[Characteristics, use and toxicity of fluorochemicals: review of the literature]. / Caratteristiche, uso e tossicità dei fluorurati: revisione della letteratura.

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are perfluorinated surfactants used to produce polymers and telomers whose carbon chain can be differently long. Polytetrafluoroethylene (PTFE), namely Teflon, is the chief fluoropolymer and it has been widely utilised over the last decades and all over the world. Indeed, its particular physical and chemical properties make it difficult to replace this substance in several industries (textile, paper, chemical, fire-fighting foam industry). Perfluoroalkyl-compounds may be considered ubiquitous and, in particular, it has been shown that PFOS may be concentrated in the food chain. Concerns about possible toxic effects of these chemicals date back to seventies, but only in 2000 the Environmental Protection Agency (EPA) stated PFOA and PFOS withdrawal to avoid environmental pollution. In 2002 the Organisation for Economic Co-operation and Development reported that these substances are bio-persistent, tend to accumulate in different tissues of living organisms and are toxic to mammalians. In 2006 EPA established that every PFOA emission will be eliminated not later than 2015. Actually, health effects of perfluoroalkyl-compounds on humans remain controversial, in spite of a number of experimental and epidemiological studies. Research focuses on possible endocrine disruption, thyroid and liver carcinogenicity, and development alteration. Our article reviews the main studies concerning PFOS and PFOA industrial and environmental toxicology.

Saliva as an analytical tool to measure occupational exposure to toluene.

OBJECTIVE: To describe a sensitive and rapid method for the determination of toluene in saliva. Biomonitoring of toluene exposure is commonly performed by determination of urinary hippuric acid, o-cresol or toluene itself. The analysis of blood toluene has been verified as another method for biomonitoring. However, drawing blood is invasive and can often not be performed at the workplace for hygienic reasons. Sampling of saliva may be non-invasive, easy to perform and a viable alternative for biomonitoring in the workplace. METHODS: We measured the solvent concentration in saliva specimens of 5 healthy volunteers studied in the laboratory and a group of 36 workers exposed to toluene in the synthetic leather industry. Saliva was collected into Salivette (Sarstedt, Germany) devices by sterile cotton rolls placed in the mouth and then squeezed into pre-weighted vials. Environmental toluene was collected for the duration of a work-shift by Radiello (FSM, Italy) passive samplers. Toluene in urine and saliva (head space analysis) and in environmental samples was measured by GC-MS. RESULTS: Environmental toluene levels ranged from 0.22 to 57.20 mg/m(3), while the concentrations of the solvent in saliva and urine ranged from 0.12 to 18.30 microg/L, and from 0.47 to 26.64 microg/L, respectively. The correlation coefficients (r) between biological and environmental levels of toluene were 0.77 and 0.93, respectively, for saliva and urine samples. CONCLUSION: This preliminary study suggests that saliva may offer many advantages over 'classical' biological fluids such as blood as it is readily accessible and collectible: therefore saliva toluene may be considered as a possible biomarker of exposure to toluene.

[Indoor air quality in an Italian military submarine]. / Qualità dell'aria in una nave sommergibile della marina militare Italiana in condizioni operative.

In recent years there has been increasing interest on studies concerning indoor air quality and focusing on risk factors for exposed subjects. Particularly, airborne chemicals, whose adverse effects are well known, have been identified and determined in means of transport as in other indoor places. As concerns chemical air concentrations in submarines, only a limited number of studies have been published. This paper reports measured concentration data for organic compounds (total volatile organic compounds, substances with a chemical bond S-O, nitrogen compounds, carbon monoxide, carbon dioxide, and different organic solvents) in the air sampled during an 8-h period in an Italian Military submarine, under routine operations. We observed that a periodicalfresh-air intake operation (snorkel) might cause temporary increase of contaminants levels in indoor air. Moreover, we could find that pollutants sometimes reach notable peak concentrations being potentially able to induce adverse health effects in crewmembers. Our data highlight the need to promote further investigations.

