Biological monitoring of nitrous oxide exposure in surgical areas

Exposure to nitrous oxide in surgical theaters was evaluated for duration, numbers, and types of surgical procedures. The concentration of the gas in the air was 92-444 ppm. Before and after the surgical sessions, samples of urine and expired air were collected from surgical theater personnel for gas determination. Nitrous oxide concentrations in urine and in expired air showed a good correlation with gas concentration in the air (r = 0.760 and r = 0.921, respectively). Moreover, a good correlation (r = 0.823) between gas concentration in urine and that in expired air was also found. A biological threshold limit value (TLV) of 20.6 micrograms/liter for urine and of 29.6 ppm for expired air was calculated, based on the limit of 50 ppm in the air proposed by the American Conference of Governmental Industrial Hygienists (ACGIH). Other biological TLVs corresponding to higher proposed limits (200 and 500 ppm) were also calculated.     

Occupational lead exposure aboard a tall ship

To evaluate occupational exposures to lead in shipfitters cutting and riveting lead-painted iron plates aboard an iron-hulled sailing vessel, we conducted an environmental and medical survey. Lead exposures in seven personal (breathing zone) air samples ranged from 108 to 500 micrograms/m3 (mean 257 micrograms/m3); all were above the Occupational Safety and Health Administration (OSHA) standard of 50 micrograms/m3. In two short-term air samples obtained while exhaust ventilation was temporarily disconnected, mean lead exposure rose to 547 micrograms/m3. Blood lead levels in ten shipfitters ranged from 25 to 53 micrograms/dl (mean, 37.8 micrograms/dl); levels in three of these workers exceeded the upper normal limit of 40 micrograms/dl. Blood lead levels in shipfitters were significantly higher than in other shipyard workers (mean 10.0 micrograms/dl; p less than 0.001). Smoking shipfitters (mean, 47 micrograms/dl) had significantly higher lead levels than nonsmokers (mean, 32 micrograms/dl; p = 0.03). Lead levels in shipfitters who wore respirators were not lower than in those who wore no protective gear (p = 0.68). Four shipfitters had erythrocyte protoporphyrin (EP) concentrations above the adult upper normal limit of 50 micrograms/dl. A close correlation was found between blood lead and EP levels (r = 0.70). Prevalence of lead-related symptoms was no higher in shipfitters than in other workers. No cases of symptomatic lead poisoning were noted. These data indicate that serious occupational exposure to lead can occur in a relatively small boatyard.     

Isopropanol exposure: environmental and biological monitoring in a printing works.

Occupational exposure to isopropanol was studied in 12 workers by testing environmental air, alveolar air, venous blood, and urine during their work shift. Isopropanol, which ranged in environmental air between 7 and 645 mg/m3, was detected in alveolar air, where it ranged between 4 and 437 mg/m3, but not in blood or in urine. Alveolar isopropanol concentration (Ca) was significantly correlated with environmental isopropanol concentration (Ci) at any time of exposure. The value of the arithmetical Ca/ci ratio was 0.418 (SD 0.101). Acetone, which is a metabolite of isopropanol, was found in alveolar air, blood, and urine in concentrations that were higher during exposure than before. Alveolar and blood acetone concentrations were highly correlated with alveolar isopropanol concentrations at any time during exposure. Acetone ranged between 0.76 and 15.6 mg/l in blood, between 4 and 93 micrograms/l in alveolar air, and between 0.85 and 53.7 mg/l in urine. Alveolar (Ca) and blood (Cb) acetone concentrations were highly correlated (r = 0.67), with a Cb/Ca ratio of 101. Alveolar isopropanol uptake ranged between 0.03 and 6.8 mg/min and was highly correlated with environmental isopropanol concentration (r = 0.92). During exposure, acetone eliminated by the lungs ranged between 20 and 273 mg in seven hours and in urine between 0.3 and 9.6 mg in seven hours. Acetonuria was higher the next morning than at the end of exposure.     

