DNA damage in workers exposed to pigment grade titanium dioxide (TiO2) and association with biomarkers of oxidative stress and inflammation.

The present study was aimed at investigating DNA damage, micronuclei frequency and meta-nuclear alterations in buccal cells of workers involved in pigment-grade TiO2 production (15 exposed and 20 not-exposed). We also assessed associations of genotoxicity biomarkers with oxidative stress/inflammatory biomarkers in urine and exhaled breath condensate (EBC), as well as possible associations between biomarkers and reported respiratory symptoms. In spite of compliance with TiO2 Occupational Exposure Limits, results showed increased direct/oxidative DNA damage and micronuclei frequency in exposed workers. Genotoxicity parameters were associated with oxidative stress/inflammation biomarkers in urine and EBC, thus confirming that TiO2 exposure can affect the oxidative balance. Workers with higher genotoxic/oxidative stress biomarkers levels reported early respiratory symptoms suggesting that molecular alterations can be predictive of early health dysfunctions. These findings suggest the need to assess early health impairment in health surveillance programs and to address properly safety issues in workplaces where TiO2 is handled.

In vitro cytotoxicity assessment of pristine and carboxyl-functionalized MWCNTs.

The wide use of carbon nanotubes (CNTs) in consumer products, i.e. composites, coatings, food packaging, etc, raise concerns about the adverse effects that CNTs can induce in humans and environment. Yet, there is no global consensus regarding risks that CNTs may pose, while controversial evidence exists also on the toxic effects associated with chemical surface modification, a prerequisite for their incorporation in different matrices. Moreover, there is limited information available about the underlying mechanisms, especially when cells' interactions with the nanomaterial is assessed by imaging techniques. The present study aims at evaluating the in vitro cytotoxicity of pristine and oxygen functionalized multi-walled CNTs (MWCNTs) by assessing cell viability and apoptosis in combination with scanning electron microscopy (SEM) observations of stabilised cells. Direct observation of adenocarcinoma human epithelial cells (A549) was performed after incubation with 12.5, 50 and 100 µg/ml MWCNTs, for 0.5, 1 and 3 h, simulating a real exposure scenario during an accident, taking into account industrial safety issues during the production and use of the nanomaterial. Functionalized MWCNTs induced higher time- and dose-dependent toxic effects as compared to pristine. The SEM observations revealed the damaging effect on the cell membrane, offering insights about the toxic mechanism that takes place.

Reference ranges of oxidative stress biomarkers selected for non-invasive biological surveillance of nanotechnology workers: Study protocol and meta-analysis results for 8-OHdG in exhaled breath condensate.

In the field of engineered nanomaterials (ENMs) and other airborne particulate exposure biomonitoring, circulating oxidative stress biomarkers appear promising. These biomarkers could be monitored in different biological matrices. Exhaled breath condensate (EBC) enables their measurements in the respiratory tract, without affecting airway function or creating inflammation. The 8-hydroxy-2-deoxyguanosine (8-OHdG) was found increased in the EBC of ENM-exposed workers. Our objectives were to assess the reference range of 8-OHdG in the EBC and to identify determinants of its inter- and intra-individual variability. The meta-analysis was stratified by analytical method (chemical versus immunochemical analysis) and resulted in a between-study variability over 99 % of the total variability. The between-study variability completely dominated the within-studies variability. By using a mixed model with study ID as a random effect rather than a meta-regression, only smoking was evidenced as a potential determinant of 8-OHdG inter-individual variability, and only when immunochemical analysis was used. To our knowledge, this is the first meta-analysis aimed at estimating reference values for 8-OHdG in the EBC. The estimated values should be considered preliminary, as they are based on a limited number of studies, mostly of moderate to low quality of evidence. Further research is necessary to standardize EBC sampling, storage and analytical methods. Such a standardization would enable a more accurate estimation of the reference ranges of the 8-OHdG and potentially other biomarkers measurable in the EBC, which are essential for a meaningful interpretation of the biomonitoring results.

