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Simple Summary Benzene is produced by diverse petroleum transformation processes and it is widely employed in industry despite its oncogenic effects. In fact, occupational exposure to benzene may cause hematopoietic malignancy. The leukemogenic action of benzene is particularly complex. Possible processes of onset of hematological malignancies have been recognized as a genotoxic action and the provocation of immunosuppression. However, benzene can induce modifications that do not involve alterations in the DNA sequence, the so-called epigenetics changes. Acquired epigenetic modification may also induce leukemogenesis, as benzene may alter nuclear receptors, and cause changes at the protein level, thereby modifying the function of regulatory proteins, including oncoproteins and tumor suppressor proteins. Abstract Benzene carcinogenic ability has been reported, and chronic exposure to benzene can be one of the risk elements for solid cancers and hematological neoplasms. Benzene is acknowledged as a myelotoxin, and it is able to augment the risk for the onset of acute myeloid leukemia, myelodysplastic syndromes, aplastic anemia, and lymphomas. Possible mechanisms of benzene initiation of hematological tumors have been identified, as a genotoxic effect, an action on oxidative stress and inflammation and the provocation of immunosuppression. However, it is becoming evident that genetic alterations and the other causes are insufficient to fully justify several phenomena that influence the onset of hematologic malignancies. Acquired epigenetic alterations may participate with benzene leukemogenesis, as benzene may affect nuclear receptors, and provoke post-translational alterations at the protein level, thereby touching the function of regulatory proteins, comprising oncoproteins and tumor suppressor proteins. DNA hypomethylation correlates with stimulation of oncogenes, while the hypermethylation of CpG islands in promoter regions of specific tumor suppressor genes inhibits their transcription and stimulates the onset of tumors. The discovery of the systems of epigenetic induction of benzene-caused hematological tumors has allowed the possibility to operate with pharmacological interventions able of stopping or overturning the negative effects of benzene.

The adverse effects associated with exposure to flour dust have been known since the 1700s. The aim of the study was to assess the occupational exposure to flour dust in Italian facilities, identify the activities characterized by the highest exposure, and provide information to reduce workers&rsquo, exposure. The study was performed in different facilities such as flourmills (n = 2), confectioneries (n = 2), bakeries (n = 24), and pizzerias (n = 2). Inhalable flour dust was assessed by personal and area samplings (n = 250) using IOM (Institute of Occupational Medicine) samplers. The results showed personal occupational exposure to flour dust over the American Conference of Governmental Industrial Hygiene (ACGIH) and the Scientific Committee on Occupational Exposure Limit (SCOEL) occupational limits (mean 1.987 mg/m3, range 0.093&ndash, 14.055 mg/m3). The levels were significantly higher for dough makers in comparison to the dough formers and packaging area subjects. In four bakeries the industrial hygiene surveys were re-performed after some control measures, such as installation of a sleeve to the end of pipeline, a lid on the mixer tub or local exhaust ventilation system, were installed. The exposure levels were significantly lower than those measured before the introduction of control measures. The exposure level reduction was observed not only in the dough making area but also in all bakeries locals.

The aim of this study was to evaluate the levels of As, Be, Bi, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Se, Tl, V, and Zn, by inductively coupled plasma-mass spectrometry (ICP-MS) in the urine of two groups of patients with two different types of metal-on-metal (MoM) total hip prostheses (ASR DePuy&reg, group A, 25 patients, total Met-Met System Lima&reg, group B, 28 patients). The determination of metals reflected a steady-state release (group A: 9 years after surgery and group B: 6 years after surgery). The results obtained confirmed the increase of Co and Cr urinary levels in both group when compared with the reference values for the general population adopted by the Italian Society of Reference Values (SIVR). In particular, Co and Cr levels exceeded the threshold values in urine, respectively, of 30 &mu, g and 21 &micro, g, adjusted to creatinine based on the threshold in whole blood of 7 &mu, g/L proposed by the Medicines and Healthcare Products Regulatory Agency (MHRA). Regarding the other investigated metals, significantly higher values were found in Group A than in Group B. These differences could be due to the type of hip prosthesis implanted, the longer period of time since the implantation, as well as many other factors such as diet, age, drug consumption, physical activity, or presence of dental fillings. The continuous monitoring over the years of metal concentrations in patients carrying a prosthesis could be useful to better identify the sources of these metals.

Dithiocarbamates (DTC) are the most commonly used synthetic fungicides in the Prosecco District (PD) of Treviso. The DTC biomarker is urinary ethylenethiourea (u-ETU). The aims of this biomonitoring study are to describe the level of u-ETU in residents in PD and to identify the factors associated with DTC exposure. In 2012 (baseline), we randomly extracted data for 126 children (3–5 years) and their families (260 adults), who were resident in 8 municipalities of PD and not occupationally exposed to DTC, from the local health database. For each subject, we obtained urine samples and socio-demographic, lifestyle and dietary information. In 2014 (after intervention), we evaluated the possible changes in u-ETU in 54 adults and 55 children at high risk of DTC exposure. The median baseline u-ETU was 0.35 µg/L. Approximately 5% of the samples had a u-ETU concentration > 5 µg/L. No u-ETU concentration exceeded 21 µg/L. Determinants of a higher u-ETU concentration were wine consumption (OR 2.04) and personal use of pesticides (OR 2.70) for adults; and living within 30 m from a vineyard (OR 9.51) and the pesticides use in the family (OR 6.25) for children. A significant u-ETU reduction in 49 adults and 25 children was observed from baseline to after intervention (p = 0.01). Wine consumption and production and DTC use in gardening influenced u-ETU concentrations in this population, although the levels were relatively low. The reduction in u-ETU from baseline to time after intervention probably reflects the effects of public health interventions.

Artificial stone is increasing in popularity in construction applications, including commercial and residential countertops. Eco-friendliness, durability, and resistance to staining, make artificial stone attractive to consumers. Health concerns have arisen during manufacturing of artificial stone due to increased incidence of silicosis after relatively short exposure. Three artificial stone samples (A, B, and C) and one natural granite sample were subjected to cutting and grinding in a controlled environment. Gravimetric analysis, X-Ray diffraction, and scanning electron microscopy with energy dispersive spectroscopy were employed to determine crystalline silica concentrations and particle morphology of bulk and respirable particles. Silica content of bulk dust from artificial samples A and B was 91%, sample C was &lt, 10%, while granite was 31%. Silica percent in the respirable fraction for samples A and B was 53% and 54%, respectively, while sample C was &lt, 5% and granite was 8%. Number concentrations for samples A and B were mainly in the nano-fraction, indicating potential for translocation of silica particles to other organs outside of the lungs. Respirable dust concentrations inside the chamber were well above Occupational Safety and Health Administration standards for all materials, indicating that confined-space exposures require ventilation to lower risks of acute silicosis regardless of the nature of the stone.

Non-occupational lead poisoning is not rare, mainly occurring in domestic situations in children, but also in adults. Lead poisoning was observed in a 65 years-old woman non-exposed to risk that caught our attention with a diagnostic suspicion of acute intermittent porphyria according to recurrent episodes of abdominal pain and neuropathy of upper limbs. Acute intermittent porphyria was excluded by a laboratory investigation that showed instead severe lead poisoning. After several thorough examinations of the domestic environment, the source of intoxication has been detected in some cooking pots that released high concentrations of lead. Ethylenediamine tetracetic acid disodium calcium therapy (three cycles) reduced consistently blood lead concentration and, after one year, neuropathy was almost entirely recovered.

