Brain fluorodeoxyglucose positron emission tomography (¹8FDG PET) in patients with acute thallium intoxication.

OBJECTIVE: Thallium toxicity induces cellular injury through impaired Na-K-ATPase activity. The aim of this study was to investigate functional imaging and the long-term clinical-imaging correlations of thallium toxicity. MATERIALS AND METHODS: We measured thallium concentrations in blood, urine, stools, and hair of a 48-year-old woman and a 52-year-old man (patients 1 and 2) in the first 3 months after exposure to thallium containing water, and studied their neuropsychological functions. Using fluorodeoxyglucose positron emission tomography ((18)FDG PET) scans, we examined the brain involvement and correlated the image findings with the clinical presentations. RESULTS: On the 1st, 30th, and 61st days after exposure, the thallium concentrations in patient 1 were 2056, 311, and 7.5 µg/L in the blood, and 11400, 4570, and 36.4 µg/L in the urine. The concentrations in patient 2 were 956, 235, and 15.6 µg/L in the blood, and 11900, 2670, and 101 µg/L in the urine. On the 40th, 50th and 89th days after exposure, the thallium concentration in the stools were 21.6, 3.6, and 0.35 µg/g in patient 1, and 22.2, 3.2, and 0.37 µg/g in patient 2. Executive function, perceptual motor speed, and learning memory were initially abnormal but recovered particularly within the first year. The first (18)FDG PET studies of both patients disclosed a decreased uptake of glucose metabolism in the cingulate gyrus, bilateral frontal, and parietal lobes 2-5 months after exposure. The follow-up (18)FDG PET scan of patient 2 revealed a partial recovery. CONCLUSION: This study indicates that damage to the central nervous system after acute thallium poisoning may be reversible after a long-term follow-up. Brain (18)FDG PET demonstrated the brain involvement and was correlated with cognitive impairment.

Field protection effectiveness of chemical protective suits and gloves evaluated by biomonitoring.

OBJECTIVES: To determine the effectiveness of protective suits and gloves by biomonitoring. METHODS: Fifteen male spray painters at a ship coating factory were studied for two weeks. Workers wore no protective clothing during the first week and wore protective suits and gloves during the second week. Sampling was conducted on four consecutive working days each week. Ethyl benzene and xylene in the air were collected by using 3M 3500 organic vapour monitors. Urine was collected before and after each work shift. RESULTS: Urinary mandelic acid (MA) and methyl hippuric acid (MHA) levels were divided by the personal exposure concentrations of ethyl benzene and xylene, respectively. Mean (SE) corrected MA and MHA concentrations in the first week were 1.07 (0.18) and 2.66 (0.68) (mg/g creatinine)/(mg/m3), and concentrations in the second week were 0.50 (0.12) and 1.76 (0.35) (mg/g creatinine)/(mg/m3) in the second week, respectively. Both MA and MHA concentrations in the second week (when spray painters wore protective suits and gloves) were lower than in the first week, respectively (p<0.001, p = 0.011). Mean decrease in MA and MHA biomarkers were 69% and 49%, respectively. CONCLUSION: This study successfully evaluated the effectiveness of chemical protective suits and gloves by using biomarkers as urinary MA and MHA. This method is feasible for determining the performance of workers wearing personal protective equipment. Moreover, the experimental results suggest that dermal exposure may be the major contributor to total body burden of solvents in spray painters without protective suits and gloves.

Development and evaluation of an air-curtain fume cabinet with considerations of its aerodynamics.

