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Biomedical subjects

G Johanson

Publications and source records attributed to G Johanson.

At least 73 records · Page 4Linked to original sources
PubMed1989

Analysis of ethylene glycol ether metabolites in urine by extractive alkylation and electron-capture gas chromatography.

Alkoxyacetic acids are metabolically formed and excreted in urine after exposure to ethylene glycol monoalkyl ethers (alkoxyethanols) or their acetate esters. This paper presents a sensitive method based on extractive alkylation for determination of alkoxyacetic acids in urine. Alkoxyacetate ions were extracted from 200 microliters urine into methylene chloride, with tetrabutylammonium acting as counter ion, and derivatized with pentafluorobenzyl bromide in a single step. After separation of the methylene chloride phase, evaporation, and dissolution of the residues in hexane the esters were analyzed by fused silica capillary column gas chromatography and electron capture detection. The esters formed were stable for at least 2 weeks at room temperature. The limit of quantification was estimated to 2 microM (corresponding to an injected amount of 2 pg) for methoxyacetic (MAA) and ethoxyacetic acid (EAA) in urine. The corresponding values for butoxyacetic acid (BAA) were 4 microM and 5 pg, respectively. The detector response was linear up to 80 microM and the formation of derivative at least up to 1 mM. The method error may be reduced by using a second alkoxyacetic acid derivative, EAA, BAA or 2-pentoxyacetic acid (PAA), as an internal standard. The sensitivity, stability, reduced number of extractions, and small volumes of reagents and sample needed make the present method useful in biomonitoring of occupational exposure to ethylene glycol ethers.

Alkylation↗
PubMed1988

Aspects of biological monitoring of exposure to glycol ethers.

Glycol ethers are frequently used as solvents, detergents, and emulsifiers alone or as components in industrial and consumer products. The monomethyl and monoethyl ethers of ethylene glycol, and their acetate esters, are teratogenic and embryotoxic and cause testicular damage in laboratory animals, while the monobutyl ether causes hemolysis of the red blood cells. The adverse effects are attributed to the acid metabolites methoxy-, ethoxy- and butoxyacetic acid, respectively. The glycol ethers may readily enter the body by inhalation as well as dermal uptake. Biological monitoring of exposure to glycol ethers has therefore been suggested. This paper reviews physical properties, occurrence, analysis, toxicity, and toxicokinetics of the most common glycol ethers and then discusses toxicokinetic aspects of biological monitoring. The effect of physical exercise and the relative importance of respiratory and percutaneous absorption on the internal exposure to glycol ethers are illustrated. Monitoring the acid metabolite in urine is suggested as the best index of exposure. Intra- and inter-individual variability, dose-dependent toxicokinetics, and metabolic induction and inhibition are examples of possible sources of error in the estimation of internal exposure from the urinary excretion of acid metabolite.

Adult↗
PubMed1988

Spreadsheet programming--a new approach in physiologically based modeling of solvent toxicokinetics.

Physiological models are useful tools in the understanding of organic solvent toxicokinetics. An approach is presented where a physiological model is designed and solved by means of a spreadsheet macro instruction on a personal computer. The spreadsheet template is easy to use. Model parameters are entered and stored in tabular form, and any parameters and variables may be plotted. The model may be changed by editing the spreadsheet template, allowing compartments to be added, nonlinear metabolism to be introduced, etc. Accordingly, the kinetics of any substance and its metabolites, and any route of exposure may be modeled. The spreadsheet approach of physiologically based kinetic modeling is illustrated by simulating inhalation exposure to four organic solvents (acetone, 2-butoxyethanol, methylene chloride and styrene) in humans at various work loads. The results of the simulations are graphically compared with experimental data. By separating resting and working muscle tissue, the model successfully predicted the solvent concentrations not only in arterial but also in venous blood samples at various work loads (shown for acetone and methylene chloride).

Acetone↗
PubMed1988

Liquid/air partition coefficients of six commonly used glycol ethers.

The toxicokinetics of organic solvents depend largely on their tissue solubilities. Liquid/air partition coefficients (pcs) of six commonly used glycol ethers (2-methoxyethanol (ME), 2-ethoxyethanol (EE), 2-isopropoxyethanol (PE), 2-butoxyethanol (BE), 2-ethoxyethyl acetate (EEA), and 1-methoxy-2-propanol (MP] were determined in vitro using a head space technique. The liquids used were physiological saline, human blood, and olive oil. The pcs were calculated after gas chromatographic quantification of the glycol ethers in the air phase. The water-air pcs ranged from 3800 to 36,000, increasing in the order EEA, BE, MP, PE, EE, ME. These values corresponded closely to the blood/air pcs with one exception--EEA could not be detected in the air phase after addition to blood. The oil/air pcs ranged from 530 to 5400, increasing in the order ME, MP, EE, PE, EEA, BE.

