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In several recent epidemiological studies blood lead levels (BLLs) even below the current CDC intervention level of 10 microg/dl have been associated with reduced neurocognitive capacities of children, with no clear evidence of a "safe" threshold. We analyzed the relationship between the BLLs and the neurocognitive capacities of 205 Sardinian students aged 11 to 15 years, using 2 tests of the Swedish Performance Evaluating System (SPES) and the full-scale Intelligence Quotient (IQ) derived from the Wechsler Intelligence Scale for Children (WISC). The studied population included 104 children (61 males and 43 females) living in Portoscuso, a town 2 Km far from a lead smelter (mean BLLs: 5.98 +/- 2.2; max 11.5 microg/dl), and 101 age-matched students (55 males and 46 females) living in Sant'Antioco, a town about 20 Km far from the same smelter (mean BLLs: 2.08 +/- 0.8; max 4.5 microg/dl). Subjects with BLLs above 4 microg/dl performed worse in the SPES tests and scored about 5.0 points less on the full-scale IQ compared to the students with lower BLLs. The adjusted regression coefficients derived from the multivariate analysis showed that higher BLLs were significantly associated with worse performances in the SPES tests and with reduced IQ (0.94 points for each microg/dl of BLL). This study confirms the potential neurotoxicity of low-levels of lead suggesting the need of lowering the actual CDC "limit of concern" for children to values lower than 4 microg/dl, improving at the same time the environmental primary prevention for limiting the lead exposure of subjects living near the lead smelter.

In several recent studies blood lead levels below 100 microg/L have been associated with reduced neurocognitive capacities and neurobehavioural performances in children, with no clear evidence of the lowest "safe" level not associated to adverse effects on the CNS. We analyzed blood lead concentration and the results of 5 neurocognitive tests, two derived from the Swedish Performance Evaluating System (SPES) and three from the Wechsler Intelligence Scale for Children-Revised (WISC-R), in 139 Sardinian adolescents living in Portoscuso, a town 2 Km far from a lead smelter, and in 72 age-matched students living in S. Antioco, a town about 15 Km far from the same smelter. The blood lead concentrations were lower than 100 microg/l in almost subjects, but, in average, significantly higher particularly among males, in the Portoscuso group compared to controls. The regression coefficients derived from the multivariate stepwise analysis, adjusted for the student's age and gender and for the educational and socio-economic level of parents, showed that reduced performances in neurocognitive test were significantly associated to increasing blood lead concentrations. According to previous our surveys in the same area and to the recent scientific literature on this topic, the present study suggests the need to further low the blood lead levels, considered by the U.S. CDC in 1991 as potentially "safe" for the children's CNS, to a threshold possibly < 50 microg/L.

Among 273 students (age 11-16 years) living in two small towns located respectively 2 (Portoscuso) and 15 kilometres (S. Antioco) far from the industrial area of Portovesme, the respiratory risk associated to cigarette smoking and environmental pollution was evaluated by the ISAAC questionnaire and standardized spirometry. The prevalence of parent's smoking was high in both groups (66.3% and 59.4%). Smoking during pregnancy was reported by 15% of mothers, without significant differences between the two schools. The prevalence of smokers among students was similar comparing the two groups (7% vs 6%). The prevalence of asthma in the whole population was significantly associated to skin positivity to common allergens, to the familiarity for asthma and to the environmental tobacco smoking, particularly if maternal. Spirometric values were significantly lower among students living in Portoscuso than among those of the S. Antioco school, with an evident interaction between the residential factor and the tobacco smoking, active and/or passive, in reducing the forced end- expiratory flows. Our results support the significant role of tobacco smoking, active and passive, particularly if derived from maternal smoking during pregnancy, in increasing the prevalence of respiratory disorders and lowering lung function in children. Living in Portoscuso, because of higher environmental exposure to airborne pollutants of industrial origin, has been shown as a relevant factor further lowering the lung function among the studied sample.