Biological monitoring for occupational exposure to toluene

A study was undertaken to examine the relationship between exposure of workers to toluene in the work environment and biological indicators of toluene exposure. The biological indicators studied were toluene in expired air, toluene in blood obtained by the finger prick method, and urinary hippuric acid. The study was undertaken in a factory in Singapore that manufactures speakers for audio systems. A total of 86 female workers exposed to toluene at the workplace and a control group of workers not exposed to toluene were examined. All of them were teetotalers, were nonsmokers, and gave no history of chronic drug usage. The 8-hr time-weighted average exposure level of toluene ranged from 1.6 ppm to 263 ppm. The study showed the expected toluene levels in finger prick blood was 1.4 micrograms/mL after an 8-hr exposure to 100 ppm of toluene. Toluene concentration in expired air of 16 ppm after an 8-hr exposure to 100 ppm compared favorably with other studies. The toluene in blood/expired air ratio was observed to be lower than in other studies. In this study, the expected urinary hippuric acid level for a 100-ppm exposure to toluene was 2.7 g/g creatinine. This level is higher than that recorded in other studies. The results showed that at low levels of toluene, urinary hippuric acid is not a valuable indicator of exposure. Toluene in expired air is the most reliable biological indicator of exposure to toluene.     

Biological monitoring of the occupational exposure to halothane (fluothane) in operating room personnel

The concentration of halothane (fluothane) in the ambient atmosphere was determined in five operating theaters of two hospitals in Italy. The concentrations of halothane in the ambient air exceeded the NIOSH recommended time-weighted average exposure levels (median value: 10.38 mg/m3). Halothane was detected in the urine of 58 exposed subjects (anesthetists, surgeons, and nurses). A significant correlation was found between the halothane concentration in urine produced during the shift (Cu, micrograms/L) and halothane environmental concentration (CI, mg/m3) (Cu = 0.242 x CI + 3.51) (N = 58; r = 0.92; p less than 0.0001). The results show that the urinary halothane concentration can be used as an appropriate biological exposure index. The biological values proposed are: 92 micrograms/L, corresponding to a 50 ppm of environmental exposure; 6.5 micrograms/L, corresponding to 2 ppm of environmental exposure and 3.9 micrograms/L, corresponding to a 0.5 ppm of environmental exposure.     

Occupational chronic exposure to metals

Stainless steel welders (n = 103) were examined. To estimate external exposure, personal air sampling was used. Internal exposure was quantified by the determination of nickel levels in erythrocytes, plasma and urine. Men and women (n = 123) were examined for control purposes. In the plasma and erythrocytes of the controls the nickel concentration was below the level of detection (less than 1.8 micrograms/l). The element concentrations in urine were between less than 0.1 and 13.3 micrograms/l. Of the controls 95% showed nickel levels in urine below 2.2 micrograms/l (reference value). The average concentration of nickel in the air was 93 +/- 81 micrograms/m3. The average concentration of nickel in the plasma samples was 4.9 +/- 4.0 micrograms/l (95th percentile 12.8 micrograms/l). In erythrocytes nickel could not be detected. The nickel concentrations in the urine of the welders were 18.5 +/- 28.5 micrograms/l on average (95th percentile 52.5 micrograms/l). Only a weak correlation between the nickel levels of plasma and urine could be detected (Curine = 2.07 + 8.45 Cplasma; r = 0.294; p less than 0.01). Based on our results and on the reported literature a future limit value for the nickel concentration in urine should lay between 30 and 50 micrograms/l. This value corresponds to an external exposure of 500 micrograms nickel per cubic metre.     

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.     

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.     

Kinetics of 1,1,1-trichloroethane in volunteers; Influence of exposure concentration and work load

Summary 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.     

三氯乙烯对接触工人外周血微核率的影响

目的　研究空气中三氯乙烯 (trichloroethylene ,TCE)浓度和接触工人外周血淋巴细胞微核发生率及尿中三氯乙酸 (trichloroacticacid ,TCA)浓度的剂量 反应关系 ,在染色体水平上探讨三氯乙烯对人体可能产生的危害以及接触 反应关系。方法　选择接触三氯乙烯至少三个月的工人和无接触三氯乙烯及其它有毒物质的某防疫站就业前体检工人作为研究对象 ,测定空气中三氯乙烯浓度、个体接触三氯乙烯浓度、外周血淋巴细胞微核发生率和尿中三氯乙烯的浓度。结果　接触组外周血淋巴细胞微核发生率 ,与对照组相比有升高 (P <0 0 1) ;个体接触三氯乙烯浓度和尿中三氯乙酸浓度呈正相关关系 (r =0 .761,P <0 0 0 1) ,而个体接触三氯乙烯浓度、尿中三氯乙酸浓度与外周血微核发生率均无相关关系。结论　①本现场研究表明三氯乙烯接触可导致微核生成增加 ;但不能确定三氯乙烯的遗传毒性作用 ;②尿中三氯乙酸浓度可以作为三氯乙烯接触水平的评价指标。     

Acute effects of trichloroethylene on blood concentrations and performance decrements in rats and their relevance to humans.

