[Guidelines for assessment and management of risks caused by benzene for workers at gas stations]. / Linee guida per la valutazione e la gestione dei rischi da benzine per la salute dei lavoratori addetti alle stazioni di servizio carburanti.

The European regulations classify gasoline as "carcinogenic agent" because of its content of benzene (> 0.1%). Consequently the preventive and protective actions towards the petrol station attendants prescribe, before all, the elimination of the agent or the reduction of the exposure and the risk to the minimum. Well known are currently a series of preventive measures able to produce appreciable reduction of the risk: reduction of the benzene content of gasoline, vapor recovery systems, self-areas or do-it-yourself, specific procedures for working. Exposure assessment is an essential step in order to establish the need for further preventive measure and to verify their efficacy. The exposure levels to gasoline of the petrol station attendants can be influenced by a variety of factors other than benzene air concentrations and therefore biological monitoring can give some sensible advantage in respect to air monitoring. Dosage of benzene in expired air, in urine, or in blood give a very good estimation of the exposure to benzene but they are not test largely practicable today, because analytical, economical, organizational reasons. Recent studies suggest that the dosage in urine of trans,trans muconic acid (ttMA) or phenil mercapturic acid can be useful biomarkers of recent exposure, even at low levels of exposure such as in filling stations. Exposure conditions to gasoline vapors in filling stations are rapidly changing thanks to some technological innovations and legal restrictions and the exposure levels are much below the occupational air standards, Toxicological and epidemiological data (although not yet conclusive at low doses) suggest to carry out however health and epidemiological surveillance programs for the working population. A program for the health surveillance and biological monitoring is here proposed: a clinical examination, integrated with haematological tests and biological monitoring tests, must be carried out in pre-employment and subsequently repeated yearly in the highest exposure conditions. When the exposure levels should decrease the examinations could be carried out every two years.

Reference values of urinary chromium in Italy.

OBJECTIVES: The paper describes the results of a polycentric study for the assessment of reference values of urinary chromium (U-Cr) in the Italian population. METHOD: A total of 890 subjects (58.3% males and 41.7% females) were selected on the basis of standardized criteria in eight different areas of Italy. Urinary chromium was determined on morning spot samples collected using standardized procedures. The U-Cr was determined independently by three laboratories using an Electrothermic atomization-Atomic Absorption Spectrometry (ETA-AAS) method with a detection limit of 0.05 microgram/l, adopting-for the statistical analysis-the median value of the results of the three laboratories. The between-laboratories within-subjects standard deviation was 0.049 microgram/l. Due to the high proportion (approx, 28%) of undetectable chromium levels, the geometric mean (GM) and geometric standard deviation (GSD) were estimated using a procedure of linear interpolation. The analysis of the effects of some variables (sex, age, center, residence, smoking and drinking habits) on the U-Cr values, was also performed, by multiple regression analysis after logarithmic transformation, using GM and SD. RESULTS: The reference value of U-Cr was of 0.08 microgram/l as an estimated GM, whereas the expected distribution ranged from not detectable (nd) (95% CI = nd-0.06) to 0.24 microgram/l (95th percentile; 95% CI = 0.20-0.31). Among the variables studied, only geographical area and sex significantly influenced the U-Cr levels. In subjects selected in the provinces of Bari and Venice values of U-Cr were significantly lower than those determined in subjects residing in other areas. CONCLUSIONS: From our investigation the reference values for U-Cr were lower than those obtained in previous investigations. In addition it confirms a further reduction in U-Cr levels following the previous decline reported in the 1970s and 1980s. In over 20 years U-Cr values in the general population dropped from values greater than 1 microgram/l to values between 0.5 and 0.2 microgram/l. The reasons of this progressive decline cannot be attributed in our opinion to a reduced intake of the metal, but mainly to the improvement in analytical instrumentation and methods. A further decrease may be ascribed to a more accurate definition of the reference groups and to a better control of pre-analytical factors. Considering that the reference values for U-Cr are much lower than those determined some decades ago, toxicological studies in order to verify the significance of biological limit values currently suggested for chromium seem to be necessary.

Non-occupational lead exposure and hypertension in northern Italy.

