A screening tool to prioritize public health risk associated with accidental or deliberate release of chemicals into the atmosphere.

The Chemical Events Working Group of the Global Health Security Initiative has developed a flexible screening tool for chemicals that present a risk when accidentally or deliberately released into the atmosphere. The tool is generic, semi-quantitative, independent of site, situation and scenario, encompasses all chemical hazards (toxicity, flammability and reactivity), and can be easily and quickly implemented by non-subject matter experts using freely available, authoritative information. Public health practitioners and planners can use the screening tool to assist them in directing their activities in each of the five stages of the disaster management cycle.

Determination of dimethyl sulfoxide and dimethyl sulfone in urine by gas chromatography-mass spectrometry after preparation using 2,2-dimethoxypropane.

A method for routinely determination of dimethyl sulfoxide (DMSO) and dimethyl sulfone (DMSO(2)) in human urine was developed using gas chromatography-mass spectrometry. The urine sample was treated with 2,2-dimethoxypropane (DMP) and hydrochloric acid for efficient removal of water, which causes degradation of the vacuum level in mass spectrometer and shortens the life-time of the column. Experimental DMP reaction parameters, such as hydrochloric acid concentration, DMP-urine ratio, reaction temperature and reaction time, were optimized for urine. Hexadeuterated DMSO was used as an internal standard. The recoveries of DMSO and DMSO(2) from urine were 97-104 and 98-116%, respectively. The calibration curves showed linearity in the range of 0.15-54.45 mg/L for DMSO and 0.19-50.10 mg/L for DMSO(2). The limits of detection of DMSO and DMSO(2) were 0.04 and 0.06 mg/L, respectively. The relative standard deviations of intra-day and inter-day were 0.2-3.4% for DMSO and 0.4-2.4% for DMSO(2). The proposed method may be useful for the biological monitoring of workers exposed to DMSO in their occupational environment.

Preliminary screening method for the determination of inorganic arsenic in urine.

A simple and rapid method was developed for the routine determination and classification of inorganic arsenic based on its clinical and forensic properties. Inorganic arsenic was isolated from urine by using copper granules, which was then made to react with ammonium molybdate in order to detect its presence with the naked eye. Based on studies of extraction and reaction conditions, e.g., reaction temperature and time, a colorimetric screening method was established. The reaction mixture was measured by a spectrophotometer, and there was linearity from 0.05 to 2.0microg/ml and the correlation coefficients of the calibration curves were greater than 0.99. The coefficients of intra-day variation at 0.2 and 2.0microg/ml of inorganic arsenic in urine were 9.6 and 4.2%, respectively (n=5). The minimum detectable level in urine is 0.03microg/ml, and it is possible to detect the lowest level of poisoning according to the published reports. The proposed method was applied to a poisoning case wherein the patient ingested NEOARSEN BLACK with alcohol, which contained 45% of arsenic trioxide. This method produced positive results in all the urine samples tested, and this method is useful for the screening of inorganic arsenic based on its clinical properties because it enables the detection of inorganic arsenic in urine without expensive equipment.

Extraction of amphetamines and methylenedioxyamphetamines from urine using a monolithic silica disk-packed spin column and high-performance liquid chromatography-diode array detection.

To overcome the limitations of solid-phase extraction, we developed a device comprising a spin column packed with octadecyl silane-bonded monolithic silica for extracting amphetamines and methylenedioxyamphetamines from urine. Urine (0.5mL), buffer (0.4mL), and methoxyphenamine (internal standard) were directly put into the preactivated column. The column was centrifuged (3000rpm, 5min) for sample loading and washed. The adsorbed analytes were eluted and analyzed by high-performance liquid chromatography, without evaporation. The results were as follows: linear curves (drug concentrations of 0.2-20microg/mL); correlation coefficients >0.99; detection limit, 0.1microg/mL. The proposed method is not only useful for drugs from biological materials but also highly reproducible for the analysis of these drugs in urine.

[Simplified rapid test for poisons in emergency and critical care medicine].

In emergency and critical care medicine, it is important to guess which poisons that patients have taken or been exposed to. The assumption and identification of save lives. Therefore an accurate screening system is required to treat acute poisoning patients in clinical toxicology. However, the ability of a medical center is not sufficient to analyze poisonous substances using analytical equipment. Moreover, the handling and maintenance of the equipment are tedious and costly. To improve these problems, a simple detection method should be established to identify poisons and to treat acute patients in emergency and critical care medicine. In our laboratory, various supports have been attempted for the training of analysts who cope with poisoning incidents and accidents due to toxic substances. Moreover, a simple detection method for toxic substances utilized in the medical center was developed without using expensive analysis apparatus. However, it is impossible to detect and identify chemical warfare agents in a clinical laboratory, because of possible secondary exposure to such dangerous substances in insufficient analytical laboratory equipment. Therefore it is necessary to contact related organizations possessing the proper facilities.

Histological brain alterations following prenatal methamphetamine exposure in rats.

