Breath, urine, and blood measurements as biological exposure indices of short-term inhalation exposure to methanol

Due to their transient nature, short-term exposures can be difficult to detect and quantify using conventional monitoring techniques. Biological monitoring may be capable of registering such exposures and may also be used to estimate important toxicological parameters. This paper investigates relationships between methanol concentrations in the blood, urine, and breath of volunteers exposed to methanol vapor at 800 ppm for periods of 0.5, 1, 2, and 8 h. The results indicate factors that must be considered for interpretation of the results of biological monitoring. For methanol, concentrations are not proportional to the exposure duration due to metabolic and other elimination processes that occur concurrently with the exposure. First-order clearance models can be used with blood, breath, or urine concentrations to estimate exposures if the time that has elapsed since the exposure and the model parameters are known. The 0.5 to 2-h periods of exposure were used to estimate the half-life of methanol. Blood data gave a half-life of 1.44±0.33 h. Comparable but slightly more variable results were obtained using urine data corrected for voiding time (1.55±0.67 h) and breath data corrected for mucous membrane desorption (1.40±0.38 h). Methanol concentrations in blood lagged some 15–30 min behind the termination of exposure, and concentrations in urine were further delayed. Although breath sampling may be convenient, breath concentrations reflect end-expired or alveolar air only if subjects are in a methanol-free environment for 30 min or more after the exposure. At earlier times, breath concentrations included contributions from airway desorption or diffusion processes. As based on multicompartmental models, the desorption processes have half-lives ranging between 0.6 and 5 min. Preliminary estimates of the mucous membrane reservoir indicate contributions of under 10% for a 0.5-h exposure and smaller effects for longer periods of exposure. Received: 1 August 1996 / Accepted: 24 January 1998     

Alveolar breath sampling and analysis to assess trihalomethane exposures during competitive swimming training.

Alveolar breath sampling was used to assess trihalomethane (THM) exposures encountered by collegiate swimmers during a typical 2-hr training period in an indoor natatorium. The breath samples were collected at regular intervals before, during, and for 3 hr after a moderately intense training workout. Integrated and grab whole-air samples were collected during the training period to help determine inhalation exposures, and pool water samples were collected to help assess dermal exposures. Resulting breath samples collected during the workout demonstrated a rapid uptake of two THMs (chloroform and bromodichloromethane), with chloroform concentrations exceeding the natatorium air levels within 8 min after the exposure began. Chloroform levels continued to rise steeply until they were more than two times the indoor levels, providing evidence that the dermal route of exposure was relatively rapid and ultimately more important than the inhalation route in this training scenario. Chloroform elimination after the exposure period was fitted to a three compartment model that allowed estimation of compartmental half-lives, resulting minimum bloodborne dose, and an approximation of the duration of elevated body burdens. We estimated the dermal exposure route to account for 80% of the blood chloroform concentration and the transdermal diffusion efficiency from the water to the blood to in excess of 2%. Bromodichloromethane elimination was fitted to a two compartment model which provided evidence of a small, but measurable, body burden of this THM resulting from vigorous swim training. These results suggest that trihalomethane exposures for competitive swimmers under prolonged, high-effort training are common and possibly higher than was previously thought and that the dermal exposure route is dominant. The exposures and potential risks associated with this common recreational activity should be more thoroughly investigated.     

Influence of tap water quality and household water use activities on indoor air and internal dose levels of trihalomethanes