Introduction: Clusters of silicosis related to fabrication of quartz conglomerates have been recently reported. The prognosis of this form of silicosis has not been established. Aim: To evaluate the progression of silicosis in workers exposed to quartz conglomerate. Methods: A short-term follow-up of workers with silicosis was performed. Lung function tests, high resolution computed tomography (HRCT) and levels of airborne crystalline silica during activity in the finishing lines were assessed at diagnosis and after 12 months. Results: We studied 18 cases of silicosis (age at diagnosis: range 25-53 yr; duration of exposure to quartz conglomerate dust: 3.5-10 yr, and average workplace silica dust levels: 0.260-0.744 mg/m3). At diagnosis, 50% of subjects exhibited an impairment of DLco (75.7±15% predicted). The most common spirometric alteration (38% of cases) was a restrictive pattern based on TLC (5.73±1.02L and 85.5±13% pred.). HRCTs showed well-defined rounded opacities and enlarged mediastinal lymph-nodes. During follow-up period, wet or automatic finishing was introduced and all workers were supplied with Filtering Face Piece-3 masks. At follow-up, the levels of airborne silica had been drastically reduced (0.009-0.013 mg/m3). We observed a significant decline of TLC (-0.41±0.7L and -6±10% pred., p=0.008), while DLco was stable. A slight increase of HRCT opacities was detected in 6 subjects. No significant relationship between HRCT and TLC worsening was observed. Conclusions: Silicosis due to quartz conglomerates seems characterized by an accelerated lung function decline, despite a reduction of exposure to silica dust. Spirometry appears the most sensitive tool to monitor the progression of the disease.

The purpose of the study is to evaluate the urinary levels of free 2,5-hexanedione (2,5-HD) in Italian subjects non-occupationally exposed to n-hexane, in order to define background values in non-occupational settings. The study was carried out on 99 subjects of the general population. The analysis of free 2,5-HD was performed by gas chromatography-mass spectrometry. Personal information about the subjects was ascertained by means of a self-administered questionnaire. The urinary levels of free 2,5-HD were in the range of &lt, 12.0&ndash, 77.9 &micro, g/L (5th&ndash, 95th percentiles). The urinary excretion of the metabolite did not seem to be influenced by gender, age, smoking habit or area of residence. Statistically significant differences (p = 0.03) were found between the free 2,5-HD urinary levels according to the vehicular traffic intensity within the area of residence and to body mass index of subjects. The background levels of free 2,5-HD found in this study could contribute to the definition of reference values of general population non-occupationally exposed and could be useful to the toxicologists and industrial hygienists to determine whether workers have been exposed to higher levels of n-hexane than the general population.

Exposure to low levels of benzene may cause acute myeloid leukemia in humans. Epigenetic effects in benzene exposure have been studied for tumor suppressor genes and oxidative stress-related genes, but other cellular pathways must be explored. Here, we studied promoter DNA methylation of IL6, CYP2E1 and iNOS in blood cells from three groups of workers: a) gas station attendants (GS) exposed to low levels of benzene; b) plastic shoe factory workers (PS) exposed to other solvents different to benzene and c) administrative workers as a reference group with no solvent exposure (C).IL6 promoter methylation was higher in GS workers (p 0.05). Also in GS, CYP2E1 promoter methylation negatively correlated with benzene levels (r = -0.47, p 0.05); iNOS promoter methylation positively correlated with CYP2E1 promoter methylation (r = 0.29, p 0.05), cumulative time of exposure (r = 0.31, p 0.05) as well as with urinary levels of S- Phenyl mercapturic acid (SPMA), (r = 0.55, p 0.05). Our results demonstrate alterations in the inflammation pathway at the epigenetic level associated with exposure to benzene. Correlations between iNOS methylation with both CYP2E1 methylation and urinary SPMA levels represent novel evidence about CYP2E1 epigenetic regulation and activity related with nitrosative stress, making promoter methylation status of these genes a potential biomarker in early stages of oncogenesis.

Human exposure to n-hexane has been associated with subfertility and, experimentally, with a decrease in follicular development. In order to assess occupational exposure to n-hexane on ovarian function and gonadotropic hormones, we studied Mexican women labouring in a leather shoe factory (n = 34). Individual environmental levels for seven solvents, n-hexane included, were measured; also, urinary 2,5-hexanedione (2,5-HD) was determined. For ovarian function and hormonal status, FSH, LH, oestradiol and anti-Müllerian hormone (AMH) levels were determined. We performed all determinations also in a reference group, administrative workers with no exposure to solvents (n = 32). Results: N-hexane and urinary 2,5-HD levels were higher in exposed group (p 0.001). More cases of oligomenorrhea as well as longer time for getting pregnant were observed in exposed women compared with controls; a positive association was found between menstrual cycle length and "time for getting pregnant" (p = 0.010); significant associations between FSH serum levels and 2,5-HD urinary levels (post-shift sample) were observed in non-smokers participants presenting oligomenorrhea from exposed group. Also, we found a trend for lower oestradiol levels in exposed participants with current smoking habit (p = 0.059). Conclusions: 2,5-HD urinary levels are associated with decreased gonadotropins levels; hence, n-hexane should be considered an endocrine disruptor in reproductive-age women.

(1) Background: The products of guanine oxidation in DNA and RNA excreted in urine are 8-oxo-7,8-dihydroguanine (8-oxoGua), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and 8-oxo-7,8-dihydro-2&rsquo, deoxyguanosine (8-oxodGuo). Despite intra and inter-individual variability, it is possible to identify situations that significantly increase the levels of these compounds when comparing urinary concentrations of some workers to those of the general population. (2) Methods: urines from gasoline pump attendants (58 from Saudi Arabia and 102 from Italy), 24 workers of a fiberglass reinforced plastics plant, 17 painters and 6 divers were analyzed by HPLC/MS-MS. To test the individual variability, two subjects provided daily samples for one month, and 132 urine samples from the general population were analyzed. (3) Results: We summarized the results for each biomarker, and found the following were statistically higher than in the general population: 8-oxoGua in fiberglass and Italian gasoline workers, 8-oxodGuo in fiberglass and both Saudi Arabian and Italian gasoline workers, 8-oxoGuo in fiberglass workers, both Saudi Arabian and Italian gasoline workers, and painters after the working shift. (4) Conclusions: these results confirm that both 8-oxodGuo and 8-oxoGuo are valuable biomarkers for occupational exposures to dangerous chemicals and seem to suggest that 8-oxoGuo, related to RNA oxidation, is a suitable biomarker to evaluate short term, reversible effects of occupational exposures even within the health-based limit values.

