Carbon disulphide

Summary Carbon disulphide (CS₂), a reagent of rayon production, is known for its high toxic potential and has therefore been the subject of many clinical studies. The aims of the study presented here were to determine the effective exposure to CS₂ and to compare the validity of the different exposure indicators. Internal and external exposure to CS₂ was investigated in 362 male workers of a viscose factory. The CS₂ air concentrations measured through stationary air monitoring in five different work areas (n = 39) were compared with the values of active personal air monitoring (n = 51) and passive personal air monitoring (n = 352). In addition, in all investigations biological monitoring was carried out by measuring the 2-thio-1,3-thiazolidine-carboxylic acid (TTCA) excretion in urine. A significant correlation was found between the data for active and passive personal air sampling (y = 0.99, x + 0.31, r = 0.968). The results of the stationary measurements led, however, to values which were systematically too low. The validity of TTCA excretion in urine as a parameter of biological monitoring could for the first time be verified in a large sample of subjects. There was a linear correlation between TTCA values in the urine related to both volume and creatinine [y (TTCAmg/g creatinine) = 0.315 x (ml CS₂/m³ air) + 0.59] and the CSZ values in the air. Nevertheless, TTCA excretion proved to be dependent upon creatinine so that the excreted amounts related to creatinine described the individual exposure more exactly.     

Experimental human exposure to carbon disulfide

Summary Six human volunteers were exposed to 10 and 20 ppm carbon disulfide at rest and to 3 and 10 ppm carbon disulfide under a 50 W level of physical exercise during four consecutive periods of 50 min. At the start of the experiments, at the end of the exposure periods and during the post-exposure period, urine was sampled and the concentration of 2-thiothiazolidine-4-carboxylic acid (TTCA) was determined. It was established that only a small percentage, ranging from 0.7 to 2.2% of the absorbed carbon sulfide was transformed into TTCA. The excretion rate of TTCA (mol TTCA h^–1) was found to be the best parameter in evaluating the respiratory uptake of carbon disulfide over a range of 37.9 to 163.3 mg CS₂ compared to the urinary concentration of TTCA (mole TTCA ml^–1) or the creatinine corrected concentration of TTCA (mmol TTCA mol^–1 creatinine). The total amount of TTCA (mol TTCA) excreted proved to be independent of the urinary flow (ml h^–1), the estimates of the individual fatty tissue content and the urinary pH. No correlation was found between the respiratory uptake of carbon disulfide (mg CS₂) and the excretion rate of TTCA within each exposure condition of 3, 10 or 20 ppm carbon disulfide, respectively.     

A cross-sectional study on the brainstem auditory evoked potential among workers exposed to carbon disulfide

Summary In order to clarify the chronic effect of carbon disulfide (CS₂) on the central nervous system (CNS), the brainstem auditory evoked potential (BAEP) was measured in spinning workers exposed to CS₂ in a viscose rayon manufacturing factory and unexposed workers in Japan. Workers exposed to CS₂ were divided into three groups according to length of exposure: current spinning workers with an exposure duration of more than 240 months (L group, n = 34), current spinning workers with an exposure duration of 24–84 months (S group, n = 25), and former spinning workers with an exposure duration of more than 120 months (R group, n = 16). Unexposed controls were selected from workers in a nylon filament factory using the same criteria (N group; n = 40). BAEP records were analyzed based on the latencies of three main components (I, III, V) and interpeak latencies (I–III IPL, III–V IPL, I–V IPL). Latencies of component V, III–V IPL, and I–V IPL in the L group were significantly greater (P < 0.01, P < 0.05, P < 0.05, respectively). The significantly, higher III–V IPL in the L group suggested that in humans, chronic exposure to CS₂ involves the auditory ascending tract in the brainstem. Recovery from this neurotoxic effect is apparently possible, as the BAEP parameters in the R group were not significantly higher than those of the N group despite the long previous CS₂ exposure of the R group.     