Air↗
PubMed1988

Influence of water on the percutaneous absorption of 2-butoxyethanol in guinea pigs.

Anesthetized guinea pigs were exposed for 2 h to aqueous solutions (5-100%, corresponding to 0.38-7.6 mol/l) of 2-butoxyethanol (ethylene glycol monobutyl ether, BE) by epicutaneous administration in a sealed glass ring on the clipped back of the animal. After a recovery period of 2 h, the animals were exposed to undiluted BE in a second glass ring for an additional period of 2 h. Blood samples were obtained via the carotid artery and analyzed for BE by gas chromatography. To reduce the influence of interindividual variation in the kinetics, the dermal uptake rate of BE from the water solutions was expressed relative to that of the undiluted solvent obtained from the second exposure period of the same animal. The relative percutaneous uptake rates were approximately equal from the 5, 10, 20, and 100% solutions of BE, while they were approximately twice as high from the 40 and 80% solutions. The results suggest that water facilitates the percutaneous absorption of BE.

Animals↗
PubMed1988

Percutaneous absorption of 2-butoxyethanol in man.

The percutaneous absorption of the commonly used glycol ether 2-butoxyethanol (ethylene glycol monobutyl ether) was investigated in 12 exposure experiments with five men. The subject kept two or four fingers immersed in neat butoxyethanol for 2 h. Arterialized capillary blood samples were collected from the other hand before, during, and up to 4 h after the exposure and analyzed for butoxyethanol by gas chromatography. Urine was collected for 24 h and analyzed for the metabolite butoxyacetic acid, also by gas chromatography. The presence of butoxyethanol in blood and of butoxyacetic acid in urine confirmed that butoxyethanol enters the systemic circulation in man in vivo during dermal exposure. Percutaneous uptake rates were calculated from measured blood levels of butoxyethanol with the use of kinetic parameters (clearance and volume of distribution) obtained in earlier experiments with the same subjects. The uptake rates ranged from 7 to 96 nmol.min-1.cm-2. The results indicate that persons exposing large portions of their skin to butoxyethanol are at risk of absorbing acutely toxic doses.

Ethylene Glycols↗
PubMed1986

Elimination kinetics of 2-butoxyethanol in the perfused rat liver--dose dependence and effect of ethanol.

The elimination kinetics of 2-butoxyethanol (ethylene glycol monobutyl ether, EGBE) were studied in the once-through isolated perfused rat liver system in the presence and absence of ethanol. Dose-dependent Michaelis-Menten kinetics in the elimination of EGBE were observed in the investigated concentration range. The apparent Michaelis constant range from 0.32 to 0.70 mM while the maximum elimination rate ranged from 0.63 to 1.4 mumol/min/g liver (parallel tube model) in six different experiments. The maximum intrinsic clearance varied between 0.7 and 2.0 ml/min/g liver. In the presence of 17.1 mM ethanol (0.1%) the extraction ratio of EGBE decreased from 0.44 to 0.11. The results support the hypothesis that EGBE is mainly metabolized via oxidation by alcohol dehydrogenase in the rat liver. The concentration dependence occurred at plausible in vivo doses.

Animals↗
PubMed1986

Physiologically based pharmacokinetic modeling of inhaled 2-butoxyethanol in man.

The arterial blood concentration of 2-butoxyethanol (ethylene glycol monobutyl ether) was simulated in a physiologically based pharmacokinetic model developed for a 70-kg man. Elimination data (Vmax and Km) were extrapolated from the perfused rat liver, while flows and volumes were from the literature. Simulated inhalation exposure to 2-butoxyethanol at 20 ppm (0.8 mmol/m3) and physical exercise at 50 W agrees well with the results from experimental exposure of human volunteers under identical conditions. In further simulations, the marked effects of physical exercise and co-exposure to ethanol are illustrated. The relatively rapid decay of 2-butoxyethanol in all compartments indicates that the parent compound is not likely to accumulate in the body. Further, linear kinetics may be expected at occupational inhalation exposure to 2-butoxyethanol. The study serves as an example of how a physiologically based pharmacokinetic model may be used to illustrate some aspects of occupational solvent exposure.

Administration, Inhalation↗
PubMed1986

Toxicokinetics of inhaled 2-butoxyethanol (ethylene glycol monobutyl ether) in man.