Prevalence of headache in patients with Parkinson's disease and its association with the side of motor symptom onset.

We compared the lifetime prevalence and the prevalence of headache during the previous year in patients with Parkinson's disease (PD) and control subjects. We also investigated the association between the side of PD symptom onset and the side of the headache. We interviewed 98 consecutive patients with an established diagnosis of PD between December 2010 and January 2012. The control group consisted of the 98 oldest sex-matched individuals from the nationwide Brazilian headache database. PD patients showed a significantly lower prevalence (40.8%) of headache in the previous year than controls (69.4%) (adjusted OR 0.5, CI 95% 0.2-0.9, p = 0.03). PD patients also showed a lower prevalence of headache throughout life (74.5%) than controls (93.9%) (adjusted OR 0.2, CI 95% 0.1-0.6, p = 0.01). Considering only patients who presented headache during the previous year, PD patients showed a higher association with occurrence of migraine than tension-type headache compared with controls (adjusted OR 3.3, CI 95% 1.2-8.9, p = 0.02). The headache side was ipsilateral to the side of PD onset in 21 patients (84%), with a concordance of 85.7% on the left side and 81.8% on the right side (p < 0.01). The prevalence of primary headache was significantly lower in patients with PD than controls. The predominant side of headache was ipsilateral to the side of initial motor signs of PD.

Airway barrier dysfunction induced by exposure to carbon nanotubes in vitro: which role for fiber length?

Although carbon nanotubes (CNTs) are increasingly used, their biological effects are only incompletely characterized. However, experimental evidence suggests that the intratracheal instillation of CNTs causes the formation of interstitial granulomas and progressive pulmonary fibrosis in rodents. Using human epithelial Calu-3 cells as a model of airway epithelium in vitro, we have recently reported that the exposure to commercial multi-walled CNTs (MWCNTs) causes a progressive decrease of the transepithelial electrical resistance (TEER), pointing to a CNT-dependent impairment of the epithelial barrier function. To characterize better this behavior, we compared the effects of two types of MWCNTs and single-walled CNTs (SWCNTs) of different lengths on the TEER of Calu-3 monolayers. All the materials were used at a dose of 100 microg/mL corresponding to an exposure of 73 microg/cm(2) of cell monolayer. Only the longer MWCNTs and SWCNTs cause a significant decrease in TEER. To elucidate the mechanism underlying the changes in barrier function, the expression of the junction proteins occludin and ZO-1 has been also assessed. No significant decrease in the mRNA for either protein is detectable after the exposure to any type of CNTs. It is concluded that the impairment of barrier function in Calu-3 monolayers is a peculiar effect of CNTs endowed with clear cut fiber properties and is not referable to marked changes in the expression of junction proteins.

Cardiac autonomic regulation after lung exposure to carbon nanotubes.

The ultrafine (UF) component of airborne pollution may impair cardiovascular autonomic control, a high-risk condition for cardiovascular adverse events. Since engineered nanoparticles, such as single-walled carbon nanotubes (SWCNTs) share physicochemical properties with UF, they might have similar adverse effects. Aim of the study was to evaluate arterial baroreflex function (BRF) at baseline, 24 h after the first instillation, immediately before the second one, and 2 weeks later, in adult Wystar-Kyoto conscious rats undergoing two intratracheal instillations of SWCNT (eight rats) or phosphate buffer saline (PBS) (five rats) at 2-week interval. During each session, 30-min continuous recording of arterial pressure and pulse interval was performed by a telemetered catheter implanted in the abdominal aorta of the rats. BRF was studied by the sequence technique. SWCNTs dispersed in PBS (1 mg/ml) were administered immediately after sonication (1 microg/g body weight). A significant decrease in the number of baroreflex sequences (from 498 +/- 27.1 at baseline to 287 +/- 40.2 at the recording performed after 4 weeks; P < 0.05) was observed in SWCNT-instilled rats, whereas no significant change was detected in controls. These data suggest that SWCNTs may alter the BRF, thus affecting the autonomic cardiovascular control regulation.

