Concentration In Alveolar Air Research Articles

Physiologically Based Modeling of n-Hexane Kinetics in Humans Following Inhalation Exposure at Rest and Under Physical Exertion: Impact on Free 2,5-Hexanedione in Urine and on n-Hexane in Alveolar Air

We used a modified physiologically based pharmacokinetic (PBPK) to describe/predict n-hexane (HEX) alveolar air concentrations and free 2,5-HD urinary concentrations in humans exposed to n-HEX by inhalation during a typical workweek. The effect of an increase in workload intensity on these two exposure indicators was assessed and, using Monte Carlo simulation, the impact of biological variability was investigated. The model predicted HEX alveolar air concentrations at rest of 19.0 ppm (25 ppm exposure) and 38.7 ppm (50 ppm exposure) at the end of the last working day (day 5), while free 2,5-HD urinary concentrations of 3.4 μ mol/L (25 ppm) and 6.3 μ mol/L (50 ppm) were predicted for the same period (last 4.5 hours of Day 5). Monte Carlo simulations showed that the range of values expected to occur in a group of 1000 individuals exposed to 50 ppm of HEX (95% confidence interval) for free 2,5-HD (1.7–14.7 μ mol/L) is much higher compared with alveolar air HEX (33.4–46 ppm). Simulations of exposure at 50 ppm with different workloads predicted that an increase in workload intensity would not greatly affect both indicators studied. However, the alveolar air HEX concentration is more sensitive to modifications of workload intensity and time of sampling, after the end of exposure, compared with 2,5-HD. The PBPK model successfully described the HEX alveolar air concentrations and free 2,5-HD urinary concentrations measured in human volunteers and is the first, to our knowledge, to describe the excretion kinetics of free 2,5-HD in humans over a 5-day period.

Neuromotor effects of acute ethanol inhalation exposure in humans: a preliminary study.

Ethanol (ETOH) is added to unleaded gasoline to decrease environmental levels of carbon monoxide from automobiles emissions. Therefore, addition of ETOH in reformulated fuel will most likely increase and the involuntarily human exposure to this chemical will also increase. This preliminary study was undertaken to evaluate the possible neuromotor effects resulting from acute ETOH exposure by inhalation in humans. Five healthy non-smoking adult males, with no history of alcohol abuse, were exposed by inhalation, in a dynamic, controlled-environment exposure chamber, to various concentrations of ETOH (0, 250, 500 and 1,000 ppm in air) for six hours. Reaction time, body sway, hand tremor and rapid alternating movements were measured before and after each exposure session by using the CATSYS 7.0 system and a diadochokinesimeter. The concentrations of ETOH in blood and in alveolar air were also measured. ETOH was not detected in blood nor in alveolar air when volunteers were exposed to 250 and 500 ppm, but at the end of exposure to 1,000 ppm, blood and alveolar air concentrations were 0.443 mg/100ml and 253.1 ppm, respectively. The neuromotor tests did not show conclusively significant differences between the exposed and non-exposed conditions. In conclusion, this study suggests that acute exposure to ethanol at 1,000 ppm or lower or to concentrations that could be encountered upon refueling is not likely to cause any significant neuromotor alterations in healthy males.