In order to avoid the inherent aerodynamic difficulties of the conventional fume hood, an innovative design--the 'air curtain-isolated fume hood' is developed. The new hood applies a specially designed air curtain (which is generated by a narrow planar jet and a suction slot flow at low velocities) across the sash plane. The hood constructed for the study is full size and transparent for flow visualization. The aerodynamic characteristics are diagnosed by using the laser-light-sheet-assisted smoke flow visualization method. Four characteristic air-curtain flow modes are identified in the domain of jet and suction velocities when the sash remains static. Some of these characteristic flow modes have much improved flow patterns when compared with those of the conventional fume hoods. From the viewpoint of the aerodynamics and mass transport, the results indicate that the air curtain properly setup across the sash opening allows almost no sensible exchange of momentum and mass between the flowfields of the cabinet and the outside environment. Two standard sulfur hexafluoride (SF6) tracer gas concentration measurement methods following the ANSI/ASHRAE 110-1995 standard and the prEN14175 protocol for static test are employed to examine the contaminant leakage levels. Results of the rigorous examinations of leakage show unusually satisfactory hood performance. The leakage of the tracer gas can approach almost null (<0.001 p.p.m.) if the jet and suction velocities are properly adjusted.

Evaluation of the effectiveness of personal protective equipment against occupational exposure to N,N-dimethylformamide.

The objectives of this study were to evaluate the protective effectiveness of various personal protective equipment and the respective exposure contributions from respiratory and skin exposures of N,N-dimethylformamide (DMF) with a self-comparison study design. Two high-, four intermediate- and four low-DMF exposure workers from a synthetic leather factory were monitored in airborne DMF concentrations and N-methylformamide (NMF) concentrations in urine across four consecutive days. The workers were designated to wear no personal protective equipment on the first day. The barrier cream, rubber gloves and rubber gloves plus respirator were used on the second, third and fourth days, respectively. Person-to-personal observation was performed in the field to record all high and low exposure tasks during work for each subject. Protective effectiveness index (PEI) was used to evaluate different glove effectiveness. We concluded that the direct skin contact to the strong skin penetrates like DMF could be a more significant exposure source than the respiratory exposure in the actual occupational environment. The provision of protective equipment from skin exposure could be more important than that from respiratory exposure. The application of barrier cream could be as effective as wearing impermeable rubber gloves in the prevention from the skin penetrate in the occupational settings.

Exposure to traffic exhausts and oxidative DNA damage.

AIMS: To assess the relations between exposure to traffic exhausts and indicators of oxidative DNA damage among highway toll station workers. METHODS: Cross-sectional study of 47 female highway toll station workers exposed to traffic exhausts and 27 female office workers as a reference group. Exposure assessment was based on average and cumulative traffic density and a biomarker of exposure, urinary 1-hydroxypyrene-glucuronide (1-OHPG). Urinary 8-hydroxydeoxyguanosine (8-OHdG) was used as a biomarker of oxidative DNA damage. Plasma nitric oxide (NO) was measured as an indicator of oxidative stress related to traffic exhaust exposure. RESULTS: The mean concentration of urinary 8-OHdG was substantially higher among the exposed non-smokers (13.6 microg/g creatinine) compared with the reference non-smokers (7.3 microg/g creatinine; difference 6.3, 95% CI 3.0 to 9.6). The mean concentration of NO among the exposed (48.0 micromol/l) was also higher compared with the reference non-smokers (37.6 micromol/l; difference 10.4, 95% CI -0.4 to 21.2). In linear regression adjusting for confounding, a change in log(8-OHdG) was statistically significantly related to a unit change in log(1-OHPG) (beta = 0.372, 95% CI 0.081 to 0.663). CONCLUSIONS: Results indicate that exposure to traffic exhausts increases oxidative DNA damage. Urinary 8-OHdG is a promising biomarker of traffic exhaust induced oxidative stress.

Total body burden arising from a week's repeated dermal exposure to N,N-dimethylformamide.