Comparative genotoxicity of cobalt nanoparticles and ions on human peripheral leukocytes in vitro.

Owing to the increasing development of nanotechnology, there is a need to assess how engineered nanomaterials can interact with living cells. The main purpose of the present study was to assess whether metal cobalt nanoparticles (CoNP 100-500 nm) are genotoxic compared to cobalt ions (Co(2+)). Uptake experiments were carried out by incubating peripheral blood leukocytes (PBLs) with (57)Co(2+) (added to stable Co(2+) 10(-2) M to obtain concentrations in the range of 10(-5) to 10(-4) M) or with (60)CoNP for 24 and 48 h. Whereas intracellular Co(2+) showed slight or no variations over the baseline levels, CoNP were taken up efficiently leading to intracellular CoNP concentrations of 485 +/- 106.1 and 970 +/- 99 fg per cell after 24 and 48 h, respectively. The genotoxicity end points considered in this study were the frequency of binucleated micronucleated (BNMN) cells and the percentage of tail DNA (% Tail DNA) fragmentation by means of the comet assay. Genotoxic effects were evaluated by incubating PBLs of three healthy donors with subtoxic concentrations (10(-5) to 8 x 10(-5)M) of Co(2+) in the form of cobalt chloride, CoNP and 'washed' CoNP, the latter to exclude any interference by Co(2+). On a group basis, Co(2+) induced a clear trend in the increase of the BNMN frequency, whereas CoNP showed only minor changes. Moreover, we observed a high variability among donors in the induction of micronuclei. The comet assay showed a statistically significant dose-related increase in % Tail DNA for CoNP (P < 0,001), whereas Co(2+) did not induce significant changes over control values. These findings suggest that nanosized Co can be internalized by human leukocytes and can interact with DNA leading to the observed genotoxic effects, which are, however, modulated both by donor's characteristics and/or by Co(2+) release.

[Interaction between carbon nanotubes and cardiovascular autonomic nervous system regulation: proposal of an animal model and preliminary findings]. / Interazione tra nanotubi di carbonio e controllo cardiovascolare del sistema nervoso autonomo: presentazione di un modello sperimentale animale e risultati preliminari.

BACKGROUND: Altered autonomic cardiovascular regulation (ACR) may mediate the association between single-wall carbon nanotubes (SWCNT) exposure and adverse cardiovascular events. MATERIAL AND METHODS: 400 mg of SWCNT in 400 ml of phosphate buffer saline (PBS) or 400 ml of PBS were randomly given to 7 Wystar-Kyoto rats (400 g body wt) previously implanted in abdominal aorta with a telemetry transmitter for recordings of arterial pressure signals. Recordings were performed at baseline, 24 hours and two weeks after intratracheal instillation. The beat-by-beat time series of systolic arterial pressure (SAP) and PR interval were analyzed to identify sequences of three or more consecutive beats in which SAP and PR changed in the same (baroreflex sequences) or in the opposite direction (nonbaroreflex sequences). The mean individual slope of the sequences was calculated and taken as a measure of the baroreflex (BRS) and nonbaroreflex sensitivity for that period. RESULTS: The 24 hour BRS response showed a 100% increase (from 4.6 to 9.2 msec/mmHg) in controls, whereas it was blunted in cases (from 5.1 to 6.1 msec/mmHg) (p < 0.05). CONCLUSIONS: Our study demonstrates that this rat model is suitable to study the ACR during exposure to SWCNT and suggests a blunted BRS response after SWCNT instillation.

[Carbon nanotubes (CNT) and nanoparticles (NP): interaction with lung epithelium and other biological systems]. / Nanotubi di carbonio (NTC) e nanoparticelle (NP): interazione con i sistemi biologici con particolare riferimento all'apparato respiratorio.