BACKGROUND: Previous research has addressed the issue that low-level blood lead concentration could be associated with an increased risk of hypertension. METHODS: This paper examines the cross-sectional association between blood lead and hypertension in 630 adult males not employed in activities characterized by specific exposure to lead and living in two Northern Italian cities (Verona and Brescia). The participants, aged 26-69 years, constituted a random sample of the patients in the practice of a general practitioner (Verona) and of regular blood donors (Brescia). Logistic regression analysis was used to evaluate the effects of selected variables (blood lead, blood cadmium, zinc erythroprotoporphyrin, haemoglobin, whole blood viscosity, age, body mass index, smoking habits and alcohol consumption) on the probability of being hypertensive. RESULTS: The blood lead concentration (range: 4.3-46.9 micrograms/dl; median: 14.8 micrograms/dl) was very similar in the two samples, whereas the prevalence of hypertension was significantly higher in the Verona sample than in the Brescia sample (20.4% versus 8.3%). Hypertensive subjects showed significantly higher blood lead levels than normotensive ones. In a preliminary (univariate) analysis blood lead levels, body mass index (BMI) and age were each significantly related to the prevalence of hypertension. After adjusting for age and/or BMI, statistical significance of the relationship between blood lead and hypertension was lost.CONCLUSIONS. The present study showed that blood lead is weakly related to hypertension in non-occupationally exposed men. The statistical significance of this association disappeared when age and BMI were used to make adjustments.

Carbon disulfide in blood: a method for storing and analysing samples.

Concentrations of free and acid-labile carbon disulfide in human blood were determined by gas chromatography mass-spectrometry. Carbon disulfide was measured in the blood of 62 subjects not occupationally exposed to the solvent, and in 27 subjects treated with disulfiram (which is partially biotransformed into carbon disulfide). In blood, a small part of carbon disulfide is free (it can be analysed without any blood treatment); most carbon disulfide is bound ("acid labile" carbon disulfide), and requires acid hydrolysis to become free and detectable. During the first phase of our study, stored samples of blood (storage at 4 degrees C for 15-40 days) were used. Later, we analysed fresh blood samples. A significant decrease in carbon disulfide was found in stored samples in comparison to fresh samples. During storage, free and acid-labile carbon disulfide in blood decreased respectively to 26% and 27% of the initial concentration within a month. In fresh samples, free carbon disulfide concentrations in blood showed a median of 139 ng/l in normal subjects. Acid-labile carbon disulfide concentrations were much higher (median 2743 ng/l). Free and acid-labile carbon disulfide in blood were closely correlated (r = 0.9358). Blood samples stored at -80 degrees C maintained a constant concentration of carbon disulfide over almost three weeks.

[Statistical aspects of the definition of reference values]. / Aspetti statistici della definizione dei valori di riferimento.

The criteria adopted in the study of reference values have a great influence on the statistical analysis of the data. To avoid a poor statistical treatment of the data, the scope of the study must be well defined: a study to establish reference values for a chemical in the body fluids of a population is not a survey to prove relations among variables and the chemical. In this latter case, criteria to select subjects and methods are different. Confusion between the two types of surveys can lead to poor results. Reference subjects must be selected with precision, using reproducible criteria. It can be suggested to pick-up subjects from a variety of sub-groups of the population. It must be used selection criteria strictly defined to exclude from the study groups of subjects having specified characteristics (patients, resident in contaminated-zone...). The use of partition criteria is useful to know the distribution of some characteristics in the population, or to describe reference values in particular subgroups. On the contrary, partition can not be used to study relationships. Particular attention must be payed in choosing number of strata and variable of partition. When a population is analysed for reference values, the choice of subjects and relevant variables must be made after consulting a statistician.

Blood acetone concentration in "normal people" and in exposed workers 16 h after the end of the workshift.

Acetone levels were measured by gas chromatography mass spectrometry (GC-MS) in environmental and alveolar air, blood and urine of 89 non-occupationally exposed subjects and in three groups of workers exposed to acetone or isopropanol. Acetone was detected in all samples from non-exposed subjects, with mean values of 840 micrograms/l in blood (Cb), 842 micrograms/l in urine (Cu), 715 mg/l in alveolar air (Ca) and 154 ng/l in environmental air (Ci). The ninety-fifty percentiles were 2069 micrograms/l in Cb, 2206 micrograms/l in Cu and 1675 ng/l in Ca. The blood/air partition coefficient of acetone was 597. Correlations were found in Cb, Cu and Ca. In specimens sampled at the end of the workshift from subjects occupationally exposed to acetone, a correlation was found in the blood, urine, alveolar and environmental air concentrations. The blood/air partition coefficient of acetone was 146. On average, the blood acetone levels of workers were 56 times higher than the environmental exposure level, and the concentration of acetone in alveolar air was 27% more than that found in inspiratory air. The half-life for acetone in blood was 5.8 h in the interval of 16 h between the end of the workshift and the morning after. The morning after a workshift with a mean acetone exposure of 336 micrograms/l, blood and urinary levels were 3.5 mg/l and 13 mg/l, respectively, which were still higher than those found in "normal" subjects. It can be concluded that endogenous production of acetone and environmental exposure to acetone or isopropanol do not affect the reliability of biological monitoring of exposed workers, even 16 h after low exposure.

