This study was carried out to evaluate changes in the breathing pattern of divers during exercise at an elevated ambient air pressure equivalent to a depth of 30 m of seawater.
A total of 22 healthy male subjects performed graded bicycle exercise in a dry hyperbaric chamber up to a maximum of 3.5 W kg(-1) body weight at normal (0.1 MPa) and at elevated ambient air pressure (0.4 MPa). The exercise ventilation (VE), tidal volume (VT), breathing frequency (BF), oxygen uptake (VO2), carbon dioxide elimination (VCO2), and heart rate (HR) were measured. Perceived dyspnea was assessed by Borg scale ratings.
Comparison of respiratory indices between conditions (0.1 versus 0.4 MPa) revealed a significant reduction in VE, VT, BF, and HR during exercise at 0.4 MPa. VO2 and VCO2 did not differ significantly between conditions. Likewise, no significant difference between conditions emerged in perceived dyspnea.
Ventilation is significantly impaired during heavy bicycle exercise at 0.4 MPa. This is obviously not apparent with regard to subjective perception of dyspnea.
Nine healthy sitting males evaluated the intensity of vertical whole-body vibration (WBV) in z-axis at four frequencies (F1 = 0.63 Hz, F2 = 1.25 Hz, F3 = 2.5 Hz, F4 = 5 Hz) and two intensities (I1 = 1 ms-2 rms, I2 = 2 ms-2 rms) by cross-modality matching (CMM). The subjects were simultaneously exposed to low-frequency noise at two levels (L1 = 65 dBA, L2 = 86 dBA). L1 and L2 were context conditions which did not have to be evaluated by CMM. The results indicate a flat response between F2 and F3; the sensitivity increases towards F1. Different exponents of Stevens' power law for the frequencies of WBV contradict the frequency range tested to be a sensory continuum. L2 caused practically significantly stronger sensations of the WBV-intensity from F1 to F3 (I1) and at F2 (I2). No synergistic effect of noise and WBV was shown at F3I2. Weighting factors were calculated for all exposure conditions using Stevens' power law. The weighting of F2 and F3 contradicts that of the International Standard ISO 2631-1985 (E). The results enable recommendations for the frequency weighting of WBV between 0.63 and 1 Hz, as well as for the equivalence of noise and WBV with combined exposure.
A recent publication by Schwarz et al. describes the effects of exposure of human fibroblast and lymphocytes to radiofrequency-electromagnetic fields at frequencies used for communication with mobile phones. Even at very low specific absorption rates of 0.05 W/kg, thus well below internationally accepted exposure limits, significant effects were seen in fibroblasts whose DNA molecules were damaged as assessed by their comet tail factor (CTF) in the comet assay.
Areas of concern
The CTF mean values and the standard deviations of the replicates revealed very low coefficients of variation, ranging from 1.2 to 4.9% (average 2.9%), which are in contrast to much higher variations reported by others. Moreover, inter-individual differences of the CTF values strongly disagree with the previously published data from the same group of researchers.
The critical analysis of the data given in the figures and the tables furthermore reveal peculiar miscalculations and statistical oddities which give rise to concern about the origin of the reported data.
Uptake and hepatotoxicity of 1,1-dichloroethylene (vinylidene chloride, VDC) was investigated with the isolated perfused rat liver:
VDC, at concentrations of 670, 2150, 3400, 5000, and 6500 ppm, was evaporated in the thermostat and introduced into the perfusion medium for 3 hours under steady-state conditions. During this period the VDC concentration in the perfusate rose linearly from 4.8 to 34.8μg/ml.
The difference between the concentrations in the perfusate, determined before and after hepatic passage (prehepatic and posthepatic concentration, respectively) as a function of the hepatic flux was used to investigate VDC uptake. With increasing prehepatic concentrations of VDC, metabolization approached a saturation characteristic. At a concentration of 4.8μg/ml perfusate, 2.5 pmol/g liver is metabolized within 3 hours, and at 34.8μg/ml the respective value is 8.6μmol/g liver.
Inhibitors of microsomal cytochrome P-450-dependent drug metabolism, e.g., 2-diethylaminoethyl-2, 2-diphenylvalerate (SKF 525-A) or 6-nitro-1, 2, 3-benzotthiadiazole (0.02 mmol) decrease the uptake just slightly. Stronger inhibition (40 %) was achieved with pyrazole (200 mmol). 5,6-Dimethyl-1, 2, 3-benzothiadiazole was found inactive.