Carbon nanotubes (CNT) and nanoparticles (NP) represent new classes of technological materials with innovative properties. Although inhalation is less likely for engineered nanomaterials (NM) compared with ambient or mineral dust particles, this can happen during bulk manufacture and handling of freely dispersable NP at workplace. Both environmental and engineered NP are able to cause oxidative stress, reactive oxygen species (ROS) generation, NF-kappaB activation, but some of the possible NM interactions with biological systems may result in additional forms of injury. NP can impair fagocytosis, can enhance macrophage sensitivity to chemotactic factors (MCP-1), thus worsening antigen-mediated inflammation. Metal NP (e.g. TiO2, Al2O3 and Fe3O4) can impair mitochondrial function, leading to a dramatic reduction of the intracellular glutathione pool, thus compromising cell viability and morphology. CNTs are a man-made form of crystalline carbon currently attracting intense research efforts because of their unique properties, that make them suitable for many uses in biomedicine and pharmacology. CNTs stimulate TNF-alpha production in the lung, inducing inflammatory reactions, but they can also cross cell membranes reacting with DNA and aminoacidic residues, leading to cell apoptosis. Larger CNTs could have features of conventional fibers and show the ability to stimulate mesenchymal cell growth and to cause lung granulomas formation and fibrotic reactions. These results suggest that NM are potentially hazardous to humans and that strict industrial hygiene measures should be taken to limit exposure during their manipulation.

Relationship between genotoxicity biomarkers in somatic and germ cells: findings from a biomonitoring study.

A biomonitoring study to evaluate chromosome and DNA damage respectively in somatic and germ cells of a group of male workers exposed to styrene by using biomarkers of genotoxicity was carried out. Styrene-exposed workers from three different areas of Tuscany and healthy subjects, of comparable mean age, sex and lifestyle characteristics, as a control group not exposed to chemicals, have been enrolled. In addition to previous reports [L. Migliore, A. Naccarati, A. Zanello, R. Scarpato, L. Bramanti and M. Mariani (2002) Hum. Reprod., 17, 2912-2918; L. Migliore, A. Naccarati, F. Coppedè et al. (2006) Pharmacogenet. Genomics, 16, 87-99] we present now data on a cross-sectional investigation involving a homogeneous group of subjects for which data on both somatic and germ cells have been obtained from individuals (42 exposed and 25 controls). Somatic cell genotoxicity was assessed by analysing the frequency of micronucleated binucleated cells (MNBN) in blood lymphocytes. The micronucleus assay was coupled with centromeric fluorescence in situ hybridization (FISH) analysis. Primary DNA damage in germ cells was evaluated by alkaline single-cell gel electrophoresis (Comet assay) and the percentage of the tail DNA (%TD) was used as parameter of Comet evaluation. Moreover, to investigate the frequencies of aneuploidy and diploidy in sperm, we performed multicolour FISH, using DNA probes specific for the centromeric regions of sex chromosomes and chromosome 2, in decondensed sperm nuclei of samples with normal semen parameters in a subgroup of individuals. Mandelic and phenylglyoxylic acids (MAPGA) in end of shift samples were determined as biomarkers of internal dose. MAPGA excretion was consistent with an exposure to styrene above the threshold limit value-time weighted average concentration of 20 p.p.m. Styrene workers showed significantly higher frequency of MNBN as compared to controls (13.8 +/- 5.2 versus 6.2 +/- 5.1; P < 0.001), due to higher proportions of both micronuclei (MN) arising from chromosomal breakage (C-MN) and harbouring whole chromosomes (C+MN). DNA damage in sperm cells was also higher among styrene-exposed, the %TD being 11.02 +/- 2.99 versus 7.42 +/- 2.30 in controls (P < 0.001). The incidence of aneuploidy and diploidy for the tested chromosomes in sperm did not show a statistically significant difference between workers and controls. However, a positive correlation was found between genotoxic damage detected in somatic and in germ cells, even after removing the effect of age (r = 0.475; P < 0.001). Although cytogenetic biomarkers detected both in somatic and germ cells were interrelated, no relationships were apparent with exposure parameters. Styrene exposure may increase the likelihood of both chromosome and DNA damage in somatic and germ cells, thus supporting the hypothesis of an interference on reproductive capacity among exposed workers. This is the first time that a field study shows a correlation between two biomarkers of genotoxicity evaluated at the same time in somatic and germ cells.