BACKGROUND: Hazardous chemicals and their metabolites may accumulate in the body following repeated airborne exposures and skin contact. AIMS: To estimate the contribution of skin absorption to total body burden of N,N-dimethylformamide (DMF) across a working week in two groups with similar levels of respiratory exposure but dissimilar skin contact. METHODS: Twenty five workers in a synthetic leather (SL) factory, 20 in a copper laminate circuit board (CLCB) factory, and 20 age and sex matched non-DMF exposed subjects, were recruited. Environmental monitoring of DMF exposure via respiratory and dermal routes, as well as biological monitoring of pre-shift urinary N-methylformamide (U-NMF), were performed for five consecutive working days. RESULTS: Environmental and biological monitoring showed no detectable exposure in controls. The average airborne DMF concentration (geometric mean (GM) 3.98 ppm, geometric standard deviation (GSD) 1.91 ppm), was insignificantly lower for SL workers than for CLCB workers (GM 4.49, GSD 1.84 ppm). Dermal DMF exposure and U-NMF values, however, were significantly higher for SL workers. A significant pattern of linear accumulation was found across a five day work cycle for SL workers but not for CLCB workers. CONCLUSIONS: Dermal exposure to DMF over five consecutive days of occupational exposure can result in the accumulation of a significant DMF body burden. The long term exposure response under both repeated and intermittent conditions of substantial skin exposure is worthy of note.

Aerodynamic characteristics and design guidelines of push-pull ventilation systems.

Aerodynamic characteristics such as the flow patterns, velocity field, streamline evolutions, characteristic flow modes and characteristic flow regimes of the push-pull ventilation system are cross-examined by using the laser-light sheet smoked-flow visualization method and laser Doppler velocimetry. Four characteristic flow modes, which are denoted as dispersion, transition, encapsulation and strong suction, are identified in the domain of the push-jet and pull-flow velocities at various open-surface tank widths and rising gas velocities. It is argued phenomenologically, from the aerodynamic point of view, that operating the system in the strong suction regime would be a better strategy than operating it in other characteristic regimes for the consideration of capture efficiency. Design guidelines are developed and summarized based on the results obtained from this study. The regression formulas for calculating the critical values of the push-jet and the pull-flow velocities are provided for easy access. The sulfur hexafluoride tracer gas validation technique is performed to measure the capture efficiency. The results of tracer gas validations are consistent with those obtained from the aerodynamic visualization and measurements. The operation points obtained by employing the American Conference of Governmental Industrial Hygienists design criteria are compared with the results obtained in this study for both the aerodynamics and the capture efficiency. Methods for improving the capture efficiency and energy consumptions are suggested.

Evaluation of the protective effectiveness of gloves from occupational exposure to 2-methoxyethanol using the biomarkers of 2-methoxyacetic acid levels in the urine and plasma.

AIMS: To evaluate the protective effectiveness of gloves from occupational exposure to 2-methoxyethanol (2-ME); and to examine the association of 2-methoxyacetic acid (MAA) in urine and plasma collected simultaneously from low 2-ME exposure and high 2-ME exposure workers in a semiconductor copper laminate circuit board manufacturing plant. METHODS: Eight hour time weighted breathing zone monitoring was performed to verify the 2-ME exposure classification between workers in regular and special operations. Urine and plasma samples were simultaneously collected from 74 exposed and 80 non-exposed workers. MAA concentrations in the urine (UMAA) and plasma (PMAA) were measured using previously published methods. Three types of gloves worn by workers (cotton, rubber, and no gloves) were recorded by direct observations in the workplace and validated by person-to-person interview. Protective effectiveness indices (PEI) were used to evaluate the glove effectiveness. RESULTS: There was no detectable 2-ME/MAA in the air, or in urine and plasma samples in non-exposed workers. The average UMAA and PMAA in special operations were 72.63 mg/g Cr. and 29.72 mg/l, significantly higher than values in regular operations (5.44 mg/g Cr. and 2.58 mg/l, respectively). PMAA showed satisfactory correlation to UMAA in all participants from both regular and special operations. The rubber gloves provided significant reduction in 2-ME uptake, whereas cotton gloves provided little protection with fluctuating effectiveness, based on PEI estimates. CONCLUSIONS: PMAA, similar to UMAA, could serve as a specific biomarker for 2-ME exposure. Wearing impermeable rubber gloves during high risk tasks can reduce major 2-ME exposure. Other improvements, including engineering control, should be provided to diminish worker exposure to 2-ME in occupational environments.