[The principles and applied aspects concerning the prediction and prevention of noise damage under current regulations]. / Considerazioni su alcuni principi ed aspetti applicativi riguardanti previsione e prevenzione del danno da rumore nella attuale normativa.

From a comparison between the present Italian regulations and the main international guidelines regarding the assessment and prevention of effects of industrial noise, three main aspects emerge: firstly, the aims of the regulations (i.e. the characteristics and levels of hearing handicap to be prevented); secondly, the models for evaluating the probability of hearing loss; lastly, the limit values and the preventive measures adopted. The Italian regulations with respect to the ISO, ACGIH, NIOSH guidelines and regulations of other European countries, do not supply any precise indications regarding the aforementioned aspects. As a consequence, measures must be adopted to prevent any type of hearing impairment and the level of the noise has to be reduced to the minimum by acting on the environment, machinery and using individual protective devices.

Blood styrene concentrations in a "normal" population and in exposed workers 16 hours after the end of the workshift.

Blood styrene was measured by a gas chromatography-mass spectrometry method in 81 "normal people" and in 76 workers exposed to styrene. In the normal subjects, styrene was also tested in alveolar and environmental air. Styrene was found in nearly all (95%) blood samples. Average styrene levels in the normal subjects were 221 ng/l in blood (Cb), 3 ng/l in alveolar air (Ca) and 6 ng/l in environmental air (Ci). Styrene levels did not differ significantly between smokers and nonsmokers, 95% of values being below 512 ng/l in Cb, 7 ng/l in Ca and 15 ng/l in Ci. In workers with an average exposure to styrene of 204 micrograms/l, at the end of the workshift, mean blood styrene concentration was 1211 micrograms/l. In blood samples collected at the end of the Thursday shift, styrene levels were significantly higher (1590 micrograms/l) than those found at the end of the Monday shift (1068 micrograms/l). A similar difference was found in samples taken the morning after exposure (60 and 119 micrograms/l, respectively). Significant correlations between blood and environmental styrene were found both at the end of the shift and the morning after exposure (r = 0.61 and 0.41, respectively). In workers occupationally exposed to styrene, 16 h after the end of the workshift, blood styrene (94 micrograms/l) was significantly higher than that found in the normal subjects (0.22 microgram/l). The half-life of blood styrene was 3.9 h.

Reference values for blood toluene in the occupationally nonexposed general population.

Blood toluene was measured by gas chromatography--mass spectrometry in 232 occupationally nonexposed subjects, consisting of 126 rural and 106 urban workers, and 37 chemical workers. Mean blood toluene was significantly lower in rural (698 ng/l) and urban workers (984 ng/l) than in chemical workers (2789 ng/l). Blood toluene was not significantly different between the rural and urban workers or among the urban workers with different jobs. Smokers had significantly higher levels (median 606 ng/l) than nonsmokers (median 424 ng/l). Subjects who had smoked at least one cigarette in the last 2 h before blood sampling had significantly higher blood toluene (median 1170 ng/l) than those who had not smoked during this time (median 693 ng/l), for whom the level was not significantly different from that in nonsmokers. Blood toluene in the total population was less than 2863 ng/l in 95% cases.

Blood concentrations of carbon disulphide in dithiocarbamate exposure and in the general population.

Blood carbon disulphide (CS2), both free and total, was determined by gas chromatography-mass spectrometry in 112 "normal" subjects and in 20 subjects employed in a dithiocarbamate factory, comprising ten blue-collar workers involved in dithiocarbamate production and ten white-collar office staff. The ten production workers were examined over two workshifts, the first at the beginning of the week (Monday) and the second after an intervening period of at least 1 day. Three blood samples were taken for each shift studied, one prior to starting work, one at the end of the shift and the third 16 h after the end of the shift (on the following morning). The mean CS2 blood levels measured in the 112 normal subjects was 663 ng/l for the free fraction and 3178 ng/l for the total. In 16 blood samples taken from the ten dithiocarbamate factory office workers, the mean free and total CS2 blood levels were 846 and 4140 ng/l, respectively, i.e. not significantly different from those observed in the normal subjects. At the end of the first 8-h shift, the ten dithiocarbamate factory production workers had free and total CS2 values of 1070 and 8471 ng/l, respectively, which were significantly higher than those observed prior to starting work (240 and 4738 ng/l). All the total CS2 levels measured in the shop-floor workers, with the sole exception of the values recorded prior to the start of the Monday shift (4738 ng/l), ranged from 7047 to 8471 ng/l and were significantly higher than those measured in the white-collar staff (4140 ng/l).