Nanomaterials and lung toxicity: interactions with airways cells and relevance for occupational health risk assessment.

Engineered nanoparticles (NP) comprise various classes of technological materials with innovative properties. Although inhalation is less likely for engineered nanomaterials (NM) compared with ambient or mineral dust particles, this can happen during bulk manufacture and handling of freely dispersible NP. In this mini-review we summarize recent data on NP and CNT (carbon nanotubes) hazards, with particular emphasis on toxic effect on lung and in cell culture of lung origin. Owing to the highest deposition efficiency in the alveolar area, primary interactions of NM occur with epithelial and alveolar macrophages (AM). Scarce data are available to date on the cell mechanisms underlying NM permeability across the airway epithelium, but the absorption of NP through airways does not seem to require epithelial mediation, suggesting rather the involvement of alternative mechanisms such as AM-dependent dissemination. The relationship between toxicity and particle characteristics may be complex, involving size, surface area and surface chemistry. Some NM act according to an oxidative stress paradigm, but possible NM interactions with biological systems may result in additional forms of injury. In particular, CNT, a man-made forms of crystalline carbon, are currently attracting intense research efforts because of their unique properties, which make them suitable for many uses in biomedicine and pharmacology. Although CNT stimulate cytokine production and induce inflammatory reactions, they could behave also as conventional fibers, showing the ability to cause lung granulomas and fibrotic reactions in experimental animals. Production and marketing of NM is advancing much more rapidly than research on NM safety. This phenomenon will have a strong impact on the approach of occupational physicians to health risks from NP. In literature increasing evidence suggests that NM are potentially hazardous to humans and that strict industrial hygiene measures should be taken to limit exposure during their manipulation. Moreover, given the uncertainty about the NM features endowed with pathogenetic relevance, the toxicological properties of a specific NP should be evaluated on an individual basis by new screening strategies based on current acquisitions.

Shift work and autoimmune thyroid disorders.

Stress induces autoimmune disorders by affecting the immune response modulation. Recent studies have shown that shift work stress may enhance the onset of the autoimmune Graves hyperthyroidism. On the other hand, the possible association between occupational stress and autoimmune hypothyroidism has not yet been investigated. In order to detect the possible association between shift work and subclinical autoimmune hypothyroidism we investigated the prevalence of isolated anti-peroxidase thyroid (TPO) autoantibodies in 220 shift workers and in 422 day-time workers. Subclinical autoimmune hypothyroidism was diagnosed by the concomitant presence of high anti-TPO values and TSH levels higher than 2.51 mU/l. Anti TPO antibodies were measured by chemiluminescent technology (Advia Centaur) (a value above 60 IU/l was considered altered). Subclinical autoimmune hypothyroidism was diagnosed in 7.7 percent shift workers and in 3.8 percent day-time workers with a statistically significant difference: Odds Ratio (OR) 2.12, 95 percent Confidence Interval (CI) 1.05 to 4.29; p=0.03. The difference persisted after multivariate analysis taking into account age, sex, smoking habits, alcohol intake, familial history of autoimmune thyroid disease and exposure to radiation as possible confounders: OR. 2.24, 95 percent CI.1.01 to 4.94, p 0.05. Altered anti- TPO autoantibodies were found in 13.6 percent shift workers and in 8.6 percent day-time workers OR. 1.64, 95 percent CI.1.03 to 2.74, p=0.05. The significant difference was still detectable after multivariate analysis: OR. 1.95, 95 percent CI. 1.09 to 3.48, p=0.02. Our data show a significant association between shift work and autoimmune hypothyroidism. This finding may have implications in the health surveillance programs.