[The significance of enviromental and biological monitoring in workers employed in service stations after the elimitation of tetraethyl lead from gasoline]. / Il significato del monitoraggio ambientale e biologico nei lavoratori addetti alle stazioni di servizio dopo la eliminazione del piombo tetraetile dalle benzine.

The chemical risk in service stations may be due to toxic compounds present in fuel (particularly benzene and additives) and to the emission of exhausts and fine particulate from vehicles. Owing to the elimination of lead (Pb) from fuel and to the necessity of lowering CO emission, several oxygenated additives have been added to fuel, in particular methyl-tert-butyl-ether (MTBE), whose toxic properties are at present under investigation. The introduction of reformulated gasoline (RFG) and the use of catalytic converters (with possible release of platinum (Pt) in the environment) may have modified the risks for workers employed in service stations. The paper shows data collected from 26 subjects (divided into three specific tasks, namely: fuel dispenser, "self-service" attendant and controller, and cashier) to estimate the actual chemical risk and to compare it with the previous data taken from literature. For this purpose, besides performing the usual medical surveillance, we measured the environmental concentrations of benzene, MTBE and formaldehyde, the urinary levels of benzene metabolites S-phenylmercapturic acid (S-PMA) and t,t-muconic acid (MA) and of unmodified MTBE, and the blood concentrations of Pb and Pt for each subject. Mean values of these compounds were, respectively: 38.81 microg/m3; 174.04 microg/m3; 10.38 microg/m3; 2.36 microg/g creatinine; 96.57 microg/g creatinine; 1.41 microg/L; 7.00 microg/100 mL; 0.0738 ng/ml. The above values were much lower than the corresponding limit values reported by ACGIH and DFG. In particular, after the introduction of vapour recycle systems and the widespread use of "self-service" systems, airborne benzene concentration dropped from 300/400 microg/m3 to lower than 100 microg/m3, without noticeable increasing of exposure to formaldehyde. The disappearing of Pb from gasoline leads to a progressive lowering of its blood levels, while the possible risks due to the very low amounts of Pt released from catalytic converters have still to be defined exactly. Taken all in all, our results seem to indicate that, after the elimination of tetraethyl lead, the chemical risk for workers employed in service stations is now lower than in the past.

[Biological monitoring of occupational exposure to desflurane]. / Monitoraggio biologico dell'esposizione occupazionale a desflurane.

In these last years Desflurane (D) has become used, alone or in combination with nitrous oxide, in surgical procedures. Occupational exposed groups include anesthesiologists, other physicians, (e.g. surgeons) and operating room nurses. Desflurane is a halogenated methylethylether which is administered by inhalation. Desflurane is halogenated exclusively with fluorine. The blood/gas partition coefficient of Desflurane is 0.42. Changes in the clinical effects of Desflurane rapidly follow changes in the inspired concentration. Studies in man indicate that Desflurane washes into the body rapidly. It also washes out of the body rapidly, allowing flexibility in adjustment of the depth of anaesthesia. Desflurane is eliminated via the lungs, undergoing only minimal metabolism (0.02%). In order to investigate the role of urinary D as an indicator of occupational exposure to Desflurane (CI, ppm), CI was measured in 21 members of operating room staffs. For the measurement of environmental concentration of Desflurane (CI), the ambient air was sampled using personal passive dosimeters. The analyte was desorbed by a water-methanol mixture and was analysed by means a gas chromatograph--mass spectrometer (GC-MSD) and headspace technique. The biological monitoring of exposed workers was conducted by determining the concentration of Desflurane in urine (Cu, microgram/L). Urine concentrations of Desflurane were determined by headspace analysis using GC-MSD. Significant correlations were found between the environmental Desflurane concentration and the urinary concentrations. The correlation between CI (ppm) and Cu (microgram/L) was: Log D (Cu, microgram/L) = .191 + .922 * LogCI; r = .916 On the basis of the equation it was possible to establish tentatively the biological limit values corresponding to the respective occupational exposure limit values proposed for Desflurane.

[Biological monitoring of occupational exposure to sevoflurane]. / Monitoraggio biologico dell'esposizione professionale a sevoflurane.