Occupational exposure to trihalomethanes in indoor swimming pools

The study evaluated occupational exposure to trihalomethanes (THMs) in indoor swimming pools. Thirty-two subjects, representing the whole workforce employed in the five public indoor swimming pools in the city of Modena (Northern Italy) were enrolled. Both environmental and biological monitoring of THMs exposure were performed. Environmental concentrations of THMs in different areas inside the swimming pools (at the poolside, in the reception area and in the engine-room) were measured as external exposure index, while individual exposure of swimming pool employees was estimated by THMs concentration in alveolar air. The levels of THMs observed in swimming pool water ranged from 17.8 to 70.8 μg/l; the mean levels of THMs in ambient air were 25.6±24.5 μg/m 3 in the engine room, 26.1±24.3 μg/m 3 in the reception area and 58.0±22.1 μg/m 3 at the poolside. Among THMs, only chloroform and bromodichloromethane were always measured in ambient air, while dibromochloromethane was detected in ambient air rarely and bromoform only once. Biological monitoring results showed a THMs mean value of 20.9±15.6 μg/m 3. Statistically significant differences were observed according to the main job activity: in pool attendants, THMs alveolar air were approximately double those observed in employees working in other areas of the swimming pools (25.1±16.5 μg/m 3 vs. 14.8±12.3 μg/m 3, P<0.01). THMs in alveolar air samples were significantly correlated with THMs concentrations in ambient air ( r=0.57; P<0.001). Indoor swimming pool employees are exposed to THMs at ambient air levels higher than the general population. The different environmental exposure inside the swimming pool can induce a different internal dose in exposed workers. The correlation found between ambient and alveolar air samples confirms that breath analysis is a good biological index of occupational exposure to these substances at low environmental levels.

Estimation of Background Exposure to Toluene Using a Physiologically‐Based Kinetic Model

Estimation of Background Exposure to Toluene Using a Physiologically‐Based Kinetic Model: Crispin H. Pierce, et al. Department of Environmental Health, University of Washington—Estimation of environmental exposure to toxicants has generally been limited to concentration measurements in air, water, and foods. Measurement of background levels of toxicants in biological tissues for this purpose has been limited by analytical detection. After developing a sensitive headspace GC‐MS method, we conducted 33 controlled human exposures of 50 ppm 1Hg8‐toluene and 50 ppm 2H8‐toluene for 2 h, and measured concentrations in blood and breath for 100 h post‐exposure. Blood and breath samples from a separate cohort of 9 men exposed to 2H8‐toluene only were also measured for background 1H ‐toluene levels. A physiologically‐based kinetic (PBK) model, previously constructed and validated in an analysis of the 2H8‐toluene data, was used to predict the level of ambient 1H8‐toluene exposure that produced the observed breath levels. The model‐derived estimate of mean background 1H8‐toluene exposure was 47 ± 44 ppb (mean ± s.d.), which is consistent with indoor air measurements from this and previous studies of 3‐27 ppb and outdoor measurements of 2‐43 ppb. According to the PBK model, background exposure was expected to produce an average blood concentration of 5.9 nmol/l, which was within a measured range of 3‐16 nmol/l, and a corresponding alveolar air concentration of 310 nmol/m3, within a range of 138‐764 nmol/m3. This work extends the use of physiologic modeling to back‐predict environmental dose, and found that significant differences in inter‐individual 1H8‐toluene background exposures exist.

Evaluation of dermal and respiratory chloroform exposure in humans.

Chloroform is a known contaminant of chlorinated drinking water and of swimming pool water disinfected with chlorine or one of its derivatives. Few data exist regarding the importance of dermal and inhalation exposure routes to the chloroform body burden resulting from domestic and recreational use of chlorinated water. In our experimental study involving 11 male swimmers, we quantified the body burden resulting from exposure to various concentrations of chloroform in water and air of an indoor swimming pool, during a daily 55-min exercise period. From the first to the sixth exercise period, CHCl3 mean concentration in water was increased from 159 micrograms/l to 553 micrograms/l. Corresponding mean air CHCl3 level ranged from 597 ppb to 1630 ppb. To dissociate the dermal exposure route from that of inhalation, swimmers used scuba tanks during an additional exercise period. Chloroform concentrations were measured in alveolar air before and after each exercise period, as well as after 35 min of physical activity. Chloroform levels in water and air were measured every 10 min. We examined the relationship between alveolar air concentration (a measure of body burden) at 35 and 55 min and environmental chloroform concentrations by using multiple regression models. The natural logarithm of alveolar air concentration was strongly correlated with aqueous chloroform concentration both at 35 (p2 < 0.001, r2 = 0.75) and 55 min (p < 0.001, r2 = 0.86). The relationship with air concentrations was also statistically significant (35 min: p < 0.001, r2 = 0.58, 55 min: p < 0.001, r2 = 0.63).(ABSTRACT TRUNCATED AT 250 WORDS)

Chloroform in alveolar air of individuals attending indoor swimming pools.