[Environmental and biological monitoring of exposure to polycyclic aromatic hydrocarbons in workers of an electric steel foundry]. / Monitoraggio ambientale e biologico dell'esposizione ad idrocarburi policiclici aromatici in lavoratori di una acciaieria elettrica.

AIMS: To assess and classify exposure to Polycyclic Aromatic Hydrocarbons (PAHs) in some specific working areas of a steel foundry operating with a continuous casting process and evaluate biomonitoring data in different job tasks. METHODS: Exposure to dusts and six PAHs classified as carcinogenic by EU directives was studied in a cohort of 35 male foundry workers (aged 41.1 +/- 6.9 years), who were examined both prior to and at the end of the work-shift (06:00 a.m.-02:00 p.m.) in two different periods. The urinary excretion of 1-hydroxypyrene (1-OH-P) was measured as a biomarker of exposure to pyrene. RESULTS: PAHs concentrations ranged from 461.8 to 935.6 ng/m3 near the continuous casting area, whereas lower values were measured near the ladle furnace. End of shift 1-OH-P values were higher in 11 non-smoking workers involved in continuous casting process as compared to those employed in mantenance and furnace areas (median of the second determination: 5.70 microg/g creatinine--range: 1.24-21.24 vs 1.17 microg/g creatinine--range: 0.23-4.49; p< 0.001). 1-OH-P excretion was significantly correlated with both the sum of six carcinogenic PAHs and pyrene airborne concentrations. In two biomonitoring sessions, 9.1% and 34.3% of the workers respectively showed end-of-shift 1-OH-P values exceeding the occupational exposure limit (OEL) (4.4 microg/g creatinine or 2.3 micromol/mol(-1) creatinine) recommended for coke-oven workers. CONCLUSIONS: 1-OH-P is a useful biomarker in assessing PAH exposure and is associated with job category at a Steelplant. Due to exposure variability, to assess risk associated with PAHs exposure, biological monitoring should be carried out periodically.

[Indicators of pulmonary epithelial damage among workers at a foundry exposed to airborne pollutants]. / Indicatori di danno epiteliale polmonare in lavoratori di una acciaieria elettrica esposti ad inquinanti aerodispersi.

Foundry ambient air contains very high concentrations of noxious substances, such as particulate matter and gaseous pollutants, which can target the respiratory epithelium. Serum concentrations of the 16-kDa Clara cell protein (CC16-S) may reflect both the integrity of the epithelial barrier and smoke-induced Clara cell toxicity. To evaluate whether CC16-S is a sensitive biomarker of early respiratory disturbances, it was determined in a group of 35 foundry male workers (aged 41.1 +/- 6.9 years) examined both prior to and at the end of their work-shift (06:00 a.m.-02:00 p.m.). Exposure to inhalable/respirable dusts and PAH was characterized; urinary excretion of 1-hydroxypyrene (1-OH-P) and naphtol was measured to assess exposure to pyrene and naphthalene, respectively. CC16 serum levels decreased at the end of the shift (10.7 +/- 3.82 micrograms/L vs. 8.39 +/- 3.05 micrograms/L; p < 0.01); such decrements were significantly larger in more exposed workers. Although smokers had lower baseline values as compared to non smokers, both subgroups showed an average decrease of 30% in CC16-S concentrations at the end of shift. CC16-S was also negatively correlated with 1-OH-P, but not with naphtol concentrations. Decreased CC16-S levels can result from citotoxicity and would represent an useful biomarker of pneumotoxicity in foundry workers exposed to complex mixtures.