[The exposure to tobacco smoke of the employees of a telephone company]. / Esposizione al fumo di tabacco degli impiegati di un'azienda telefonica.

Smoking habits were studied in a group of employees of a telephone company. The smokers were 34% of the subjects interviewed. The non-smokers said that they were bothered by other people smoking everywhere and also to a considerable extent at the workplace. Differences between smokers and non-smokers and between exposed and non-exposed non-smokers were studied by measuring expired CO and urinary cotinine. An expired CO concentration of 10 ppm discriminated between smokers and non-smokers. A mean urinary cotinine concentration of about 16 ng/mg was found in the exposed non-smokers, corresponding to the direct smoking of 1/10 of a cigarette per day. The search for the metabolic phenotype of destromethorphane, which was taken as an indicator of susceptibility to contract lung cancer due to IPA, showed that there were no differences between smokers and non-smokers since the rapid metabolizers, and therefore subjects potentially exposed to risk of lung cancer due to tobacco smoke, prevailed in both groups.

Blood concentration of carbon disulphide in "normal" subjects and in alcoholic subjects treated with disulfiram.

Assay of free and acid labile carbon disulphide (free and total CS2 respectively) in human blood was performed by gas chromatography/spectrometry. The method used a large dynamic head space volume and a "cryogenic trap". Blood CS2 concentration was measured in 42 subjects not occupationally exposed to CS2 (group A) and in 11 alcoholic subjects (group B) treated with disulfiram. Free CS2 concentration showed a mean value of 261 ng/l in the 42 subjects in group A and 9482 ng/l in eight subjects of group B. Total CS2 concentration was 897 ng/l and 40,084 ng/l in groups A and B respectively. Differences between the groups were highly significant for concentrations of both free and total CS2. Total CS2 concentration was about four times as high as free CS2 concentration in both groups. A significant correlation was found between free and total CS2 concentration both in group A and in group B. In the alcoholic subjects (group B), blood concentrations of both free and total CS2 were related to time of sampling after treatment with disulfiram.

[Exposure to silicon carbide fibers in the production of carborundum]. / Esposizione a fibre di carburo di silicio nella produzione del carborundum.

Recent reports have shown that not only silicon carbide dusts but also fibres are liberated into the working environment during the various phases of silicon carbide production (using Acheson furnaces), thus creating a further potential health hazard. An environmental hygiene survey was conducted in a silicon carbide production plant with the aim of quantifying airborne dusts and fibres. Although dust levels were below 50% of the TLV, high concentrations of fibres were observed (analyzed via optical microscopy using the criteria for asbestos fibres), which in some locations reached levels of 2000 fibres/litre with means (GM) between 100 and 780 fibres/litre according to department. These results are assessed in the light of the growing interest of researchers in the experimental effects of silicon carbide fibres.

Tentative reference values for some elements in broncho-alveolar lavage fluid.

The concentrations of Fe, Mn, Pb and Cr have been determined in broncho-alveolar lavage (BAL) fluid of 25 subjects without occupational or abnormal environmental exposure to metals, using the AAS method. The numerous factors which can interfere with the results in pre-analytical and in analytical phases are stressed. Metals concentrations in BAL are expressed in micrograms/l. They were not correlated with the volume of fluid recovered, the total cells, alveolar macrophages and erythrocytes. The results were not modified by stratification considering age and sex. Iron concentrations were higher than others, probably due to higher environmental exposure and partly to its essential role in humans. The diagnostic significance of element determination in BAL fluid and the relationship with exposure and lung load is discussed.

Is hypertension a confounding factor in the assessment of blood lead reference values?

In order to evaluate whether hypertension can be considered as a confounding factor in the setting up of reference values for blood lead, we examined the results of a cross sectional study which evaluated the relationship between lead in blood and hypertension in a sample of 254 males and 271 females of a general population not occupationally exposed to lead. The statistical analysis and in particular the multiple logistic regression showed that, even if some well-known confounding factors such as age, sex, overweight, smoking and alcohol are taken into account, blood lead levels are well correlated with hypertension. The results suggest that even modest lead absorption is able to influence the probability of being hypertensive. The relationship between blood lead and hypertension and their relationship with the main confounding factors involved in the determination of reference values of metals in blood are discussed.