(1) Background: The oxidized guanine derivatives excreted into urine, products of DNA and RNA oxidation and repair, are used as biomarkers of oxidative damage in humans. This study aims to evaluate oxidative damage in gasoline pump attendants occupationally exposed to benzene. Benzene is contained in the gasoline but it is also produced from traffic and from smoking. (2) Methods: Twenty-nine gasoline pump attendants from two major cities of Saudi Arabia and 102 from Italy were studied for urinary 8-oxo-7,8-dihydroguanine (8-oxoGua), 8-oxo-7,8-dihydro-2&prime, deoxyguanosine (8-oxodGuo), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and S-phenyl-mercapturic acid (SPMA) for benzene exposure and urinary cotinine for smoking status assessment by liquid chromatography-tandem mass spectrometry. Airborne benzene was also assessed in the Italian group by gas-chromatography with flame ionization detector (GC-FID). (3) Results: The results suggest that high levels of benzene exposure can cause an accumulation of SPMA and bring about the formation of the oxidation biomarkers studied to saturation. At low exposure levels, SPMA and oxidation biomarker levels were correlated among them and were associated with the smoking habit. (4) Conclusions: The study confirms the association between benzene exposure and the excretion of nucleic acid oxidation biomarkers and enhances the importance of measuring the smoking habit, as it can significantly influence oxidative damage, especially when the exposure levels are low.

A group of 142 bakers was studied in order to investigate the relationship between higher/lower respiratory signs/symptoms and inflammation biomarkers and occupational exposure to flour dust. A complete upper and lower respiratory tract evaluation was performed. Seven percent of bakers complained of lower respiratory symptoms, while 22% of them complained of upper respiratory symptoms. Fifty five percent of the bakers were allergic, and 37.1% showed sensitization to occupational allergens. Abnormal spirometries were found in 15% of bakers, while fractional exhaled nitric oxide (FeNO) was above the normal reference in 24.5% of them. Moreover, 23.8% of bakers were found to be hyposmic. Population mean peak nasal inspiratory flow (PNIF) was in the normal range even if almost all the workers suffered from neutrophilic rhinitis at nasal cytology with the number of nasal neutrophils increasing with the increase of the duration of exposure to flour dust (p = 0.03). PNIF and FEV1 (forced expiratory volume in the 1st second) showed a positive correlation (p = 0.03, r = 0.19). The Tiffeneau index decreased with the increase of dust (p = 0.017). A similar result was obtained once we divided our population into smokers and non-smokers (p = 0.021). Long-term exposure to bakery dusts can lead to a status of minimal nasal inflammation and allergy.

Background Our primary endpoint was to use nasal cytology to compare woodworkers with unexposed subjects to see if wood dust exposure correlates with specific patterns of inflammatory or infectious rhinitis. A secondary endpoint was to identify any differences in the exposed group's nasal symptoms or nasal cytology by years of exposure or personal exposure levels. Methods Ninety-two woodworkers and 90 controls were assessed using a questionnaire and nasal cytology (on nasal mucosa obtained by scraping). Wood dust exposure was investigated using personal sampling methods. Results Woodworkers reported significantly more nasal symptoms than controls (p < 0.00001). The woodworkers' nasal smears revealed more neutrophils (p = 0.001) and significantly higher mean neutrophil scores (p = 0.001) than control smears. Lymphocytes were also found more often in the woodworkers' rhinocytograms (statistical trend, p = 0.06). Neutrophilic rhinitis was diagnosed more frequently in the exposed workers than in controls (chi-square = 5.97, p < 0.05). Woodworkers with lymphocytes in their nasal smears had been exposed to wood dust for longer periods of time (statistical trend; p = 0.06). No differences in nasal symptoms or cell counts emerged when woodworkers were stratified by levels of personal exposure. Conclusion Nasal cytology should be further investigated in woodworkers before considering it a screening method for identifying woodworkers with chronic inflammatory rhinitis.

Introduction Hearing loss in occupational exposure to a solvent mixture has been already reported; however, mixture in those reports did not contain ethylbenzene, a compound showing peripheral ototoxicity in animals exposed to high levels. In this work, we evaluated the auditory brainstem pathway in two samples of workers exposed to different levels of a solvent mixture where ethylbenzene was present, compared to a reference group. Material and methods Individual exposure levels for up to seven compounds were obtained in two groups: Exposed (n=21 gas station attendants, GS, and leather shoe factory workers, LS) and Non-exposed (n=21, administrative workers) all of them from the city of Leon Guanajuato, Mexico. The click-evoked auditory brainstem response test was performed in both groups. Results Toluene, n-hexane, acetone, ethylbenzene, xylene and methyl ethyl ketone exposure levels were higher in LS (p Conclusion Our results point out to a central affection in the auditory system caused by ethylbenzene in a dose response manner. Workers exposed to ethylbenzene levels far below the permissible exposure limit should be closely monitored for early ototoxicity effects.

Introduction Former studies in rodents and cell lines have demonstrated ovarian toxicity caused by n-hexane and/or 2,5-hexanedione (2,5HD). In women occupationally exposed to solvents, variables ”menstrual cycle period” and ”time for getting pregnant” have been longer compared with controls, without identifying a compound responsible for those effects. Material and methods We studied a group of Mexican women labouring in a shoe Factory (n=32). Individual environmental levels for seven compounds, included n-hexane, were measured. Also, urinary 2,5HD and seric FSH and anti-Mullerian hormone (AMH) as potential biomarkers of ovarian toxicity, in addition to a gyneco-obstetric history were obtained. We performed all tests and questionnaires in a reference group as well (n=32). Results Mean exposure levels to n-hexane (49.2±39.6 mg/m 3 ) and toluene (30.8±24.5 mg/m 3 ) were the highest observed. There were no significant differences in serum FSH and AMH concentrations between groups (p>0.05). Exposed group showed prolonged menstrual cycles (p=0.007) and augmented time for getting pregnant compared with controls (p=0.007). Also in the exposed group, signifcant correlations were observed between FSH levels and n-hexane (r=−0.34, p=0.028) as well as FSH and 2,5HD (r=−0.33, p=0.029). Conclusions n-hexane exposure may be responsible for a prolonged menstrual cycle. As judged by the correlations between FSH with n-hexane and 2,5HD this affection could be in the endocrine pathway rather than in the ovary itself. n-hexane could act as endocrine disruptor in women of reproductive age.

The urinary excretion rate is calculated based on short-term, defined time sample collections with a known sample mass, and this measurement can be used to remove the variability in urine concentrations due to urine dilution. Adjustment to the urinary excretion rate of hippuric acid was evaluated in 31 healthy volunteers (14 males and 17 females). Urine was collected as short-term or spot samples and tested for specific gravity, creatinine and hippuric acid. Hippuric acid values were unadjusted or adjusted to measurements of specific gravity, creatinine or urinary excretion rate. Hippuric acid levels were partially independent of urinary volume and urinary flow rate, in contrast to specific gravity and creatinine, which were both highly dependent on the hippuric acid level. Accordingly, hippuric acid was independent on urinary specific gravity and creatinine excretion. Unadjusted and adjusted values for specific gravity or creatinine were generally closely correlated, especially in spot samples. Values adjusted to the urinary excretion rate appeared well correlated to those unadjusted and adjusted to specific gravity or creatinine values. Thus, adjustment of crude hippuric acid values to the urinary excretion rate is a valid procedure but is difficult to apply in the field of occupational medicine and does not improve the information derived from values determined in spot urine samples, either unadjusted or adjusted to specific gravity and creatinine.

