Hypersensitivity to 2-(2-butoxyethoxy)ethanol.
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Air Pollution, Indoor↗
Biomedical subjects
G Johanson
Publications and source records attributed to G Johanson.
Experimental data from closed chamber gas uptake studies in rodents suggest lower uptake rate of chemical than calculated from literature values on alveolar ventilation.
Experimental data obtained in vivo with the closed-chamber gas uptake technique have been reported for a series of volatile chemicals. Pharmacokinetic analyses of these data have been performed either by using a two-compartment model or physiological models. In the former the transfer rate of chemical from ambient air to body is defined by the clearance of uptake. In the latter models the transfer rate depends on alveolar ventilation, cardiac output, and blood: air partition coefficient. In this communication we describe the quantitative relationship between clearance of uptake and alveolar ventilation, cardiac output, and blood: air partition coefficient. Theoretical values of clearance of uptake were calculated for a variety of volatile chemicals using literature data on alveolar ventilation, cardiac output, and blood: air partition coefficient. For most chemicals the experimentally determined values in rats and mice were about 60% of the theoretical values. This suggests that the inhalatory uptake rate of chemical may be overestimated if literature values of alveolar ventilation are used in physiological pharmacokinetic models for rodents.
Animals↗
Facial injuries due to criminal violence: a retrospective study of hospital attenders.
The material comprised 222 assault victims whose injuries required attention at the Departments of Oral Surgery and Ear, Nose, and Throat diseases, the Central Hospital in Falun or corresponding departments at the Karolinska Institutet, Stockholm or the University Hospital in Huddinge. Information was obtained from patient records. One hundred and thirty-eight patients had fractures and the remainder had flesh-wounds, haematomas or swellings. The most frequent fracture site was the nasal bone followed by the jaws. Forty-one per cent of the patients in Falun and 28 per cent in Stockholm reported the assaults to the police: in Falun the proportion of women victims who reported the assault was significantly higher than those who did not. The willingness to notify the police of the violence was not influenced by the use of drugs or the seriousness of the injuries. The study showed that violence in suburban Stockholm was aggravated: one-third of the patients in the study required hospitalization compared to a quarter in a rural area.
Adolescent↗
Root development of the lower third molar and its relation to chronological age.
Methods based on radiological, distinguishable stages of tooth formation can be used to estimate chronological age in young persons. The best precision and accuracy of these methods of age estimation is obtained when many teeth are under development and when the individual growth rate is rapid. That is during early years-in childhood. After an age of about 14 years it becomes more difficult since all permanent teeth but the wisdom teeth have completed their development and only these remain to be used for age estimation. The aim of this study was to examine the radiological development of the root of the mandibular third molar and to explore its usefulness in age estimation. Also the differences between two independent observers were studied. The observers classified the development of the mandibular third molars, as seen in a panoramic radiograph, into seven defined stages. The two observers agreed in about 84% of the cases in their registration of the different stages, but a significant difference was found between the observers. The mineralisation of the third molar's root was found to start at the age of 15 years and the root was fully formed at about 20 years. Some minor differences were found between sexes in the time sequence of the mineralisation. The study also shows that there is a rather low precision in the age estimation with the method used. In general, a standard deviation of about 1 to 2 years was found around the mean age of the different developmental stages.
Adolescent↗
New Swedish occupational standards for some organic solvents.
In 1987, the Swedish government requested a unique investigation of the consequences of a 50% reduction of permissible exposure levels (PEL) for organic solvents. As a result, 29 solvents were investigated and for 25 of them a reduction--if not to 50%--was suggested. For 13 of the solvents, there existed scientific arguments for a reduction of the PEL. For 12 solvents, no specific biomedical information was available. Presumed interactions between solvents may have influenced the decisions, but technological/economic feasibility criteria may also have been used by the regulators. This suggests that the use of technological/economic feasibility criteria can give lower PELs than health criteria. This is within the intentions of the Swedish Work Environment Act.