Polymorphism of xenobiotic-metabolizing enzymes and excretion of styrene-specific mercapturic acids.

The role of polymorphic xenobiotic-metabolizing enzymes in the interindividual variability of phenylhydroxyethyl mercapturic acids (PHEMAs) was investigated in 56 styrene-exposed workers. Ambient monitoring was carried out using passive personal samplers (geometric mean, 157 mg/m3 8-h time-weighted average; geometric standard deviation, 2.90). Biomonitoring was based on mandelic acid and phenylglyoxylic acid in urine spot samples collected at the end of the work shift ("end-of-shift") and prior to the subsequent shift ("next morning"). Four PHEMA diastereoisomers, namely (R,R)-M1, (S,R)-M1, (S,R)-M2, and (R,R)-M2, were determined by HPLC/tandem mass spectrometry. The genotypes of glutathione S-transferases M1-1 (GSTM1), T1-1 (GSTT1) and P1-1 (GSTP1), and microsomal epoxide hydrolase (EPHX) were characterized by PCR-based methods. Workers bearing the GSTM1pos genotype showed PHEMA concentrations five and six times higher (in end-of-shift and next-morning samples, respectively) as compared to GSTM1null people. In GSTM1pos subjects, (R,R)-M1 was the main mercapturate affected by the GSTM1 status, accounting for 54 and 68% of total PHEMAs in end-of-shift and next-morning samples, respectively. Compared to GSTM1null, GSTM1pos subjects excreted more -M1 than -M2 and more (R,R)-M1 and (S,R)-M2 than (S,R)-M1 and (R,R)-M2 diastereoisomers. Thus, GSTM1-1 is the main isoenzyme catalyzing GSH-conjugation of styrene-7,8-oxide in humans and it seems to act in a regio- and stereoselective way. PHEMAs cannot be recommended as biomarkers of exposure to styrene, unless the GSTM1 genotype is considered in data interpretation. Their role as biomarkers of susceptibility deserves further studies.

Inter- and intra-individual sources of variation in levels of urinary styrene metabolites.

OBJECTIVE: Given the paucity of studies that have examined variability in biological measures of exposure to workplace contaminants, we quantified the intra- and inter-individual sources of variation in urinary levels of mandelic acid (MA) and phenylglyoxylic acid (PGA) among workers exposed to styrene. A secondary objective was to examine effects of job task and the timing of sampling during the workweek on the variation in workers' urinary styrene metabolite levels. METHODS: As part of routine biological monitoring, a total of 1,714 measurements of MA and PGA collected from 331 workers between 1985 and 1999 from eight reinforced-plastics plants were abstracted from laboratory reports. To evaluate sources of variation in levels of urinary styrene metabolites, we applied random-effects models. The influence of job task and day of sampling on metabolite levels was examined using mixed-effects models. RESULTS: PGA levels were characterized by less variation than levels of MA, as were metabolite levels expressed in terms of urinary creatinine concentration. The relative magnitude of the inter-individual to the intra-individual source of variation was generally higher for post-shift urine samples than for pre-shift urine samples. As expected, urinary metabolite levels were highest for laminators and for samples collected at the latter end of the workweek. Owing to the effects of variation from day-to-day, estimates of workers' exposures that rely on single measurements would generally perform poorly in a regression analysis designed to examine effects resulting from chronic exposure. However, the bias in an observed slope coefficient would be diminished if a second or third urine sample were collected. CONCLUSIONS: Quantification of the intra- and inter-individual sources of variation provides useful information that can be used to design optimal sampling strategies, which would allow for the collection of sufficient data to estimate workers' exposures reliably when evaluating health risks associated with occupational contaminants.

Polymorphism of quinone-metabolizing enzymes and susceptibility to ozone-induced acute effects.