Background and aims Sinonasal cancers (SNCs) are rare neoplasms, accounting for about 3 % of head and neck cancers, with squamous cell carcinoma (SCC) and adenocarcinoma (ADC) as the most common subtypes. ADCs present strong associations with occupational wood dust exposure. Preventive measures have progressively reduced wood dust concentrations in workplaces but no study has evaluated the effectiveness of such interventions. Few studies indicate associations between ADC and exposure to solvents, which is common in the shoe industry, but this hypothesis still needs confirmation. Methods In a case-case study, we contrasted 32 ADCs against 21 Non-Adenocarcinoma Epithelial Tumors (NAETs) – all recruited from the same clinical setting (Padua’s University Hospital; period 2004–2015) – using questionnaires and clinical records to collect information on potential predictors. Non-occupational factors were age, sex, smoking, allergy and chronic sinusitis. Occupational factors were intensity and frequency of wood dust exposure, protection from wood dust, type of wood (in woodworking); frequency of exposure to leather dust or mastic/solvent (in shoemaking). Odds-ratio (OR), 95 % confidence interval (95 % CI) and two-tail p-values were obtained through stepwise backward logistic regression for each industry, always using as reference patients never employed in either trade and adjusting for non-occupational risk factors. Results Adjusted OR was 22.5 (95 % CI = 3.50–144; p = 0.001) and 9.37 (95 % CI = 1.29–67.6; p = 0.026), respectively, in patients with low or high degree of protection against wood dust. In the shoe industry, adjusted OR was 1 and 18.8 (95 % CI = 1.29–174; p = 0.030), respectively, in patients with low or high exposure to only mastic/solvent; and 1 and 22.5 (95 % CI = 2.07–244; p = 0.011), respectively, in patients with low or high exposure to only leather dust. Discussion and conclusions The questionnaire used was able to estimate with simple algorithms past exposures in wood and footwear industries. The case-case design considerably increased the validity of this small study. Results in this study were always consistent with the extant literature; this could support reliability of novel findings. In woodworking, respiratory protective equipment and local exhaust ventilation reduced the risk of occupational SNC; in footwear manufacture, where preventive interventions were seldom adopted, SNC risk was significantly greater for high exposure from mastic/solvent and leather dust. Electronic supplementary material The online version of this article (doi:10.1186/s12995-016-0124-7) contains supplementary material, which is available to authorized users.

Assessing CYP2E1 phenotype in vivo may be important to predict individual susceptibility to those chemicals, including benzene, which are metabolically activated by this isoenzyme. Chlorzoxazone (CHZ), a specific CYP2E1 substrate, is readily hydroxylated to 6-OH-chlorzoxazone (6-OH-CHZ) by liver CYP2E1 and the metabolic ratio 6-OH-CHZ/CHZ in serum (MR) is a specific and sensitive biomarker of CYP2E1 activity in vivo in humans. We used this MR as a potential biomarker of effect in benzene-treated rats and, also, in humans occupationally exposed to low levels of benzene. Male Sprague-Dawley rats (375-400g b.w.) were treated i.p. for 3 days with either a 0.5ml solution of benzene (5mmol/kg b.w.) in corn oil, or 0.5ml corn oil alone. Twenty-four hours after the last injection, a polyethylene glycol (PEG) solution of CHZ (20mg/kg b.w.) was injected i.p. in both treated and control animals. After 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, and 240min from injection, 0.2ml blood was taken from the tip tail and stored at -20 degrees C until analysis. A modified reverse phase HPLC method using a 5microm Ultrasphere C18 column equipped with a direct-connection ODS guard column, was used to measure CHZ and its metabolite 6-OH-CHZ in serum. No statistically significant difference in the MR was observed, at any sampling time, between benzene-treated and control rats. The concentration-versus-time area under the curve (AUC), however, was lower (p

Personal exposure to PM(10) measured in different seasons in a sample of asthmatic subjects living in Padova (Northern Italy) was compared with simultaneously measured outdoor PM(10) concentrations. The specific contribution of ambient PM(10) and other factors to individual exposure was evaluated in one of the areas of Europe with the worst air pollution. Thirty-one asthmatic subjects (21 non-smokers and 10 smokers) carried personal PM(10) monitors for six 24-hr sessions, in different seasons of the year. Concomitant daily 24-hr ambient PM(10) concentrations were measured by air quality monitoring networks. A multivariate analysis was performed to identify factors explaining personal exposure to PM(10), using a random effect model. The analysis on the 31 subjects referred to a total of 155 observations. The mean personal PM(10) exposure was higher (range 79.3-126.1microg/m(3)) than the outdoor concentrations (range 37.3-85.4microg/m(3)) in all seasons; and personal exposures varied less than outdoor PM(10) levels from one season to another. Smokers had significantly higher personal PM(10) concentrations than non-smokers (127.99 vs 78.8microg/m(3); T=-5.70; p0.001). Moderate correlations emerged between outdoor and personal PM(10) concentrations. The correlation improved after excluding subjects exposed to active or passive smoking (median Pearson's R 0.41 vs 0.26). Considering all the subjects, smoking was the main factor affecting personal exposure, contributing to 41% of the variability. Outdoor PM(10) concentrations (25%), temperature (12%) and season (15%) also contributed to personal PM(10) exposure. Outdoor PM(10) (46%), temperature (20%), season (19%) and time spent indoors (6%) were significantly associated with personal exposure in non-smokers. We concluded that it is crucial to perform personal monitoring and to evaluate the complexity of factors that contribute to individual PM exposure. While tobacco smoke was the primary source of PM(10) in all subjects, the contribution of ambient components was particularly relevant for the personal exposure levels of our non-smokers living in a highly-polluted environment.

There is conflicting evidence on the level of anesthetics that impairs neurobehavioral performance, leading to differences in exposure standards (25 or 50 ppm for N(2)O). Thirty-eight operating room nurses and 23 unexposed nurses were asked to provide information on confounding variables: age, gender, years of schooling, alcohol and coffee consumption, smoking, length of work, symptoms (Euroquest) and results of Block Design test. Afterward, all workers were repeatedly examined (on Monday and Friday of a working week, before and after workshift) for stress and arousal (Mood Scale) and complex reaction times (Color Word Vigilance, CWV), the latter being the outcome. Individual exposure was assessed through urinary end-shift concentrations of nitrous oxide (N(2)O) and isoflurane. According to the highest value of urinary excretion of N(2)O in the week, exposed workers were subdivided in three groups (13;or =13 and27; andor = 27 microg/l). The values of 13 and 27 microg/l correspond to environmental concentrations of 25 and 50 ppm, respectively. In order to take into account the pre-existing abilities of exposed and reference workers, and investigate the neurobehavioral changes over time, longitudinal data were analyzed by a two-stage regression model and analysis of variance for repeated measures (MANOVA). The former method, controlling for confounding factors and Monday morning CWV (which conveyed the pre-existing ability of the subjects), showed that, with respect to unexposed nurses, reaction times were significantly (p0.020) higher only in workers with urinary N(2)Oor = 27 microg/l. Therefore, at MANOVA, all subjects were categorized in two classes (N(2)O urinary concentrationsoror = 27 microg/l), and CWV results were adjusted for the confounding variables and effects of stress and arousal, taken concurrently with CWV. CWV significantly (p0.039) decreased over a working week (indicating a learning effect) in workers with urinary N(2)O27 microg/l, while remained steady (indicating impairment of neurobehavioral performance) in those with urinary N(2)O27 microg/l.

