Monitoring of occupational exposure to 1-butanol by diffusive sampling and urinalysis

 Objectives: To investigate the possibility of applying diffusive air sampling and urinalysis (for mother compound and metabolites) to the monitoring of exposure of factory workers to 1-butanol. Methods: The performance of carbon cloth in adsorbing 1-butanol vapor in air was studied by experimental exposure of the cloth to 1-butanol at 50, 100, 200 or 400 ppm for up to 10 h. 1-Butanol in the exposed cloth was extracted with carbon disulfide and this was followed by gas-chromatographic (GC) analysis. Urine samples were collected from factory workers occupationally exposed to 1-butanol and from rats exposed experimentally to 1-butanol vapour (up to 200 ppm). The urine samples were analyzed by GC without any pretreatment, or after treatment with hydrochloric acid or hydrolase preparation. Results: The performance of the carbon cloth was such that it adsorbed 1-butanol in proportion to the concentration (up to 400 ppm) and the duration (up to 10 h) of exposure, and responded quantitatively to a 15-min exposure up to 400 ppm. The amount of 1-butanol (after enzymic or acid hydrolysis) in post-exposure urine samples from rats was proportional to the exposure intensity. The proportion of free 1-butanol in total 1-butanol (i.e., free+conjugated) in urine was higher after 100 or 200 ppm exposure (35–40%) than after 50 ppm exposure (about 8%). There was a significant increase in total 1-butanol concentration (but not in free 1-butanol) in shift-end urine samples of workers exposed to 1-butanol at concentrations up to 3 ppm. Conclusions: Diffusive sampling with carbon cloth as an adsorbent can be applied to ambient air monitoring of exposure to 1-butanol. Urinalysis for 1-butanol after hydrolysis is sensitive enough to detect occupational 1-butanol vapour exposure at 3 ppm. Received: 29 January 1996 / Accepted: 3 May 1996     

Occupational exposure to polycyclic aromatic hydrocarbons in a graphite-electrode producing plant: biological monitoring of 1-hydroxypyrene and monohydroxylated metabolites of phenanthrene

 Objective. The objective of this study was to assess external and internal exposure to polycyclic aromatic hydrocarbons (PAHs) of workers who are employed in a graphite-electrode producing plant. Additionally we wanted to contribute to the question of biological limit values in order to reduce exposure to tolerable levels. Methods. At five different working places 12 stationary and 16 personal air measurements were carried out to determine the concentrations of phenanthrene, fluoranthene, pyrene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[a]pyrene and dibenz[a, h]anthracene in air. In addition, we investigated the excretion of 1-, 2+9-, 3- and 4-hydroxyphenanthrene and of 1-hydroxypyrene in the urine of 67 workers by a very sensitive and practical high-performance liquid chromatographic (HPLC) method with fluorescence detection; 2- and 9-hydroxyphenanthrene could not be separated with our analytical method. Results. During the production of graphite electrodes significantly higher PAH exposures were found in the baking and impregnation area than in the crushing, graphitisation and conditioning area. The results of personal air measurements (mean values of the sum of eight PAHs) are: 29.3 (baking), 23.4 (impregnation), 5.2 (crushing), 1.3 (graphitisation) and 0.4 μg/m³ (conditioning). Stationary air measurements yielded similar concentrations. Workers employed in the baking and impregnation areas excreted the highest amount of PAH metabolites in urine. The 1-hydroxypyrene concentrations (median) were: 23.4 (baking), 22.0 (impregnation), 9.6 (crushing), 1.8 (graph itisation) and 2.3 μg/g creatinine (conditioning). The corresponding concentrations of the sum of monohydroxylated phenanthrene metabolites (median) were: 23.1, 36.0, 10.4, 4.6 and 7.6 μg/g creatinine. Within the monohydroxylated phenanthrene metabolites 3-hydroxyphenanthrene predominates with a percentage of 43%. Our results showed that a benzo[a]pyrene concentration in air of 2 μg/m³ would lead to 1-hydroxypyrene concentrations in urine of 20–74 μg/g creatinine. That means that corresponding values in the literature which lie between 4.4 and 6.2 μg/g creatinine are due to other conditions of exposure and cannot be applied to graphite-electrode producing plants. Conclusions. Although to date there are no obligatory biological exposure limits for metabolites of PAHs in urine, it must be concluded that the internal PAH exposure is too high at some work places in this plant, as is generally the case in graphite-electrode producing plants. This is probably caused by skin absorption of PAHs. So for the prevention of health hazards by PAH, internal exposure must be measured using biological monitoring. Although it has not been possible to establish biological exposure limits for PAHs until now, we suggest a reduction in skin contact with these substances and thereafter use of the 90th percentile of the results of biological monitoring as “action levels” for corrective measures. Received: 20 May 1996/Accepted: 18 July 1996     