VDC uptake was significantly elevated (35 %) following pretreatment of rats with 1, 1, 1-trichloro-2, 2-bis (p-chlorophenyl)-ethane (DDT) and to a lesser degree after phenobarbital (10 %). This stimulation of the uptake rate was not correlated with enhanced hepatotoxicity of VDC, as evidenced by the concentrations of the serum glutamate-oxaloacetate transaminase (SGOT), the serum glutamate-pyruvate transaminase (SGPT) and they-glutamyl transpeptidase (γ-GT) in the perfusate.
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.
Nine healthy male students were exposed to singular atmospheric concentrations of m-xylene (8.2 mumol/l; 200 ppm) or 1,1,1-trichloroethane (TCE) (8.2 and 16.4 mumol/l; 200 and 400 ppm), and also to a combination of xylene (8.2 mumol/l) and TCE (16.4 mumol/l) for 4 h per day at 6-day intervals. The effects of the atmospheric xylene and TCE concentrations on psychophysiological functions such as reaction time, body balance and CFF thresholds were studied. The exposures to xylene alone and to the lower TCE concentrations usually tended to improve the performances, whereas the higher TCE concentration alone or in combination with xylene tended to have an opposite effect, although statistically significant changes in performance, as compared to the control values, were rare. The results thus suggest a biphasic effect of TCE on the central nervous system (CNS), slight stimulation of the CNS at lower and depression at higher TCE concentrations. The results also revealed that xylene and TCE together exhibited neither kinetic interaction nor synergistic nor antagonistic effects on the CNS functions studied.
The relatively high and almost constant absorption/min of trichloroethylene (TRI) is explained by the relatively high partition coefficient between blood and air (?b/g = 15) combined with the rapid metabolism (75 %). Tetrachloroethylene (PERC) has about the same ?b/g as TRI, but the metabolism is insignificant (2 %); therefore, the amount taken up/min decreases in the course of exposure. The ?b/g (5) for 1,1,1-trichloroethane (MC) is smaller, the metabolism is insignificant (3.5 %), therefore the capacity of the body to absorb MC is relatively small and in consequence the uptake/min decreases fast in the course of exposure. Due to the lower ?b/g the excretion of MC after exposure is much faster than of PERC. As a result of the metabolism of TRI only a relatively small amount of TRI absorbed is excreted by the lungs after exposure.
Six male volunteers were exposed for 4 h to 70 ppm 1,1,1-trichloroethane (methylchloroform, MC) at rest, to 145 ppm. MC at rest, and to 142 ppm MC at rest combined with work load (2 times 30 min, 100 W). Minute volume and concentration in exhaled air were measured to estimate the uptake. MC and its metabolites trichloroethanol (TCE) and trichloroacetic acid (TCA) were determined as far as present in blood, exhaled air and urine. The uptake/min decreased in the course of exposure to 30 % of the initial uptake. The total uptake was more influenced by minute volume than by body weight or amount of adipose tissue. During work load the uptake increased to 2.3 fold and the minute volume to 3 fold the value at rest. In the post exposure period the quotients of the concentrations in blood and in exhaled air for MC and TCE remained nearly constant at 8.2 and 14,000, respectively. Following exposure about 60–80% of the amount taken up was excreted unchanged by the lungs, while until 70 h after exposure the amount of TCE and TCA excreted in urine represented about 2% and 0.5% of the uptake.
Gas chromatography and gas chromatography-mass spectrometry were employed to analyze 22 samples of technical grade 1,1,1-trichloroethane for impurities. Eighteen contained vinylidene chloride (1,1-dichloroethylene) (30-900 micrograms/ml) and further contaminants were identified as 1,1-dichloroethane (11), trichloroethylene (12), and 1,1,2-trichloroethane (9). Nitromethane (18), 1,2-epoxybutane (19), tert. butanol (7), and dioxane (10) were detected as stabilizers. It is recommended that the manufacturers should eliminate vinylidene chloride and stabilizers which carry a carcinogenic and/or mutagenic risk, from technical samples of 1,1,1-trichloroethane.
