[Operative guidelines for the shoe industry: health surveillance]. / Indicazioni operative per le attività calzaturiere: sorveglianza sanitaria.

Medical surveillance of workers exposed to occupational risk factors means secondary prevention and entails medical activities which are related to the assessed risk. In particular, the chief risk factors evaluated in the footwear industry frequently imply medical surveillance of exposed workers. These risk factors include organic solvents and chemicals, leather dust, noise, repetitive movements and upper limb overload, vibrations, manual lifting action and video display terminal operation. We consider some operative standardized and validated protocols for medical surveillance of these industry employees.

["Wachstum" oder "Revolution"? Ernst Cassirer und die Wissenschaftsgeschichte].

"Growth" or "Revolution"? Ernst Cassirer and History of Science. Ernst Cassirer's contributions to history of science have been long time neglected. The aim of this paper is to show the historical and philosophical framework of Cassirer's engagement in this field, starting from his seminal work about the problem of knowledge in science and philosophy of the modern age. Moreover the author suggests that Cassirer's late studies about Galilei and the origins of mathematical science are of some interest in order to comprehend both his commitment to contemporary history of science (from Burtt to Koyré) and his intellectual heritage for our agendas in a post-Kuhnian era.

Perfluorooctane sulfonate and perfluorooctanoic acid in surgical thyroid specimens of patients with thyroid diseases.

BACKGROUND: Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are ubiquitous compounds that may act as endocrine disruptors, neurotoxic agents, and fetal development perturbing substances and may also be carcinogenic, as recently demonstrated in experimental animal models. There is little information on the potential for these compounds to affect the thyroid. Therefore, this study was performed to measure the intrathyroidal levels of PFOA and PFOS in surgical specimens of thyroid glands and to determine if there was a relationship between the concentrations of these substances and the clinical, biochemical, and histologic phenotype of the patients from whom the thyroids were obtained. We also sought to determine if there was a relationship between tissue and serum levels of both PFOA and PFOS. METHODS: PFOA and PFOS were measured in 28 patients undergoing thyroid surgery for benign (15 multinodular goiters and 7 Graves' disease) and malignant (5 papillary and 1 follicular carcinoma) thyroid disorders. RESULTS: PFOA and PFOS were detectable in all surgical specimens of thyroid tissue. Their median concentrations were 2.0 ng/g (range = 0.4-4.6 ng/g) and 5.3 ng/g (range = 2.1-44.7), respectively. Intrathyroidal concentrations of PFOA and PFOS were similar in the thyroids of patients with thyroid diseases as in thyroid glands obtained at autopsy. There was no relationship between the intrathyroidal concentrations of either PFOA or PFOS and the underlying thyroid disease. A significant correlation between the serum and the tissue levels of PFOS was found in all patients. The serum concentrations of PFOA and PFOS were significantly higher than those in the correspondent surgical specimens. CONCLUSIONS: These observations do not support the view that PFOA and PFOS are actively concentrated in the thyroid. PFOA and PFOS, however, are both found in surgical and autopsy thyroid specimens. Therefore, further studies to determine if they have disrupting effects in thyroid cells or tissue, and studies to compare populations with and without these compounds in their thyroid glands, are important.

Evaluation of urinary biomarkers of exposure to benzene: correlation with blood benzene and influence of confounding factors.