N-Acetyl-S-(dichlorophenyl)cysteines as suitable biomarkers for the monitoring of occupational exposure to 1,2-dichlorobenzene

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. Received: 10 October 1995 / Accepted: 18 March 1996     

Urinary lead as a possible surrogate of blood lead among workers occupationally exposed to lead

Objectives: The aim of the present study is to investigate whether lead (Pb) in urine (Pb-U) can be a valid surrogate of lead in blood (Pb-B), the traditional biomarker of exposure to lead in occupational health. Methods: Blood and spot urine samples were collected from 258 workers of both sexes occupationally exposed to lead. The samples were analyzed for lead by graphite furnace atomic absorption spectrometry, and the correlation between Pb-B and Pb-U was examined by linear regression analysis before and after logarithmic conversion. Results: The correlation coefficient (0.824; P < 0.01) was largest when the relationship between Pb-B and Pb-U was examined with 214 cases of one sex (i.e., men) after Pb-U was corrected for a specific gravity (1.016) of urine (Pb-Usg) and both Pb-B and Pb-Usg were converted to logarithms. The geometric means (GMs) of Pb-B and Pb-Usg for the 214 men were 489 μg/l and 81 μg/l, respectively. When Pb-Usg was assumed to be 100 μg/l in this set of correlations, the 95% confidence range of Pb-B for the group mean was narrow, i.e., 543–575 μg/l (with GM of 559 μg/l), whereas that for individual Pb-B values was as wide as 355–881 μg/l. Conclusions: The correlation of Pb-U with Pb-B among workers occupationally exposed to Pb was close enough to suggest that Pb-U may be a good alternative to Pb-B on a group basis, but not close enough to allow Pb-U to predict Pb-B on an individual basis. Received: 6 April 1999 / Accepted: 17 July 1999     

Antimony in Drinking Water, Red Blood Cells, and Serum: Development of Analytical Methodology Using Transversely Heated Graphite Furnace Atomization-Atomic Absorption Spectrometry

An atomic absorption spectrometric (AAS) method has been developed for determining μg/L levels of Sb in samples of water and blood. The AAS method is based on the concept of stabilized temperature platform furnace atomization (STPF) realized through the use of a transversely heated graphite atomizer (THGA) furnace, longitudinal Zeeman-effect background correction, and matrix modification with palladium nitrate-magnesium nitrate-nitric acid. The method of standard additions is not mandatory. The detection limit (3 standard deviations of the blank) is 2.6 μg Sb/L for the water, red blood cells (RBCs), and serum samples. Data are presented on the degree of accuracy and precision. The THGA-AAS method is simple, fast, and contamination-free because the entire operation from sampling to AAS measurement is carried out in the same tube. The method has been applied to the determination of Sb in some leachate tap water samples derived from a static copper plumbing system containing Sn/Sb solders, and in small samples (0.5 ml) of RBCs and serum derived from rats given Sb-supplemented drinking water. Received: 10 August 1996/Accepted: 20 November 1996     

Blood benzene concentrations in workers exposed to oxygenated fuel in Fairbanks,Alaska