The object of this study was to examine the immediate nervous effects of variable 1,1,1-trichloroethane (TCE) exposure combined with physical exercise. The effects on the quantitative electroencephalography (EEG), visual evoked potentials (VEP) and body sway were analyzed. Nine male volunteers were exposed to either a stable or a fluctuating exposure pattern with the same time-weighted average concentration of 200 ppm (8.1 mumol/l). In both cases, the subjects engaged in physical exercise during the exposures. Exercise alone induced an increase in the dominant alpha frequency in the EEG and, after an initial drop, an increase in the alpha percentage with a concomitant decrease in theta, whereas delta and beta bands remained unaffected. By contrast, exposure to TCI and exercise did not affect the alpha, theta or delta activities but induced changes in beta during the morning recordings at peak exposure to TCE. The body sway tended to decrease slightly during the fluctuating TCE exposure, and the later peaks in VEPs showed slight prolongations. Overall, no deleterious effects of exposure were noted.
Absorption and excretion of 1,1,1-trichloroethane, as well as the kinetics of formation and elimination of trichloroethanol (TCE) and trichloroacetic acid (TCA) were simulated by a mathematical model. The results of this model were compared with experimental one on pulmonary elimination of the solvent and urinary excretion of the metabolites. The influences of duration and repetition of exposure on the pulmonary and urinary eliminations were studied. A tentative method of biologic monitoring is proposed. Theoretically, the most suitable method of biologic monitoring is proposed. Theoretically, the most suitable method to estimate the exposure is by two determinations, before and after a work shift. Following this procedure, analysis of TCE in the urine is more sensitive than determination of 1,1,1-trichloroethane in the breath. As an indicator of exposure risk, TCA is not considered sensitive enough if variations in the inspired concentration occur.
Irritating effects of organic solvents have usually been measured by means of questionnaires. The aim of the present study was to evaluate the sensitivity of different methods of detecting subclinical irritating effects.
Twelve healthy, non-smoking students were exposed to 200 ppm and to 20 ppm 1,1,1-trichloroethane in an exposure chamber, using a crossover design. The amounts of interleukins (IL)-1beta, IL-6 and IL-8 and prostaglandin E(2) (PGE(2)) in nasal secretions were measured. Mucociliary transport time was determined with the saccharine test. Ciliary beat frequency of nasal epithelial cells was measured with video-interference contrast microscopy. Subjective symptoms were assessed by questionnaire.
Concentrations of ILs were significantly elevated after exposure to 200 ppm 1,1,1-trichloroethane (IL-1beta 82.4 vs. 28.8 pg/ml (medians), P=0.003; IL-6 12.2 vs. 7.2 pg/ml, P=0. 01; IL-8 549 vs. 424 pg/ml, P=0.007), whereas the other parameters remained unchanged.
The interleukins measured proved to be sensitive indicators of irritating effects of 1,1, 1-trichloroethane. The German threshold limit (MAK value) of 200 ppm 1,1,1-trichloroethane does not prevent the subclinical inflammation of nasal mucosa.
The purpose of the present study was to investigate the influence of different exposure scenarios on the elimination of trichloroethylene (TRI) and 1,1,1-trichloroethane (1,1,1-TRI) in alveolar air and other biological fluids in human volunteers. In addition, it was sought to establish an interactive process between experimental data gathering and simulation modeling in an attempt to predict the influence of the different scenarios of exposure to TRI and 1,1,1-TRI on their respective biological monitoring indices and thus to establish the flexibility and validity of simulation models. Two adult male and two adult female Caucasian volunteers were exposed by inhalation, in a dynamic controlled exposure chamber, to various concentrations of TRI (12.5-25 ppm) or 1,1,1-TRI (87.5-175 ppm) in order to establish the influence of exposure concentration, duration of exposure, variation of concentration within day, and work load on biological exposure indices. The concentrations of unchanged solvents in end-exhaled air and in blood as well as the urinary excretion of trichloroethanol (TCE) and trichloroacetic acid (TCA) 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; this proportionality was still observable in 1,1,1-TRI expired air samples 16 h after the end of the third exposure day. In the case of urinary excretion of TCE and TCA, the proportionality between excretion and exposure concentration was not as good. It was once again observed that the slow excretion of both metabolites leads to progressive cumulation and that their urinary determination is subject to considerable interindividual variations. After adjustment (lowering) of the exposure concentration to account for a prolongation of the duration of exposure (from 8 to 12 h) it was observed that the concentrations of TRI or 1,1,1-TRI towards the end of both exposure periods are more a reflection of the actual exposure concentration than of the exposure duration. Despite important interindividual variations, these adjusted and nonadjusted exposures led to almost identical average total urinary excretion over 24 h) of TCE and TCA after exposure to 1,1,1-TRI, as was also the case for TCE but not for TCA after exposure to TRI. Induced within-day variations in the exposure concentration led to corresponding but not proportional changes in alveolar air concentrations for both solvents. After exposure to peak concentrations there was a lag period before alveolar air concentrations returned to prepeak levels. At the end of repeated 10-min periods of physical exercise at 50 W, alveolar air concentrations of TRI were increased by 50% while those of 1,1,1-TRI increased by only 12%. After optimization of the physiologically based toxicokinetic model parameters with experimental data collected during the first exposure scenario, results pertaining to the three other scenarios were adequately simulated by the optimized models. Overall, the results of the present study suggest that alveolar air solvent concentration is a reliable index of exposure to both TRI and 1,1,1-TRI under various experimental exposure scenarios. These results also suggest that urinary excretion of TCE and TCA must be interpreted with caution when assessing exposure to either solvents. For exposure 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.