This study was designed to clarify the nature of effects of trichloroethylene (TCE) on the central nervous system, and to determine the critical concentrations in blood associated with specific behavioural changes. This was achieved by a follow up of the whole time course of TCE intoxication during and after exposure. The effects of a single four hour exposure to TCE on signalled bar press shock avoidance in rats were tested by methods previously applied to investigate the acute neurobehavioural effects of exposure to toluene. Even low exposure to TCE induced shock avoidance performance decrements in rats. Rats exposed to 250 ppm TCE showed a significant decrease both in the total number of lever presses and in avoidance responses at 140 minutes of exposure compared with controls. The rats did not recover their pre-exposure performance until 140 minutes after the exhaustion of TCE vapour. Exposures in the range 250 ppm to 2000 ppm TCE for four hours produced concentration related decreases in the avoidance response rate. No apparent acceleration of the reaction time was seen during exposure to 1000 or 2000 ppm TCE. The latency to a light signal was somewhat prolonged during the exposure to 2000 to 4000 ppm TCE. It is estimated that there was depression of the central nervous system with slight performance decrements and the corresponding blood concentration was 40 micrograms/ml during exposure. Depression of the central nervous system with anaesthetic performance decrements was produced by a blood TCE concentration of about 100 micrograms/ml. These results showed effects of TCE on the central nervous system that were considered to be a function of both the exposure concentration and the duration of exposure, which are closely related to the TCE concentration in blood.     

Pharmacokinetics of trichloroethylene in volunteers,influence of workload and exposure concentration

Summary Four male volunteers inhaled for 4 h 70 and 140 ppm trichloroethylene (TRI) at rest and also at rest combined with exercise. To estimate the amount retained in the body (dose), minute volume and concentration in exhaled air were determined. Concentrations of TRI, trichloroethanol (TCE) and trichloroacetic acid (TCA) were determined in blood. Exhaled air was analysed for TRI and TCE; urine for TCE and TCA.During more than 60 h after exposure the concentration of TRI and TCE in blood and exhaled air were proportional to the dose, but the interindividual variation was large; workload increased the dose, but no influence was found on the distribution and metabolism. The total recovery was 67%; 10% as TRI by the lungs and in urine 39% as TCE and 18% as TCA.     

Urinary methylchloroform rather than urinary metabolites as an indicator of occupational exposure to methylchloroform

In order to compare methylchloroform (MC, or 1,1,1-trichloroethane) per se and its metabolites in urine as indicators of occupational exposure to this solvent, 50 male solvent workers were studied in the second half of a working week to evaluate the exposure-excretion relationship. The time-weighted average intensity of solvent exposure of individuals during an 8-h shift was monitored by personal diffusive sampling. Urine samples were collected near the end of the shift and were analyzed for MC and its metabolites [i.e., trichloroacetic acid (TCA), trichloroethanol (TCE) and total trichloro-compounds (TTC; the sum of TCA and TCE)] by head-space gas chromatography. MC per se, TCA, TCE, and TTC in urine correlated significantly (P < 0.01) with MC in ambient air, and among the four the correlation coefficient was highest for MC. The same results were obtained by multiple regression analysis in which ambient air MC was taken as the dependent variable and either the three indicators urinary MC, TCA, and TCE or the two indicators urinary MC and TTC were taken as independent variables. Taking the specificity and selectivity of the analyte as well as the simple and hazardous chemical-free procedure of analysis into consideration, it is concluded that MC is the analyte of choice as an indicator of occupational exposure to MC, when urine is selected as a specimen available by noninvasive sampling.     