Alveolar air samples were collected from 163 subjects at indoor swimming pools and from 77 nonexposed subjects. Chloroform was present in all samples collected from exposed subjects (median = 695.02 nmol/m3). It was found at very low levels in 53% of samples from nonexposed subjects. Alveolar air chloroform levels from people attending indoor swimming pools (mean value within each sampling session) were correlated with environmental air concentration (r = 0.907, p = .002). Analysis of variance showed that levels of chloroform in alveolar air depend on environmental air concentration, age, intensity of the sport activity, and kind of swimming. Chloroform levels in samples collected from competitive swimmers versus nonswimming visitors were different (F = 10.911, p = .001). Moreover, their pattern of swimming may affect chloroform concentration in alveolar air. The analysis of chloroform in alveolar air assesses indoor exposure in healthy subjects simply and at low cost.

Methylene Chloride Exposure in Industrial Workers

Methods of environmental and biological monitoring were applied in order to evaluate exposure to methylene chloride in workers operating in a factory where this substance was used as a solvent. For the measurement of methylene chloride in environmental concentration, the ambient air was sampled by using personal passive dosimeters. The activated charcoal was desorbed with CS2 and injected into a gas chromatograph connected with a mass spectrometer. The biological monitoring of exposed workers was performed by determining the concentration of CO in alveolar air (CA, ppm) and methylene chloride in urine (Cu, μ/L). Immediately after the end of the exposure, a urine sample was collected avoiding solvent loss and using gas-tight samplers. Excretion level in urine was determined by using headspace gas chromatography linked to a mass spectrometer. The CO was determined at the end of the shift by using a portable instrument. A group of 20 workers (12 smokers and 8 nonsmokers) in the manufacturing plant were monitored. No significant correlation was observed among the CO of all subjects and the concentration of methylene chloride in ambient air. When those workers who smoked were removed from the analysis, a correlation between the methylene chloride concentration in air and the CO concentration in alveolar air was found. Significant linear correlation was found between the environmental concentration of methylene chloride in the breathing zone and methylene chloride concentration in urine.

METHYLENE CHLORIDE EXPOSURE IN INDUSTRIAL WORKERS

Methods of environmental and biological monitoring were applied in order to evaluate exposure to methylene chloride in workers operating in a factory where this substance was used as a solvent. For the measurement of methylene chloride in environmental concentration, the ambient air was sampled by using personal passive dosimeters. The activated charcoal was desorbed with CS2 and injected into a gas chromatograph connected with a mass spectrometer. The biological monitoring of exposed workers was performed by determining the concentration of CO in alveolar air (CA, ppm) and methylene chloride in urine (Cu, mu/L). Immediately after the end of the exposure, a urine sample was collected avoiding solvent loss and using gas-tight samplers. Excretion level in urine was determined by using headspace gas chromatography linked to a mass spectrometer. The CO was determined at the end of the shift by using a portable instrument. A group of 20 workers (12 smokers and 8 nonsmokers) in the manufacturing plant were monitored. No significant correlation was observed among the CO of all subjects and the concentration of methylene chloride in ambient air. When those workers who smoked were removed from the analysis, a correlation between the methylene chloride concentration in air and the CO concentration in alveolar air was found. Significant linear correlation was found between the environmental concentration of methylene chloride in the breathing zone and methylene chloride concentration in urine.

Effect of various exposure scenarios on the biological monitoring of organic solvents in alveolar air. I. Toluene and m-xylene.