Sevoflurane has been used in the last few years in brief surgical operations, either alone or in combination with nitrous oxide. Occupationally exposed groups include anesthesiologists, surgeons and operating room nurses. In 1977 the National Institute for Occupational Safety and Health (NIOSH) recommended that occupational exposure to halogenated anesthetic agents (halothane, enflurane, and isoflurane), when used as the sole anesthetic, should be controlled so that no worker would be exposed to time-weighted average concentrations greater than 2 ppm during anesthetic administration. When halogenated anesthetics are associated with nitrous oxide, NIOSH recommends that the limit value should not exceed 0.5 ppm. We think these recommendations can be extended to sevoflurane. Metabolism of sevoflurane is catalyzed by cytochrome P-450; this involves oxidation of the fluoromethyl side chain of the molecule, followed by glucuronidation. Two urinary metabolites of sevoflurane have been identified: inorganic fluoride (which, however, is not specific) and a non-volatile compound that yields hexafluoroisopropanol (HFIP) when digested with the enzyme beta-glucuronidase. In order to investigate the role of urinary HFIP as an indicator of occupational exposure to sevoflurane (CI, ppm), CI was measured in 145 members of 18 operating room staffs. The measurements of the time-weighted average of CI in the breathing zone were made by means of diffusive personal samplers. Each sampler was exposed during the whole working period. Sevoflurane was desorbed with CS2 from charcoal and the concentrations were measured on a gas chromatograph (GC) equipped with a mass selective detector (MSD). The GC was equipped with a 25 meter cross-linked phenylmethylsilicon column (internal diameter 0.2 mm). GC conditions were as follows: injector column temperature = 200 degrees C; column temperature = 30 degrees C; carrier gas = helium; injection technique of samples = splitless. The analytical conditions for the MSD were the following: ion mass monitored = 131 m/e; dwell time = 50 msec; selected ion monitoring window time = 0.1 amu; electromultiplier = 400 V. Urine samples were collected near the end of the shift and were analyzed for HFIP by head-space gas chromatography after glucuronide hydrolysis. 0.5 ml of urine and 1.5 ml of 10 M sulfuric acid were added to 21.8 ml headspace vials. The vials were immediately capped, vortexed, and loaded into the headspace autosampler. Samples were maintained at 100 degrees C for 30 min, after which glucuronide hydrolysis was 99% complete. Analyses were performed on a GC equipped with a MSD. The analytical conditions for urine analysis were as follows: cross-linked 5% phenylmethylsilicon column (internal diameter 0.2 mm, length 25 m); column temperature = 35 degrees C; carrier gas = helium. The analytical conditions for the MSD were: monitored ions = 51.05 and 99; dwell time = 100 ms; selected ion monitoring window time = 0.1 amu; electromultiplier voltage = 2000 Volt. With our analytical procedure, the detection limit of HFIP in urine was 20 micrograms/L. The variation coefficient (CV) for HFIP measurement in urine was 8.7% (on 10 determinations; mean value = 1000 micrograms/L). The median value of CI was 0.77 ppm (Geometric Standard Deviation = 4.08; range = 0.05-27.9 ppm). The correlation between CI and HFIP (Cu, microgram/L) was: Log Cu (microgram/L) = 0.813 x Log CI (ppm) + 2.517 (r = 0.79, n = 145, p < 0.0001). On the basis of the equation it was possible to establish tentatively the biological limit values corresponding to the respective occupational exposure limit values proposed for sevoflurane. According to our experimental results, HFIP values of 488 micrograms/L and 160 micrograms/L correspond to airborne sevoflurane concentrations of 2 and 0.5 ppm respectively.

[Technical note: proposal of a routine method of accurate measurement of urinary trans,trans-muconic acid]. / Nota tecnica: proposta di un metodo routinario per il dosaggio accurato dell'acido t,t-muconico nelle urine.