Haematological effects among silk screening workers exposed to 2-ethoxy ethyl acetate.

BACKGROUND: 2-Ethoxy ethyl acetate (2-EEA) is a solvent with broad industrial and commercial applications. It has been reported to cause hematological toxicity, infertility, and teratogenesis. AIMS: To investigate the haematological effects in 2-EEA exposed workers. METHODS: Workers from one silk screening shop (n = 29), using 2-EEA as the major cleaning and printing solvent, were recruited as a high exposure group. Workers with indirect and non-exposure to 2-EEA (n = 56) were recruited as the comparison group. Venous blood was collected for blood routine examination. Air concentration of 2-EEA in this plant was measured by eight hour personal sampling. RESULTS: The geometric mean (GM) of air concentration of 2-EEA in the high exposure group was 7.41 ppm (range 1.35-16.5 pppm). The mean exposure of female workers (GM = 9.34 ppm) was significantly higher than that of male workers (GM = 4.87 ppm). The GM of air 2-EEA concentration in the comparison group was 0.07 ppm (range: non-detectable to 3.62 ppm, n = 26). The haemoglobin and haematocrit in the female high 2-EEA exposure workers were significantly lower than those of female workers in the comparison group. No difference was found between male 2-EEA high exposure and comparison group workers. The haemoglobin, haematocrit, and RBC count in the study population had a significant dose-response relation with air 2-EEA levels. CONCLUSION: Results suggest that 2-EEA is a haematological toxicant, which leads to anaemic status in high exposure female workers.

Predictors of whole-body vibration levels among urban taxi drivers.

To identify a set of important WBV predictors that could be used to develop a statistical instrument for exposure assessment in a large epidemiologic study, a total of 432 WBV measures were taken from a sample of 247 male drivers in Taipei City, Taiwan. In accordance with the ISO 2631-1 (1997) methods, we measured the frequency-weighted vertical acceleration (z-axis) over drivers' seat surface, under conditions representing different types of rides (vacant vs. short vs. long) assigned to random destinations. Mixed effect models were used to analyse the WBV data including repeated measures. For this group of urban taxi drivers regularly exposed to WBV of low intensity (mean = 0.31 ms( - 2), ranging from 0.17 to 0.55 ms( - 2) r.m.s.), our analyses indicated that average driving speed was the primary predictor (p < 0.0001). As average driving speed increased, measured vertical acceleration increased in a quadratic-linear manner (p < 0.0001). Other WBV predictors, after adjusting for the effects of other covariates, included automobile manufacturer (p = 0.02), engine size (p = 0.04), body weight (p = 0.002), age (p = 0.02), use of seat cushion (p = 0.03), and traffic period (p = 0.02). Our study suggests that a similar statistical approach could be employed in future studies to improve the quality and efficiency of WBV exposure assessment in professional drivers.

Follow up study of haematological effects in workers exposed to 2-methoxyethanol.

AIMS: To examine the association between 2-methoxyethanol (2-ME) exposure and haematological effects, as well as the recovery from these haematological effects with continuous reduction in exposure to 2-ME. METHODS: Twenty nine exposed and 90 non-exposed workers were recruited. Haematological parameters, eight hour full shift personal exposure to 2-ME, and urinary 2-methoxyacetic acid (MAA) were repeatedly measured in three consecutive surveys within six months. RESULTS: Results of haematological examination in the first exposure survey showed that haemoglobin, packed cell volume, and red blood cell count in the male exposed workers were significantly lower than those in the comparison workers. The frequency of anaemia in the exposed group (42%) was significantly higher than that in the comparison group (3%). The haematological effects were significantly associated with the urinary MAA of exposed workers. The haematological effects had returned to normal in the first follow up survey 2.5 months later, when a reduction in 2-ME exposure was noted. Haematological results of the second follow up examination six months later remained normal. The mean airborne exposure of 2-ME in the three surveys dropped from 35.7 to 2.65, then to 0.55 ppm. The mean urinary MAA of exposed workers in the three surveys was reduced from 57.7 to 24.6, then to 13.5 mg/g creatinine (n = 29). The reduction in exposure through both inhalation and potential dermal contact with 2-ME might account for the haematological recovery. CONCLUSION: 2-ME is a haematological toxin which leads to anaemia in exposed workers. However, the toxic haematological effects of 2-ME persist for only a short period of time after cessation or reduction of exposure.

