A new HPLC fluorimetric method to monitor urinary delta-aminolevulinic acid (ALA-U) levels in workers exposed to lead

Summary A new sensitive HPLC method for the determination of urinary delta-aminolevulinic acid (ALA-U) was used to evaluate the relationship between blood-lead (Pb-B) and ALA-U levels in male workers exposed to lead. The differences between the ALA-U levels determined by this method (ALAU-HP) and by a colorimetric method (ALA-U-CL) are discussed. The HPLC method gave values similar to the ALA-U-CL values at high ALA-U level. However, at low blood-lead levels (58 ± 22 g/l, n = 23), the mean ALA-U-HP level corrected by urinary creatinine level was one-third of the corrected ALA-UCL level (0.83 ± 0.14 and 2.4 ± 0.5 mg/g creatinine, respectively). A significant increase of the mean corrected ALA-U-HP level was observed at 162 ± 22 g/l Pb-B (P < 0.05, n = 26), while that of ALA-UCL was observed at 245 ± 30 g/l Pb-B (P < 0.01, n = 37). The regression equation based on the logistic model fitted well to the relationship data between the Pb-B level and the percentage of the subjects with corrected ALA-U-HP above the cut-off point (1.12 mg/g creatinine) and the expected Pb-B level for 50% response was 270 g/l Pb-B, while it did not fit well to the relationship data between Pb-B level and the percentage of the subjects with corrected ALAU-CL above the cut-off point (3.5 mg/g creatinine). The maximum responses for the two sets of corrected ALA-U levels were both observed at 625 ± 25 g/l. The corrected ALA-U level by HPLC method seems to be a useful indicator for biological monitoring of exposure to lead at low levels (< 400 g/l Pb-B = health-based biological limit, WHO) as well as high ones.     

Assessment of thyroid,testes, kidney and autonomic nervous system function in lead-exposed workers

Summary The objective of the study was to assess whether moderate occupational exposure to lead may be associated with early changes in potential target organs (thyroid, testes, kidney, autonomic nervous system). Workers exposed to lead in a lead acid battery factory (n = 98; mean blood lead 51 g/dl, range 40–75 g/dl) and 85 control workers were examined. None of the indicators of kidney function (in urine: retinol-binding protein, ₂-microglobulin, albumin,N-acetyl--d-glucosaminidase; in serum: creatinine, ₂-microglobulin), endocrine function (follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, thyroxine, triiodothyronine) and autonomic nervous system (R-R interval variations on the electrocardiogram) were correlated with lead exposure (blood lead or duration of exposure) or showed significantly different mean values between the exposed group and controls. These results and an assessment of the published data suggest that compliance with the Directive of the Council of the European Communities on lead exposure (health surveillance in workers whose lead in blood exceeds 40 g/dl and removal from exposure when blood lead exceeds 70–80 g/dl) would prevent the occurrence of significant biological changes in the majority of lead-exposed workers.     

Investigations on neurotoxicity of chemical substances at the workplace

Summary A cross-sectional study was performed in order to investigate the influence of chronic lead-exposure on the peripheral nervous system. We examined 148 male workers of a storage battery manufacturing plant, who had been exposed to lead metal and inorganic lead compounds for 1 to 28 years (mean 11 years). Fifteen workers with non-occupational risks of peripheral neuropathy (former diseases, alcohol abuse, medication) were excluded from the study. The investigation program comprised: case history, physical examination, analyses of blood- and urine-samples and determination of maximal motor, mixed and sensory conduction velocity (NCV) of the ulnar and median nerve of the right forearm. Objectively no worker showed any signs of health effects related to lead exposure. The Biological Monitoring included the determination of (1) Blood-lead level (Pb-B), (2) Free erythrocyte porphyrins (FEP), (3) -Aminolevulinic acid dehydratase (ALA-D) and (4) -Aminolevulinic acid in urine (ALA-U). Further time-weighted-average (TWA)-values of Pb-B were calculated on the basis of several determinations over the period 1975–1981. The following actual (TWA) median values resulted: Pb-B 53 g/dl (54 g/dl), ALA-U 5.6 mg/l (8.4 mg/l), FEP 2.0 mg/l (2.0 mg/l). The Biologischer Arbeitsstoff Toleranz Wert (BAT) of 70 g//dl for Pb-B was exceeded in 15 workers (11%), and of 15 mg/l for ALA-U in 30 cases (23%). In comparison with age-matched controls, the lead workers showed a mild slowing of NCV with mean values between 0.8 and 2.0 m/s. Multiple stepwise regression analyses revealed statistically significant correlations between the four NCV and age as well as Pb-B. There were better correlations by using TWA than actual data of Pb-B. Consideration of the results of the regression analyses, together with an evaluation of the individual neurophysiological status as a function of internal lead exposure, a dose-effect-relationship was found only in the case of Pb-B exceeding 70 g/dl. From our study it is concluded that chronic lead exposure resulting in blood-lead levels of below 70 g/dl is no occupational risk causing a functionally significant slowing of nerve conduction velocities.With Grants from the Deutsche Forschungsgemeinschaft, Bonn (Project no. Va 23/19-1)     