A method for routine measurement of urinary trans,trans-muconic acid. A method is proposed which allows the accurate determination of urinary trans,trans-muconic acid (Ma) by HPLC with UV detection. Sample pretreatment consists of a first purification on strong anionic exchange (SAX) cartridges followed by extraction on "end capped" reversed-phase (C18-EC) ones. Purified samples are directly injected onto a chromatographic column (C18, 150 x 4.6 mm I.D., 3 microns) which is eluted with water: methanol: acetic acid (97:2:1, v/v) mixture followed by a "spike" of acetonitrile. The retention time of MA is 15 min, the coefficient of variation is lower than 3%, the limit of detection is 7 micrograms/l. The method seems suitable for accurate biological monitoring of subjects exposed to benzene.

Biological monitoring of workers exposed to carbon disulfide (CS2) in a viscose rayon fibers factory.

The exposure-excretion relationship to carbon disulfide (CS2) vapor in 407 exposed workers was studied during the second half of the working week. Carbon disulfide concentrations were also determined in 50 nonexposed subjects. The geometric mean value for CS2 in urine samples from the latter was: 0.23 microgram/l (95% upper limit = 0.52 microgram/l) when log-normal distribution was assumed. Among the exposed workers, the CS2 level in urine samples collected after the first half shift exceeded the 95% upper limit of nonexposed subjects in every case. The time-weighted average intensity of exposure to CS2 vapor was measured using personal diffusive samplers (in which carbon cloth served as an adsorbent). CS2 concentrations in urine were determined in samples collected at the end of the first half shift from the 407 exposed cases as well as from 50 nonexposed controls. There was a significant correlation (p < 0.0001) between the exposure to CS2 vapor at concentrations of up to 64 mg/m3 and the levels of CS2 measured in the urine samples after four hours of exposure. The correlation indicated that a mean level of 15.5 micrograms CS2/l urine (95% confidence range, 13.8-17.1 micrograms/l) was excreted following an exposure to CS2 at 31 mg/m3 (the current occupational exposure limit).

Biological monitoring of the occupational exposure to halothane (fluothane) in operating room personnel.

The concentration of halothane (fluothane) in the ambient atmosphere was determined in five operating theaters of two hospitals in Italy. The concentrations of halothane in the ambient air exceeded the NIOSH recommended time-weighted average exposure levels (median value: 10.38 mg/m3). Halothane was detected in the urine of 58 exposed subjects (anesthetists, surgeons, and nurses). A significant correlation was found between the halothane concentration in urine produced during the shift (Cu, micrograms/L) and halothane environmental concentration (CI, mg/m3) (Cu = 0.242 x CI + 3.51) (N = 58; r = 0.92; p less than 0.0001). The results show that the urinary halothane concentration can be used as an appropriate biological exposure index. The biological values proposed are: 92 micrograms/L, corresponding to a 50 ppm of environmental exposure; 6.5 micrograms/L, corresponding to 2 ppm of environmental exposure and 3.9 micrograms/L, corresponding to a 0.5 ppm of environmental exposure.

[Stability of esters in the blood in vitro]. / Studio sulla stabilita' degli esteri nel sangue in vitro.

The aim of this paper was to evaluate the lambda values of this group of solvents experimentally, by means of an analytical method which has already been used for other solvents. During our experiments we found that most acetates we tested (n-butyl-acetate; sec.butyl-acetate; ter-butyl-acetate; ethyl-acetate; amyl-acetate; methyl-acetate; n-propyl-acetate) were particularly unstable and hydrolyzed rapidly in alcohol and in the corresponding acid. The "in vitro" behaviour of these substances allow to draw the following conclusions: 1) For the acetates it is not possible to measure the values since the involved substances are chemically unstable in blood. 2) As it was shown by the half-life times of the "in vitro" acetates, the alcohols and the corresponding acids, are released rapidly in blood. 3) The biological monitoring of the acetates in expired air is not very significant; perhaps it is better to measure the corresponding alcohol in expired air. 4) In some cases the TLV of the alcohols is much lower than for the corresponding acetates; this finding and the rapid biotransformation we observed make us think that the TLV's proposed for some acetates are too high.