Computer simulation of particle overlap in fiber count samples.

Fibrous aerosols are of great importance to industrial hygienists because of the severe health risks that may be associated with inhaling such particles. Previous studies on measurement error due to overloading of fibers and nonfibrous particles on the collected sample indicate that a 100-1300 fiber/mm2 filter area is the best filter loading density to reduce bias in fiber counts. The present study investigated the upper fiber and particle concentration limits for reliable counting and identification and the possibility of a procedure for correcting observed fiber counts to account for fiber masking due to overlapping particles or fibers. A computer-generated grid was used to simulate the light microscope graticule field. The resolution of 2000 x 2000 was found to accurately represent the shape of the fibers and nonfibrous particles. Bivariate lognormal distributions were used to describe the length and width distributions of the fibers. The capability of distinguishing particle-overlapped fibers (defined as the resolution index), the coverage of the graticule field, the filter surface loading density, size distributions of fibers and particles, and the fiber-to-particle concentration ratio were the primary parameters in this study. The counting efficiency was found to consistently decrease with increasing filter surface loading density and decreasing resolution index. The recommended upper limit of filter surface fiber density depended not only on the number concentration ratio but also on the filter surface loading densities and size distributions of fibers and particles. The advantage of using a thoracic preseparator on counting efficiency was calculated and found to improve counting efficiency significantly when the count median diameter of nonfibrous particles was close to or larger than the thoracic 50% cutoff point of 10 microm.

Collection efficiency and capacity of three samplers for acidic and basic gases.

This paper compares the collection efficiency and capacity of a coated porous metal disk with those of a silica gel tube and an impinger at the acid or basic aerosol concentration of two times the permissible exposure limitation (Taiwan IOSH, Institute of Occupational Safety and Health), relative humidity of 80 +/- 5%, and temperature of 30 +/- 3 degrees C in the laboratory. Using 5% sodium carbonate/glycerin coating, the collection efficiencies of the porous metal disk for nitric acid, hydrogen chloride, and hydrogen fluoride are found to be higher than those of the silica gel tube and the impinger when the sampling time is less than 3.0 h. The gas collection capacity of the porous metal disk coated with 5% sodium carbonate is calculated to be 3.9, 5.8, and >2.5 mg for nitric acid, hydrogen chloride, and hydrogen fluoride, respectively. For ammonia, the porous metal disk coated using 4% citric acid performs slightly better than the impinger, and the corresponding capacity is slightly greater than 33.6 mg.

Urinary 2-methoxy acetic acid accumulation in response to 2-methoxy ethanol exposure.