Acetates↗
Gas chromatographic determination of butoxyacetic acid in human blood after exposure to 2-butoxyethanol.
Venous blood samples from five male volunteers exposed to 20 ppm 2-butoxyethanol (BE) for 2 h were collected at 0, 2, 4, and 6 h from the start of exposure and analyzed by gas chromatography after simultaneous ion-pair extraction and derivatization with pentafluorobenzyl bromide. Butoxyacetic acid (BAA), a major metabolite of BE, was found in all samples except those collected prior to exposure. This is the first time to our knowledge that the analysis of BAA in human blood has been reported. Concentrations of BAA in blood ranged from 22 to 60 microM. These concentrations were about two orders of magnitude lower than those causing swelling and hemolysis of human erythrocytes in vitro. The BAA blood level peaked after 2-4 h. The decrease between 4 and 6 h indicates an average half-time of BAA in blood of about 4 h, which is in accordance with previously observed half-times in urine. The low renal clearance of BAA (22-39 ml/min) indicates extensive binding to blood proteins and poor tubular secretion of the substance. Binding of BAA to blood components is also indicated by the low apparent volume of distribution of approximately 15l.
Absorption↗
Percutaneous uptake and kinetics of methyl isobutyl ketone (MIBK) in the guinea-pig.
Continuous intravenous infusion of 0.478 mumol/min methyl isobutyl ketone (MIBK) was performed for 30 min in pentobarbital-anesthetized guinea-pigs. Epicutaneous exposure for 150 min was carried out 2.5 h later after administration of MIBK to a sealed glass ring on the clipped back of the animals. Arterial blood was analyzed for MIBK by gas chromatography. Blood clearance averaged 201 ml.min-1.kg-1 body wt. A maximum percutaneous uptake of 1.1 mumol.min-1.cm-2 was reached 10-45 min after the onset of exposure and decreased to 0.56 mumol.min-1.cm-2 during the latter part of exposure.
Administration, Cutaneous↗
Modelling of respiratory exchange of polar solvents.
Physiologically based pharmacokinetic (pbpk) models are frequently used to describe the kinetics of inhaled gases and vapours. In these models the conducting airways of the respiratory tract are generally assumed to act as inert tubes. The function of the inert tubes is merely to conduct the vapour to the alveolar regions where the actual exchange between ambient air and body takes place. Such an 'inert tube' model may be adequate to describe the inhalation and exhalation kinetics of inert vapours, for example non-polar solvents which have a low water solubility. Experimental data suggest, however, that the 'inert tube' model may be erroneous for polar solvents which have a high water solubility. To explore this possibility further a tentative pbpk model was developed. Model structure and parameters were obtained from the literature on lung anatomy and physiology and by visual fitting to experimental acetone, carbon dioxide, diethyl ether and ethanol data. The model was written and solved by spreadsheet programming on a personal computer. Simulations were carried out to illustrate the difference between end-exhaled and alveolar air and how water solubility and workload influence the uptake and excretion kinetics of polar solvents. It is concluded that the model is valuable for predicting the lung kinetics of polar vapours under various circumstances. It may therefore be useful in the development of biological monitoring methods based on breath sampling and help us to understand and to explain experimental data.
Computer Simulation↗
Percutaneous absorption of 2-butoxyethanol vapour in human subjects.
Four male volunteers were exposed at rest for two periods of two hours, separated by a one hour exposure free interval, to 50 ppm 2-butoxyethanol (BE) vapour generated in an exposure chamber. During the first two hour period the men were exposed by mouth only via a respiratory valve connected by tubes to the exposure chamber. During the second exposure period the men were exposed by skin only while sitting inside the exposure chamber, naked except for shorts, and wearing a respiratory protection mask supplied with compressed air. Capillary blood samples were collected at regular intervals and analysed for BE by a gas chromatographic method. Two experiments separated by at least two weeks were carried out with each volunteer, one at "normal" (23 degrees C, 29% relative humidity) and one at raised (33 degrees C, 71% relative humidity) air temperature and humidity in the chamber. The average concentration in blood and the calculated rate of uptake of BE were about three to four times higher during dermal exposure than during inhalation exposure. These experiments suggest that dermal uptake of BE accounts for about 75% (45-85% in individual experiments) of the total uptake during whole body exposure to BE vapour. Thus it appears that the use of a respiratory protection mask will not protect efficiently against exposure to BE vapours. A tendency towards increased percutaneous absorption rate was seen in the raised temperature and humidity condition.