The role of the genetic polymorphism of NAD(P)H:quinone oxidoreductase (NQO1) and glutathione-S-transferase micro-1 (GSTM1) in the responsiveness to O(3)-induced acute effects was investigated in 24 healthy nonsmokers performing 2-h bike rides at ambient O(3) varying from 32 to 103 ppb. Before and after rides, each subject performed spirometric tests and provided a blood sample for the measurement of the Clara cell protein CC16. NQO1 and GSTM1 polymorphisms were characterized by polymerase chain reaction- based methods. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct was also measured in DNA of peripheral leukocytes. Rides at O(3) > 80 ppb resulted in significant decrements of pulmonary function tests and increased levels of serum CC16, consistent with mild impairment in respiratory function and increased lung epithelial permeability, respectively. Whereas NQO1wt and GSTM1null subjects showed both functional changes and increased serum CC16 after acute O(3) exposure, people with other haplotypes showed a rise in serum CC16 but no changes in lung function tests. In NQO1wt and GSTM1null subjects, partial correlation analysis showed that functional decrements and increased serum CC16 are closely associated with each other and with O(3) levels, whereas no such relationships were found among subjects bearing other haplotypes. An increased reaction rate between O(3) and hydroquinones would be consistent with the greater increase in 8-OHdG after O(3) exposure in this "susceptible" group.

One shot: a novel method to dilate the nephrostomy access for percutaneous lithotripsy.

BACKGROUND AND PURPOSE: The creation of the nephrostomy access is a fundamental step of percutaneous nephrolithotripsy (PCNL). Dilation of the track is usually achieved with multiple incremental flexible exchange dilators of the Amplatz type, metal telescoping dilators of the Alken type, or a balloon. Currently, balloon dilation is regarded as the most modern and safest system, though it has the disadvantage of relatively high cost. The aim of this study was to demonstrate that a procedure that we named "one shot," which consists of a single dilation of the track with a 25F or 30F Amplatz dilator, compares favorably in terms of efficacy, costs, and length with the other techniques of track dilation, without a significant increase in morbidity. PATIENTS AND METHODS: Seventy-eight consecutive patients who underwent PCNL for stone disease from June 1998 to July 1999 were considered and divided into three groups according to the type of tract dilation used: A (Alken telescoping dilators), B (balloon), or C (one shot). Radiologic exposure, blood loss, and costs were evaluated. RESULTS: The one-shot procedure compared favorably with both of the other dilation techniques without an increase in morbidity and with significant reductions in X-ray exposure and costs. Indeed, significant differences in estimated blood loss were observed between groups B and C and the minor bleeding for group C. CONCLUSION: Our experience indicates that one-shot dilation is feasible in the majority of patients. It is as safe and effective as the technique regarded today as the gold standard but less time consuming and less expensive. These encouraging results should be confirmed by further studies.

Assessment of neurobehavioral performance as a function of current and cumulative occupational lead exposure.

A cross sectional field study was planned to assess neurotoxic effects caused by low-level occupational lead exposure. Two groups of 66 workers and 86 controls were examined with a battery including a questionnaire on neurotoxic symptoms, the measure of performance at neurobehavioral testing, the detection of visual contrast sensitivity, and the dosage of serum prolactin. Both current and cumulative exposure to lead were defined. The average PbB was 27.50 +/- 28 microg/dl (median 28, range 6-61) in the exposed and 8.11 +/- 4.47 microg/dl (median 7, range 2-21). The test results were controlled for possible confounders including age, schooling, alcohol and coffee intake. Significant differences were observed between exposed and controls regarding neurotoxic symptoms reporting, the exposed reporting more frequently mood changes and abnormal fatigue. The exposed subjects showed a decreased visual contrast sensitivity, and a marked increase of prolactin secretion. No changes emerged regarding neurobehavioral testing. The alterations observed resulted associated to the current lead exposure and not to the cumulative indices. A safe exposure level was calculated on the basis of dose-response relationship with prolactin alteration, yielding a PbB value of 10 microg/dl.