Nonfatal acute inhalation of trichloroethylene (TRI) at work was described. The subject, male, 54 years old, was drawn unconscious by a metal-degreasing machine and immediately sheltered in intensive care unit. Other than basic life support and common laboratory indices, blood and urine were collected to measure dose and kidney effect parameters such as TRI in blood and urine, trichloroethanol (TCE) and trichloroacetic acid (TCA) in urine, and total urinary proteins (TUP), urinary glutamine synthetase (GS) and urinary N-acetyl-beta-D-glucosaminidase (NAG). Two hours after accident, TRI in blood was 9 mg/l, but after 38 h it was below 1 mg/l. TCE and TCA have a peak 11 and 62 h after poisoning, respectively. Acute renal involvement was revealed by a peak of urinary proteins and enzymes 7 h after exposure with a second peak 74 h after. Seven day after hospitalisation the patient was dismissed with complete recovery. This nonfatal intoxication with TRI shows that the exposure was approximately 150 ppm, three times the ACGIH TLV (50 ppm) and that kidney was the only organ affected. Urinary enzymes, in particular GS, are good indices to monitor transient effects of TRI on the kidney.

It has been suggested that high-frequency audiometry (HFA) could represent a useful preventive measure in exposed workers. The aim was to investigate the effects of age, ultrasound and noise on high-frequency hearing thresholds. We tested 24 industrial ultrasound-exposed subjects, 113 industrial noise-exposed subjects and 148 non-exposed subjects. Each subject was tested with both conventional-frequency (0.125–8 kHz) and high-frequency (9–18 kHz) audiometry. The hearing threshold at high frequency deteriorated as a function of age, especially in subjects more than 30 years old. The ultrasound-exposed subjects had significantly higher hearing thresholds than the non-exposed ones at the high frequencies, being greatest from 10 to 14 kHz. This hearing loss was already significantly evident in subjects with exposure

Objectives: Recently published works showed that occupational exposure to antineoplastic drugs (ANPD) is still frequent in hospital settings, despite significant safety policy improvements. The aim of this study was to assess the current level of occupational exposure to ANPD and any potentially associated cytogenetic damages in hospital nurses routinely handling ANPD. Methods: Occupationally ANPD-exposed (n = 71) and ANPD-unexposed (n = 77; control) nurses were recruited on a voluntary basis from five hospitals in Northern and Central Italy. Evaluation of surface contamination and dermal exposure to ANPD was assessed by determining cyclophosphamide (CP) on selected surfaces (wipes) and on exposed nurses’ clothes (pads). The concentration of unmetabolized CP—as a biomarker of internal dose—was measured in end-shift urine samples. Biomonitoring of genotoxic effects (i.e., biological effect monitoring) was conducted by analyzing micronuclei (MN) and chromosome aberrations (CA) in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e., glutathione S-transferases) were analyzed as well. Results: We observed a significant increase in MN frequency (5.30 ± 2.99 and 3.29 ± 1.97; mean values ± standard deviation; p

Background Fluoride, a main metabolite, and one degradation product of sevoflurane (SEV), called Compound A, are known to cause kidney effects in experimental animals. Other than in volunteers and patients, no research is available on exposed workers. The possible effects on the kidney in workers exposed in surgical areas were studied. Methods Subjects exposed to SEV and nitrous oxide (N2O) in surgical areas (N = 61) using open (N = 25) or semi-closed (N = 36) circuits were submitted to biological monitoring. The same biological indices were determined in 43 controls also. Sevoflurane (SEVU), nitrous oxide (N2OU), total urinary proteins (TUP), N-acetyl-β-D-glucosaminidase (NAGU), and glutamine synthetase (GSU) were measured in urine. Results The mean values of environmental exposure were 31.3 ppm (range 0.9–111.6 ppm) for N2O and 0.28 ppm (range 0–1.88 ppm) for SEV. Exposed subjects had significantly higher excretion of TUP; a higher, not significant, excretion of GSU was also observed in subjects using open circuits. A significant correlation was found in all exposed subjects between NAGU and SEVU (r = 0.303, P

In this study, the correlation of indicators of external (i.e. mean daily intake of condensate, nicotine, tobacco and tobacco proteins, and daily number of cigarettes smoked) and of internal tobacco-smoke exposure (i.e. urinary 1-pyrenol, nicotine and its metabolites and trans,trans-muconic acid) with urinary mutagenicity, detected on YG1024 Salmonella typhimurium strain with S9, were examined in 118 smokers. An increase in urinary mutagenicity was clearly significantly correlated with each external and internal indicators of exposure to tobacco smoke (correlation coefficient (r) ranging between 0.22 and 0.54, P

This study aimed to correlate environmental sevoflurane levels with urinary concentrations of sevoflurane (Sev-U) or its metabolite hexafluoroisopropanol (HFIP) in order to assess and discuss the main issues relating to which biomarker of sevoflurane exposure is best, and possibly suggest the corresponding biological equivalent exposure limit values. Individual sevoflurane exposure was measured in 100 healthcare operators at five hospitals in north-east Italy using the passive air sampling device Radiello ® , and assaying Sev-U and HFIP concentrations in their urine collected at the end of the operating room session. All analyses were performed by gas chromatography-mass spectrometry. Environmental sevoflurane levels in the operating rooms were also monitored continuously using an infrared photoacoustic analyzer. Our results showed very low individual sevoflurane exposure levels, generally below 0.5 ppm (mean 0.116 ppm; range 0.007–0.940 ppm). Sev-U and HFIP concentrations were in the range of 0.1–17.28 μg/L and 5–550 μg/L, respectively. Both biomarkers showed a statistically significant correlation with the environmental exposure levels (Sev-U, r = 0.49; HFIP, r = 0.52), albeit showing fairly scattered values. Sev-U values seem to be influenced by peaks of exposure, especially at the end of the operating-room session, whereas HFIP levels by exposure on the previous day, the data being consistent with the biomarkers’ very different half-lives (2.8 and 19 h, respectively). According to our results, both Sev-U and HFIP are appropriate biomarkers for assessing sevoflurane exposure at low levels, although with some differences in times/patterns of exposure. More work is needed to identify the best biomarker of sevoflurane exposure and the corresponding biological equivalent exposure limit values.

The frequency of chromosome aberrations (CA) and micronuclei (MN) was investigated in the peripheral lymphocytes of workers occupationally exposed to low or very low concentrations of benzene. The study included 43 exposed workers (all males), namely 19 fuel-tanker drivers and 24 filling-station attendants, and 31 male subjects with no occupational exposure to the toxicant (controls). Benzene exposure was verified by means of environmental monitoring with passive personal samplers (Radiello ® ), and through biological monitoring, i.e. by measurement of urinary trans , trans -muconic acid, S -phenylmercapturic acid and benzene. The frequency of CA and MN in peripheral lymphocytes was determined according to standard procedures. Exposure to benzene was found to be significantly higher for fuel-tanker drivers (median 246.6 μg/m 3 ) than for filling-station attendants (median 19.9 μg/m 3 ). Both groups had significantly higher exposure than controls (median 4.3 μg/m 3 ). No increased frequency of CA and MN was observed in either fuel-tanker drivers or filling-station attendants compared with controls. In all subjects examined as a single group, the frequency of MN was significantly dependent on age. Only in the fuel-tanker drivers was the frequency of MN found to depend not only on age, but also on exposure to benzene. In conclusion, the frequency of MN, but not of CA, could be influenced by exposure to benzene concentrations of up to one order of magnitude lower than the threshold limit value (time-weighted average).