Individual exposure to trihalomethanes (THMs) in tap water can occur through ingestion, inhalation, or dermal exposure. Studies indicate that activities associated with inhaled or dermal exposure routes result in a greater increase in blood THM concentration than does ingestion. We measured blood and exhaled air concentrations of THM as biomarkers of exposure to participants conducting 14 common household water use activities, including ingestion of hot and cold tap water beverages, showering, clothes washing, hand washing, bathing, dish washing, and indirect shower exposure. We conducted our study at a single residence in each of two water utility service areas, one with relatively high and the other low total THM in the residence tap water. To maintain a consistent exposure environment for seven participants, we controlled water use activities, exposure time, air exchange, water flow and temperature, and nonstudy THM sources to the indoor air. We collected reference samples for water supply and air (pre-water use activity), as well as tap water and ambient air samples. We collected blood samples before and after each activity and exhaled breath samples at baseline and post-activity. All hot water use activities yielded a 2-fold increase in blood or breath THM concentrations for at least one individual. The greatest observed increase in blood and exhaled breath THM concentration in any participant was due to showering (direct and indirect), bathing, and hand dishwashing. Average increase in blood THM concentration ranged from 57 to 358 pg/mL due to these activities. More research is needed to determine whether acute and frequent exposures to THM at these concentrations have public health implications. Further research is also needed in designing epidemiologic studies that minimize data collection burden yet maximize accuracy in classification of dermal and inhalation THM exposure during hot water use activities.     

Biological monitoring and possible health effects in workers occupationally exposed to methyl methacrylate

Summary Monitoring by means of blood and urine analysis for methanol was successfully applied in 32 male workers who were exposed to methyl methacrylate (MMA) monomer at 6 ppm as a geometric mean and at 112 ppm as the maximum. Measurement of time-weighted average (TWA) intensity of the vapor exposure was successfully conducted with a diffusive sampler with activated carbon cloth as an adsorbent. Methanol concentrations in whole blood, serum, and urine samples were measured by headspace gas chromtography. The methanol concentrations in the three biological samples collected at the end of 8-h workshifts related linearly with the TWA MMA vapor concentrations, with correlation coefficients of 0.8–0.9. Quantitative evaluation of MMA in vapor and of methanol in urine suggests that only 1.5% of MMA inhaled will be excreted in urine as methanol. There were no significant clinical symptoms or abnormal hematological or serum biochemical findings at this exposure level, except that some workers complained throat irritation and frequent cough and sputa. The results indicate that biological monitoring by analysis for methanol is sensitive enough to detect MMA exposure at levels at which no serious health effects are to be expected.     

PBTK modeling demonstrates contribution of dermal and inhalation exposure components to end-exhaled breath concentrations of naphthalene

BACKGROUND: Dermal and inhalation exposure to jet propulsion fuel 8 (JP-8) have been measured in a few occupational exposure studies. However, a quantitative understanding of the relationship between external exposures and end-exhaled air concentrations has not been described for occupational and environmental exposure scenarios. OBJECTIVE: Our goal was to construct a physiologically based toxicokinetic (PBTK) model that quantitatively describes the relative contribution of dermal and inhalation exposures to the end-exhaled air concentrations of naphthalene among U.S. Air Force personnel. METHODS: The PBTK model comprised five compartments representing the stratum corneum, viable epidermis, blood, fat, and other tissues. The parameters were optimized using exclusively human exposure and biological monitoring data. RESULTS: The optimized values of parameters for naphthalene were a) permeability coefficient for the stratum corneum 6.8 x 10(-5) cm/hr, b) permeability coefficient for the viable epidermis 3.0 x 10(-3) cm/hr, c) fat:blood partition coefficient 25.6, and d) other tissue:blood partition coefficient 5.2. The skin permeability coefficient was comparable to the values estimated from in vitro studies. Based on simulations of workers' exposures to JP-8 during aircraft fuel-cell maintenance operations, the median relative contribution of dermal exposure to the end-exhaled breath concentration of naphthalene was 4% (10th percentile 1% and 90th percentile 11%). CONCLUSIONS: PBTK modeling allowed contributions of the end-exhaled air concentration of naphthalene to be partitioned between dermal and inhalation routes of exposure. Further study of inter- and intraindividual variations in exposure assessment is required to better characterize the toxicokinetic behavior of JP-8 components after occupational and/or environmental exposures.     