Seven male volunteers were exposed to 2-butoxyethanol at the Swedish occupational exposure limit (20 ppm or 0.85 mmol/m3) during light physical exercise (50 W) on a bicycle ergometer. The exposure took place in an exposure chamber and lasted 2 h. Expired air was collected at regular time intervals for estimation of the respiratory uptake of the solvent. Arterialized capillary blood and urine were sampled during and after the exposure period and analyzed for 2-butoxyethanol and its metabolite butoxyacetic acid. A new sensitive method for analyzing 2-butoxyethanol in biological specimens is described. 2-Butoxyethanol was derivatized with pentafluorobenzoyl chloride and analyzed by gas chromatography with electron capture detection. The respiratory uptake of 2-butoxyethanol averaged 10.1 mumol/min or 57% of the inspired amount. The concentration in blood reached a plateau level of 7.4 mumol/l. The apparent values of elimination half-time, mean residence time, total blood clearance, and steady-state volume of distribution were 40 min, 42 min, 1.2 1/min and 54 l, respectively. The amount of 2-butoxyethanol excreted in urine was less than 0.03% of the total uptake, while that of butoxyacetic acid ranged from 17 to 55%.

Acetates↗
PubMed1986

Percutaneous uptake rate of 2-butoxyethanol in the guinea pig.

The percutaneous absorption rate and elimination kinetics of 2-butoxyethanol (ethylene glycol monobutyl ether) were estimated in the guinea pig. An intravenous bolus dose of 42 or 92 mumol/kg of body weight was administered into the jugular vein of 10 pentobarbital-anesthetized animals. Epicutaneous administration of 2-butoxyethanol followed 2.5 h later in one or two sealed glass rings on the clipped back of the animal. Arterial blood samples were obtained and then analyzed for 2-butoxyethanol by gas chromatography. Following the intravenous dose, the apparent total clearance and mean residence time of 2-butoxyethanol were calculated to be 128 ml X min-1 X kg-1 (SD 30%) and 4.7 min (SD 30%), respectively. During the latter part of the 2-h skin exposure, the concentration of 2-butoxyethanol in the blood appeared to level off at an average concentration of 21 mumol/l (SD 45%). The absorption rate through the skin was estimated to be 0.25 (range 0.05-0.46) mumol X min-1 X cm-2 (SD 49%). The skin uptake rate in the guinea pig was extrapolated to man for a comparison of the percutaneous absorption of liquid solvent with respiratory uptake of solvent vapor. The extrapolation indicated a risk of acute adverse effects when large areas of the skin are exposed to 2-butoxyethanol.

Animals↗
PubMed1985

The effects of ethanol on the kinetics of toluene in the perfused rat liver.

In the isolated perfused rat liver as a metabolizing system, ethanol (17.1 mM) added directly to the perfusion medium decreased the extraction ratio of toluene (concentration range 0.2-16.4 microM) by 17-33%. The Michaelis-Menten constant, Km, was calculated to 3.9 microM and the maximum elimination rate, Vmax, to 10.8 and 11.4 nmol/min/g in the absence and presence of ethanol, respectively. The results indicate that the inhibitory effect of ethanol on the elimination of toluene is competitive. In a physiologically operating system, it must be taken into account that the elimination of toluene, apart from being influenced by the hepatic blood flow, may also be affected by lowered enzyme capacity for the metabolism of toluene.

Animals↗
PubMed1984

Denture marking.

Reluctance about the identification marking of dentures has been the result of high costs and technical marking problems. The ID band system described here is inexpensive, fast, and requires no expensive special equipment. Embedding the band in a suitable part of the denture provides fully legible, radiopaque, lasting evidence of the denture wearer's identity. Since 1981, all dentures made in Sweden have been legally required to be marked.

Adult↗
PubMed1981

Education in forensic odontology.

The present state of education in forensic odontology is surveyed. Courses in the subject within dental schools are directed mainly towards dental students (lectures, seminars, demonstrations), but also towards chairside assistants, dental hygienists and laboratory technicians. Extra-mural postgraduate education is directed towards private practitioners, but includes community dental health officers and colleagues serving in the defence forces; the question of 'qualification' is discussed. Finally, a wide range of non-dental personnel is approached (medical and law students, community health officers, forensic medical experts, police technicians etc.). The authors concur that independent departments of forensic odontology are now needed at all major dental schools; only here can the manpower and the facilities be developed to cope with this wide spectrum of education, and only here can recognized academic positions be ensured for those who--together with other specialists--must handle an increasing extra-mural case load, from which all material for education and research is subsequently to be derived.

Education, Dental↗
PubMed1981

The dental X-ray file of crew members in the Scandinavian Airlines System (SAS).

In 1977, the Scandinavian Airlines System (SAS) established a dental X-ray file of all crew members. Its aim was to have immediately available an adequate set of physical antemortem data useful for identification in case of a fatal crash. Recently, an investigation into the quality and suitability of this material was carried out. The radiographs of 100 Danish, 100 Norwegian, and 100 Swedish pilots were picked at random and evaluated for formal deficiences, technical deficiencies, treatment pattern as useful for identification purposes, and the presence of pathology. The major results of the investigation were that a number of formal and technical deficiencies were disclosed, that the treatment pattern would seem adequate for identification purposes, and that a number of pathological findings were made, several of which had to be considered possible safety risks in the form of barodontalgia.

Adult↗