Objective: Spot urine samples were investigated to determine correlations between urinary creatinine and specific gravity, and intra- and inter-day variations other than gender- and age-dependence of urinary concentrations. Methods: Urinary creatinine concentrations and specific gravity were determined in 534 spot samples (385 from men and 149 from women). Subjects' ages ranged between 18 and 68 years. Spot urine samples were also collected from 14 male subjects before and after a 1-week work-shift for the evaluation of intra- and inter-day variations of creatinine and specific gravity. Results: In spot samples, creatinine concentrations ranged between 0.16 and 4.36 g/l and specific gravity between 1.002 and 1.037. A high correlation (r=0.82, P < 0.001) was observed between creatinine and specific gravity; male subjects showed significantly higher values of creatinine (P < 0.001) than did female subjects (1.90 ± 0.74 and 1.41 ± 0.72 g/l, respectively) and specific gravity (1.023 ± 0.006 and 1.020 ± 0.007, respectively). In addition, creatinine but not specific gravity significantly decreased (P < 0.02) in subjects older than 50 years, compared with those under 40. Conclusions: Results confirm the gender-dependence of creatinine concentrations in spot specimens and also show age-dependence, indicating the need for these aspects to be considered when the range of acceptable samples is to be set. No significant intra- or inter-day variations were observed for the two parameters. Lastly, the possibility of a comparison of differently adjusted values was indicated by a conversion formula derived from adjustments to creatinine and the corresponding specific gravity of a hypothetical urinary value, as follows: specific gravity adjusted values= 1.48 × creatinine adjusted values.

Blood and urine perchloroethylene and urine trichloroacetic acid, as markers of exposure, and serum AST, ALT, GGT and creatinine, urine total solutes and proteins, angiotensin converting enzyme, N-acetyl-ß-D-glucosaminidase and glutamine synthetase, as markers of effect, were measured in 40 dry-cleaning and 45 ironing-shop female workers. Average perchloroethylene air level in the dry-cleaning shops was 59.7 mg m(-3), i.e. three-fold lower than the current A.C.G.I.H. TLV-TWA (170 mg (m-3)). No statistically significant difference in the mean values of any of the effect markers was observed between the two groups, except for AST which was significantly higher in drycleaners. In addition, a statistically significant correlation was observed in dry-cleaners between environmental perchloroethylene and total urinary solutes (r = 0.308, plt; 0.05) or urine glutamine synthetase (r= 0.469, plt; 0 .01), between glutamine synthetase and blood perchloroethylene in post-shift (r= 0.406, plt; 0.01) or urinary perchloroethylene in post(r= 0.571, plt; 0.001) or pre-shift (r= 0.586, plt; 0.001), and between urinary perchloroethylene in pre-shift and GGT (r= 0.407, plt; 0.05). Interestingly, some statistically significant correlations between exposure and effect indices were found in ironing-shop workers alone, as in all subjects. Finally, transaminases, GGT and total urinary proteins were influenced by age and alcohol consumption which were significantly higher in dry-cleaners, thus providing an explanation for some of the correlations observed. In conclusion, our results show a dose-related increase of glutamine synthetase activity,a marker of damage of the pars recta of the kidney proximal tubule, in the urine of female subjects exposed to perchloroethylene concentrations in the work environment lower than current A.C.G.I.H. TLV-TWA.

Objective: To establish if serum levels of interleukin-10 (IL-10) in subjects exposed to benzene are connected with age, working years, and employment age. Methods: We evaluated serum levels of IL-10 in 51 employees working in oil refinery (group A) and in 16 office workers who resided in the same area (group B). Results: There was no statistically significant difference between serum concentrations of IL-10 in groups A and B. There was a statistically significant dependent relationship in group A between age, working years, and serum concentration of IL-10. There was a statistically significant and positive dependent relationship in group A between serum concentration of IL-10 and employment age. Conclusions: The role played by IL-10 in benzene immune suppression may be relevant and attention should be directed toward assessment of age, working years, and employment age in benzene-exposed populations.

OBJECTIVES: People who handle antineoplastic drugs, many of which classified as human carcinogens by International Agency for Research on Cancer, are exposed to low doses in comparison with patients; however, the long duration of exposure could lead to health effects. The aim of this work was to evaluate DNA damage in white blood cells from 63 nurses who handle antineoplastic drugs in five Italian hospitals and 74 control participants, using different versions of the Comet assay. METHODS: Primary DNA damage was assessed by using the alkaline version of the assay on leucocytes, whereas to detect DNA oxidative damage and cryptic lesions specifically, the Comet/ENDO III assay and the Comet/araC assay were performed on leucocytes and lymphocytes, respectively. RESULTS: In the present study, no significant DNA damage was correlated with the work shift. The exposed population did not differ significantly from the reference group with respect to DNA primary and oxidative damage in leucocytes. Strikingly, in isolated lymphocytes treated with araC, lower data dispersion as well as a significantly lower mean value for the percentage of DNA in the comet tail was observed in exposed participants as compared with the control group (p

a b s t r a c t The environmental and biological monitoring of benzene exposure is crucial to prevent the toxic effects of this solvent in workers. The degree of correlation, however, between the two and of different biomark- ers among them varies, particularly at low levels of exposure, depending on various factors, including variability in metabolizing enzymes and smoking habits. To investigate these further, a cohort of 28 petrochemical workers (6 smokers and 22 non smokers) was monitored throughout ten consecutive days, on two occasions, two years apart, by collecting in total 173 environmental and biological samples. The airborne benzene levels, the urinary t,t-muconic acid (t,t-MA) and S-phenylmercapturic acid (S-PMA) concentrations, and the glutathione S-transferases (GST) M1 and T1 genotypes were measured. S-PMA was the only metabolite statistically correlated with airborne benzene levels (r = 0.447, P < 0.0001), par- ticularly in non smokers (r = 0.667, P < 0.0001), the smoking habit being the only variable influencing metabolite excretion. Finally, a reduced S-PMA excretion was found to be associated with the GSTT1, but not the GSTM1, null genotype. In conclusion, the results show that S-PMA, but not t,t-MA, is able to mon- itor exposure to low benzene concentrations and confirm that the GSTT1 null genotype has a significant influence on metabolite excretion. The influence of the GSTT1 null genotype, however, was low, even when studying each subject with several urine samples.