A real-time in-vivo method for studying the percutaneous absorption of volatile chemicals

Realistic estimates of percutaneous absorption following exposures to solvents in the workplace, or through contaminated soil and water, are critical to understanding human health risks. A method was developed to determine dermal uptake of solvents under non-steady-state conditions using real-time breath analysis in rats, monkeys, and humans. The exhaled breath was analyzed using an ion-trap mass spectrometer, which can quantitate chemicals in the exhaled breath stream in the 1-5 ppb range. The resulting data were evaluated using physiologically-based pharmacokinetic (PBPK) models to estimate dermal permeability constants (Kp) under various exposure conditions. The effects of exposure matrix (soil versus water), occlusion versus non-occlusion, and species differences on the absorption of methyl chloroform, trichloroethylene, and benzene were compared. Exposure concentrations were analyzed before and at 0.5-hour intervals throughout the exposures. The percentage of each chemical absorbed and the corresponding Kp were estimated by optimization of the PBPK model to the medium concentration and the exhaled-breath data. The method was found to be sufficiently sensitive for animal and human dermal studies at low exposure concentrations over small body surface areas, for short periods, using non-steady-state exposure conditions.     

Personal exposure to JP-8 jet fuel vapors and exhaust at air force bases

JP-8 jet fuel (similar to commercial/international jet A-1 fuel) is the standard military fuel for all types of vehicles, including the U.S. Air Force aircraft inventory. As such, JP-8 presents the most common chemical exposure in the Air Force, particularly for flight and ground crew personnel during preflight operations and for maintenance personnel performing routine tasks. Personal exposure at an Air Force base occurs through occupational exposure for personnel involved with fuel and aircraft handling and/or through incidental exposure, primarily through inhalation of ambient fuel vapors. Because JP-8 is less volatile than its predecessor fuel (JP-4), contact with liquid fuel on skin and clothing may result in prolonged exposure. The slowly evaporating JP-8 fuel tends to linger on exposed personnel during their interaction with their previously unexposed colleagues. To begin to assess the relative exposures, we made ambient air measurements and used recently developed methods for collecting exhaled breath in special containers. We then analyzed for certain volatile marker compounds for JP-8, as well as for some aromatic hydrocarbons (especially benzene) that are related to long-term health risks. Ambient samples were collected by using compact, battery-operated, personal whole-air samplers that have recently been developed as commercial products; breath samples were collected using our single-breath canister method that uses 1-L canisters fitted with valves and small disposable breathing tubes. We collected breath samples from various groups of Air Force personnel and found a demonstrable JP-8 exposure for all subjects, ranging from slight elevations as compared to a control cohort to > 100 [mutilpe] the control values. This work suggests that further studies should be performed on specific issues to obtain pertinent exposure data. The data can be applied to assessments of health outcomes and to recommendations for changes in the use of personal protective equipment that optimize risk reduction without undue impact on a mission.     

Elimination of volatile organic compounds in breath after exposure to occupational and environmental microenvironments.

Breath measurements offer the potential for a direct and noninvasive evaluation of human exposure to volatile organic compounds (VOCs) in the environments in which people live and work. This research study was conducted to further evaluate and develop the potential of this exposure assessment methodology. Several people were exposed to the atmosphere in six microenvironments for several hours. Air concentrations of VOCs were measured during these exposures and breath samples were collected and analyzed at multiple time points after the exposure to evaluate elimination kinetics for 21 VOCs. A new alveolar breath collection technique was applied. Elimination half-lives were estimated using a mono- and bi-exponential model. The alveolar breath collection and analysis methodology proved to be very useful for collecting many samples in short time intervals and this capability was very important for more accurately describing the initial phase of the decay curves. Breath decay curves were generated from samples collected over a four hour period after exposure for 21 of 24 target VOCs. A biexponential function generally provided a better fit for the decay data than did the monoexponential function, supporting a multi-compartment uptake and elimination model for the human body.     

Biological monitoring of workers exposed to benzene in the coke oven industry

Workers in the coke oven industry are potentially exposed to low concentrations of benzene. There is a need to establish a well validated biological monitoring procedure for low level benzene exposure. The use of breath and blood benzene and urinary phenol has been explored in conjunction with personal monitoring data. At exposures of about 1 ppm benzene, urinary phenol is of no value as an indicator of uptake/exposure. Benzene in blood was measured by head space gas chromatography but the concentrations were only just above the detection limit. The determination of breath benzene collected before the next shift is non-specific in the case of smokers. The most useful monitor at low concentrations appears to be breath benzene measured at the end-of-shift.     