Clinical and neurobehavioural study of the acute and chronic neurotoxicity of styrene

A cross sectional field study of workers exposed to styrene was performed to evaluate possible acute and chronic neurotoxic effects. A total of 36 workers of four companies handling polyester resin materials for one to 16 years (median: 7 years) and two control groups were each examined on a Monday. The control group 1 (formed to compare acute effects) consisted of 20 men from two companies with no exposure to neurotoxic chemicals. To compare chronic effects, a second control group was formed by "one to one matching" with respect to age, socioeconomic status, and pre-exposure intelligence level. Ambient air monitoring using active sampling (short time) and passive samplers (long time) showed styrene in air concentrations as follows: range 3-251 ppm (median: 18 ppm) and concentrations 140-600 ppm during lamination of the inside of boats. For biological monitoring the results were as follows (postshift samples: range/median): styrene in blood: 5-482 micrograms/dl (39 micrograms/dl), mandelic acid urine: 0.01-3.64 g/l (0.21 g/l), and phenylglyoxylic acid urine: 0.01-0.87 g/l (0.19 g/l). The clinical examination found no signs or symptoms of peripheral neuropathy or encephalopathy. The principal work related health complaints were acute, reversible irritation of the eyes that occurred after exposure to styrene concentrations of 200 ppm or more. The neurobehavioural tests showed no significant differences in acute effects (p greater than 0.05) between the two groups or between preshift and postshift testing. Nor were there any significant differences in the relevant neurobehavioural variables between the styrene workers and the controls. It is concluded that occupational exposure to styrene concentrations in air up to 100 ppm causes no adverse acute or chronic effects on the central nervous system.     

Clinical and neurobehavioural study of the acute and chronic neurotoxicity of styrene.

A cross sectional field study of workers exposed to styrene was performed to evaluate possible acute and chronic neurotoxic effects. A total of 36 workers of four companies handling polyester resin materials for one to 16 years (median: 7 years) and two control groups were each examined on a Monday. The control group 1 (formed to compare acute effects) consisted of 20 men from two companies with no exposure to neurotoxic chemicals. To compare chronic effects, a second control group was formed by "one to one matching" with respect to age, socioeconomic status, and pre-exposure intelligence level. Ambient air monitoring using active sampling (short time) and passive samplers (long time) showed styrene in air concentrations as follows: range 3-251 ppm (median: 18 ppm) and concentrations 140-600 ppm during lamination of the inside of boats. For biological monitoring the results were as follows (postshift samples: range/median): styrene in blood: 5-482 micrograms/dl (39 micrograms/dl), mandelic acid urine: 0.01-3.64 g/l (0.21 g/l), and phenylglyoxylic acid urine: 0.01-0.87 g/l (0.19 g/l). The clinical examination found no signs or symptoms of peripheral neuropathy or encephalopathy. The principal work related health complaints were acute, reversible irritation of the eyes that occurred after exposure to styrene concentrations of 200 ppm or more. The neurobehavioural tests showed no significant differences in acute effects (p greater than 0.05) between the two groups or between preshift and postshift testing. Nor were there any significant differences in the relevant neurobehavioural variables between the styrene workers and the controls. It is concluded that occupational exposure to styrene concentrations in air up to 100 ppm causes no adverse acute or chronic effects on the central nervous system.     

Arsenic levels in blood, urine, and hair of workers applying monosodium methanearsonate (MSMA)

Uptake and excretion of total arsenic from monosodium methanearsonate (MSMA) in workers who applied the herbicide was followed during the spraying season. Urine, blood, and hair samples were collected and air samples were taken from the workers' breathing zone. Arsenic concentrations in air samples ranged from 0.001-1.086 micrograms/m3. Blood and urine arsenic values ranged from 0.0-0.2 mg/L and 0.002-1.725 mg/L, respectively. The geometric mean arsenic concentration in urine increased during the week but returned to base levels on weekends. Hair arsenic concentrations ranged from 0.02-358.0 mg/kg, increased during the spraying season, and returned to pre-season levels once herbicide application ceased. Three workers had higher than normal pre-exposure hair values. However, only one of the three workers had consistently above normal values throughout the study period.     