CYP2E1, an inducible enzyme present in different human tissues, metabolizes several potentially toxic substances including many volatile organic compounds (VOCs). One indirect way to monitor exposure to VOCs may be, therefore, the assessment of CYP2E1 activity in vivo using the chlorzoxazone (CHZ) test.To compare CYP2E1 activity in two groups of workers: one with a known occupational exposure to VOCs (exposed group) and the other employed in administrative tasks at two universities (control group) from the city of León, Guanajuato, México.(1) Passive diffusion monitors were used to evaluate individual levels of exposure to toluene, benzene and ethylbenzene in 48 persons (24 tannery workers and 24 administrative controls) during a 8h work shift; (2) after 12h fasting 500mg CHZ, a selective probe for assessing CYP2E1 activity, was orally administered and, after 2h, a venous blood sample was collected for HPLC plasmatic quantitative determination of CHZ and its mean metabolite 6-hydroxychlorzoxazone.Toluene mean exposure levels were higher in the exposed group (2.86±2ppm vs. 0.05±0.005ppm; p0.001). Also, in this group CYP2E1 activity was lower (p0.05) and it decreased as the accumulated months of labor exposure increased (negative correlation, p0.05). These results are in line with previous findings obtained from shoemakers exposed to various solvents but, interestingly, they are partly in contrast with those of another study in printers.In spite of the relatively low levels of toluene exposure found for tannery workers, an effect on CYP2E1 activity was evident. Although the mechanism of this interaction is still unknown, the decrease in CYP2E1 activity per se might represent a health risk, considering that these workers may be less protected against other CYP2E1 substrates present in the labor setting or derived from an intentional exposure.

Simple aromatic hydrocarbon benzene occurs naturally in crude oil and petroleum. Benzene has been internationally recognised as a haematotoxin and carcinogen. The involvement of oxidative stress is a major susceptibility factors for benzene hematotoxicity in humans. Advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEs) are modified structures which can serve as markers of oxidative stress. The aim of this study is to assess modification of circulating AOPPs and AGEs, as early markers of oxidative stress, in subjects exposed to low dose of benzene. Furthermore the genetic polymorphism of glutathione-S-transferase (GST) may be related to health effects of benzene exposure, in fact both genotype T1 (GSTT1) and M1 (GSTM1) are involved in the detoxification of benzene oxide. The study was performed on 54 workers oil refinery employees. A group of 32 healthy age-matched subjects was included as controls. The AOPPs serum levels in oil refinery employees were higher in a statistically significant way than those measured in controls, but there were no significant changes in serum AGE levels between both groups. However, GST polymorphisms had not influence on serum levels of both biomarkers, so demonstrating that production of circulating AGEs and AOPPs in benzene parity-exposed workers levels is not dependent by GST genotypes. We can conclude that, in this condition, AOPPs are more sensitive marker of low benzene exposure than AGEs.

Background Some industrial hygiene studies have assessed occupational exposure to antineoplastic drugs; other epidemiological investigations have detected various toxicological effects in exposure groups labeled with the job title. In no research has the same population been studied both environmentally and epidemiologically. The protocol of the epidemiological study presented here uses an integrated environmental and biological monitoring approach. The aim is to assess in hospital nurses preparing and/or administering therapy to cancer patients the current level of occupational exposure to antineoplastic drugs, DNA and chromosome damage as cancer predictive effects, and the association between the two. Methods/Design About 80 healthy non-smoking female nurses, who job it is to prepare or handle antineoplastic drugs, and a reference group of about 80 healthy non-smoking female nurses not occupationally exposed to chemicals will be examined simultaneously in a cross-sectional study. All the workers will be recruited from five hospitals in northern and central Italy after their informed consent has been obtained. Evaluation of surface contamination and dermal exposure to antineoplastic drugs will be assessed by determining cyclophosphamide on selected surfaces (wipes) and on the exposed nurses' clothes (pads). The concentration of unmetabolized cyclophosphamide as a biomarker of internal dose will be measured in end-shift urine samples from exposed nurses. Biomarkers of effect and susceptibility will be assessed in exposed and unexposed nurses: urinary concentration of 8-hydroxy-2-deoxyguanosine; DNA damage detected using the single-cell microgel electrophoresis (comet) assay in peripheral white blood cells; micronuclei and chromosome aberrations in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e. glutathione S-transferases) will also be analysed. Using standardized questionnaires, occupational exposure will be determined in exposed nurses only, whereas potential confounders (medicine consumption, lifestyle habits, diet and other non-occupational exposures) will be assessed in both groups of hospital workers. Statistical analysis will be performed to ascertain the association between occupational exposure to antineoplastic drugs and biomarkers of DNA and chromosome damage, after taking into account the effects of individual genetic susceptibility, and the presence of confounding exposures. Discussion The findings of the study will be useful in updating prevention procedures for handling antineoplastic drugs.

This study was aimed to identify useful biomarkers of exposure and effect in workers exposed to low levels of benzene, and to evaluate any correlations existing between these parameters. Benzene exposure was measured in 33 petrochemical industry operators (PIO), 28 service station attendants (SSA), 21 gasoline pump maintenance workers (GPMW) and 51 non-exposed controls by GC-FID analysis. Samples were collected with personal passive samplers (Radiello ® ). End-shift urine samples were collected for t,t-muconic acid (t,t-MA) determination by HPLC and for S-phenylmercapturic acid (S-PMA) measurement by HPLC-MS/MS. The alkaline version of the comet assay and, in a subgroup of 19 SSA and 16 control subjects, chromosomal aberrations (CA) and glutathione (GSH) levels were measured in peripheral blood lymphocytes. Personal benzene exposure was significantly higher in PIO, SSA and GPMW as compared to controls. The urinary excretion of the two metabolites showed a significant increase in SSA (p = 0.0258 and p = 0.0001, for t,t-MA and S-PMA, respectively) and in PIO (p = 0.0013 and p = 0.0001, for t,t-MA and S-PMA, respectively) as compared with the control group, while no such increase was observed for GPMW, for whom occupational exposure was not continuous and occurred on specific working days only. Significant increases of DNA damage were found by the comet assay for tail moment (TM) and tail length (TL) in SSA (p < 0.0001 and p = 0.008, for TM and TL, respectively) and PIO (p < 0.0001 and p < 0.0001, for TM and TL, respectively) when compared with controls. The PIO group also displayed a significant increase in the number of cells with comet (p < 0.0001). Smoking habits did not appear to interfere with these results in any of the groups. No difference was found in percentage of CA between exposed workers and controls. Significant correlations were found, in all groups, between benzene exposure and the more representative comet parameter TM (r = 0.509, p = 0.007; r = 0.525, p = 0.017 and r = 0.420, p = 0.046 in SSA, GPMW, and PIO, respectively). A trend of negative correlation was observed between DNA damage and either GSH or urine S-PMA for exposed workers. In summary, in present study urinary S-PMA and DNA damage by the comet assay were both sensitive to exposure to low levels of benzene, and GSH seems to play an important defence role against benzene-dependent DNA damage.