Dermal absorption of benzene: implications for work practices and regulations

Because the risk of leukemia for workers exposed to 1 ppm of benzene for 40 years is estimated to be 70% greater than the risk for unexposed persons, the National Institute for Occupational Safety and Health (NIOSH) and the American Conference of Governmental Industrial Hygienists (ACGIH) recommend that the allowable airborne exposure level be 0.1 ppm. Using an experimentally determined dermal flux (permeability) value for benzene through skin, the authors calculated the amount of benzene absorbed through a known surface area (e.g., hands) during exposures where solvents contaminated with benzene were used for cleaning. Even at current contamination levels, which are less than 0.1% in most products, the amount of benzene absorbed through the skin over a long period can be significant, depending on exposure time and exposed skin surface areas. In the example given, the risk for leukemia was increased by 42%. Therefore, the authors recommend that the liquid benzene concentration that triggers labeling, worker education, and protective measures to minimize skin exposure be reduced from 0.1% to 0.01%.     

Biological monitoring of workers exposed to benzene in the coke oven industry.

Workers in the coke oven industry are potentially exposed to low concentrations of benzene. There is a need to establish a well validated biological monitoring procedure for low level benzene exposure. The use of breath and blood benzene and urinary phenol has been explored in conjunction with personal monitoring data. At exposures of about 1 ppm benzene, urinary phenol is of no value as an indicator of uptake/exposure. Benzene in blood was measured by head space gas chromatography but the concentrations were only just above the detection limit. The determination of breath benzene collected before the next shift is non-specific in the case of smokers. The most useful monitor at low concentrations appears to be breath benzene measured at the end-of-shift.     

Trichloroethene levels in human blood and exhaled breath from controlled inhalation exposure.

The organic constituents of exhaled human breath are representative of bloodborne concentrations through gas exchange in the blood/breath interface in the lungs. The presence of specific compounds can be an indicator of recent exposure or represent a biological response of the subject. For volatile organic compounds, sampling and analysis of breath is preferred to direct measurement from blood samples because breath collection is noninvasive, potentially infectious waste is avoided, the sample supply is essentially limitless, and the measurement of gas-phase analytes is much simpler in a gas matrix rather than in a complex biological tissue such as blood. However, to assess the distribution of a contaminant in the body requires a reasonable estimate of the blood level. We have investigated the use of noninvasive breath measurements as a surrogate for blood measurements for (high) occupational levels of trichloroethene in a controlled exposure experiment. Subjects were placed in an exposure chamber for 24 hr; they were exposed to 100 parts per million by volume trichloroethene for the initial 4 hr and to purified air for the remaining 20 hr. Matched breath and blood samples were collected periodically during the experiment. We modeled the resulting concentration data with respect to their time course and assessed the blood/breath relationship during the exposure (uptake) period and during the postexposure (elimination) period. Estimates for peak blood levels, compartmental distribution, and time constants were calculated from breath data and compared to direct blood measurements to assess the validity of the breath measurement methodology. Blood/breath partition coefficients were studied during both uptake and elimination. At equilibrium conditions at the end of the exposure, we could predict actual blood levels using breath elimination curve calculations and a literature value partition coefficient with a mean ratio of calculated:measured of 0.98 and standard error (SE) = 0.12 across all subjects. blood/breath comparisons at equilibrium resulted in calculated in vivo partition coefficients with a mean of 10.8 and SE = 0.60 across all subjects and experiments and 9.69 with SE = 0.93 for elimination-only experiments. We found that about 78% of trichloroethene entering the body during inhalation exposure is metabolized, stored, or excreted through routes other than exhalation.     