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 effects of low-level lead exposure on children's intelligence quotient (IQ) were investigated in 64 Sardinian adolescents (13-16 years old). To estimate potential early adverse effects on the Central Nervous System (CNS) due to very low-level lead, the Intelligence Quotient (IQ) of adolescents with present blood lead concentrations (PbB) generally below 10 microg/dl was measured. We analyzed blood lead concentration and individual IQ of 32 Sardinian children living in Portoscuso, a town 2 Km far from a lead smelter, and of other 32 controls living in S. Antioco, a town about 15 Km far from the same smelter. The Wechsler Intelligence Scale for Children Revised (WISC-R) was administered. The relation between IQ and blood lead concentration was estimated by linear multivariate models adjusting for several potential confounders, such as the educational and socio-economic level of the parents. The blood lead concentration was in average significantly higher in the Portoscuso group compared to controls. The linear model applied to the total population studied (n 64) showed that the blood lead concentration was inversely and significantly associated with IQ, with an extrapolated decline of 1.29 points in total IQ for each microg/dl increase of lead blood concentration. According to the recent scientific literature on this topic, results of our pilot study suggest the need to further lower the blood lead concentration for children to a threshold significantly below 10 microg/dl, value till now considered "safe" for the children's CNS.

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).

The mortality of 918 Sardinian lead-smelter workers followed between 1972 and 2001 is reported. The assessment of individual exposure to inorganic lead was based on several environmental and blood lead measurements available, for each department and task, between 1985 and 2001. The mortality for all cancers was within the expected numbers (SMR 1.01, n 108). Even if not statistically significant, the mortality for gastric cancer (SMR 1.22, n 4), for lung cancer (SMR 1.21, n 18) and for lymphomas and leukaemias (SMR 1.82, n 6) was higher than that expected from the regional rates during the follow-up. Only for the lung cancer mortality a statistically significant upward trend with increasing categories of lead exposure was observed (SMR 1.96, 95% CI 1.02-3.68 for the highest exposure group). Our study, even if of small size, suggests an association between occupational exposure to inorganic lead and lung cancer risk.

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.

To investigate the relationship between exposure to polycyclic aromatic hydrocarbons (PAHs) and mortality for specifc cancer sites, 1152 men, employed for at least 1 year at a prebake aluminium smelter, were followed-up from 1972 until 31 December 2001. Exposure to PAHs was estimated from a detailed reconstruction of the working history experienced in the plant by each cohort member and from several environmental and personal shift-sampling measurements available, by task and working department, since 1979. Furthermore, information on smoking habits, previous jobs before engagement in the smelter and main clinical findings observed during the follow-up were collected from the personal medical files. This study showed no increased mortality for lung cancer or bladder cancer associated to exposure to PAHs. Mortality for pancreatic cancer, based on 6 observed deaths, was significantly higher than expected in the whole cohort (SMR 2.4; 95%CI 1.1-5.2) and particularly among workers employed in the anodes factory of the plant (SMR 5.0, 95%CI 2.1-12.1), where a relatively consistent exposure to PAHs has been estimated. The nested case-control study planned for pancreatic cancer cases, confirmed that, also after controlling for cigarette smoking, PAH exposure experienced in the anodes factory was associated with a significant increased risk of pancreatic cancer. A pre-existent diabetes mellitus and a potential occupational exposure to pesticides experienced in previous agricultural jobs were found as concurrent significant covariates increasing the risk. In conclusion, the relatively high exposure to PAHs, experienced in the anodes factory and particularly in the green-mill department of this prebake aluminium reduction plant, cannot be ruled out as one of the main factors in the multifactorial aetiology of the pancreatic cancers observed in this study.

Starting from a short review of the recent epidemiological studies available in the international literature concerning the association between silica, silicosis and lung cancer, the results of two mortality studies performed in Sardinia are reported. The first study concerns a 20-year follow-up of 1741 miners employed in 1973 in two metalliferous Sardinian mines. In the second study the cause specific mortality of 724 patients with silicosis, firstly diagnosed by standard chest x-ray between 1964 and 1970 in our Institute, has been analysed by a cohort study extended to December 31, 1997. The findings indicate that the slight increased lung cancer mortality observed in these cohorts, more than to the severity of radiological silicosis or to the entity of the cumulative exposure to crystalline silica dust in itself, was significantly associated to other risk factors as cigarette smoking, airflow obstruction and radon-daughters exposure in underground mines.