PURPOSE: trans,trans-Muconic acid (t,t-MA) is generally considered as a useful biomarker of exposure to benzene. However, because of its lack of specificity, concerns about its value at low level of exposure have recently been raised. The aim of this study was (a) to compare t,t-MA, S-phenylmercapturic acid (SPMA) and benzene (B-U) as urinary biomarkers of exposure to low levels of benzene in petrochemical workers and, (b) to evaluate the influence of sorbic acid (SA) and genetic polymorphisms of biotransformation enzymes on the excretion of these biomarkers. METHOD: A total of 110 workers (including 24 smokers; 2-10 cigarettes/day) accepted to take part in the study. To assess external exposure to benzene, air samples were collected during the whole working period by a passive sampling device attached close to the breathing zone of 98 workers. Benzene was measured in blood (B-B) samples taken at the end of the shift, and was considered as the reference marker of internal dose. Urine was collected at the end of the shift for the determination of B-U, SPMA, t,t-MA, SA and creatinine (cr). B-U and B-B were determined by head-space/GC-MS, SPMA and SA by LC-MS, t,t-MA by HPLC-UV. RESULTS: Most (89%) personal measurements of airborne benzene were below the limit of detection (0.1 ppm); B-B ranged from <0.10 to 13.58 mug/l (median 0.405 microg/l). The median (range) concentrations of the urinary biomarkers were as follows: B-U 0.27 microg/l (<0.10-5.35), t,t-MA 0.060 mg/l (<0.02-0.92), SPMA 1.40 microg/l (0.20-14.70). Urinary SA concentrations ranged between <3 and 2,211 microg/l (median 28.00). Benzene concentration in blood and in urine as well as SPMA, but not t,t-MA, were significantly higher in smokers than in non-smokers. The best correlation between B-B and urinary biomarkers of exposure were obtained with benzene in urine (microg/l r = 0.514, P < 0.001; microg/g cr r = 0.478, P < 0.001) and SPMA (microg/l r = 0.495, P < 0.001; microg/g cr r = 0.426, P < 0.001) followed by t,t-MA (mg/l r = 0.363, P < 0.001; mg/g cr r = 0.300, P = 0.002). SA and t,t-MA were highly correlated (r = 0.618, P < 0.001; corrected for cr r = 0.637). Multiple linear regression showed that the variation of t,t-MA was mostly explained by SA concentration in urine (30% of the explained variance) and by B-B (12%). Variations of SPMA and B-U were explained for 18 and 29%, respectively, by B-B. About 30% of the variance of B-U and SPMA were explained by B-B and smoking status. Genetic polymorphisms for biotransformation enzymes (CYP2E1, EPHX1, GSTM1, GSTT1, GSTP1) did not significantly influence the urinary concentration of any of the three urinary biomarkers at this low level of exposure. CONCLUSION: At low levels of benzene exposure (<0.1 ppm), (1) t,t-MA is definitely not a reliable biomarker of benzene exposure because of the clear influence of SA originating from food, (2) SPMA and B-U reflect the internal dose with almost similar accuracies, (3) genetically based inter-individual variability in urinary excretion of biomarkers seems negligible. It remains to assess which biomarker is the best predictor of health effects.

Determination of perfluorooctanoic acid and perfluorooctanesulfonate in human tissues by liquid chromatography/single quadrupole mass spectrometry.

A method is described that permits the measurement of the levels of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) in human liver, kidney, adipose tissue, brain, basal ganglia, hypophysis, thyroid, gonads, pancreas, lung, skeletal muscle and blood, even in subjects not occupationally exposed to these compounds. The purification of samples involved the use of trifunctional (tC18) and strong anion-exchange (SAX) solid-phase extraction cartridges, and the analysis utilized a high-performance liquid chromatograph coupled to a single quadrupole mass spectrometer (LC/MS). The analyses were conducted on a mixed-bed reversed-phase column by gradient runs using 3 mM ammonium acetate/methanol mixtures at different proportions as the mobile phase. The detector was used in electrospray negative ion mode by recording simultaneously the ions m/z 413.0 (PFOA) and 499.0 (PFOS). Perfluorononanoic acid (PFNA), added to the samples before the purification, was used as the internal standard (ion monitored = m/z 463.6). The recovery rates of the extraction procedure ranged from 79.6 to 95.6% (CV% 1.7-7.4%) for PFOA, from 79.7 to 100.8% (CV% = 1.2-7.1) for PFOS, and from 89.1 to 102.3% (CV% = 0.9-5.2 %) for PFNA. The calibration curves were linear up to at least 400 ng of analytes per gram of tissue. The detection limits (signal-to-noise ratio = 3) were 0.1 ng/g for both PFOA and PFOS measured in all tissues except adipose tissue, where the limits were about 0.2 ng/g. The content of analytes in tissues varied from 0.3 to 3.8 ng/g (respectively: basal ganglia and lung) for PFOA, and from 1.0 to 13.6 ng/g (respectively: skeletal muscle and liver) for the linear isomer of PFOS. The method is suitable to evaluate the content of PFOA and PFOS in different tissues taken from the general population exposed to very low concentrations of these pollutants.