 Objective: In November 1992 residents of Fairbanks, Alaska became concerned about the potential health effects of an oxygenated fuel program during which 15% (by volume) methyl tertiary butyl ether (MTBE) was added to gasoline. To address those concerns, we earlier completed a survey of occupational exposure to MTBE. We conducted a follow-up survey of workers’ exposure to benzene from gasoline in Fairbanks. Design: Cross-sectional exposure survey. Methods: We examined blood concentrations of benzene from a convenience sample of workers taken in December 1992 during the oxygenated fuel program and from another convenience sample of workers taken in February 1993 after the program was suspended. Results: In December, the median blood benzene concentration of samples taken from four mechanics after their workshift (postshift) was 1.32  μg/l (range, 0.84–2.61 μg/l), and seven nonmechanics (drivers and other garage workers) had a median postshift blood benzene concentration of 0.27 μg/l (range, 0.09– 0.45 μg/l). In February, nine mechanics had a median postshift blood benzene concentration of 1.99 μg/l (range, 0.92–3.23 μg/l), and nine nonmechanics had a median postshift blood benzene concentration of 0.26 μg/l (range, 0.2–0.46 μg/l). Conclusion: Mechanics had higher blood benzene concentrations than did nonmechanics, but further study is needed to determine the impact of the oxygenated fuel program on exposure to benzene. Received: 6 November 1995/Accepted: 2 April 1996     

Background exposure of urban populations to lead and cadmium: comparison between China and Japan

Objectives: To assess and compare the background exposure of the general population to lead (Pb) and cadmium (Cd) in China and in Japan. Methods: Food duplicates and peripheral blood samples were collected from nonoccupationally exposed subjects, viz 202 Chinese women in four Chinese cities (Beijing, Shanghai, Nanning, and Tainan) and 72 Japanese women in three Japanese cities (Tokyo, Kyoto, and Sendai) in the years 1993–1995. Wet-ashing and graphite furnace atomic absorption spectrometric methods were used for the determination of Pb and Cd levels in food and blood samples. Results: Geometric mean (GM) dietary Pb intake (25.8 μg/day) and the GM Pb concentration in blood (56.7 μg/l) in Chinese were significantly higher than in Japanese women (11.6 μg/day in food and 32.1 μg/l in blood), whereas Cd in food (32.1 μg/day) and Cd in blood (1.92 μg/l) in Japanese were significantly higher than in Chinese women (9.9 μg/day in food and 1.07 μg/l in blood). The intake of Pb and Cd via boiled rice accounted for 3.6% and 31.1% of the total dietary burden in Chinese, and 12.1% and 32.7% in Japanese, respectively. The Cd burden was acquired almost exclusively through the dietary route, whereas the Pb burden came from both air and food, especially in the case of the Chinese population. Conclusions:  The background Pb exposure in the Chinese population was higher than that in the Japanese population, whereas Cd exposure was lower in Chinese women than in their Japanese counterparts. Received: 4 March 1996 / Accepted 3 May 1996     

Determination of platinum in workroom air and in blood and urine from nursing staff attending patients receiving cisplatin chemotherapy