The results of single exposure studies with exposure to trichloroethylene, TRI, (Monster et al., 1976), to 1,1,1-trichloroethane, MC, (Monster et al., 1979b) and to tetrachloroethylene, PERC, (Monster et al., 1979c) were used to study the precision in estimating the individual uptake from measured biological parameters after exposure. With simple linear and multiple linear regression analysis the individual uptake of TRI, MC and PERC was estimated from the concentrations of solvents and metabolites in biological media (blood, urine, exhaled air) at 2 h and at 20 h after exposure. The best results are obtained by estimation from the concentrations in blood, particularly of the solvents themselves. Including results of simultaneously measured concentrations in exhaled air or urine did not improve the estimate.
The objectives of this study were threefold. First, to examine the hepatic effects of occupational exposure to 1,1,2-trichloro-1,2,2-trifluoroethane (FC 113) using conventional and newer tests (serum bile acids) of hepatobiliary function. Second, to assess the effects of altered work practices that included a reduced exposure to a different halogenated solvent (trichloroethylene) on the same parameters of liver function; and finally, to gather further data to support or refute the contention that serum bile acid (SBA) levels could provide a sensitive biological marker of exposure to these solvents.
Two groups of workers (control and exposed) in an Australian steel industry participated in the study. The exposed group (n = 5-6) comprised individuals who had either exposure to FC 113 (68.2 +/- 12.6 ppm) or trichloroethylene (8.9 +/- 3.1 ppm) during the application of these solvents in a cleaning procedure, whereas the control group (n = 7-11) was composed of non-solvent-exposed office workers in the same company. The initial investigation involved exposure to FC 113 while a follow-up study was undertaken after changes in work practices were made including replacement of FC 113 with trichloroethylene (TRI).
Standard liver function tests and individual serum bile acids (ISBA) were measured before and after exposure to solvents and simultaneously in the control subjects by enzymatic methods and high performance liquid chromatography (HPLC), respectively.
Statistical analysis of the data showed a significant increase in the concentration of total serum bile acids (TSBA), some of the subgroups of SBA, and a few of the ISBA in workers after a period of exposure to FC 113. After TRI replaced FC 113 together with other changes in work practices to give substantial reduction in exposure to solvent, a repeat study also found elevated SBA after the cleaning procedure but to a lesser extent. No other indications of adverse liver effects, as measured by conventional parameters of hepatobiliary function, were detected.
Exposure to FC 113 was clearly associated with a significant rise in SBA levels, which are sensitive indicators of liver function. This finding is consistent with, and provides further support for, our previous investigations on chlorinated aliphatic hydrocarbon solvents which showed that SBA levels are a sensitive biological marker of exposure to these solvents. Changes in work practices including replacement of FC 113 resulted in a reduced effect on SBA, consistent with lower exposures.
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.
A physiologically based mathematical model is described for the human inhalation pharmacokinetics of 1,1,2-trichloro-1,2,2-trifluoroethane (FC113). Physiological parameters for the model are derived from the scientific literature. Partition coefficients are determined from in vitro measurements. Predictions of the resulting model for breath and blood concentrations compare well with results of a human volunteer study described in a companion paper (Woollen et al. 1990). Using this data some alternative models are also examined with different choices of physiological parameters and partition coefficients. The mathematical model is used to examine the consequences of metabolic elimination of FC113. A value for metabolic clearance is estimated using the during-exposure breath concentration data; however, the concentrations of FC113 in breath or blood during and after exposure are shown to be insensitive to metabolic clearance. Consequently, no firm conclusion can yet be drawn as to whether FC113 is metabolised by man.