The present study was undertaken to investigate the influence of different exposure scenarios on the elimination of toluene and m-xylene in alveolar air and other biological fluids in human volunteers. The study was also aimed at establishing the effectiveness of physiologically based toxicokinetic models in predicting the value of biological monitoring data after exposure to toluene and m-xylene. Two adult male and two adult female white volunteers were exposed by inhalation, in a dynamic, controlled-environment exposure chamber, to various concentrations of toluene (21-66 ppm) or m-xylene (25-50 ppm) in order to establish the influence of exposure concentration, duration of exposure, variation of concentration within day, and work load on respective biological exposure indices. The concentrations of unchanged solvents in end-exhaled air and in blood as well as the urinary excretion of hippuric acid and m-methyl-hippuric acid were determined. The results show that doubling the exposure concentration for both solvents led to a proportional increase in the concentrations of unchanged solvents in alveolar air and blood at the end of a 7-h exposure period. Cumulative urinary excretion of the respective metabolites exhibited a nearly proportional increase. Adjustment of exposure concentration to account for a prolongation of the duration of exposure resulted in essentially identical cumulative urinary excretion of the metabolites. Induced within-day variations in the exposure concentration led to corresponding but not proportional changes in alveolar concentration for both solvents, depending on whether or not sampling preceded or followed peak exposure to solvent. At the end of repeated 10-min periods of physical exercise at 50 W, alveolar air concentrations of both solvents were increased by 40%. Experimental data collected during the present study were adequately simulated by physiologically based toxicokinetic modeling. These results suggest that alveolar air solvent concentration is a reliable index of exposure to both toluene and m-xylene under various experimental exposure scenarios. For clinical situations likely to be encountered in the workplace, physiologically based toxicokinetic modeling appears to be a useful tool both for developing strategies of biological monitoring of exposure to volatile organic solvents and for predicting alveolar air concentrations under a given set of exposure conditions.

Biological monitoring of occupational exposure to tetrahydrofuran.

Occupational exposure to tetrahydrofuran (THF) was studied by analysis of environmental air, blood, alveolar air, and urine from 58 workers in a video tape manufacturing plant. Head space gas chromatography (GC) with an FID detector was used for determination of THF concentration in alveolar air, urine, and blood. Environmental exposure to THF was measured by personal sampling with a carbon felt passive dosimeter. When the end of shift urinary THF concentrations were compared with environmental time weighted average (TWA) values, urinary THF concentration corrected for specific gravity correlated well with THF concentration in air (r = 0.88), and uncorrected urinary THF concentration gave a similar result (r = 0.86). Correction for creatinine in urine weakened the correlation (r = 0.56). For exposure at the TWA concentration of 200 ppm the extrapolated concentration of THF was 33 mumol/l in blood and 111.9 mumol/l (61 mumol/g creatinine) or 109 mumol/l at a specific gravity of 1.018 in urine. The correlation between exposure to THF and its concentration in exhaled breath and blood was low (r = 0.61 and 0.68 respectively). Laboratory methodological considerations together with the good correlation between urinary THF concentration and the environmental concentration suggest that THF concentration in urine is a useful biological indicator of occupational exposure to THF.

Exposure to fluorotrichloromethane (R-11).

Three volunteers were exposed to fluorotrichloromethane (R-11) under experimental conditions. Solvent levels in ambient and alveolar air, in blood and urine were measured. The mean concentration of R-11 in ambient air was 657 ml/m3. The average values of pulmonary retention and solvent levels in alveolar air and blood were 18.2%; 537 ml/m3 and 2.8 mg/l. Inter-individual variations of these parameters are negligible. R-11 concentrations in urine--in contrast to blood or alveolar air--depend on the dose taken up. After termination of exposure, R-11 concentrations in alveolar air and in blood are excreted with biological half-lives of seven and eleven minutes respectively during the first phase of elimination and with 1.8 and 1.0 h respectively during the second phase of elimination. Though ambient monitoring should, in most cases, be sufficient for the prevention of occupational diseases, the R-11 concentration in alveolar air seems to be the best parameter if biological monitoring seems to be necessary.

Exposure to xylene and ethylbenzene. I. Uptake, distribution and elimination in man.