 Aim: A cross-sectional investigation was carried out to assess possible relations between styrene-induced changes in three peripheral markers of catecholaminergic dysfunction and self-reported symptoms of neurotoxicity. Subjects: Male workers (n=46) aged 14–60 (mean 29.5) years who had been exposed to styrene for an average of 6 (0.2–29) years were recruited in glassfiber reinforced plastics plants. A control group of 30 blue-collar workers aged 22–52 (mean 35) years and with no history of exposure to chemicals was recruited from local industries. Styrene exposure ranged from 5 to 120 ppm (8 h-TWA), the median level being relatively low (25 ppm, 8 h-TWA). Styrene metabolites, mandelic and phenylglycoxylic acids (MAPGA) in the “next morning” urine spot samples ranged from 32.0 to 931.1 mg/g creatinine (median 186.5). Methods: Platelet monoamine oxidases B (MAO B) and dopamine β-hydroxylase (DBH) activities were assessed using methods based on HPLC and electrochemical detection. Plasma prolactin (PRL) was measured by a commercially available immunoassay. Questionnaire 16 (Q16) was used to survey self-reported symptoms. Results: Although there was no difference in DBH activity between exposed workers and controls, the most highly exposed workers had significantly lower activity than control subjects. A tendency to lower platelet MAO B activity in exposed than in control subjects was observed. The prevalence of plasma DBH and platelet MAO B values below the lower reference limit was similar in the two groups. PRL values exceeding the upper reference limit were higher (14/46 vs 2/30) among styrene-exposed workers, who also exhibited significantly higher median levels (10.0 vs 5.7 μg/l) than control subjects. Although the number of reported symptoms was similar among exposed and control subjects, in the exposed group it was positively associated with urinary MAPGA (Rho=0.30, P=0.04). Of the three peripheral markers of catecholaminergic dysfunction, plasma DBH was the only parameter negatively related to both urinary MAPGA (F=9.56, P=0.003) and the number of reported symptoms (Rho=0.23, P=0.05). Conclusions: Plasma PRL appears to be a sensitive marker of styrene-induced tubero-infundibular dopaminergic dysfunction in male subjects. DBH in plasma and MAO B in platelets seem to be less suitable markers for biomonitoring effect at the individual level, although DBH was related to the number of reported symptoms and to internal dose. Further studies on a larger and more exposed population are necessary to clarify the significance of these markers for health and their predictive value with regard to both subjective disturbances and concurrently administered performance tests. Received: 9 January 1996/Accepted: 11 April 1996     

Biological monitoring of workers exposed to 4,4′-methylene-bis-(2-orthochloroaniline) (MOCA)

Objective: The objective of the study was to validate a new and simple method to determine MOCA in the urine of exposed workers. Methods: The separation, identification and quantification of urinary MOCA were performed in spiked urines by a sensitive and practical high-performance liquid chromatography (HPLC) method and applied to urine samples of 11 workers occupationally exposed to MOCA; the postshift urinary levels of MOCA in their urine samples with and without hydrolysis, “total” and “free” MOCA respectively, were determined. In addition, we investigated the use of citric or sulfamic acid as preservatives of urine samples. Results: The “total” and “free” MOCA were extracted with isooctane from hydrolysed and nonhydrolysed 20-ml urine samples respectively. After evaporation, the residue was dissolved in 4 ml of 2 · 10⁻² M aqueous hydrochloric acid and analysed by an isocratic HPLC system using both ultraviolet (UV) detection at 244 nm and electrochemical detection working in oxidation mode (0.9 V) with an Ag/AgCl reference electrode. Mobile phase (50% acetonitrile in water containing 0.4% acetate buffer solution pH = 4.6) was used to complete the 20-min analysis. “Free” and “total” MOCA were chromatographed on a reversed-phase C8 column (5 μm; 250 mm × 4 mm). The standard curve of MOCA was linear over the range 5–500 μg/l in human urine. The detection limit was 1 μg/l for a 20-μl injection volume; the repeatability ranged from 5.6 to 1.3% (n = 6) for spiked urines at 5 and 500 μg/l, with a percentage recovery of 94 ± 3%. The reproducibility of the method was 7.3% (n = 4) for spiked urine at 10 μg/l. The use of sulfamic acid as a preservative of urine samples is important to improve the precision and accuracy of the analysis. Conclusion: The results indicate that these analytical procedures using conventional apparatus may be used routinely and reliably with large numbers of urine samples for biological monitoring of the exposure to MOCA. The occupational exposure to MOCA in some factories in France is studied in the second part of this work. Received: 10 November 1998 / Accepted: 25 March 1999     

Ethnic differences in biological monitoring of several organic solvents. I. Human exposure experiment

