalgams. After first evaluating the relationship between mercury exposure and each indicator of effect, further assessment was performed to identify the earliest effects related to mercury exposure among those who resulted in being associated in the preliminary elaboration. Two latent variables "exposure" and "effect" were identified, integrating respectively the different forms of exposure (occupational, due to dental amalgams and fish consumption) and the indicators of effects (FT, BAMT, PRL, sIL8, beta(2)MG). Confounding factors (age, alcohol, body mass index (BMI)) were considered in the same model. This further analysis showed that an inverse association of occupational exposure to mercury with PRL and BAMT, with Hg-U mediating the effect on PRL, was predominant with respect to the other form of mercury exposure, the other indicators of effect and the confounders. In conclusion, this study supports the finding of alterations of neuroendocrine secretion and motor coordination at very low occupational exposure levels of inorganic mercury, below the current ACGIH Biological Exposure Index. These changes occur at lower levels than other subtle effects on the renal function and the immunitary system. On the contrary, dental amalgams and small-size fish consumption do not seem to be associated to any adverse health effect at these exposure levels.

Objectives: The aim of this paper was both to evaluate the internal dose of Hg in occupationally exposed workers (35 Chloralkali workers) compared to that of non occupationally exposed controls (40 workers of the same plant of Portotorres and 22 residents on the island of Carloforte, usual consumers of local fish, mostly tuna fish with relatively high Hg levels) and to assess the relevance of environmental and individual exposure factors linked to lifestyle, sea fish consumption and amalgam fillings., Methods: All subjects filled out a questionnaire concerning the working history and lifestyle. The amalgam fillings area was measured by medical inspection using a standardised schedule attached to the questionnaire. Mercury in urine (HgU) was measured in all cases, while in a subgroup of our study total blood mercury (HgB) and its organic and inorganic component were also assessed. Furthermore, for 8 of the Carloforte group mercury in hair was also available., Results: Values of urinary mercury excretion of the Chloralkali workers were significantly higher (median value of 15.4, range 4.8-35.0 micrograms/g creatinine, 94.3% of the cases having values > 5 micrograms/g creatinine) than those observed both among the reference group (median value of 1.9, range 0.4-5.6 micrograms/g creatinine, 12.5% of the cases having values a little greater than 5 micrograms/g creatinine) and among the residents in Carloforte (median value of 6.5, range 1.8-21.5 micrograms/g creatinine, 59.1% of the cases having values > 5 mcg/g creatinine). The HgU values observed in this group were in turn significantly higher than those of the non occupationally exposed workers living near Sassari (p = 0.03). Only in this last group were the HgU concentrations statistically significantly related to the extension of the amalgam fillings area (Pearson r = 0.53, p < 0.01). In the Carloforte group HgU was significantly related to the number of fish meal consumed per week (Pearson r = 0.48, p < 0.02). HgB (median value of 5.9, range 3.4-21.6 micrograms/l) as well as its inorganic component (median value of 2.4, range 1.8-4.6 micrograms/l) were significantly higher in the Chloralkali group compared to the other two groups. In all cases of the Carloforte group the ratio between the organic component and the total HgB was higher than 85%, while this ratio was significantly lower in the other two groups. The relationship between HgU and HgB was statistically significant, considering both total blood mercury and the inorganic and the organic components separately. A statistically significant relationship between the sea fish consumption per week and both total HgB (Pearson r = 0.82) and the organic component in this matrix (Pearson r = 0.84, p < 0.001) was observed among 16 non-occupationally exposed subjects. However, the significant relationship between organic blood mercury and sea fish consumption was almost entirely supported by the data observed in the Carloforte group. Total hair mercury levels analysed in 8 subjects of the Carloforte group were high (median value of 9.6, range 1.4-34.5 micrograms/g) and significantly related to sea fish consumption, and to both the individual Hg urinary excretion (Pearson r = 0.83) and to the organic component of blood mercury (Pearson r = 0.87)., Conclusions: According to several experimental human and animal trials and to some recent studies on methylmercury toxicokinetic models, our results suggest that the organic compounds absorbed by usual sea fish consumption may be partially demethylated, increasing the inorganic Hg concentration in the kidney and consequently its urinary excretion, as was observed in the Carloforte group.