Urinary 2-methoxy acetic acid reportedly has a long half-life (77.1 hr) in humans. The authors studied urinary 2-methoxy acetic acid in a group of 18 workers exposed to 2-methoxy ethanol from Monday to Saturday following a 7-d cease in production. The weekly time-weighted average exposure concentration of 2-methoxy ethanol was 4.5 ppm. The urinary 2-methoxy acetic acid of exposed workers was increased significantly, from 18.5 microg/ml (10.6 mg/gm creatinine) on Monday (prior to work) to 48.4 microg/ml (46.5 mg/gm creatinine) on Friday (after work), to 51.2 microg/ml (45.6 mg/gm creatinine) on Saturday after work. These levels occurred, despite that fact that the daily mean time-weighted average 2-methoxy ethanol exposures were very consistent and were close to the current Taiwan Permissible Exposure Limit of 5 ppm. These urinary 2-methoxy acetic acid levels were much higher than levels that occur with inhalation only, and they demonstrate that skin absorption is a significant contributor to 2-methoxy ethanol exposure. The high background concentrations of 2-methoxy acetic acid in the preshift urine samples following a 7-d production halt confirm that there is a long half-life of 2-methoxy acetic acid in humans. The determination of urinary 2-methoxy acetic acid is recommended for exposure assessment of 2-methoxy ethanol.

A new technology to measure skin absorption of vapors.

Skin vapor absorption is one of the major exposure routes for some widely used chemicals (e.g., 2-methoxy ethanol), but a good apparatus with which exposure can be measured is currently unavailable. In this study, a polished stainless-steel chamber-combined with computer-controlled auto-feedback software and hardware, real-time gas sensors, and an auto-injection microsyringe-was proposed as new technology. In addition, the machines had activated-charcoal tubes and cold traps, both of which simulated the skin uptake and validated the reliability of the proposed system. The exposure concentrations, relative humidity, and temperature were effectively controlled at 25+/-0.5 ppm (or 300+/-10 ppm), 80+/-2%, and 27.5+/-0.5 degrees C, respectively. The relative errors between the quantity of 2-methoxy ethanol collected in either the charcoal tubes or the cold traps and the quantity of ME injected to maintain a constant exposure were less than 5%. The authors also used this new technology to successfully measure skin absorption of ME vapor in 6 volunteers. The authors concluded that this new technology is a direct, continuous, noninvasive, and simple tool with which to measure skin absorption of vapors.

Measurement of percutaneous uptake of 2-methoxy ethanol vapor in humans.

Absorption of vapors through skin has been largely ignored in occupational health, although for ethylene glycol ethers this route of exposure could be more important than inhalation. We used an automated concentration and humidity controlled system to measure real-time percutaneous absorption of 2-methoxy ethanol (ME) vapor in seven volunteers. The exposure concentration (300 +/- 10 ppm or 25 +/- 0.5 ppm), humidity (80 +/- 2%), and temperature (27.5 +/- 0.5 degrees C) were controlled throughout the experiments. Uptakes during 4-hour single-arm exposure at 25 ppm and 300 ppm were 7.0 mg and 65.3 +/- 25.0 mg, respectively, with corresponding uptake rates of 1.36 micrograms/cm2/hr and 13.2 +/- 5.0 micrograms/cm2/hr. Percutaneous absorption was consistent and unsaturated during exposure. Because the permeability constant of ME vapor (14.0 +/- 5.3 cm/hr) was much higher than that of many widely used organic chemicals, we concluded that vapor absorption through skin is a significant contributor to overall ME exposure.

Haematological and spermatotoxic effects of ethylene glycol monomethyl ether in copper clad laminate factories.

OBJECTIVES: To investigate the effects of ethylene glycol monomethyl ether (EGME) on haematology and reproduction in exposed workers. METHODS: 53 Impregnation workers from two factories that make copper clad laminate with EGME as a solvent were recruited as the exposed group. Another group of 121 lamination workers with indirect exposure to EGME was recruited as the control group. Environmental monitoring of concentrations of EGME in air and biological monitoring of urinary methoxyacetic acid (MAA) concentrations were performed. Venous blood was collected for routine and biochemical analyses. Semen was collected from 14 workers exposed to EGME for sperm analysis and was compared with 13 control workers. RESULTS: Results of haematological examination showed that the haemoglobin, packed cell volume, and red blood cell count in the male workers exposed to EGME were significantly lower than in the controls. The frequency of anaemia in the exposed group (26.1%) was significantly higher than in the control group (3.2%). However, no differences were found between the female workers exposed and not exposed to EGME. After adjustment for sex, body mass index, and duration of employment, red blood cell count was significantly negatively associated with air concentrations of EGME, and haemoglobin, packed cell volume, and red blood cell count were significantly negatively associated with urinary concentrations of MAA. The pH of semen in the exposed workers was significantly lower than in the control workers, but there were no significant differences in the sperm count or sperm morphology between the exposed and control groups. CONCLUSION: It can be concluded that EGME is a haematological toxin, which leads to anaemia in the exposed workers. However, the data from this study did not support the theory of a spermatotoxic effect of EGME.