 Objectives: In order to improve the reliability of biological monitoring and the development of biological limit values, ethnic differences for several organic solvents were studied in Orientals and Caucasians. Methods: Six Caucasian and six Oriental volunteers were exposed to each organic solvent in an exposure chamber for 6 h. Exposure concentration to each organic solvent studied was 50 ppm for perchloroethylene, 50 ppm for styrene and 100 ppm for m-xylene, respectively. Biological monitoring was carried out for the parent organic solvents in exhaled air and in blood, and for the metabolites in urine during and after exposure. Results: Caucasians showed higher concentrations of perchloroethylene in exhaled air than Orientals after exposure. But Caucasians showed lower concentrations of styrene in the exhaled air than Orientals during the second half of exposure and after it. Orientals showed lower concentrations of urinary metabolites than Caucasians except for mandelic acid. There were no statistically significant differences in the concentrations of solvent in blood for all three solvents. Conclusions: Implications of these differences in biological levels, under identical exposure conditions, are discussed in the context of biological monitoring. Received: 17 April 1996 / Accepted: 18 July 1996     

Evaluation of urinary cadmium and lead as markers of background exposure of middle-aged women in Korea

Objective: The present study was initiated to investigate the validity of cadmium (Cd) and lead (Pb) in urine in comparison with the metals in blood as a biological marker of nonoccupational exposure of general populations to these metals as environmental pollutants. Design: Peripheral blood samples, morning spot-urine samples, and 24-h total food duplicate samples were collected from 107 nonsmoking women (aged 30–59 years) in four urban and rural survey sites in Korea. Methods: Portions of the samples were digested by heating in the presence of mineral acids, and the digests were analyzed for Cd and Pb by graphite furnace atomic absorption spectrophotometry. The metal concentrations in urine were adjusted for creatinine concentration and a specific gravity of 1.016. The analyte levels were evaluated on an individual basis (n = 107) and also on a group basis, i.e., in terms of geometric means for the survey sites (n = 4). Results: Cd in urine correlated with Cd in blood on an individual as well as survey-site basis and tended to correlate with Cd in food duplicates on a group basis. The correlation of Pb in urine with Pb in blood was weaker than that of Cd in urine with Cd in blood when evaluated on an individual and survey-site basis. Pb in urine correlated with Pb in food duplicates either weakly or even negatively when examined on a survey-site basis. Conclusions: Cd in urine proved to be valid as a biological marker of environmental exposure of general populations, whereas less support was obtained for Pb in urine as an exposure marker. Received: 5 May 1997 / Accepted: 28 August 1997     

Neurotoxicity of long-term low-level exposure to carbon disulphide: results of questionnaire, clinical neurological examination and neuropsychological testing

 Objective. Carbon disulphide (CS₂) is highly neurotoxic. There is ample evidence of damage to the peripheral and central nervous system. The air concentration at which such adverse effects can first be observed is presently a subject of controversy. Methods. In a cross-sectional study of CS₂-exposed workers from the viscose industry and healthy controls, data on neurological complaints, basic laboratory diagnosis, clinical neurological examination and neuropsychological testing were evaluated. Data were from 222 workers in the viscose industry exposed to CS₂ and 191 employees from the same factory with similar physical and psychological stress factors but without occupational contact with neurotoxic substances. Multiple linear or multiple logistic regression analysis was used to check for statistical differences. Results. The median of the CS₂-measurements using personal air sampling was below the current maximum concentration permissible (MAK value) in Germany (10 ppm) in all departments. The threshold limit value was, however, exceeded in almost 10% of the persons investigated. Exposure fluctuated between <0.2 and 65.7 ppm (median of all departments was 4.02 ppm). As a parameter of internal exposure, CS₂-metabolite 2-thio1,3-thiazolidine-4-carboxylic acid (TTCA) concentrations in the urine of the exposed persons were between <0.16 and 10.9 mg/g creatinine (median 1.43 mg/g). Conclusions. Neither an increase in subjective complaints nor an increase in pathological findings in clinical-neurological and neuropsychological examination could be found in persons exposed to CS₂ at the exposure levels described. Received: 19 December 1995/Accepted: 18 July 1996     