Carbon disulphide

The reported investigations on the uptake of carbon disulphide (CS₂) and the excretion of its metabolite 2-thiothiazolidine-4-carboxylic acid (TTCA) were based on results from 403 personal air samples (352 passive and 51 active samples) and 362 TTCA determinations in biological material measured during a field study on the adverse effects due to CS₂ exposure. The external exposure ranged from below the detection limit (0.2 ppm) to 66 ppm and the urinary TTCA excretion from below the detection limit (0.16 mg./1) to 33.4 mg/1. The excretion of TTCA in postshift urine related to creatinine and volume showed a linear correlation to the CS₂ air concentration. On the basis of these results the influence on the internal exposure of physical work load, dermal exposure and individual parameters (age, Brocaindex, disturbed skin barrier) was evaluated. Correlations between the TTCA values in the postshift urine and the individually measured CS₂ concentrations were carried out separately for individual departments and persons with and without indications of a disturbed skin barrier. In order to be able to judge the individual internal exposure related to external exposure, a personal quotient was formed from the TTCA level in the urine and the CS₂ air concentration measured on the same day (relative interal exposure RIE index = TTCA mg/g creatinine/CS₂ in ppm). On investigating interindividual differences, higher relative internal exposures were found in persons with a heavy physical work load and more intensive skin contact. It could be shown for a large group of persons exposed to CS₂ that a pathological skin condition leads to an increase in the dermal penetration rate of hazardous substances. By means of the RIE index it could be shown that the TTCA excretion related to the individual external exposure increases significantly with a decreasing Broca index, which must be taken into consideration with greatly overweight persons and exposures in the range of the currently valid threshold limit values. The interindividual differences in internal exposure found at the same ambient air concentration emphasize the importance of biological monitoring for individual health protection and the setting of biological threshold limit values.Dedicated to Professor G. Zehnert on the occassion of his 65th birthday     

A six year follow up study of the subclinical effects of carbon disulphide exposure on the cardiovascular system

Aims: A six year prospective cohort study was conducted to clarify whether the current carbon disulphide (CS₂) exposure level is low enough to prevent subclinical health impairment and/or to ameliorate health effects due to previous high exposure. This paper describes the effects on the cardiovascular systems.

Methods: The study subjects were 432 male workers exposed to CS₂ and 402 non-exposed workers in Japan, all of whom were examined in 1992–93. A total of 251 CS₂ exposed, 140 formerly exposed, and 359 non-exposed workers participated in the follow up survey (follow up rate 89.9%) in 1998–99. Mean duration of exposure was 19.3 years at the end the study. Mean CS₂ and 2-thiothiazolidine-4-carboxylic acid (TTCA) concentrations were 5.0 ppm and 1.6 mg/g creatinine. Health items examined were serum biochemical indices including lipids and coagulation-fibrinolysis factors, blood pressure, aortic stiffness, ophthalmography, and electrocardiography at rest and after Master's double 2 step test. Potential confounding factors were adjusted for.

Results: Incidence of ischaemic findings, defined as Minnesota codes I, IV_1–3, V_1–3 (at rest and after the load), or receiving treatment for ischaemia, was significantly higher in the exposed workers, especially for the spinning/refining workers (adjusted OR 2.1; 95% CI 1.1 to 4.0) or the highest quartile of six year mean TTCA (adjusted OR 3.9; 95% CI 1.8 to 8.7), although the observed increase in risk was diminished when rigorous ECG criteria were applied. Incidence of retinal microaneurysm was increased with marginal significance. Among cardiovascular risk factors we examined, only blood pressure values were significantly increased in the exposed workers.

Conclusions: Increased risk of ischaemic electrocardiogram findings among Japanese viscose rayon workers was observed. Although its clinical significance is to be discussed, the current Japanese occupational exposure limit for CS₂, 10 ppm, would be high to prevent subclinical cardiovascular effects in this study population.

     

Biological monitoring of workers occupationally exposed to carbon disulphide in a rayon plant in Brazil: Validity of 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine samples taken in different times, during and after the real exposure period

Fifteen workers from a rayon plant in Brazil were monitored. Air samples were taken during a mean period of 5.8 hours out of an 8 hour workshift, in three different adsorbing tubes. Five urine samples were taken at 4 hour interval from the beginning of the shift, and at the beginning of the next shift in which 2-thiothiazolidine-4-carboxylic acid (TTCA) concentration was analysed. Data from seventeen individuals were statistically studied, with the aim of establishing the best and the most practical sampling strategy of biological monitoring for workers occupationally exposed to CS₂. For those chronically exposed to CS₂, TWA air concentration lower than 30 and higher than 10 mg/m³, it was found that the higher the exposure levels, the lower was TTCA concentration in the end of shift urine samples. The results may be explained by dietary habits and/or by the small number of examined population or even eventual casualty. On the other hand they raise other hypothesis involving the chronicity of exposure which may lead to important changes in metabolism influencing the excretion rate of TTCA.     