Human inhalation pharmacokinetics of 1,1,2-trichloro-1,2,2-trifluoroethane (FC113)

Seven male volunteers were exposed to atmospheric concentrations of either 1980, 4100 or 7630 mg m-3 1,1,2-trichloro-1,2,2-trifluoroethane (FC113) for 4 h. Blood and expired air samples were collected during the exposure period and for several days subsequently and analysed for FC113. Blood and breath concentrations of FC113 were related to the administered dose with some variation between individuals. The low blood/breath ratios measured are consistent with the low solubility of FC113 in blood. The absorption and elimination of FC113 can be described by a three-compartment model and the average half-lives of elimination of FC113 in breath were 0.22, 2.3 and 29 h. A pulmonary retention during the exposure period of 14% was measured but only 2.6 to 4.3% of the dose was recovered unchanged in breath after the exposure period, suggesting that FC113 could be metabolised following inhalation exposure. It is concluded that a practical method for biological monitoring during occupational exposure would be to measure end-tidal breath concentrations of FC113 in samples taken the morning after exposure. The predictive value of such a measurement can be improved if the results are normalised to the body fat content of individual workers which can be estimated from height and weight measurements.     

Time-resolved cutaneous absorption and permeation rates of methanol in human volunteers

This paper reports on an experimental study of dermal exposure to neat methanol in human volunteers for the purposes of estimating percutaneous absorption rates, permeation kinetics, baseline (pre-exposure) levels of methanol in blood, and inter- and intrasubject variability. A total of 12 volunteers (seven men and five women) were exposed to methanol via one hand for durations of 0 to 16 min in a total of 65 sessions, making this the largest controlled study of percutaneous absorption for this common solvent. In each session, 14 blood samples were collected sequentially and analyzed for methanol. These data were used to derive absorption rates and delivery kinetics using a two compartment model that accounts for elimination and pre-exposure levels. The pre-exposure methanol concentration in blood was 1.7 ± 0.9 mg l⁻¹, and subjects had statistically different mean concentrations. The maximum methanol concentration in blood was reached 1.9 ± 1.0 h after exposure. Delivery rates from skin into blood lagged exposure by 0.5 h, and methanol continued to enter the systemic circulation for 4 h following exposure. While in vitro studies have reported comparable lag times, the prolonged permeation or epidermal reservoir effect for such miscible solvents has not been previously measured. The mean derived absorption rate, 8.1 ± 3.7 mg cm⁻² h⁻¹, is compatible with that found in the other in vivo study of methanol absorption. Both in vivo absorption rate estimates considerably exceed in vitro estimates. The maximum concentration of methanol in blood following an exposure to one hand lasting ∼20 min is comparable to that reached following inhalational exposures at a methanol concentration of 200 ppm, the threshold limit value-time weighted average (TLV-TWA). While variability in blood concentrations and absorption rates approached a factor of two, differences between individuals were not statistically significant. The derived absorption and permeation rates provide information regarding kinetics and absorbed dose that can help to interpret biological monitoring data and confirm mathematical models of chemical permeation. Received: 11 October 1996 / Accepted: 10 April 1997     

Dermal exposure assessment to benzene and toluene using charcoal cloth pads

Charcoal cloth pads have been used to assess volatile chemicals on the skin in a laboratory setting; however, they have not yet been applied to measure dermal exposure in occupational settings. This study aimed at evaluating whether charcoal pads can be used to assess dermal exposure to benzene and toluene in workers of a petrochemical plant. Inhalation and dermal exposure levels to benzene and toluene were assessed for workers of a petrochemical plant performing different jobs. Benzene uptake was assessed by determining S-phenylmercapturic acid in workers' urine samples. Dermal exposure levels on the charcoal pads were adjusted for ambient air levels of benzene and toluene by subtracting the amount of benzene or toluene measured in personal air from the amount of benzene or toluene measured on the charcoal pad. In general, measured external and internal exposure levels were low. The estimated contribution of the dermal route to internal benzene exposure levels was less than 0.06% for all jobs. Toluene personal air concentrations and benzene and toluene dermal exposure levels differed statistically significantly between job titles. For benzene, differences between jobs were larger for adjusted dermal exposures (maximum 17-fold, P = 0.02) than for inhalation exposures (maximum two-fold, P = 0.08). Also for toluene, although less clear, differences between jobs were larger for adjusted dermal exposures (maximum 23-fold, P = 0.01) as compared to inhalation exposures (maximum 10-fold, P = 0.01). Charcoal pads appeared to measure dermal exposures to benzene and toluene in addition to ambient air levels. Future studies applying charcoal cloth pads for the dermal exposure assessment at workplaces with higher dermal exposure to organic solvents may provide more insight into the biological relevance of dermal exposure levels measured by charcoal cloth pads. In addition, the design of the dermal sampler might be improved by configuring a dermal sampler, where part of the sampler is protected against direct contact and splashes, but still permeable for the gas phase. This design would most likely result in a better ability to correct for airborne concentrations at a given body location.     