Propylene glycol monomethyl ether (PGME) occupational exposure

An analytical method was developed for the determination of free and conjugated PGME-α in urine. The method involves a solid-phase extraction on LC-18 columns and a GC/FID analysis after derivatization with trimethysilylimidazole. The assay was linear (least-squares regression coefficient 0.996), specific, reproducible (intraassay variability 10%, interassay variability 10%), and allowed a high level of PGME recovery (more than 90%). The assay was applied to the analysis of urine samples from three workers who were occupationally exposed to PGME to estimate their exposure. The highest value of PGME concentration in urine was 7.78 mg/l. Air concentrations of PGME ranged between 20 and 40 ppm. A statistically significant correlation was found between measurements of external exposure and PGME in urine. An important fraction of PGME in urine was found to be conjugated. Received: 6 July 1999 / Accepted: 27 December 1999     

Correlation between urine and blood concentrations, and dietary intake of cadmium and lead among women in the general population of Japan

Objective: To examine whether lead (Pb) in urine and cadmium (Cd) in blood, especially the former, can be used as markers of environmental exposure of general populations to these metals. Methods: Between 1991 and 1998, spot urine and peripheral blood samples, together with 24 h duplicates of food intake were collected from 607 non-smoking adult women in 30 survey sites (SS) in seven administrative regions all over Japan. Urine, blood and food duplicate samples were analyzed by inductively-coupled plasma spectrometry, for Cd and Pb in urine (Cd-U and Pb-U), in blood (Cd-B and Pb-B) and in food duplicates (Cd-F and Pb-F). Correlation between the measurements was examined by regression analysis. Results: The Cd-B correlated closely with Cd-U, and both Cd-B and Cd-U with Cd-F, on an individual basis (n = 607), on an SS basis (n = 30) and on a regional basis (n = 7). The Pb-U however did not correlate with Pb-B on a regional basis although they correlated with each other when analyzed on an individual as well as SS basis. Moreover, the correlation coefficients between Pb-U and Pb-B were much smaller than those between Cd-U and Cd-B. Neither Pb-U nor Pb-B showed significant correlation with Pb-F on any levels of statistical analysis. Conclusions: Both Cd-B and Cd-U can be employed as biomarkers of environmental Cd exposure. The reliability of Pb-U for use in place of Pb-B appeared to be small. Received: 21 January 1999 / Accepted: 2 November 1999     

In vivo measurements of lead in fingerbone in active and retired lead smelters

 Object. The aim of this study was to determine the bone lead concentration in lead smelters and reference subjects, relate them to the lead concentration in blood (B-Pb) and urine (U-Pb), and to use the measured bone lead to calculate a biological half-life for lead in bone. Method and design. The lead concentration in the second phalanx of the left index finger (bone-Pb) was determined in vivo using an X-ray fluorescence technique. The study population comprised 89 smelters with a history of long-term exposure to lead (71 active and 18 retired) and 35 reference subjects (27 active and 8 retired) with no known occupational exposure to lead. Bone-Pb was related to the previous lead exposure, estimated as a time-integrated B-Pb (CBLI). Results. The retired smelters had the highest bone-Pb (median value 55 μg/g wet weight, as against 23 μg/g in active smelters) and 3 μg/g in the reference subjects. A strong positive correlation was observed between the bone-Pb and the CBLI among both active (r _s =0.73; P<0.001) and retired (r _s =0.71; P=0.001) smelters. The corresponding correlations between the bone-Pb and the period of employment were of the same magnitude. For retired workers, there were positive correlations between the bone-Pb and the B-Pb (r _s =0.58; P=0.011) and U-Pb (r _s =0.56; P=0.02). Multiple regression analyses showed that bone-Pb was best described by the CBLI, which explained 29% of the observed variance (multiple r ²) in bone-Pb in active workers and about 39% in retired workers. The estimated biological half-life of bone-Pb among active lead workers was 5.2 years (95% confidence interval 3.3–13.0 years). Conclusions. The high bone-Pb seen in retired workers can be explained by the long exposure periods, the higher exposure levels in earlier decades, and the slow excretion of lead accumulated in bone. The importance of the skeletal lead pool as an endogenous source of lead exposure in retired smelters was indicated by the associations between the B-Pb or U-Pb, on the one hand, and the bone-Pb, on the other. In active workers, the ongoing occupational exposure was dominant. The in vivo X-ray fluorescence technique is still mainly a research tool, and more work has to be done before it can be used more widely in clinical practice. However, over the next decade we can anticipate retrospective, prospective and cross-sectional epidemiological studies in which bone lead determinations reflecting the previous lead exposure in both occupationally and nonoccupationally lead exposed populations are related to various types of adverse health outcomes. Such studies will improve our knowledge of dose–response patterns and provide data that will have an impact on hygienic threshold limit values and prevention of lead-induced diseases. Received: 2 October 1995/Accepted: 8 March 1996     