Industrial xylene is a mixture of xylene and ethylbenzene. Twelve male subjects were exposed to industrial xylene in inspired air, six subjects in series I to 870 mg/m3 at rest (30 min) and light exercise on a bicycle ergometer (90 min) and six subjects in series II to 435 mg/m3 at rest (30 min) and during exercise of increasing work loads (90 min). The measurements of xylene uptake were performed continuously with the Douglas bag technique. In both series, about 60% of the amount of xylene supplied to the lungs was taken up. In both series, the concentration in alveolar air was relatively low throughout the entire exposure. The relative concentration in alveolar air displayed a linear correlation to the percentage uptake in the lungs. The ratio between the concentration in arterial blood (mg/kg) and alveolar air (mg/l) amounted to 30--40 at the different work loads. The total amount of xylene expired after the exposure was estimated from the alveolar concentration and alveolar ventilation. In series I, with a total uptake of 1.4 g, the subjects expired about 70 mg, i.e., about 5%. The corresponding value in series II was 40 mg of a total uptake of 1.0 g, i.e., about 4%.

Exposure to toluene in a photogravure printing plant. Concentration in ambient air and uptake in the body.

Workers in the photogravure printing industry were studied concerning exposure of toluene. The study included determination of exposure with personal air sampling and with direct reading physical instruments and determination of the concentration in alveolar air. Uptake of toluene in the body was ascertained with a direct and an indirect method. The physiological work load was determined with pulmonary ventilation measurements, and the toluene concentration in the blood was determined. The results showed that there was no appreciable difference between exposure determined with personal air sampling and with stationary direct reading physical instruments. The study also showed that alveolar air sampling during exposure can be used when the uptake of toluene is being estimated. The alveolar air concentrations after the end of exposure reflected the uptake during exposure, but the correlation to the concentration in the inspiratory air was low. The results also showed a correlation between the concentration in alveolar air and the concentration in blood. Estimations made showed that the uptake in the body was of such a magnitude that there could be a risk of central nervous disturbances. No change in the uptake of toluene, as the percentage of the given amount, could be seen, neither during a day`s exposure nor from day to day during a week. The authors recommend measurements of alveolar air concentrations as a method for biologically monitoring toluene uptake.

Exposure to xylene and ethylbenzene. II. Concentration in subcutaneous adipose tissue.

The amount of body fat in 12 male subjects was determined by means of underwater weighing and anthropometric calculation of skeletal weight. Six subjects (group I) were exposed to 200 ppm of industrial xylene during 30 min of rest and 90 min of exercise at a work load of 50 W. Six subjects (group II) were exposed to 100 ppm for 30 min at rest and during three 3D-min periods of exercise at work loads of 50, 100 and 150 W, respectively. The amount of solvent taken up in the organism was highly correlated to the amount of body fat. When the groups were analyzed together, a correlation was found between the uptake per kilogram of body weight and the alveolar concentrations 4 and 19 h after exposure, even though the groups were exposed under different conditions. However, no correlation was found between total uptake and the alveolar air concentrations after exposure. Needle .biopsies of subcutaneous adipose tissue were taken 0.5, 2, 4 and about 22 h after the end of exposure. Industrial xylene is a mixture of ethylbenzene and 0-, mand p-xylene. The concentrations of ethylbenzene and m- and p-xylene were determined with gas chromatography after evaporation into nitrogen at 150°C. Ortoxylene, which constituted 8.8% of the inspired gas mixture, could not be separated with the column used. Elimination of ethylbenzene-xylene from adipose tissue was slow. The mean concentrations in both groups of subjects were on about the same level after 22 h as during the first 4 h after exposure. In both groups, there was a negative correlation between the concentrations in adipose tissue and the degree of obesity, i.e., obese persons had lower concentrations.

Exposure to trichloroethylene I. Uptake and distribution in man.

Fifteen healthy male subjects were exposed to about 540 and 1,080 mg/m3 of trichloroethylene (TRI) in the air during rest and exercise on a bicycle ergometer. Each subject was exposed during four 30-min periods. The arterial blood concentration increased linearly with the concentration in the alveolar air. The uptake of TRI was about 55% of the supplied amount at rest. At a work load of 150 W during the fourth period the percentage uptake decreased to about 25%. For one fairly thin subject the uptake was near zero at the end of exposure. This development was probably due to the relatively low solubility of TRI in blood and tissues. The uptake of TRI may be estimated from pulmonary ventilation and the concentration in alveolar and inspiratory air.

A simple method of measuring breath hydrogen in carbohydrate malabsorption by end-expiratory sampling.