Semen quality in workers exposed to 2-ethoxyethanol

To evaluate whether long term exposure to 2-ethoxyethanol (2EE) may affect semen quality, a cross sectional study was conducted among men exposed to 2EE used as a binder slurry in a metal castings process. Full shift breathing zone exposures to 2EE ranged from non-detectable to 24 ppm (geometric mean 6.6 ppm). Because of the potential for substantial absorption of 2EE through skin exposure, urine measurements of the metabolite of 2EE, 2-ethoxyacetic acid (2EAA) were conducted, showing levels of 2EAA ranging from non-detectable to 163 mg 2EAA/g creatinine. Only 37 exposed men (50% participation) and 39 non-exposed comparison (26% participation) from elsewhere in the plant provided a sperm sample. A questionnaire to determine personal habits, and medical and work histories, and a physical examination of the urogenital tract were also administered. The average sperm count per ejaculate among the workers exposed to 2EE was significantly lower than that of the unexposed group (113 v 154 million sperm per ejaculate respectively; p = 0.05) after consideration of abstinence, sample age, subjects' age, tobacco, alcohol and caffeine use, urogenital disorders, fever, and other illnesses. The mean sperm concentrations of the exposed and unexposed groups did not significantly differ from each other (44 and 53 million/ml respectively). No effect of exposure to 2EE on semen volume, sperm viability, motility, velocity, and normal morphology or testicular volume was detected, although some differences in the proportion of abnormal sperm shapes were observed. These data suggest that there may be an effect of 2EE on sperm count among these workers, although the possibility that other factors may be affecting the semen quality in both exposed and unexposed men in this population or that the results reflect bias introduced by the low participation rates cannot be excluded.     

Semen quality in workers exposed to 2-ethoxyethanol.

To evaluate whether long term exposure to 2-ethoxyethanol (2EE) may affect semen quality, a cross sectional study was conducted among men exposed to 2EE used as a binder slurry in a metal castings process. Full shift breathing zone exposures to 2EE ranged from non-detectable to 24 ppm (geometric mean 6.6 ppm). Because of the potential for substantial absorption of 2EE through skin exposure, urine measurements of the metabolite of 2EE, 2-ethoxyacetic acid (2EAA) were conducted, showing levels of 2EAA ranging from non-detectable to 163 mg 2EAA/g creatinine. Only 37 exposed men (50% participation) and 39 non-exposed comparison (26% participation) from elsewhere in the plant provided a sperm sample. A questionnaire to determine personal habits, and medical and work histories, and a physical examination of the urogenital tract were also administered. The average sperm count per ejaculate among the workers exposed to 2EE was significantly lower than that of the unexposed group (113 v 154 million sperm per ejaculate respectively; p = 0.05) after consideration of abstinence, sample age, subjects' age, tobacco, alcohol and caffeine use, urogenital disorders, fever, and other illnesses. The mean sperm concentrations of the exposed and unexposed groups did not significantly differ from each other (44 and 53 million/ml respectively). No effect of exposure to 2EE on semen volume, sperm viability, motility, velocity, and normal morphology or testicular volume was detected, although some differences in the proportion of abnormal sperm shapes were observed. These data suggest that there may be an effect of 2EE on sperm count among these workers, although the possibility that other factors may be affecting the semen quality in both exposed and unexposed men in this population or that the results reflect bias introduced by the low participation rates cannot be excluded.     

Assessment of exposure to polycyclic aromatic hydrocarbons in engine rooms by measurement of urinary 1-hydroxypyrene.