Biological monitoring of methylhexahydrophthalic anhydride by determination of methylhexahydrophthalic acid in urine and plasma from exposed workers

Objective: To investigate whether methylhexahydrophthalic acid (MHHP acid) in urine and plasma can be used as a biomarker for exposure to methylhexahydrophthalic anhydride (MHHPA). Methods: MHHPA in air was sampled by Amberlite XAD-2 and analysed by gas chromatography (GC) with flame ionisation detection. MHHP acid in urine and plasma was analysed by GC with mass spectrometric detection. Workers occupationally exposed to MHHPA were studied. Air levels of MHHPA were determined by personal sampling in the breathing zone. Urinary levels of MHHP acid, a metabolite of MHHPA, were determined in 27 workers. In eight workers all urine was collected at intervals during 24 h. Plasma levels of MHHP acid were determined in 20 workers. Results: The time-weighted average (TWA) air levels ranged from 5 to 60 μg MHHPA/m³ during 8-h work-shifts. The urinary levels of MHHP acid increased during exposure and decayed after the end of exposure with an estimated half-life of about 6 h. A correlation was found between the TWA air levels of MHHPA and creatinine-adjusted MHHP acid levels in urine collected during the last 4 h of exposure. A correlation was also seen between the TWA air levels of MHHPA and the plasma concentrations of MHHP acid. An exposure to 20 μg MHHPA/m³ corresponded to about 140 nmol MHHP acid/mmol creatinine and about 40 nmol MHHP acid/l plasma. Conclusion: The results indicate that MHHP acid in urine or plasma may be used for biological monitoring of the exposure to MHHPA. Received: 4 October 1996 / Accepted: 2 January 1997     

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     

High-pressure liquid chromatographic determination of toluenein urine as a marker of occupational exposure to toluene

Objective: To establish a convenient method by high-pressure liquid chromatography (HPLC) to measure toluene in urine as a marker of occupational exposure to toluene. Methods: As soon after sampling as possible, 1 ml of urine was mixed with an equal volume of acetonitrile in a 2.2-ml HPLC glass bottle, and the bottle was tightly sealed and stored at 4 °C. Immediately before HPLC determination, 100 μl methanol was added to the mixture to prevent confounding effects of glycosuria, and the bottle was spun to remove any suspended matter. An aliquot of the supernate was introduced into the HPLC system and analyzed on a PRODIGY column, with an acetonitrile – perchloric acid – phosphoric acid – water mixture serving as the mobile phase. The effluent was monitored at 191 nm. Results: The method can measure toluene in urine every 20 min; the detection limit was 2 μg/l, the coefficient of variation was less than 5%, and the recovery rate was 100%. No significant reduction in toluene concentration was observed for 1 week after storage at 4 °C. When the method was applied to end-of-shift urine samples from 13 male workers exposed to toluene at 18–140 ppm and also to urine samples from 10 nonexposed male controls, toluene in urine was linearly related to toluene exposure concentration, with a regression line passing close to the origin. The correlation coefficient was as high as 0.97 (n = 23). No toluene was detected in control urine samples. Calculations suggest that urinary toluene accounts for as little as less than 0.01% of the toluene absorbed via inhalation and that the absorbed toluene is converted almost quantitatively to hippuric acid and, by less than 0.1%, to o-cresol. Received: 25 August 1997 / Accepted: 13 February 1998     