Irritant vocal cord dysfunction at first misdiagnosed as reactive airway dysfunction syndrome.

OBJECTIVES: This report describes a case of vocal cord dysfunction at first misdiagnosed as reactive airway dysfunction syndrome (RADS). METHODS: A woman developed recurrent episodes of cough, dyspnea, and wheezing unresponsive to asthma therapy after irritant exposure to glutaraldehyde. Direct laryngoscopy was performed immediately after the induction of symptoms. RESULTS: Laryngoscopy showed a paradoxical adduction of the vocal cord on inspiration. Vocal cord dysfunction was diagnosed. CONCLUSIONS: A case of vocal cord dysfunction occurred after exposure to glutaraldhyde in a person with a history highly suggestive of RADS. Vocal cord dysfunction should always be considered in the differential diagnosis of patients with acute respiratory symptoms after exposure to irritants and with asthma-like symptoms that fail to respond to conventional asthma therapy.

Determination of urinary S-phenylmercapturic acid, a specific metabolite of benzene, by liquid chromatography/single quadrupole mass spectrometry.

A high-performance liquid chromatography/single quadrupole mass spectrometry (LC/MS) method is described for the determination of urinary S-phenylmercapturic acid (S-PMA), a specific metabolite of benzene. Urine samples were spiked with [13C6]S-PMA (used as the internal standard) and acidified; then they were purified by solid-phase extraction (SPE) on C18 cartridges. Analyses were conducted on a reversed-phase column by gradient runs with 1% aqueous acetic acid/methanol mixtures at different proportions as the mobile phase. The detector was used in electrospray negative ion mode (ESI-), the ions m/z 238 for S-PMA and 244 for [13C6]S-PMA being recorded simultaneously. The detection limit (for a signal-to-noise ratio = 3) was 0.2 microg/L, thus allowing for the measurement of background excretion of S-PMA in the general population. The use of the internal standard allowed us to obtain good precision (CV% values < 3%) and a linear calibration curve within the range of interest for monitoring occupational exposure to benzene (up to 500 microg/L). The method was applied to assay the metabolite concentration in a group of 299 workers (68 smokers and 231 non-smokers) occupationally exposed to relatively low levels of benzene (environmental concentration = 0.4-220 microg/m3, mean 11.4 microg/m3 and 236 non-exposed subjects (134 smokers and 102 non-smokers). The results clearly showed that smoking must be taken into account for the correct interpretation of the results of S-PMA measurements for the assessment of work-related benzene exposure. When only non-smokers were selected, the mean excretion of S-PMA was significantly higher in workers exposed to benzene (1.2 +/- 0.9 microg/g creatinine) than in the control group (0.7 +/- 0.6 microg/g creatinine) (p < 0.001), thus confirming the role of S-PMA as a biomarker of benzene on a group basis, even for relatively low exposure degrees.

Occupational asthma (OA) with sensitization to diphenylmethane diisocyanate (MDI) presenting at the onset like a reactive airways dysfunction syndrome (RADS).

BACKGROUND: Two types of OA are distinguished: immunological (OA with sensitization) and non-immunological, i.e., irritant induced asthma or reactive airways dysfunction syndrome (RADS). METHODS: We describe the case of a worker who developed respiratory symptoms after a spill of diphenylmethane diisocyanate (MDI) at the workplace. RADS was initially diagnosed and the worker resumed working. The progressive worsening of symptoms and the appearance of symptoms-work relationship one year later, when concentrations of isocyanates were no longer "irritant," suggested immunological OA. RESULTS: The diagnosis was confirmed by specific inhalation challenge test, followed by removal from exposure and complete recovery. CONCLUSIONS: In the case of RADS due to an agent with both irritant and sensitizing properties, history should be repeatedly assessed for a possible symptom-work relationship. If this is found, further investigations should be carried out, including specific inhalation challenges, to confirm the possibility of immunological OA.