二硫化碳接触工人尿2-硫代噻唑烷-4-羧酸排泄规律的研究

目的　探讨二硫化碳 (CS2 )接触工人尿 2 硫代噻唑烷 4 羧酸 (TTCA)的排泄规律 ,为制定CS2 短时接触生物监测提供实验依据。方法　将受试对象分为 3组进行实验 :(1) 14名非CS2 接触者在某CS2 车间暴露 2h后收集不同时段尿液 ,分析其TTCA浓度变化 ;(2 )某CS2 车间 15名CS2 接触工人三班倒休息 4 8h后上班 ,连续收集 3d班前、班中、班末尿 ,分析其TTCA浓度变化 ;(3)收集 4 0名长期接触CS2 工人班末尿 ,分析其TTCA浓度变化与工人接触CS2 的 8h时间加权平均浓度 (PC TWA)的关系。结果　第 1组研究结果显示 ,接触CS2 4h后 (此时已停止接触 2h)尿中TTCA含量达到最高值 [(1.0 3± 0 .72 )mg/gCr];第 2组研究结果显示 ,班前尿TTCA含量极低 [(0 .37± 0 .2 8)mg/gCr],与班中尿 [上班后 4h(1.2 3± 0 .71)mg/gCr]及班末尿 [(1.31± 0 .78)mg/gCr]比较 ,差异有显著性 (P <0 .0 1) ,而班中尿TTCA值与班末尿相比 ,差异无显著性 (P >0 .0 5 ) ;第 3组研究结果显示 ,班末尿TTCA值与工人PC TWA之间有直线关系 [Y(TTCAmg/gCr) =1.16 36X(CS2 mg/m3) - 5 .4 116 ]。结论　班末尿TTCA值可作为CS2 接触工人的生物监测指标。     

Levels of 2-thiothiazolidine-4-carboxylic acid (TTCA) and effect modification of polymorphisms of glutathione-related genes in vulcanization workers in the southern Sweden rubber industries

Objectives Workers in the rubber industry are exposed to a complex mixture of hazardous substances and have increased risk of developing several diseases. However, there is no up to date survey examining the exposure in the Swedish rubber industry. One of the toxic compounds in the industry is carbon disulfide (CS₂), which is biotransformed to 2-thiothiazolidine-4-carboxylic acid (TTCA). TTCA is used as a biomarker of CS₂ exposure, but there seem to exist inter- and intraindividual variability; which could partly be due to genetic variation. The aim of the study was to determine TTCA levels and the modifying effects of glutathione-related genes in a group of Swedish rubber workers. Methods Urine was collected from both exposed workers and controls during the last 4 h of the work shift. The level of TTCA in urine was analyzed by liquid chromatograpy tandem mass spectrometry. Genotyping of the single nucleotide polymorphisms GCLC-129, GCLM-588, GSTA1-52, GSTP1-105 and GSTP1-114 and deletions of GSTM1 and GSTT1 were performed with real-time PCR or ordinary PCR and subsequent agarose electrophoresis. Results The highest levels of TTCA were found among workers curing with salt bath, hot air, microwaves or fluid-bed, and lower levels were found among workers curing with injection and compression molding. Furthermore, with respect to GSTM1 and GSTT1 there were statistically significant differences in TTCA-levels between genotypes among exposed workers but not among controls. The other five polymorphisms had no impact on the TTCA levels. Conclusions The present study demonstrates relatively high levels of TTCA in urine from Swedish rubber workers. Polymorphisms in GSTM1 and GSTT1 modify the levels.     