Adult↗
A simulation study of physiological factors affecting pharmacokinetic behaviour of organic solvent vapours.
At a given external dose of an inhaled chemical the internal dose or the amount absorbed into the body varies depending on pulmonary ventilation and other physiological factors. Such variability is of concern in the development of biological indices of occupational exposure to organic solvent vapours. This paper discusses how physiological factors may influence the pharmacokinetic behaviour of inhaled organic solvent vapours, especially in relation to monitoring of biological exposure. To illustrate the discussion a computer based physiological pharmacokinetic model was used describing quantitatively the influence of body size, body fat content, and sex on the pharmacokinetic behaviour of trichloroethylene. Absorption, distribution, metabolism and excretion of trichloroethylene were found to vary according to the different anatomical features of men and women. Body build (body weight and body fat content) also affected the pharmacokinetic behaviour of this solvent.
Body Constitution↗
Effects of consumption of ethanol on the biological monitoring of exposure to organic solvent vapours: a simulation study with trichloroethylene.
This study illustrates possible influences of consumption of ethanol on the pharmacokinetic behaviour of inhaled trichloroethylene (TRI) in relation to biological monitoring of exposure. The results were obtained for a standard male worker of 70 kg by physiologically based pharmacokinetic modelling. Depending on the pattern of consumption of ethanol, enzyme inhibition or induction was assumed to prevail in this worker. The inhibition and induction were modelled by assuming competitive metabolic interaction between TRI and ethanol and increased maximum velocity (Vmax) of TRI metabolism respectively. Ingestion of moderate amounts of ethanol before the start of work or at lunch time, but not at the end of work, caused pronounced increases in blood TRI concentrations and decreases in the urinary excretion rates of TRI metabolites, this effect lasting until the next day. The effects were smaller the higher the exposure concentration of TRI. Induction of TRI metabolism, supposedly by consumption of ethanol the previous evening, caused only small changes in the pharmacokinetic profile at 50 ppm, but appreciable changes at 500 ppm.
Alcohol Drinking↗
Injuries due to violent crimes: a study of police reported assaults during 1979, 1982 and 1985 in a police district of a suburb of Stockholm, Sweden.
The study is based on a sample of 249 violent crimes reported to the police in Huddinge during 1979, 1982 and 1985. Throughout the period it was found that the violence increased not only in number but also in seriousness. Most of the cases took place during weekends and in the evenings. Different accommodations were the most common scene of the crime. The majority of victims and offenders were men. Many were foreign citizens. Three-quarters of the victims had some kind of injury, mostly haematomata and swellings. The left side of the face was the anatomical region mostly hit.
Adolescent↗
Dose-dependent kinetics of inhaled methylethylketone in man.
Physiologically based stimulation of earlier human inhalation exposure to methylethylketone (MEK) at a concentration of 200 ppm for 4 h suggested that the kinetics were dose-dependent. Two male volunteers were therefore exposed to MEK for 4 h at 3 exposure concentrations: 25, 200 and 400 ppm. Blood MEK concentrations were monitored during and after exposure. The results showed clearly that the kinetics of MEK were dose-dependent at higher exposure concentrations. Simulated exposure to MEK for 8 h suggests that saturation kinetics are reached at an exposure concentration of 50-100 ppm, depending on the physical work load.
Administration, Inhalation↗
[The use of dental log-keeping in order to trace and identify lost persons].
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Dental Records↗
Biological monitoring of exposure to ethylene glycol ethers.
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Air↗
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↗
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↗