OBJECTIVE: Machinists have an increased risk of lung cancer and bladder cancer, and this may be caused by exposure to carcinogenic compounds such as asbestos and polycyclic aromatic hydrocarbons (PAHs) in the engine room. The aim of this study was to investigate the exposure of engine room personnel to PAHs, with 1-hydroxypyrene in urine as a biomarker. METHODS: Urine samples from engine room personnel (n = 51) on 10 ships arriving in different harbours were collected, as well as urine samples from a similar number of unexposed controls (n = 47) on the same ships. Urinary 1-hydroxypyrene was quantitatively measured by high performance liquid chromatography. The exposure to PAHs was estimated by a questionnaire answered by the engine room personnel. On two ships, air monitoring of PAHs in the engine room was performed at sea. Both personal monitoring and area monitoring were performed. The compounds were analysed by gas chromatography of two types (with a flame ionisation detector and with a mass spectrometer). RESULTS: Significantly more 1-hydroxypyrene was found in urine of personnel who had been working in the engine room for the past 24 hours, than in that of the unexposed seamen. The highest concentrations of 1-hydroxypyrene were found among engine room personnel who had experienced oil contamination of the skin during their work in the engine room. Stepwise logistic regression analysis showed a significant relation between the concentrations of 1-hydroxypyrene, smoking, and estimated exposure to PAHs. No PAHs were detected in the air samples. CONCLUSION: Engine room personnel who experience skin exposure to oil and oil products are exposed to PAHs during their work. This indicates that dermal uptake of PAHs is the major route of exposure.     

Human inhalation pharmacokinetics of chlorodifluoromethane (HCFC22)

Summary Two groups of three male volunteers were exposed to atmospheric concentrations of either 327 or 1833 mg m^–3 chlorodifluoromethane (HCFC22) for 4 h. Blood, urine and expired air samples were taken during and after the exposure period and analysed for HCFC22. Urine samples were also analysed for fluoride ion. During the exposure period, blood concentrations of HCFC22 approached a plateau, and the average peak blood concentrations of 0.25 and 1.36 g cm^–3 were proportional to dose. HCFC22 concentrations in expired air were similar to the exposure concentration during the exposure period. The ratio between venous blood and breath concentrations of HCFC22 towards the end of the exposure period was on average 0.77, which is consistent with in vitro estimates of the partition coefficient. In the post-exposure period, three phases for the elimination of HCFC22 were identified, with estimated half-lives of 0.005, 0.2 and 2.6 h. HCFC22 was detected in urine samples taken in the post-exposure period, and the rate of decline was consistent with the terminal rate of elimination estimated from blood and breath measurements. On average 2.1% of the inhaled HCFC22 was recovered in breath within 26 h of exposure. This is consistent with the low solubility in blood and fat. Minimal changes in fluoride ion concentrations in urine following exposure indicate that HCFC22 is unlikely to be metabolised to a significant extent. Following inhalational exposure HCFC22 is poorly absorbed and is rapidly eliminated from the body. Possible biological monitoring strategies could be based on measurements of HCFC22 in urine or breath samples collected after the end of an exposure period.     

Occupational chronic exposure to organic solvents

Summary Twenty persons occupationally exposed to methanol were examined according to their methanol levels in blood and urine and their formic acid excretion. An 8-h exposure to a methanol concentration of 93 ml/m³ (geometric mean) in the air at the working area caused average methanol levels in blood and urine of (8.9 ± 14.7) mg/l and (21.8 ± 20.0) mg/l, respectively, and a mean formic acid excretion of (29.9 ± 28.6) mg/l. These average concentrations for the exposed group showed statistically significant increases compared to those of a control group. For the methanol workers we succeeded in] correlating their methanol levels in blood and urine. When considering the possible application of these parameters for biological monitoring, difficulties were encountered, especially for the individual case from the overlapping range in the concentrations of exposed and unexposed persons for each of the applied parameters. This range is minimum for the methanol concentration in urine. About 80% of the urinary levels from the methanol workers lies above the upper limit within the control group range. Based on our results a rough estimate shows the corresponding methanol content in urine to be about 40 mg/l for an 8-h exposure at 200 ml/m³ (German MAK value).