Epidemiological study of gastrointestinal and liver effects of carbon disulfide

Summary In the framework of an extensive health survey, 119 viscose rayon workers exposed to carbon disulfide (CS₂) and 79 workers from other plants not exposed to any toxic agent in the working environment underwent a gastrointestinal examination including a self-administered questionnaire, abdominal palpation, percussion and a number of liver function tests. In the viscose rayon factory the working conditions have not changed since 1932. Personal monitoring performed in 17 jobs showed CS₂ exposures varying from 4 to 112 mg · m^–3. For each individual a cumulative CS₂ exposure index (CS₂ index) was calculated. Univariate analysis of the questionnaire findings showed significantly higher prevalences of anorexia (37.0% vs 11.4%, P<0.0001), vomiting (12.6% vs 3.8%, P = 0.04), and recent weight loss (10.9% vs 1.3%, P = 0.009) in the exposed than in the non-exposed workers. The exposed workers had a larger total number of gastrointestinal complaints and a larger proportion reported at least one complaint at least once a month than the non-exposed ones. Abdominal tenderness was very rare in both groups. In multiple logistic regression analysis, adjusting for alcohol intake, smoking, body mass index (BMI), coffee consumption, commuting time, stress at work, shift work, educational level, family history of ulcer disease and intake of medication, significant associations with exposure were found for anorexia (P = 0.0001), nausea (P = 0.009), vomiting (P = 0.002) and flatulence (P = 0.03). Stress at work was a determinant for quite a few digestive complaints, but shift work was not significantly associated with any of them. The exposed workers had significantly lower median values for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) than the non-exposed (11.0 vs 13.5 mU/ml, P = 0.0008; 12.0 vs 13.0 mU/mL, P = 0.01, respectively. The values for liver size and -glutamyltransferase (GGT) were significantly higher in the exposed than in the non-exposed workers (72 vs 67 mm, P = 0.002; 13 vs 11 U/1, P = 0.0003, respectively). The alkaline phosphatase (AP) activity did not differ significantly between the two groups. In multiple linear regression, adjusting for alcohol, pharmaceuticals consumption and BMI, there was a slightly significant negative association between exposure and AST (P = 0.04) and positive association with liver size (P = 0.002) and GGT (P = 0.0001). Alcohol was positively associated with GGT, and BMI with ALT and GGT.     

An Epidemiologic Study of the Effects of Carbon Disulfide on the Peripheral Nerves

Abstract

Although the labor inspection had disclosed considerable exposure to carbon disulfide (CS₂) in a Belgian viscose rayon factory, the company medical officer had not diagnosed any case of polyneuropathy in association with CS₂ exposure, although this finding had been extensively reported in the literature. Personal monitoring of CS₂ exposure was performed in 17 jobs. Because the working conditions in the factory had not changed since 1932, a CS₂ cumulaiive exposure index (CS₂ index) could be calculated for each individual. Examination of the exposed subjects (n = 111) included a self-administered questionnaire, a clinical neurologic examinaiion, and electroneuromyography. Seventy-four workers from other plants, not exposed to CS₂ or to any other neurotoxcc agent, served as referents. The average CS2 exposures of the study group ranged from 4 to 112 mg/m³. The data were analyzed with multiple regression method, adjusting the effect of exposure for a number of possible confounders. Significant associations were found between the cumulative CS₂ index and symptoms consistent with polyneuropathy in the legs and with abnormal recruitment pattern and decrease of motor conduciion velocities of the peroneal nerves. Exposures to CS₂ at levels below the present threshold limit value (31 mg/m³) were associated with significant decreases of motor conduciion velocity.     

The applicability of the measurement of urinary thioethers

Summary The excretion of thioethers was measured in the urine of 6 volunteers, who were experimentally exposed to styrene, and 18 styrene workers. In addition, 12 clerks (non-smokers) and 12 sheet-metal workers (smokers) served as control groups. Diet was standardized during the experiments. Thioethers were measured by a spectrophotometric method. The volunteers were exposed to styrene, 210 mg/m³, for 2 h at a 50-W workload. An increase in thioether excretion was observed; the largest was in the urine samples collected between 0.5 and 5 h after the end of the exposure. After 43 h the excretion of thioethers was close to the preexposure level (3.5 mmol/mol creatinine). About 1% of the styrene absorbed was detected as thioethers in urine, which is only about 1/10 of the conversion reported for rats. From excretion rate curves a half-life of about 11 h was calculated for styrene thioethers. The styrene workers were employed at two plants. The average exposure to styrene (time-weighted average 8 h) was estimated to be about 115 mg/m3 (smokers in plant A), 55 mg/m³ (non-smokers in plant A) and 10 mg/m³ (non-smokers in plant B). The excretion of thioethers in exposed workers at plant A was higher by 2–4 mmol/mol creatinine than that in non-exposed controls. In plant B, where exposure was lower, an increase in that amount of thioethers excreted in the urine by exposed workers was less pronounced, and was statistically significant only when post-shift samples were compared with pre-shift samples. The results of the present study indicate that control samples should be collected both from non-exposed groups and from the exposed individuals before work shifts, to improve the likelihood of detecting genotoxic exposure in the work environment.     