When pregnant women abuse methamphetamine, the foremost concern is the potential adverse effect of this substance on fetal development. Clinical studies in humans have found that exposure to methamphetamine during brain development can cause neurobehavioral abnormalities, such as aggressive behavior, learning problems, and poor social adaptation. In the present study, we examined the effects of prenatal methamphetamine exposure on brain development in rats. The first group of pregnant rats was administered methamphetamine at a dose of 5 mg/kg/day during gestational day (GD 10 to GD 20 [MA]. The second group of pregnant rats was injected with saline vehicle only [SAL]. On GD 21 their fetuses were removed and fetal brains were observed. We found various types of morphological damage in MA fetal brains, including microgyria, ectopia, and hemorrhage. In some cases, abnormal distribution of the leptomeninx, such as breach or accumulation, was observed in addition to these histological abnormalities. Therefore, we examined the expression of laminin, which is an important component of the pia mater, in the fetal brains. However, Western blot analysis revealed that there was no difference in expression amount of laminin in whole fetal brain between the MA and SAL groups. We concluded that methamphetamine use during pregnancy can cause histological brain alterations in fetuses. Morphological alterations of brain seen in the present study and previous human studies following prenatal exposure to methamphetamine might be related to the neurobehavioral abnormalities seen in patients who had been exposed to methamphetamine in utero.

Single hair analysis of methamphetamine and amphetamine by solid phase microextraction coupled with in matrix derivatization.

A sensitive method for detection of methamphetamine (MA) and amphetamine (AP) in human hair was developed using solid phase microextraction (SPME) and one-pot derivatization. MA and AP were directly derivatized to N-propoxycarbonyl derivatives in an aqueous solution by propylchloroformate in a one-pot reaction before extraction by SPME. The derivatives were extracted to a coating of SPME from a headspace of the vial. The adsorbed derivatives were thermally desorbed in the injection port of a gas chromatograph. Pentadeuterated MA was used as an internal standard. The absolute recoveries of MA and AP from the spiked hair were 2.80-17.5%, respectively. The calibration curves showed linearity in the range of 0.05-20 ng/0.08 mg/vial for MA and 0.1-20 ng/0.08 mg/vial for AP in hair. Detection limits (S/N = 3) of MA and AP were 0.02 and 0.05 ng/0.08 mg/vial. The coefficients of variation of intraday were 1.04-26.4%. Additionally, this proposed method was applied to segmental analysis in clinical and medico-legal cases of MA intoxication.

[On-site screening of toxic substances in clinical laboratory and poisoning information system].

An accurate screening system is required to treat acute poisoning patients in clinical toxicology. However, the medical center analysis of poisonous substances using machines is not sufficient. Moreover, the handling and maintenance of such machines are tedious and costly. To improve these problems and employ effective information, we have developed a simple detection method and constructed a support system using the Internet. Various support systems have been attempted for the training of analysts who can cope with a poisoning incident (accident) involving toxic substances. Our simple detection method for toxic substances in the medical center was developed without using expensive analysis apparati. As technical support for the analysts of medical laboratories, the following items were completed: 1) training for analysts, 2) research of analytical techniques in the medical centers (accuracy management), 3) creation of an analysis manual, 4) construction of on-line analysis manuals, 5) construction of the poisoning information system on the Internet, 6) construction of a system for requesting analysis of poisoning, 7) a quick-detection method for toxic substances and 8) examination of the insurance application.

Miniaturized sample preparation method for determination of amphetamines in urine.

A simple and miniaturized sample preparation method for determination of amphetamines in urine was developed using on-column derivatization and gas chromatography-mass spectrometry (GC-MS). Urine was directly applied to the extraction column that was pre-packed with Extrelut and sodium carbonate. Amphetamine (AP) and methamphetamine (MA) in urine were adsorbed on the surface of Extrelut. AP and MA were then converted to a free base and derivatized to N-propoxycarbonyl derivatives using propylchloroformate on the column. Pentadeuterated MA was used as an internal standard. The recoveries of AP and MA from urine were 100 and 102%, respectively. The calibration curves showed linearity in the range of 0.50-50 microg/mL for AP and MA in urine. When urine samples containing two different concentrations (0.50 and 5.0 microg/mL) of AP and MA were determined, the intra-day and inter-day coefficients of variation were 1.4-7.7%. This method was applied to 14 medico-legal cases of MA intoxication. The results were compared and a good agreement was obtained with a HPLC method.

[Development of salicylic acid detector tube].

A detector tube was successfully devised for the screening of salicylic acid in urine. It, named "salicylic acid detector tube", consists of glass tube in which silica gel coated with 5% (w/w) of ferric chloride is enclosed. A pipette rubber cap was attached to an end of the tube, and another end was inserted into urine sample. The sample was then introduced into the tube, the color of the reagent immediately turned purple under the condition of more than 50 microg/ml of salicylic acid in urine. This device was useful for the emergency screening of salicylic acid in acute poisoning cases with aspirin.

Monitoring of urinary acrolein concentration in patients receiving cyclophosphamide and ifosphamide.

Acrolein, the metabolite of cyclophosphamide and ifosphamide, irritates mucous membranes and is considered pathogenetically important in hemorrhagic cystitis. Increasing fluid intake or administering sodium 2-mercaptoethanesulfonate (mesna), a thiol compound, can reduce the risk of this complication. We measured urinary acrolein concentrations using headspace-solid-phase microextraction gas chromatography and mass spectrometry (headspace-SPME-GC-MS) in 19 patients receiving cyclophosphamide and ifosphamide (36 occasions). Peak acrolein concentrations occurred at 1-12h (mean +/- S.D., 5.0+/-2.7) after starting therapy, ranging from 0.3 to 406.8 nM (39.7+/-76.7), with varying patterns over time. Maintaining high urine volume was important for preventing increases in urinary acrolein concentration, as urinary acrolein concentration tended to rise as urine volume decreased. Urinalysis detected occult blood in three cases, but the patients had no clinical symptoms of hemorrhagic cystitis. In clinical trials involving cyclophosphamide and ifosphamide, monitoring of urinary acrolein concentration could indicate when to take heightened preventive measures against hemorrhagic cystitis.