A method has been developed for the simultaneous analysis of the isomeric N-acetyl-S-(dichlorophenyl)cysteines (also known as dichlorophenylmercapturic acids, DCPMAs) in urine. This procedure allows the determination of 2,3- and 3,4-DCPMAs at the concentrations expected in the urine samples of employees occupationally exposed to 1,2-dichlorobenzene (1,2-DCB). The results of a 1,2-DCB exposure study under standardized conditions show a first-order kinetic for the excretion of DCPMAs, as well as acceptable linear correlations between the urinary concentrations of DCPMAs and the amount of inhaled 1,2-DCB. It therefore seems it would be possible to derive a biological tolerance value for 1,2-DCB based on isomeric DCPMAs as analytical parameters.
This article reports the results obtained with the biological and environmental monitoring of occupational exposure to cyclohexane using 1,2-cyclohexanediol (1,2-DIOL) and 1,4-DIOL in urine. The kinetic profile of 1,2-DIOL in urine suggested by a physiologically based pharmacokinetic (PBPK) model was compared with the results obtained in workers.
Individual exposure to cyclohexane was measured in 156 workers employed in shoe and leather factories. The biological monitoring of cyclohexane exposure was done by measurement of 1,2-DIOL and 1,4-DIOL in urine collected on different days of the working week. In all, 29 workers provided urine samples on Monday (before and after the work shift) and 47 workers provided biological samples on Thursday at the end of the shift and on Friday morning. Another 86 workers provided biological samples at the end of the work shift only on Monday or Thursday.
Individual exposure to cyclohexane ranged from 7 to 617 mg/ m3 (geometric mean value 60 mg/m3). Urinary concentrations of 1,2-DIOL (geometric mean) were 3.1, 7.6, 13.2, and 6.3 mg/g creatinine on Monday (pre- and postshift), Thursday (postshift) and Friday (pre-shift), respectively. The corresponding values recorded for 1,4-DIOL were 2.8, 5.1, 7.8, and 3.7 mg/g creatinine. A fairly close, statistically significant correlation was found between environmental exposure to cyclohexane and postshift urinary 1,2-DIOL and 1,4-DIOL on Monday. Data collected on Thursday and Friday showed only a poor correlation to exposure with a wide scatter. Both metabolites have a urinary half-life of close to 18 h and accumulate during the working week.
Comparison between data obtained from a PBPK model and those found in workers suggests that 1,2-DIOL and 1,4-DIOL are urinary metabolites suitable for the biological monitoring of industrial exposure to cyclohexane.
This is a case report of acute fatal intoxication after accidental exposure to 1,2-dichloroethane in a 51-year-old man. Clinical manifestations, blood chemistry, and autopsy findings are described. High levels of lactate and ammonia in blood had been observed before the elevation of glutamic transaminases, lactic dehydrogenase, and creatine phosphokinase. Ornithine carbamyl transferase and glutamic oxaloacetic transaminase of mitochondrial origin (m-GOT) were remarkably high.
The metabolism and toxicokinetics of cyclohexane (CH) and cyclohexanol (CH-ol), important solvents and chemical intermediates, were studied in volunteers after 8-h periods of inhalation exposure at concentrations of 1010 and 236 mg m(-3), respectively (occupational exposure limits: CH, 1050 mg m(-3); CH-ol, 200 mg m(-3)). Of the dose of absorbed parent compounds, the yields of urinary CH-ol and 1,2- and 1,4-cyclohexanediol (CH-diol) were 0.5%, 23.4%, and 11.3%, respectively, after exposure to CH and 1.1%, 19.1%, and 8.4%, respectively, after exposure to CH-ol as determined by a gas chromatography method involving hydrolysis of glucuronide conjugates. The metabolic patterns of CH and CH-ol were very similar to that of cyclohexanone (CH-one) studied in the laboratory previously. For all three compounds, peak excretion of CH-ol occurred at the end of the exposure period, after which it decayed rapidly. Excretion curves of 1,2- and 1,4-CH-diol reached maximal values within 0-6 h postexposure, with subsequent elimination half-lives being 14-18 h. The rate-limiting step in the elimination of CH compounds from the organism is renal clearance of CH-diols. Determination of CH-diols in end-of-shift urine samples is recommended as a useful new method of biomonitoring of CH, CH-ol, and CH-one at the workplace. However, due to accumulation of CH-diols in the body during repeated exposure, quantitative relationships between the exposure and the level of CH-diols have to be adjusted according to the day of sampling during the working week.