Biological monitoring of workers exposed to carbon disulfide (CS2) in a viscose rayon fibers factory

The exposure-excretion relationship to carbon disulfide (CS₂) vapor in 407 exposed workers was studied during the second half of the working week. Carbon disulfide concentrations were also determined in 50 nonexposed subjects. The geometric mean value for CS₂ in urine samples from the latter was: 0.23 μg/l (95% upper limit = 0.52 μg/l) when log-normal distribution was assumed. Among the exposed workers, the CS₂ level in urine samples collected after the first half shift exceeded the 95% upper limit of nonexposed subjects in every case. The time-weighted average intensity of exposure to CS₂ vapor was measured using personal diffusive samplers (in which carbon cloth served as an adsorbent). CS₂ concentrations in urine were determined in samples collected at the end of the first half shift from the 407 exposed cases as well as from 50 nonexposed controls. There was a significant correlation (p < 0.0001) between the exposure to CS₂ vapor at concentrations of up to 64 mg/m³ and the levels of CS₂ measured in the urine samples after four hours of exposure. The correlation indicated that a mean level of 15.5 μg CS₂/l urine (95% confidence range, 13.8–17.1 μg/l) was excreted following an exposure to CS₂ at 31 mg/m³ (the current occupational exposure limit). Am. J. Ind. Med. 33:478–484, 1998. © 1998 Wiley-Liss, Inc.     

Biological monitoring of workers exposed to carbon disulfide

Urinary 2-thiothiazolidine-4-carboxylic acid (TTCA) concentrations and corresponding personal breathing zone carbon disulfide (CS₂) air concentrations were measured for worker populations at a Tennessee rubber product facility and a Virginia viscose rayon plant. At the rubber product facility, all of the 19 workers had urinary TTCA levels less than the limit of detection (LOD) of about 0.03 mg/L, equivalent to less than 0.5 ppm of CS₂ in air. At the viscose rayon plant, five of six workers, although wearing half-mask cartridge respirators, showed increased urinary TTCA during the workshift. The cutters and spinners had the largest increases in urinary TTCA concentrations; they also had the highest breathing zone exposures to CS₂. The TTCA concentrations for three cutters and spinners did not return to normal preshift levels of <0.3 mg/g creatinine before the start of the next shift. The arithmetic mean respirator workplace protection factor (WPF) was 7.0 ± 2.2. Increase in urinary TTCA concentration during the workshift and postshift urinary TTCA concentration reflected CS₂ air concentration equally well. In conjunction with air monitoring results, urinary TTCA concentrations allow determination of the WPF afforded workers wearing respirators and identify workers not adhering to safety rules and good work practices. Workers at risk of adverse health effects from overexposure to CS₂ for any reason may thus be identified. Am. J. Ind. Med. 33:48–54, 1998. © 1998 Wiley-Liss, Inc.     

Biological monitoring of carbon disulphide and phthalate exposure in the contemporary rubber industry

Objectives: We studied the range in urinary levels of 2-thiothiazolidine-4-carboxyl acid (TTCA), a metabolite of CS₂ and phthalic acid (PA), a common metabolite of phthalates, across factories and departments in the contemporary rubber manufacturing industry. Methods: Spot urine samples from 101 rubber workers employed in nine different factories were collected on Sunday and during the workweek on Tuesday, Wednesday and Thursday at ∼4 pm. In total, 386 urine samples were successfully analyzed. Results: Levels of both biomarkers increased significantly by a factor 2 (paired t-test P-value <0.05) during the working week as compared to the Sunday biomarker levels with absolute increases of approximately 70 μg/l and 5 μmol/mol creatinine for PA and TTCA, respectively. Levels in both biomarkers did not differ markedly between working days. Increases seemed to be restricted to specific factories and/or departments (e.g. molding and curing). Conclusions: The results of this study demonstrate that rubber workers in the contemporary rubber industry are exposed to phthalates and low levels of CS₂ (∼0.05 ppm) as measured by PA and TTCA, respectively. Exposures to both compounds are largely driven by specific circumstances in factories. Therefore, when estimating exposures to phthalates and CS₂ detailed information should be collected on the type and amount of phthalate containing ester plasticizers, dithiocarbamates and thiurams used. Preferably, personal exposure data should be collected. In this case, biological monitoring seems a reasonable approach. However, in the case of PA attention should be given to individual background levels as this could lead to a substantial overestimation of the occupational contribution to total phthalate exposure.     