Objectives: The aim of this paper was to analyse the concentrations of HgU and HgB in three different groups: 122 workers exposed, 18 workers formerly exposed and 196 subjects not occupationally or environmentally exposed to mercury., Methods: All the subjects filled out a questionnaire concerning personal data, lifestyle, occupational or non-occupational exposure to Hg and medical history. The amalgam fillings area was measured by a standardised method., Results: Urinary mercury excretion was significantly greater in the group of the exposed workers respect to the group of subjects not occupationally exposed (Median value of 8.3 micrograms/g creatinine and the 5 degrees and 95 degrees percentile respectively of 2.66 e 23.50 micrograms/g creatinine against Median value of 1.2 micrograms/g creatinine and the 5 degrees and 95 degrees percentile respectively of 0.18 and 5.42 micrograms/g creatinine). U-Hg in formerly exposed workers were comparable to U-Hg in non-occupationally exposed subjects, with a median value of 1.6 micrograms/g creatinine. B-Hg values were similar in the three groups: the median value was 3.1 micrograms/l in the non-occupationally exposed, 4.0 micrograms/l in the exposed workers and 3.9 micrograms/l in the past exposed. These value were not significantly different. Among the considered variables (amalgam fillings, fish consumption, age, sex, alcohol intake, chewing-gum and smoking) dental amalgam and fish consumption were significantly related with the Hg urinary excretion and the B-Hg levels. This is particularly true considering the subjects altogether: for the exposed workers, indeed, the occupational exposure was the most relevant variable., Conclusions: The results of the present research confirmed that the U-Hg excretion in non-occupationally exposed subjects is influenced by amalgam dental fillings. Furthermore, in our study Hg urinary excretion was significantly related with fish consumption. This fact can be explained, according to several recent experimental human and animal trials, considering that methylmercury contained in fish is partially converted, through breakage of the carbon-Hg bond, into Hg inorganic forms, which accumulate in the kidney and have a urinary excretion pathway.

The genetic effects of occupational exposure to low polycyclic aromatic hydrocarbon (PAH) concentrations were investigated in primary aluminium industry workers. The study subjects were employed in a plant that uses pre-baked anode cells, and has relatively low PAH contamination. Forty-two male workers belonging to different job categories (anode fabrication, baking, rodding, electrolysis, maintenance), together with 16 male local residents with no occupational exposure to PAHs were selected for the analysis of micronuclei and DNA lesions in peripheral lymphocytes. The incidence of micronuclei determined in 1000 cytokinesis-blocked cells in each subject was not significantly different between workers and controls (8.5+/-5.4 per thousand versus 9.7+/-4.9 per thousand, respectively), nor between smokers and non-smokers (8.3+/-5.8 per thousand versus 9.2+/-5.1 per thousand), but was significantly (P<0.05) related to the subjects' age. Also the analysis of DNA damage in unstimulated and mitogen-stimulated lymphocytes by single cell gel electrophoresis (SCGE) did not show significant differences between the studied groups (average tail moment values were 0.53+/-0.53 and 0.49+/-0.45 microm in exposed subjects and controls, respectively). However, when lymphocytes were cultured in the presence of cytosine arabinoside (Ara-C, 1 microg/ml for 16h) the SCGE analysis revealed a significant (P=0.018) difference in tail moment values between aluminium workers and controls (1.73+/-1.05 microm versus 0.93+/-0.88 microm, respectively). This difference may highlight an excess of relatively stable DNA lesions, that do not affect strand integrity, and are expressed as intermediates of excision repair in stimulated cells, when gap refilling is inhibited by cytosine arabinoside (Ara-C).