Biological monitoring of styrene exposure and possible interference of acetone co-exposure

 The object of this study is the evaluation of some of the toxicokinetic effects of exposure to low concentrations of styrene, and the possible influence of simultaneous exposure to acetone. To this end we studied 19 workmen simultaneously exposed to both solvents. During a week of 4-h work shifts, the workmen underwent daily personal environmental monitoring and the collection of urine samples, at both the beginning and the end of the work period, for the determination of mandelic acid (MA) and phenylglyoxylic acid (PGA). The presence of the solvents in the atmosphere was evaluated using passive personal monitoring and gas chromatography. Average exposure to styrene and acetone were respectively 72.2 mg/m³ and 225.7 mg/m³. MA and PGA were quantified by high-performance liquid chromatography (HPLC). The daily urinary concentration averages, both at commencement and at the end of work shifts, of both the metabolites studied and of the sum of the two, were in statistically significant linear correlation with the average daily styrene exposure. Concentrations of MA and PGA in urine samples collected at the start of the work shift averaged 61.5 mg/g creatinine and 45.2 mg/g creatinine respectively, representing 41% and 72% of those at the end of the work shift which were 148.3 and 62.6 mg/g creatinine, respectively. With equal exposure to styrene, the average urinary concentrations of MA and PGA at both the beginning and end of the work shift increased significantly (P<0.001) during the working week. Moreover, we found that with equal exposure to styrene, urinary excretion of MA, PGA and MA+PGA at the end of the shift was inversely correlated with the intensity of acetone exposure (r=0.4659, 0.3410 and 0.4542 respectively, P<0.001). In conclusion, these results express slower urinary kinetics of styrene metabolites than is usually described in the literature, and favor a tendency to accumulate MA and PGA in the organism as a consequence of the retardation of urinary excretion kinetics. Acetone apparently represents one of the determining factors in this interference. Received: 3 July 1996/Accepted: 20 September 1996     

A study of ethylene glycol exposure and kidney function of aircraft de-icing workers

 Ethylene glycol levels were measured in 154 breathing zone air samples and in 117 urine samples of 33 aviation workers exposed to de-icing fluid (basket operators, de-icing truck drivers, leads and coordinators) studied during 42 worker-days over a winter period of 2 months at a Montreal airport. Ethylene glycol as vapour did not exceed 22 mg/m³ (mean duration of samples 50 min). Mist was quantified at higher levels in 3 samples concerning 1 coordinator and 2 basket operators (76–190 mg/m³, 45–118 min). In 16 cases workers’ post-shift or next-morning urine contained quantities of ethylene glycol exceeding 5 mmol/mol creatinine (up to 129 mmol/mol creatinine), with most of these instances occurring in basket operators and coordinators, some of whom did not wear paper masks and/or were accidentally sprayed with de-icing fluid. Diethylene glycol was also found in a few air and urinary samples at levels around one tenth those of ethylene glycol. Urinary concentrations of albumin, β-N-acetyl-glucosaminidase, β-2-microglobulin and retinol-binding protein were measured and compared over various periods, according to subgroups based on exposure level and according to the frequency of extreme values. These analyses did not demonstrate acute or chronic kidney damage that could be attributed to working in the presence of ethylene glycol. In conclusion, this study does not suggest important health effects of exposure to de-icing fluid in this group of workers. Potential for overexposure exists, however, in certain work situations, and recommendations on preventive measures are given. In addition, these results suggest that other routes of absorption than inhalation, such as the percutaneous route, may be important and that urinary ethylene glycol may be a useful indicator of exposure to ethylene glycol. Received: 10 March 1996/Accepted: 11 April 1996