The mortality of 918 Sardinian lead-smelter workers followed between 1972 and 2001 is reported. The assessment of individual exposure to inorganic lead was based on several environmental and blood lead measurements available, for each department and task, between 1985 and 2001. The mortality for all cancers was within the expected numbers (SMR 1.01, n 108). Even if not statistically significant, the mortality for gastric cancer (SMR 1.22, n 4), for lung cancer (SMR 1.21, n 18) and for lymphomas and leukaemias (SMR 1.82, n 6) was higher than that expected from the regional rates during the follow-up. Only for the lung cancer mortality a statistically significant upward trend with increasing categories of lead exposure was observed (SMR 1.96, 95% CI 1.02-3.68 for the highest exposure group). Our study, even if of small size, suggests an association between occupational exposure to inorganic lead and lung cancer risk.

To estimate potential early adverse effects on the Central Nervous System (CNS) due to very low exposure to inorganic lead, the Intelligence Quotient (IQ) of adolescents with present blood lead concentrations (PhB) generally below 10 micrograms/dl was measured. We analyzed blood lead concentration and individual IQ of 32 Sardinian adolescents living in Portoscuso, a town 2 Km far from a lead smelter, and of other 32 controls living in S. Antioco, a town about 15 Km far from the same smelter. The Wechsler Intelligence Scale for Children Revised (WISC-R) was administered. The relation between IQ and blood lead concentration was estimated by linear multivariate models adjusting for several potential confounders, such as the educational and socio-economic level of the parents. The blood lead concentration was in average significantly higher in the Portoscuso group compared to controls. The linear model applied to the total population studied (n 64) showed that the blood lead concentration was inversely and significantly associated with IQ, with an extrapolated decline of 1.29 points in total IQ for each microgram/dl increase of blood concentration. According to the recent scientific literature on this topic, results of our pilot study suggest the need to further lower the definition of an elevated blood lead concentration for children to a threshold significantly below 10 micrograms/dl, value till now considered "safe" for the children's CNS.

The aim of this study was double: to compare two different incremental stress protocols and to obtain reference values for a standardised exercise test in healthy workers. Firstly, eighty healthy male workers, 40 coal miners and 40 hospital workers, aged 19-54, performed in 2 different days 2 cycle ergometer tests up to exhaustion, increasing the work load respectively by 30 watts every 3 minutes (protocol A) and by 30 watts each minute (protocol B). Ventilatory and gas exchange measurements were done by a breath-by-breath apparatus equipped with a turbine and fast gas analysers for O2 and CO2. For each test the ventilatory anaerobic threshold (VAT) was blindly determined as oxygen uptake (V'O2 VAT) using standardised gas exchange and ventilatory indices (V'CO2, V'E, V'E/V'O2) that were found giving comparable results with those derived from the blood lactacte curve. Significant differences were observed between the two protocols only concerning the average work load at exhaustion and at the VAT: the highest being with the protocol B. Conversely, either the maximal oxygen uptake (V'O2 max) and the V'O2 VAT were comparable between protocols, as well as the other cardio-respiratory parameters were at these exercise levels. Oxygen uptake and heart rate increased in average linearly with the work load with very similar slopes in both protocols. Comparable results between protocols were found also as what concerns the slopes of the other physiological variables (V'E, V'CO2) analysed against the V'O2, particularly for exercise levels lower or equal to the individual VAT. Thus, these results suggest a very good comparability between the two protocols, concerning both the levels of maximal and sub-maximal aerobic capacity (V'O2 max, V'O2 VAT) and the cardio-respiratory pattern related to the oxygen uptake. Reference values for the 30 watts/3 minutes cycle ergometer stress test were achieved in other 320 healthy Sardinian workers concerning both the maximal (V'O2 max) and sub-maximal (V'O2 VAT) aerobic capacity and the range of normality for the cardio-respiratory pattern during the test, particularly for completely aerobic work loads, namely work loads not above the V'O2 VAT. These prediction equations can be useful for the evaluation of working capacity of workers employed in manual jobs characterised by moderate-to-high dynamic energy expenditure.

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.