The method of choice for the determination of 2,5-hexanedione as an indicator of occupational exposure to n-hexane

Summary To identify the method of choice for analysis of urine for 2,5-hexanedione (2,5-HD) as an indicator of occupational exposure to n-hexane, the end-of-shift urine samples of 36 n-hexane exposed male workers and 30 non-exposed male workers were analyzed for 2,5-HD under three conditions of hydrolysis, i.e. enzymic hydrolysis at pH 4.8, acid hydrolysis at pH 0.5, and without hydrolysis. The 2,5-HD concentrations thus determined were examined for correlation with 8-h, time-weighted average exposure concentrations of n-hexane measured by diffusive sampling. The regression analysis showed that the 2,5-HD concentrations without any hydrolysis correlated best with the intensity of exposure to n-hexane. No 2,5-HD was detected in the urine of the non-exposed subjects under the analytical conditions with no hydrolysis. Thus, the analysis without hydrolysis was considered to be the method of choice from the viewpoint of simplicity in analytical procedures, sensitive separation of the exposed from the non-exposed, and quantitative increase in the amount of 2,5-HD after n-hexane exposure.A part of this work was presented at the 63rd Annual Meeting of Japan Association of Industrial Health, held in Kumamoto, Japan, on 3rd–6th April, 1990     

An epidemiological study on carbon disulfide angiopathy in a Chinese viscose rayon factory

Summary To assess long-term vascular effects of occupational carbon disulfide (CS₂) exposure, we examined 376 exposed and 325 unexposed Chinese workers with a medical and work-history questionnaire, a chest-pain questionnaire, blood pressure and blood cholesterol measurements, routine urinary tests, monochromatic fundus photography and other tests. Data from 354 exposed and 177 age- and sex-matched reference workers were evaluated. Personal exposure monitorings were performed simultaneously with a passive dosimeter using gas chromatography. Monochromatic fundus photography revealed no CS₂-retinopathy characterized by microaneurysms and/or small dot hemorrhages, and no effects of CS₂ on blood pressure and blood cholesterol were found. These negative results may have been due to the low daily exposure averages, which varied between 0.01 and 12.8, with a mean of 1.5 ppm. The present study suggested that the no-effect level of CS₂ exposure on the development of retinopathy was around 2 ppm (8-h time weighted average), and the absence of adverse CS₂ effects among the workers studied supported the current standard for occupational CS₂ exposure of 10 mg M^–3 in China.     

Use of pharmaceuticals in industrial workers — possible implications for epidemiological studies

Summary A total of 129 workers exposed to carbon disulphide (CS₂) and 81 non-exposed controls were asked about their current use of pharmaceuticals, using a self-administered questionnaire. In all, 31% of the exposed and 19.8% of the non-exposed used some medicine (P = 0.08). The average number of pharmaceuticals per subject amounted to 0.71 in the exposed vs. 0.36 in the non-exposed (P = 0.049). Predominant types of medicines used were analgesics (12.4% in the exposed vs. 8.6% in the non-exposed,P = 0.50) and sedatives/hypnotics (10.1% in the exposed vs. 4.9% in the non-exposed,P = 0.21). The pharmaceuticals consumed can cause numerous (side) effects that are similar to the toxic effects of CS₂. To take into account these possibly confounding agents, a classification system for possible (side) effects of pharmaceuticals was developed, taking the dose into account. According to this method, many (side) effects of pharmaceuticals that could occur were recorded with higher frequency and intensity in the exposed subjects. Potential (side) effects that occurred significantly more frequently in the exposed than in the non-exposed were: tiredness, sedation, dizziness (20.9% vs. 4.9%,P = 0.001), excitation, anxiety (10.9% vs. 2.5%,P = 0.03), vision disturbances (7.0% vs. 0%,P = 0.01), and erection decrease (5.4% vs. 0%,P = 0.045). The implications of these findings for epidemiological studies are discussed.     

