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Objective: To critically review the literature on male reproductive toxicity of lead in animals and humans., Methods: A systematic literature search identified a total of 32 experimental studies in animals and 22 epidemiological studies, one case report on humans and five review articles or documents. The studies were evaluated by paying attention mainly to sample size, study design, exposure, and dose characterisation, analytical method standardisation, and quality assurance., Results: Several studies on rats and other rodents indicated that blood lead concentrations > 30-40 micrograms/dl were associated with impairment of spermatogenesis and reduced concentrations of androgens. However, other animal studies, mainly about histopathological, spermatozoal, and hormonal end points, indicated that certain species and strains were quite resistant to the reproductive toxicity of lead and that different testicular lead concentrations could account for these differences. The human studies focused mainly on semen quality, endocrine function, and birth rates in occupationally exposed subjects, and showed that exposure to concentrations of inorganic lead > 40 micrograms/dl in blood impaired male reproductive function by reducing sperm count, volume, and density, or changing sperm motility and morphology. No relevant effects were detected on endocrine profile., Conclusion: Several factors make it difficult to extrapolate the animal data to the human situation. The difficulties are mainly due to differences between species in reproductive end points and to the level of exposure. Concentrations of blood lead > 40 micrograms/dl seemed to be associated with a decrease in sperm count, volume, motility, and morphological alterations and a possible modest effect on endocrine profile. Dose-response relation, in particular at a threshold level, is poorly understood, and site, mode, or mechanism of action are unknown. Also, the effects were not always the same or associated in the same on sperm count and concentration. Some methodological issues and indications for future studies are discussed.

A study on the reliability of information on smoking habits and coffee drinking collected via interview was conducted among 500 subjects enrolled in a case-control study on bladder cancer in Brescia, North Italy. A total of 215 cases (incident and prevalent) and 285 controls were interviewed personally in the hospital setting by a first interviewer, and then re-interviewed by telephone by either the same interviewer or another one. Agreement between the first and second interview was evaluated using the kappa statistic and the intra-class correlation coefficient and via multiple logistic regression modelling. No important differences in reliability were found according to sex, education or case/control status, while agreement was better among subjects below 65 than among older ones, and among incident than prevalent cases. A slightly better agreement was found among subjects interviewed twice by the same interviewer than those interviewed by two different individuals, which may reflect the presence of inter-observer reliability for the latter. Overall, these results show a very high reliability of data on smoking and a fairly high reliability regarding coffee drinking as collected through face-to-face interviews.

The association between tobacco smoking, the consumption of coffee and alcohol and bladder cancer was investigated in a hospital-based case-control study in Brescia, northern Italy. A total of 172 incident cases (135 men and 37 women) and 578 controls (398 men and 180 women) were enrolled. As expected, cigarette smoking was strongly associated with bladder cancer. The odds ratios (OR) for coffee drinking adjusted for age, education, residence and cigarette smoking in current drinkers were 2.6 (95% confidence interval, CI: 1.1-6.1) in men and 5.2 (95% CI: 1.0-30.4) in women. A dose-response relationship was found in men, with the highest risk in the highest category of exposure: drinkers of more than 5 cups per day had an OR of 4.5 (95% CI: 1.2-16.8). The ORs for current alcohol drinkers were 2.1 (95% CI: 1.0-4.8) in men and 3.4 (95% CI: 1.2-9.7) in women; according to grams of ethanol drunk per day (grams/day, g/d) the ORs were: 1.7 (1-20 g/d), 1.6 (21-40 g/d), 4.3 (41-60 g/d) and 4.6 (61+ g/d) in men and 3.1 (1-20 g/d) and 3.9 (21+ g/d) in women. These results suggest that regular consumption of both coffee and alcohol can be independently associated with an increased bladder cancer risk.

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.

This article evaluates multiple exposures to metals in different types of metal welding such as manual metal arc for mild and stainless steel, continuous wire, submerged arc, laser and brazing. Environmental monitoring was carried out in eight different occupational situations and the inductively coupled plasma mass spectrometry technique was adopted in order to characterize exposure to several elements simultaneously and with high accuracy. The results showed that up to 23 elements could be measured. The highest concentrations were found for Al, Mn, Fr, Ni, Cr, Cu and Zn. For some elements such as In, Nd, I, Rb the concentrations were very low. A qualitative and quantitative variation in fume composition was observed at a certain distance from the welding point, which should be to taken into account when evaluating indirect exposures. It would also be possible, with this technique, to identify specific elements in the mixture which could also be measured in biological fluids.