Field evaluation of a passive sampler for the exposure assessment of 2-methoxyethanol.

OBJECTIVE: This paper presents a field evaluation of 3 M 3500 passive badges for measuring 2-methoxyethanol (ME) in a humid working environment. METHODS: A total of 93 pairs of side-by-side active/passive samples, 48 pairs of duplicate active samples, 52 pairs of duplicate passive samples, and three groups of six replicate active/passive samples were compared. Three groups of six replicate active charcoal/active charcoal tube with drying tube samples were also compared to evaluate the humidity effect. RESULTS: No statistical difference was found between the passive badges and active samplers. Linear regression showed the correlation to be high (r = 0.992, slope = 0.973, n = 93) over the range of 0.17-163 ppm. The mean concentration difference was -0.34 ppm and the mean relative error was 3.50%. The intraclass correlation coefficients of 48 duplicate active samples and 52 duplicate passive samples were 0.994 and 0.989, respectively. The precision of replicate passive, active, and active/drying tube samples (n = 6) were 3.84%, 7.14%, and 5.12%, respectively. CONCLUSIONS: The humidity effect for active samples was insignificant at the low sampling rate (36.3 ml/min). It is therefore concluded that the use of the passive samplers to assess ME exposure produces comparable findings to that of active sampling.

Mouse models of tumor development in neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a prevalent familial cancer syndrome resulting from germ line mutations in the NF1 tumor suppressor gene. Hallmark features of the disease are the development of benign peripheral nerve sheath tumors (neurofibromas), which can progress to malignancy. Unlike humans, mice that are heterozygous for a mutation in Nf1 do not develop neurofibromas. However, as described here, chimeric mice composed in part of Nf1-/- cells do, which demonstrates that loss of the wild-type Nf1 allele is rate-limiting in tumor formation. In addition, mice that carry linked germ line mutations in Nf1 and p53 develop malignant peripheral nerve sheath tumors (MPNSTs), which supports a cooperative and causal role for p53 mutations in MPNST development. These two mouse models provide the means to address fundamental aspects of disease development and to test therapeutic strategies.

Detection of methyl ethyl ketone in urine using headspace solid phase microextraction and gas chromatography.

Headspace solid-phase microextraction coupled with gas chromatography/flame ionization detection was developed to measure urinary methyl ethyl ketone (MEK). A fused silica fiber coated with 75 microns carboxen/polydimethylsiloxane was used to extract urinary MEK. The optimal extraction conditions were obtained when temperature was 50 degrees C, extraction time was 15 minutes, and ammonium sulfate concentration was 0.5 g/mL. The optimal desorption temperature and time were 200 degrees C and 5 minutes, respectively. The concentration range of calibration curves was 27 to 8000 ng/mL of MEK. The within-day and between-day pooled coefficients of variation (9 concentrations, triplicate samples) were 5.4% and 8.8%, respectively. The limit of detection and limit of quantitation were 4.2 ng/mL and 21.6 ng/mL, respectively. The recovery (+/- standard deviation) of MEK was 100.2% +/- 8.6% (n = 3). MEK in urine was stable for at least 1 month when stored at -20 degrees C. This method proved to be applicable for the analysis of urinary MEK of exposed workers in a plastic material printing plant. We concluded that this new method is sensitive, inexpensive, simple, and reliable for measuring the occupational exposure of MEK.