Reference values for blood benzene in the occupationally unexposed general population.

Blood benzene was determined by gas chromatography-mass spectrometry in 431 "normal" subjects, subdivided into 155 rural subjects and 276 urban subjects. Blood benzene (mean value 262 ng/l) was significantly lower in rural (200 ng/l) than in urban (296 ng/l) workers, as well as differing significantly between 293 non-smokers and 138 smokers (205 ng/l and 381 ng/l, respectively). Among non-smokers, values were significantly higher (307 ng/l) in 76 chemical workers. In the total study population, in 95% of cases blood benzene was less than 718 ng/l, the 95th percentile being 514 ng/l in non-smokers vs 901 ng/l in smokers and 576 ng/l in rural vs 822 ng/l in urban subjects. Within each population subgroup, the difference between non-smokers and smokers was statistically significant, except among office workers (non-smokers 234 ng/l, smokers 304 ng/l). Blood benzene (y) was directly proportional to the number of cigarettes smoked (x) (y = 201 + 12x; r = 0.44; n = 431), and inversely proportional to the interval between the last cigarette and the time at which the blood samples was taken (z) (log y = 6.167-0.0015z; r = -0.461; n = 135). The blood half-life of benzene was about 8h. The multiple correlation between blood benzene (Cb), number of cigarettes per day (x) and time since the last cigarette (z) is: Cb = 417 + 7.2x - 0.41z (n = 135; R = 0.20; P less than 0.00001).

[The biological levels of chloroform in the general population]. / Livelli biologici di cloroformio nella popolazione generale.

The paper reports the results of determination, via gas chromatography and mass spectrometry, of chloroform in expired air, blood and urine of a group of non-occupationally exposed blood donors. Chloroform concentrations were also measured for each subject in the air of the environment where samples were taken.

[The prospects for the appearance of pleural mesothelioma in Italy]. / Prospettive di comparsa del mesotelioma pleurico in Italia.

The mortality data of Italian males and females due to malignant tumour of the pleura, collected over a period of 7 years, from 1976 to 1985, showed a continuous, rectilinear type, increase. The increase in the quantity of asbestos that was processed from 1945 to 1979 was also rectilinear. On the basis of the well known relationship between asbestos and mortality due to mesothelioma, an extremely high correlation coefficient was obtained between quantity of asbestos processed per year and number of deaths due to malignant tumour of the pleura 25 years later. Extrapolating to the year 2000 on the basis of this relationship, it can be foreseen that at that time the deaths due to malignant tumour of the pleura in Italy will be about 1200 per year. It is recommended to apply a correction factor to this figure in order to obtain the number of true cases of mesothelioma, which are probably about 70% of the deaths attributed to tumour of the pleura.

Ubiquitous pollution by n-hexane and reference biological levels in the general population.

n-Hexane levels were determined by gas chromatography and mass spectrometry in environmental air and in the alveolar air, blood and urine of a group of subjects aged on average of 38 years who had not been occupationally exposed to this hydrocarbon. n-Hexane was found in all environmental air samples examined (n = 49), with the mean concentration being 104 ng/l (limit values, 1-279 ng/l). It was also found in all 49 samples of alveolar air, with the mean concentration being 50 ng/l (variation limit, 1-304 ng/l). In 64 samples of urine, n-hexane was found in only 50 samples, with the mean concentration being 1,417 ng/l (limit values, 34-8,820 ng/l). In 77 of the 90 blood samples taken, a mean concentration of 608 ng/l was detected (variation limit, 15-7,684 ng/l). Particularly the haematic and urinary concentration showed significant differences among the nine groups of individuals classified according to their work activity. The lowest levels were found in the blood and urine of farmers: 270 and 298 ng/l, respectively. The highest values were found for chemical workers (1,377 and 411 ng/l), respectively printers (585 and 2,691 ng/l respectively), and traffic wardens (740 and 8,820 ng/l, respectively). In all, 95% of the determinations of n-hexane yielded values of less than 255 ng/l in environmental samples, less than 105 ng/l in alveolar air, less than 1,475 ng/l in blood and less than 5,875 ng/l in urine. A comparison of these data revealed a significant correlation between environmental levels and alveolar (r/s = 0.769; P less than 0.00001), haematic (r/s = 0.624; P less than 0.0002), and urinary (r/s = 0.597; P less than 0.0005) values for n-hexane.