Chelating agents have long been used in the pharmacological treatment of lead poisoning, whose management is still a problem, particularly in developing countries. This article reviews the pharmacological properties of dimercaprole, peniclliamine. CaNa2EDTA and dimercaprosuccinic acid, examines their indications, contraindications and side effects and discusses the possible use of each drug in occupational Pb poisoning. Proposals are also presented for the treatment and follow-up of subjects with signs and symptoms of poisoning and of subjects with low-moderate Pb absorption. CaNa2EDTA seems to be the most reliable and safer chelating agent nowadays available and with a wider spectrum of action. DMSA seems to be promising in the treatment of occupational Pb poisoning. Even though there is no doubt that chelation therapy has significantly contributed to reduce mortality and morbidity from occupational Pb poisoning, the efficacy of this treatment in subjects with subtle neurological or renal damage has not yet been studied properly.

Objectives: A hospital based case-control study was conducted between 1992 and 1993 in the province of Brescia, a highly industrialised area in northern Italy, to evaluate occupational risk factors of bladder cancer., Methods: The study evaluated 355 histologically confirmed cases of bladder cancer (275 men, 80 women) and 579 controls affected by urological non-neoplastic diseases (397 men, 182 women). Lifetime occupational history, smoking and drinking habits, and sociodemographic characteristics were recorded by means of a structured questionnaire. Odds ratios (ORs) were computed with adjustment for age, smoking, alcohol and coffee consumption, education, and place of residence., Results: A significant (P < 0.05) increase of risk of bladder cancer were found in men for labourers in the construction industry (OR 2.1, 95% confidence interval (95% CI) 1.1-3.9) and for recreational and cultural services (OR 5.0, 95% CI 1.3-18.9). Increased risks, although not significant, were found for various other occupations and industries such as machinery mechanics, metal processers and polishers, blacksmiths, gunsmiths, painters; for transport workers, an increased risk with increasing duration of employment was found., Conclusions: Occupational exposures seem to contribute to bladder cancer risk in the area under study.

In order to evaluate the urinary excretion of cobalt, a study was carried out in two plants producing diamond segments and sintered wires for stone cutting. In both plants, the highest Co exposures were found during mixing and granulation of Co powders, generally performed 1-2 times per week for 1-2 h in the first plant and 3-4 h in the other. Environmental hygiene conditions were good in the first plant and poor in the other with environmental Co concentrations around the ACGIH TLV (50 micrograms/m3) in the first and many times higher (up to 8000 micrograms/m3) in the second. In two workers employed in the above mentioned jobs. Cobalt in urine (CoU) was determined in samples collected during the first day, before shift and about 2, 4, 7 and 10 h after the beginning of exposure; samples were also collected on the 2nd, 3rd and 4th day, before and at the end of the shift. The study showed that Co in urine rapidly increased in the hours following the cessation of exposure, with a peak of elimination about 2-4 h after exposure, and a subsequent decrease (more rapid for the first 24 h) in the following days. Such a pattern was apparently independent of the degree of exposure, since it was detected in both plants and confirmed also in an industrial hygienist with lower Co exposure. The data indicate that for a correct evaluation of Co exposure through CoU determination, variables such as type and characteristics of the job and most importantly, the times at which biological samples are collected should be carefully considered.

Health education represents a fundamental tool in the prevention of occupational diseases. For lead-exposed workers, work practices, personal hygiene, and life habits are certainly influences in the amount of the metal absorbed in the body. This study evaluated the effectiveness of a health education program in 50 workers exposed to inorganic lead employed in seven small factories. The study was performed in 3 phases over one year. Before the program, blood lead levels were measured, and a questionnaire was administered in order to evaluate the baseline knowledge of the workers about lead poisoning and its prevention. After the health education program, the blood lead levels decreased (from 38.2 to 32.3 micrograms/dl) and the questionnaire scores improved in a highly significant manner (p < 0.001). These results were obtained both in the short (4 months) and in the medium term (1 year). The reduction of blood lead concentrations seemed to be due to changes in hygienic behaviors and life habits, such as alcohol consumption or cigarette smoking, probably induced by an increase in specific knowledge about the prevention of lead damages.

Since 1987 at the Spedali Civili of Brescia the problem of anaesthetic gases pollution in operating surgery rooms was managed by means of periodical environmental monitoring and maintenance of the anaesthesiological equipments. The mean nitrous oxide concentrations were generally reduced to values below the limits indicated by the Italian Ministry of Health. On the contrary, a low participation of the operating room personnel was observed in the health surveillance program and this phenomenon is clearly evidenced by the progressive decrease of the number of medical examinations. In order to clarify the usefulness of health surveillance programs and to promote the adoption of "less pollutant" behaviour, a Health Education Program was planned by the Medical Administration, in collaboration with the Occupational Health Service and the Department of Anesthesiology and Intensive Care. This program will be performed at different times, including the administration of a questionnaire, the participation at information meetings, the distribution of brochures and the evaluation of environmental and biological exposure data before and after the education program.