1. A simple method is described for measuring the hydrogen concentration in alveolar air by end-expiratory sampling, by using a modified Haldane-Priestley tube and gas chromatography. Hydrogen was generated in vivo by ingestion of the non-absorbable sugar lactulose. 2. Alveolar hydrogen concentration showed a highly significant correlation with hydrogen production measured either by a rebreathing technique or by a total collection procedure. 3. The coefficient of variation of the end-expiratory method, assessed by comparing sixty-one paired results, was 11-6%. The coefficient of variation in ten measurements in one subject at 1 min intervals was 17-6%.

Exposure to methylene chloride. I Its concentration in alveolar air and blood during rest and exercise and its metabolism.

Fourteen subjects were exposed to about 870 and 1,740 mg/m3 of methylene chloride in the air during rest and physical exercise on a bicycle ergometer. The duration of each exposure period was 30 min. Each subject was exposed during four periods. The concentration of methylene chloride in the alveolar air increased in the beginning but had a tendency to level off at the end of each period. There was a high correlation between the alveolar and arterial concentration of methylene chloride. The uptake of methylene chloride was about 55 % of the supplied amount at rest, about 40% at a work load of 50 W, and about 30 and 35 % at 100 and 150 W, respectively. The concentration of carboxyhemoglobin (COHb) increased both during and after exposure. With exposure to 1,740 mg/m3 a concentration of COHb in the blood of about 0.85 g/100 ml was reached. This value corresponds to about 5.5 % COHb.

Exposure to white spirit. I. Concentration in alveolar air and blood during rest and exercise.

Fifteen healthy male subjects were exposed to 1,250 and 2,500 mg/m3 of white spirit in inspiratory air during rest and excercise on a bicycle ergometer. The white spirit contained approximately 83% aliphatic and 17% aromatic components. The duration of each exposure period was 30 minutes. The pulmonary ventilation, the cardiac output, and the concentration of white spirit (subdivided into aromatic and aliphatic components) in alveolar air, arterial blood, and venous blood were determined during and after exposure. The concentration of aliphatic and aromatic components in alveolar air tended to level off towards the close of each period. The resting level of the aromatic components increased approximately 2.0 times, and that of aliphatic components about 2.5 times, during exercise with increased intensities. The concentration of aliphatic components in arterial and venous blood increased at the start of each exposure period but tended to level off towards the close of the period. The resting value increased fourfold in work at the highest intensity. However, the concentration of aromatic components rose sharply during each period. The arterial blood concentration was about 15 times higher at the end of exposure during the heaviest exercise intensity than at rest. Pulmonary ventilation appeared to be more important to uptake in arterial blood than to circulation. The results are believed to be due to the differing solubilities of aliphatic and aromatic components in blood. Measurement of the concentration of white spirit in venous or arterial capillary blood is suggested as a biological check on exposure.

Exposure to white spirit. II. Psychological functions.

The effect of the solvent white spirit on psychological functions, such as perceptual speed, reaction time, short-term memory, numerical ability, and manual dexterity, was studied in two separate series of experiments employing 14 and 8 healthy male students, respectively. Each subject was tested repeatedly in each series in exposure to 625, 1,250, 1,875 and 2,500 mg/m3 of white spirit in inspiratory air and under control conditions with exposure to pure air. In another experimental series each subject was tested during exposure to 4,000 mg/m3 of white spirit and under control conditions. Alveolar air samples were taken every fifth minute. No effect on examined functions was observed in the first experimental series. However, a prolonged reaction time and a probably impaired short-term memory was observed in subjects exposed to 4,000 mg/m3. At this concentration of white spirit in inspiratory air an alveolar air concentration was obtaine which corresponded to values obtained in exposure to 2,500 mg/m3 during light exercise.

Electrochemical measurements of blood alcohol levels.

THE measurement of alcohol concentration in the breath is a more convenient and desirable method of enforcing the drinking and driving laws than the collection and analysis of blood samples. This method is valid because the alcohol concentration in alveolar air is proportional to the alcohol concentration in the blood; it is essential to ensure that the breath sample contains only alveolar air1,2.