The exposure to DNA reactive carcinogens is known to elicit a specific humoral immunological response, with the production of antibodies toward the carcinogen adducts. Consequently, the presence of circulating anti-carcinogen antibodies has been proposed as a marker of carcinogen exposure, and as a potential modulating factor in chemical carcinogenesis. In this work, the presence of serum antibodies to 7beta,8alpha-dihydroxy-9alpha10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-DNA (BPDE-DNA) adducts was determined in two groups of workers occupationally exposed to low doses of polycyclic aromatic hydrocarbons (PAHs), i.e. policemen (194 subjects) and workers in the aluminum industry (105 subjects). Specific anti BPDE-DNA antibodies were detected in 5.7% (11/194) of policemen and 13.3% (14/105) of aluminium industry workers. Among policemen, a small, not significant (p=0.09), prevalence of positives was observed in traffic wardens compared to office workers. A borderline significant (p=0.052) prevalence of positives was also observed in heavy smokers compared to light smokers among aluminium industry workers. These results basically support previous findings on the association between chronic exposure to polycyclic aromatic hydrocarbons and formation of anti-BPDE-DNA antibodies, even though such association appears to be weak, possibly biased by individual factors which are still largely unidentified.

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.

These guidelines mainly deal with prevention of carcinogenic effects following occupational exposure to polycyclic aromatic hydrocarbons (PAH). After some toxicological remarks, the guidelines define a possible method to demonstrate and evaluate occupational exposure to PAH. In particular, it is illustrated the strategy of environmental monitoring and indicated which PAH should be measured, with suggestion about the most appropriate analytical techniques. As regards biological monitoring, the 1-OH-pyreneseems to be currently the most useful indicator since it reflects the recent and global exposure to PAH. The guidelines also give elements to interpret monitoring data, taking into account environmental and biological reference and limit values suggested by some authors, Associations, or current regulations. The most important health effects are carcinogenic and excess risks have been described mainly for lung, bladder and skin cancer in some PAH exposed workers. The studies on cytogenetic effects showed contradictory results. On the basis of such information and current regulations, the guidelines show how to perform health surveillance in preventive and periodical examinations and how to proceed for the information and formation of exposed workers. It is not advisable, on the basis of the current scientific data, to screen asymptomatic PAH exposed workers for early diagnosis of lung or bladder cancer, nor it is opportune the use of tumor markers for health surveillance nor is genetic screening applicable for individual susceptibility evaluation outside research programs.

Objectives: To study the role of dust exposure on incidence of respiratory symptoms and decline of lung function in young coal miners., Methods: The loss of lung function (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow (MEF), carbon monoxide transfer factor (TLCO)) with time and the incidence of respiratory symptoms in 909 Sardinian coal miners (followed up between 1983 and 1993 with seven separate surveys) has been compared with the past and current individual exposures to respirable mixed coal dust. Multiple linear and logistic regression models were used simultaneously controlling for age, smoking, past occupational exposures, and other relevant covariates., Results: According to the relatively low dust exposures experienced during the follow up few abnormal chest x ray films were detected. In the cross sectional analysis of initial data, significant associations between individual cumulative exposure to dust, decrements in FEV1 and MEFs, and increasing prevalence of respiratory symptoms were detected after allowing for the covariates included in the model. The yearly decline of FVC, FEV1, and single breath carbon monoxide transfer factor (TLCO/VA) was still significantly related to the individual exposure to dust experienced during the follow up, even after allowing for age, smoking, initial cumulative exposure to dust, and initial level of each functional variable. In logistic models, dust exposure was a significant predictor of the onset of respiratory symptoms besides age and smoking., Conclusions: The results show that even moderate exposures to mixed coal dust, as in our study, significantly affect lung function and incidence of symptoms of underground miners. Although the frequency of chest x ray examination might be fixed at every three or four years, yearly measurements of lung function (spirometry, MEFs, and TLCO) are recommended for evaluation of the respiratory risk from the coal mine environment to assess the need for further preventive interventions.