The urinary excretion of 3,4-dimethylhippuric acid (34DMHA), a 1,2,4-trimethylbenzene (124TMB) metabolite, was investigated in workers exposed to 124TMB vapor. The time-weighted average of exposure to 124TMB was determined with a diffusive sampler. For biological monitoring of exposure, urine samples were collected from individual workers and analyzed for metabolites by high-pressure liquid chromatography. The concentration of urinary 34DMHA had a positive correlation with the level of exposure to 124TMB (r = 0.72). The data suggest that 34DMHA is one of the useful indicators for biological monitoring of 124TMB exposure.
The National Research Council (NRC) recently published a report. Science and Judgment in Risk Assessment, that critiqued the current approaches to characterizing human cancer risks from exposure to chemicals. One issue raised in the report relates to the use of default options for quantitation of cancer risks. Default options are general guidelines that can be used for risk assessment when specific information about a chemical is absent. Research on 1,3-butadiene represents an interesting case study in which existing knowledge on this chemical indicates that two default options may no longer be tenable: (1) humans are as sensitive as the most sensitive animal species, and (2) the rate of metabolism is a function of body surface area rather than inherent species differences in metabolic capacity. Butadiene, a major commodity chemical used in the production of synthetic rubber, is listed as one of 189 hazardous air pollutants under the 1990 Clean Air Act Amendments. Butadiene is a carcinogen in rats and mice, with mice being substantially more sensitive than rats. The extent to which butadiene poses a cancer risk to humans exposed to this chemical is uncertain. Butadiene requires metabolic activation to DNA-reactive epoxides to exert its mutagenic and carcinogenic effects. Research is directed toward obtaining a better understanding of the cancer risks of butadiene in humans by evaluating species-dependent differences in the formation of the toxic butadiene epoxide metabolites, epoxybutene and diepoxybutane. The data include in-vitro studies on butadiene metabolism using tissues from humans, rats, and mice as well as experimental data and physiological model predictions for butadiene in blood and butadiene epoxides in blood, lung, and liver after exposure of rats and mice to inhaled butadiene. The findings suggest that humans are more like rats and less like mice regarding the formation of butadiene epoxides. The research approach employed can be a useful strategy for developing mechanistic and toxicokinetic data to supplant default options used in carcinogen risk assessments for butadiene.
To investigate and compare alveolar, blood, and urine concentrations of 1,3-butadiene, 2,5 dimethylfuran, and benzene, in non-occupational exposure to these products.
Benzene, 2,5-dimethylfuran and 1,3-butadiene were measured in the breath, blood, and urine samples of 61 subjects living in small mountain villages. All 61 were regularly employed as forestry workers. Sampling was done during the long winter-season non-working period. Samples were collected after overnight rest and analysed by headspace and GC-mass spectrometry methods.
The median 1,3-butadiene level was 1.2 ng/l (range: <0.8-13.2 ng/l) in alveolar air, 2.2 ng/l (range: <0.5-50.2 ng/l) in blood, and 1.1 ng/l (range: <1-8.9 ng/l) in urine. The median benzene level was 5.7 ng/l (range: <1-24.9 ng/l) in alveolar air, 62.3 ng/l (range: 33.5-487.2 ng/l) in blood, and 63.4 ng/l (range: 25.8-1099.1 ng/l) in urine. The median 2,5-dimethylfuran level was 0.5 ng/l (range: <1-12.5 ng/l) in alveolar air, 2.5 ng/l (range: <5-372.9 ng/l) in blood, and 51.8 ng/l (range: <5-524.9 ng/l) in urine. In several cases, 2,5-dimethylfuran levels were below the detection limit in alveolar air and blood, especially in non-smokers. 1,3-Butadiene, 2,5-dimethylfuran and benzene levels were significantly higher in smokers than non-smokers in all biological media.
1,3-Butadiene and benzene, as ubiquitous pollutants, are detectable and quantifiable in human alveolar air, blood and urine. 2,5-Dimethylfuran, which is not a usual environmental pollutant, is almost always detectable in biological media, but only in smokers.