Kinetics of trichloroethylene in repeated exposure of volunteers

Summary Five male volunteers inhaled 70 ppm trichloroethylene (TRI) for 4 h on 5 consecutive days. TRI, trichloroethanol (TCE) and trichloroacetic acid (TCA) were measured, as far as present in exhaled air, blood, and urine. The uptake was 6.6 ± 0.4 mg/kg lean body mass in 4 h. The concentration of TRI in blood and exhaled air at 18 h after the 5th exposure was twice as high as at 18 h after the 1st exposure. The amount of TCE excreted per 24 h reached a level during the last exposure days, a diurnal rythm was evident. TCA in blood and urine increased during exposure days. Total recovery of the amount absorbed of TRI was 78%, 11% as TRI excreted unchanged by the lung, 43% as WE and 24% as TCA excreted in urine. Amounts of WE and TCE+TCA excreted in urine were related to lean body mass. Because of its small interindividual variation TCA in blood seems to be the most promising parameter for biological monitoring in repeated exposure.     

Reconstructing population exposures from dose biomarkers: inhalation of trichloroethylene (TCE) as a case study

Physiologically based pharmacokinetic (PBPK) modeling is a well-established toxicological tool designed to relate exposure to a target tissue dose. The emergence of federal and state programs for environmental health tracking and the availability of exposure monitoring through biomarkers creates the opportunity to apply PBPK models to estimate exposures to environmental contaminants from urine, blood, and tissue samples. However, reconstructing exposures for large populations is complicated by often having too few biomarker samples, large uncertainties about exposures, and large interindividual variability. In this paper, we use an illustrative case study to identify some of these difficulties, and for a process for confronting them by reconstructing population-scale exposures using Bayesian inference. The application consists of interpreting biomarker data from eight adult males with controlled exposures to trichloroethylene (TCE) as if the biomarkers were random samples from a large population with unknown exposure conditions. The TCE concentrations in blood from the individuals fell into two distinctly different groups even though the individuals were simultaneously in a single exposure chamber. We successfully reconstructed the exposure scenarios for both subgroups - although the reconstruction of one subgroup is different than what is believed to be the true experimental conditions. We were however unable to predict with high certainty the concentration of TCE in air.     

The relationship between external and internal doses of trichloroethylene. A simulation study using a physiological pharmacokinetic model

The relationship between external dose and internal dose of trichloroethylene (Tri) was analyzed by using a physiological simulation model. The external dose of Tri was represented by the time-weighted average (TWA) concentration in inhaled air or by the product of exposure concentration and exposure duration, and the internal dose by the area under the curve (AUC) of Tri blood concentration or by the cumulative amount of total trichloro compounds (TTC) in urine. If TWA concentrations were equal, the internal doses were also equal irrespective of whether Tri exposure was continuous, intermittent, or random. Both AUC of Tri and cumulative amounts of urinary TTC increased linearly with increase of Tri concentration in inhaled air up to 100 ppm. The increase at exposure concentrations between 100 and 500 ppm was non-linear. At concentrations above 500 ppm where Tri metabolism was saturated, AUC increased linearly again but much more sharply than the increase at concentrations below 100 ppm. In contrast, the increase of cumulative amounts approached a plateau along with Tri exposure concentration. If the exposure concentration was below the level when saturation of Tri metabolism did not occur, equal products of Tri concentration and exposure duration resulted in almost the same internal dose. In general, however, the AUC of blood concentration in a high-concentration, short-duration exposure was larger than that of a low-concentration, long-duration exposure, whereas the cumulative amount of TTC was larger in the latter than in the former.     

三氯乙烯对接触工人神经行为功能影响的初步研究

目的：了三氯乙烯（TCE）低浓度、长时间的暴露条件下对暴露人群的早期影响。方法：运用WHO推荐的神经行为功能测试组合（WHO－NCTB）对我国南方某市一区65名TCE作业工人及115名对照工人进行了神经行为功能测试,同时测定研究对象尿中TCE的代谢产物三氯乙酸（TCA）的含量。结果：接触工人车间空气中TCE平均浓度为90．8mg/m^3,接触工人班后尿TCA平均值为52．1mg/g肌酐;接触组NCTB测试项目中数字译码、简单反应时的标准差、优势手提转敏捷度、目标追踪错误数及总数得分显著差于对照组,通过等级相关分析,发现接触组班后尿TCA水平与目标追踪正确数、总数呈显著负相关;与情感问卷中困惑－迷茫项、目标追踪错误数呈显著正相关。结论：长时间接触较低浓度TCE早期可对暴露者神经行为功能产生明显影响,主要表现在短时间记忆力、注意力降低、手运动速度下降,手－眼运动协调性和稳定性差,并有一定的消极情感状态改变;尿TCA水平与以上改变呈一定的剂量－反应关系。