We evaluated the chelation test in 38 subjects exposed to lead or with suspected lead exposure, comparing the values of lead excretion at the 3rd h (PbU EDTA/3-h) and at the 24th h (PbU EDTA/24-h) after EDTA administration. Good correlation exists between PbU EDTA/3-h and PbU EDTA/24-h (r = .86) and between them and the main biological indicators of dose and effect of lead. When a second chelation test was performed in 15 subjects, a slightly better r coefficient (.93) was observed between the two tests, without reaching statistical significance. It seems difficult, in terms of the type of exposure that we considered, to use the 3-h test, on an individual basis, to predict the PbU EDTA/24-h values.

Considering that nowadays there is no unanimity about the possibility of adopting environmental and/or biological limit values in occupational exposure to carcinogens, some aspects are discussed about the mechanism of action of carcinogens, their metabolism and problems deriving from the possible multiple exposures, interactions and speciation of the different compounds. After the analysis of the results obtained by means of two different approaches by the American Conference of Governmental Industrial Hygienist and the Environmental Protection Agency of the United States, the authors examine some aspects of the qualitative and as far as possible quantitative comparison for the 16 substances included in both lists and they discuss how the mathematical models are used in the process of carcinogenic risk evaluation. Finally, it is considered the possible application even in occupational carcinogenesis of a model such as the one of the EPA.

Urinary mutagenic activity detected by the bacterial fluctuation assay, using Salmonella typhimurium TA98 and Escherichia coli WP2 uvrA with and without metabolic activation (S9 mix), was studied in a group of 21 workers exposed to inorganic lead and a control group of 22 non-occupationally exposed subjects. Occupational exposure to inorganic lead had no effect on urinary mutagenicity in the strains considered, with or without metabolic activation. In smokers (exposed and non-exposed), urinary mutagenic activity appeared to increase compared to non-smokers (exposed and non-exposed), only with Salmonella typhimurium TA98 in the presence of S9 mix.

Corticosterone has been shown to affect several patterns of glial cell and neuronal development. We have previously reported that exogenously administered corticosterone preferentially accumulated into the retinas of 8-day-old chick embryos. Moreover, we observed that it affects muscarinic cholinergic binding. Thus, we investigated the effect of different concentrations of corticosterone on retinal cells in culture. Retinas were dissected from 8-day-old embryos, dissociated and cells plated on salt-precipitated collagen. At day 5, cultures were treated with corticosterone (from 10(-9) M to 10(-7) M) for 24 h. Controls received either Dulbecco's Modified Eagle Medium (DMEM) plus 10% fetal calf serum (FCS) or DMEM only. Results show that the main effect of the hormone was inhibition of neuronal process outgrowth. Also cell aggregation, flat cell proliferation and confluency are altered in hormone-treated cultures. All these effects are reversible and can be attributed to hormone effect and not to serum deprivation.

Subfractionation of the optic tectum in chick embryos results in the isolation of two fractions enriched in synaptosomes (fraction A and fraction B). In chicks after hatching, this fractionation results in the isolation of a single synaptosomal fraction (fraction B) and of a fraction enriched in myelin membranes devoid of synaptosomes (fraction A). The lipid composition of synaptosomal fractions (A and B) and corresponding synaptosomal plasma membranes has been analyzed and compared to the lipid composition of similar fractions isolated from 2-3 day-old chicks. The phospholipid composition of fraction A in embryos was mainly represented by phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The PE content was significantly lower than that of PC, which accounted for by approximately 50%. Sphingomyelin (SP) and phosphatidylinositol (PI) accounted for by only 6% of the total membrane phospholipids. Fraction A isolated from the young chicks showed many significant changes. PC accounted for by approximately 40% and PE made up 35%. The amount of phosphatidylserine (PS) and SP increased. These data parallel our previous morphological observations, which showed that fraction A contains immature synaptosomes in embryos but myelin membranes and no synaptosomes in the young chicks. Fraction B has been shown to contain synaptosomes at all stages considered. It possessed in embryos a lipid composition similar to fraction A, except that PC content was higher in young embryos. The analyses on membrane fractions confirmed these results. On the contrary, this fraction showed many significant changes after hatching. The content of PC was significantly reduced, PE/PC ratio was significantly increased as well as ethanolamine plasmalogen (PLE) content. The percentage of PS, PI and SP were increased. The composition of fatty acids of the total fraction of phospholipids was also examined. The results parallel the observations on phospholipid classes.

Occupational exposure to beryllium (Be) is nowadays much lower than in the past. While the classic Be diseases, such as berylliosis, are clearly on the decline, attention is currently being focussed on the immunological and carcinogenic effects of Be, which suggest that subjects with low-level occupational exposure should also be accurately controlled. Urinary Be (BeU) values were determined in a sample of the general population and in a group of dental technicians exposed to environmental Be concentrations ranging from 0.04 to 1.7 micrograms/m3. The mean BeU values of these workers (0.34 micrograms/l) were higher than those of the general population (0.26 micrograms/l) and the subgroup of dental technicians exposed to higher Be air concentration showed higher BeU levels. Although at present the relationships between external and internal dose and between internal dose and early effects, are not known, we believe that biological monitoring supplies useful information on occupational Be exposure.