Improvement in the GC–MS method for determining urinary toluene-diamine and its application to the biological monitoring of workers exposed to toluene-diisocyanate

Objectives: To develop a simple and sensitive GC–MS method for determining toluene-diamine (TDA) in urine and to apply the method for biological monitoring of workers exposed to toluene-diisocyanate (TDI). Methods: After acid hydrolysis of 0.1 ml of urine, diluted tenfold with water, for 1.5 h, the free TDA formed was extracted with dichloromethane, and the heptafluorobutyric anhydride derivative was determined by GC–MS. We applied the method to the biological monitoring of 18 workers who were using an 80:20 mixture of 2,4-TDI and 2,6-TDI. Results: 2,6-TDA and 2,4-TDA were simply determined in 7 min by GC–MS. TDA levels in post-shift urine were well correlated with personal exposure levels of TDI. The correlation was improved by correction with creatinine or specific gravity in the 2,6-isomer, but not in the 2,4-isomer because of low exposure levels. From the correlation equation, the 2,6-TDA level (corrected with creatinine), corresponding to the TDI level of 5 ppb, was calculated to be 31.6 g/g Cre. TDAs in pre-shift urine also correlated significantly with the personal exposure levels of TDIs, although the slope of the correlations for pre-shift samples was 60%–70% of those for post-shift samples. The correlation between 2,4-TDA and 2,6-TDA levels was significant, although the levels of the 2,4-isomer were less than one-tenth of the 2,6-isomers in both air (personal exposure) and urine. Conclusion: The present method is simple and practicable and can be useful for biological monitoring of TDI workers.     

TTCA measurements in biomonitoring of low-level exposure to carbon disulphide

Objectives: The biomonitoring of carbon disulphide exposure is currently performed by measuring the concentration of 2-thiothiazolidine-4-carboxylic acid (TTCA) in the urine of exposed workers. Methods: In this study the effect of TTCA, which is found in some vegetables, on the biomonitoring of low-level carbon disulphide exposure was evaluated. In addition the upper reference limit (URL) of TTCA in the non-exposed Finnish population was estimated by analysing TTCA in urine samples from 116 people. The samples were collected at health centres all over Finland from people in employment and in the age group 24–64 years. The analytical measurements were made using a modern column-switching technique and the results were compared with those from the same samples using the extraction method generally in use and, until now, recommended for the determination of TTCA in urine. Results: The results obtained with the two analytical methods correlated very well with each other (r=0.9). The liquid-liquid extraction method gave results constantly about 3.5 μmol/l higher than the column-switching method. The results of this study also confirmed that many cruciferous vegetables (Cruciferae) contain endogenous TTCA (0.6–5.0 mg/kg), which is excreted unchanged in the urine. After a normal meal which included these vegetables, the TTCA concentration did not rise above the biomonitoring action level even if this was as low as 2 mmol/mol creatinine, but was easily above the URL of TTCA in the non-exposed population. The URL, calculated as the 95th percentile, was 0.3 mmol/mol creatinine. Conclusion: The results showed that the extraction method was not sufficiently specific or sensitive when the TTCA concentrations were lower than 10 μmol/l. In contrast, the column-switching method seemed to give reliable results even at these low levels, which are the levels of interest in current practice. Received: 29 September 1999 / Accepted: 27 December 1999     

Concentrations of benzene in blood and S-phenylmercapturic and t,t-muconic acid in urine in car mechanics

Summary Different parameters of biological monitoring were applied to 26 benzene-exposed car mechanics. Twenty car mechanics worked in a work environment with probably high benzene exposures (exposed workers); six car mechanics primarily involved in work organization were classified as non-exposed. The maximum air benzene concentration at the work places of exposed mechanics was 13 mg/m³ (mean 2.6 mg/m³). Elevated benzene exposure was associated with job tasks involving work on fuel injections, petrol tanks, cylinder blocks, gasoline pipes, fuel filters, fuel pumps and valves. The mean blood benzene level in the exposed workers was 3.3 g/l (range 0.7–13.6 g/1). Phenol proved to be an inadequate monitoring parameter within the exposure ranges investigated. The muconic and S-phenylmercapturic acid concentrations in urine showed a marked increase during the work shift. Both also showed significant correlations with benzene concentrations in air or in blood. The best correlations between the benzene air level and the mercapturic and muconic acid concentrations in urine were found at the end of the work shift (phenylmercapturic acid concentration: r = 0.81, P < 0.0001; muconic acid concentration: r = 0.54, P < 0.05). In conclusion, the concentrations of benzene in blood and mercapturic and muconic acid in urine proved to be good parameters for monitoring benzene exposure at the workplace even at benzene air levels below the current exposure limits. Today working as a car mechanic seems to be one of the occupations typically associated with benzene exposure.