Objectives This study analyzes the validity of new, more sensitive and speciWc urinary biomarkers of internal dose, namely, urinary benzene for benzene and urinary toluene and S-benzylmercapturic acid (SBMA) for toluene, to assess their eYcacy when compared to traditional biomarkers for biological monitoring of occupational exposure to low concentrations of these two toxic substances. Methods Assessment was made of 41 workers occupationally exposed to benzene and toluene, 18 fuel tanker drivers and 23 Wlling-station attendants, as well as 31 subjects with no occupational exposure to these toxic substances (controls). Exposure to airborne benzene and toluene was measured using passive Radiello® personal samplers worn throughout the work shift. In urine samples collected from all subjects at the end of the workday, both the traditional and the new internal dose biomarkers of benzene and toluene were assessed, as well as creatinine so as to apply suitable adjustments. Results Occupational exposure to benzene and toluene resulted signiWcantly higher in the fuel tanker drivers than the Wlling-station attendants, and higher in the latter than in controls. SigniWcantly higher concentrations of t,t-muconic acid (t,t-MA), S-phenylmercapturic acid (SPMA), urinary benzene, SBMA and urinary toluene were found in the drivers than the Wlling-station attendants or the controls. Instead, urinary phenol and hippuric acid were not diVerent in the three groups. In the entire sample, airborne benzene and toluene values were signiWcantly correlated, as were the respective urinary biomarkers, showing coeYcients ranging from 0.36 to 0.98. Subdividing the subjects by smoking habit, higher coeYcients were evident in nonsmokers than in smokers; at multiple regression analysis t,t-MA, SPMA and urinary benzene and toluene were dependent on the number of cigarettes smoked daily and on airborne benzene and toluene, respectively. Instead, SBMA was dependent only on airborne toluene. Conclusions Our research conWrmed the validity of t,t-MA and SPMA for use in the biological monitoring of exposure to low concentrations of benzene. Urinary benzene showed comparable validity to SPMA; both parameters are aVected by smoking cigarettes in the hours before urine collection, so it is best to ask subjects to refrain from smoking for 2 h before urine collection. Urinary toluene was found to be a more speciWc biomarker than SBMA.

The present study compared three methods for the determination of S-phenylmercapturic acid (S-PMA), a metabolite of benzene, in human urine: a HPLC/MS/MS technique with two different sample treatments (strong and partial hydrolysis) and a commercial assay based on anti-S-PMA monoclonal antibodies with chemiluminescence detection. Biological monitoring was done on 126 volunteers and the results were compared for the three methods and also with benzene exposure levels (range3.0-592.5 μg/m(3)). The correlation between environmental monitoring data and S-PMA levels in non-smokers (n=73) was highly significant (p0.0001, Student's t-test) for both HPLC/MS/MS methods (r=0.65 both for strong acidic hydrolysis of the urine and hydrolysis at pH 2) but not for the immunoassay, which overestimated the S-PMA levels by about 8 μg/g creatinine (creat.). Therefore the immunoassay is only useful as a semiquantitative screening test, but quantitative results need to be confirmed by a more accurate method like HPLC/MS/MS. The HPLC/MS/MS procedure with strong acid hydrolysis led to a recovery of S-PMA about double that using pH 2 hydrolysis, giving more accurate results. The difference between the results with the two methods makes it difficult to compare the strong acidic hydrolysis data with the ACGIH BEI value of 25 μg/g creat. since the BEI(®) documentation is based on data collected in pH conditions that were not always controlled, which may underestimate the true S-PMA concentration. Besides, as levels of benzene exposure were high, smoking was not considered a confounding factor. The BEI for S-PMA in end of shift urine samples could be reconsidered when sufficient data are available from studies where the analyses are carried out in comparable conditions of hydrolysis and monitoring only non-smoking subjects.

This article reports the results of a study, conducted in the framework of the scientific activities of the Italian Society for Reference Values, aimed at defining reference values of urinary trans,trans-muconic acid (t,t-MA) in the general population not occupationally exposed to benzene. t,t-MA concentrations detected in 376 subjects of the resident population in three areas of Italy, two in central (Florence and southern Tuscany) and one in northern Italy (Padua), by three laboratories, compared by repeated interlaboratory controls, showed an interval of 14.4-225.0 microg/L (5th-95th percentile) and a geometric mean of 52.5 microg/L. The concentrations measured were influenced by tobacco smoking in a statistically significant way: Geometric mean concentrations were 44.8 microg/L and 76.1 microg/Ll in nonsmokers (264 subjects) and smokers (112 subjects), respectively. In the nonsmoking population, a significant influence of gender was found when concentrations were corrected for urinary creatinine, geometric mean concentrations being 36.7 microg/g creatinine in males (128 subjects) and 44.7 microg/g creatinine in females (136 subjects). The place of residence of subjects did not seem to influence urinary excretion of the metabolite, although personal inhalation exposure to benzene over a 24-h period showed slightly higher concentrations in Padua and Florence (geometric means of 6.5 microg/m(3) and 6.6 microg/m(3), respectively) than in southern Tuscany (geometric mean of 3.9 microg/m(3)). Concentration of t,t-MA in urine samples collected at the end of personal air sampling showed little relationship to personal inhalation exposure to benzene, confirming the importance of other factors in determining excretion of t,t-MA when concentrations in personal air samples are very low.

To assess occupational exposure to electromagnetic fields, 11 microwave (MW), 4 short-wave diathermy and 15 magneto therapy devices were analysed in eight physiotherapy departments. Measurements taken at consoles and environmental mapping showed values above European Directive 2004/40/EC and ACGIH exposure limits at approximately 50 cm from MW applicators (2.45 GHz) and above the Directive magnetic field limit near the diathermy unit (27.12 MHz). Levels in front of MW therapy applicators decreased rapidly with distance and reduction in power; this may not always occur in work environments where nearby metal structures (chairs, couches, etc.) may reflect or perturb electromagnetic fields. Large differences in stray field intensities were found for various MW applicators. Measurements of power density strength around MW electrodes confirmed radiation fields between 30 degrees and 150 degrees , with a peak at 90 degrees , in front of the cylindrical applicator and maximum values between 30 degrees and 150 degrees over the whole range of 180 degrees for the rectangular parabolic applicator. Our results reveal that although most areas show substantially low levels of occupational exposure to electromagnetic fields in physiotherapy units, certain cases of over-occupational exposure limits do exist.

Objectives To determine gene-specific methylation levels (promoter region) on genes from critical cellular pathways in persons occupationally exposed to a single volatile organic compound (VOC) or to a mixture of them Method Workers from two tanneries, two shoe factories, and two gas stations were included (exposed groups to VOC’s). We also included administrative workers (reference group), all of them from the city of Leon Guanajuato, Mexico. In tannery workers we measured individual exposure levels to three different VOC’s; for the rest of the groups we measured up to 7 VOC’s. After exposure characterisation, we took blood samples and extracted DNA in order to determine, by PCR-pyrosequencing, methylation levels in genes involved in inflammation, DNA repair, oxidative stress and xenobiotic metabolism pathways. Results Only toluene environmental levels were higher in tannery workers. Workers from the leather shoe factory showed the highest exposure levels for up to five different VOC’s. There was no statistical significant difference in gene-specific methylation for tannery workers when compared to the control group. For the leather shoe factory workers, we found hypermethylation in the TNFa, SOD1 and TOP2A promoter regions compared to the control group or to other exposed groups. Gas station attendants showed hypermethylation for the IL6 gene compared to controls Conclusions Occupational exposure to a mixture of VOC’s has important effects on the methylation status of genes involved in inflammation, DNA repair and oxidative stress. These epigenetic changes, detectable at a pre-clinical stage, represent a valuable tool for performing an early risk assessment in these populations