Blood lead in the general population in Poland

Lead concentration in venous blood (Pb-B) was investigated in 1122 inhabitants (including 555 children under 10 years of age) of five Polish towns with no large industrial lead emitters (group I) and in 1246 persons (707 children under 10 years of age) living in the vicinity of zinc and copper mills (group II). The samples were analysed using electrothermal atomic absorption spectrometry (ETAAS) and the performing laboratory participated in the external quality control scheme during the study period (1992–1994). In group I the mean geometric Pb-B concentrations ranged from 23.8 to 48.3g/l in females, from 42.5 to 76.8 g/l in males and from 29.9 to 62.5 g/l in children. In group II, the mean geometric Pb-B concentrations were significantly higher and ranged from 49.4 to 105 g/l in females, from 98.5 to 149 g/l in males and from 73.7 to 114 g/l in children, the values decreasing as the distance from the source of emission increased. Cigarette smoking was found to bring about a significant increase in Pb-B levels for both males and females. A significant correlation was noted between Pb-B concentrations in mothers and children. The ratio between child and maternal Pb-B concentrations amounted to approximately 1.0 for group I and to about 0.5 for group II. These findings indicate the necessity of undertaking preventive activities over the lead-contaminated areas. However, the lead hazard in Poland seems to be associated with point sources of emission and hence does not concern the whole population.     

Erythrocyte nucleotides in lead workers

Summary We determined erythrocyte nucleotides levels in 22 lead workers with blood lead ranging from 8 to 78 g/dl. Their erythrocyte pyrimidine 5-nucleotidase (P5N) activity ranged from 19.4 to 3.4 mol uridine/h per g hemoglobin. A significant elevation of erythrocyte pyrimidine nucleotides was found, and their contents correlated inversely with erythrocyte P5N activity and positively with blood lead concentration. In particular, the contents of uridine triphosphate (UTP) and cytidine triphosphate (CTP) exhibited a high correlation with P5N activity (r= -0.56, –0.54). However, its concentration in lead workers was estimated to be much lower than that in hereditary P5N deficiency.     

Exposure to lead and cadmium of children living in different areas of North-West Germany: results of biological monitoring studies 1982–1986

Summary Between 1982 and 1986 several surveys were carried out to determine the levels of lead and cadmium in blood, urine, and shed deciduous teeth (incisors only) of children living in rural, suburban, urban, and industrial areas of North-West Germany. Blood lead (PbB) and blood cadmium (CdB) were measured in about 4000 children. In rural, suburban and urban areas the median PbB levels vary between 5.5 and 7 g/dl, with 98th percentiles varying between 10 and 13 g/dl. The median CdB levels are between 0.1 and 0.2 g/dl, with 95th percentiles between 0.3 and 0.4 g/l. Children from urban areas have significantly higher PbB levels than children from rural and suburban areas. Regarding CdB no differences could be detected. Children living in areas around lead and zinc smelters, particularly those living very close to the smelters, have substantially increased PbB and CdB levels. Children from lead worker families also have substantially increased PbB and CdB levels. The lead levels in shed milk teeth (PbT) were determined in about 3000 children. In rural, suburban and urban areas the median PbT levels are between 2 and 3 g/g, with 95th percentiles between 4 and 7 g/g. Children from urban areas have significantly higher PbT levels than children from rural and suburban areas. The highest PbT levels (on a group basis) are in children from nonferrous smelter areas. The median levels of lead in urine (PbU) are between 6 and 10 g/g creatinine, with 95th percentiles between 20 and 30 g/g creatinine. Children from polluted areas have higher PbU levels than children from less polluted areas. The median levels of cadmium in urine (CdU) are in the order of 0.1 g/g creatinine, with 95th percentiles being in the range of 0.5 and 1.0 g/g creatinine. Girls have higher CdU levels than boys. There are no differences between groups of children from different areas. Children from lead worker families have higher PbU and CdU levels than otherwise comparable children. The results of the present studies indicate a further decrease of PbB in children from North-West Germany since the CEC blood lead campaigns carried out in 1979 and 1981. The decrease of lead exposure also seems to be reflected by a decrease of tooth lead levels.The studies presented in this communication were supported by the Ministry of Work, Health and Social Affairs and the Ministry of Environment and Agriculture of Nordrhein-West-falen, FRG     

Blood toluene as a biological index of environmental toluene exposure in the “normal” population and in occupationally exposed workers immediately after exposure and 16 hours later

Blood toluene was measured in a group of 100 workers occupationally exposed to a mean 8-h environmental toluene concentration of 128 g/l (34 ppm), and in a group of 269 normal subjects without occupational exposure to toluene. The mean blood toluene of the workers at the end of the shift and the following morning, after 16 h, was 457 and 38 g/l, respectively. The normal subjects had a blood toluene level of 1.1 g/l. On the basis of the highly significant correlation between blood toluene and occupational exposure, it can be calculated that environmental toluene exposure of 188 and 377 g/l (50 and 100 ppm) gives end-of-shift blood toluene levels of 690 and 1390 g/l, respectively. The corresponding blood toluene levels on the following morning are 50 and 100 /l, respectively.     

Biological monitoring of cobalt exposure,based on cobalt concentrations in blood and urine

Summary Cobalt exposure level and its concentrations in blood and urine were determined for 175 hard metal workers. For control data, the cobalt concentrations in blood and urine were measured for 20 office workers. The exposed workers had significantly higher cobalt concentrations in both blood and urine. The relationships between exposure level and cobalt concentrations in blood and urine were linear and positive. The results clearly showed that the cobalt concentration in the blood or urine can be used as an exposure indicator. With cobalt exposure of 100 g/m³, the cobalt concentration was 0.57 to 0.79 g/dl in blood and 59 to 78 g/l in urine with 95% confidence limits. In workers using respirators, the cobalt concentrations in the blood and urine decreased to 2/5 and 1/8, respectively, of those not using respirators.     

Kybernetische Probleme der Arbeitsmedizin

Zusammenfassung Bei 35 klinisch gesunden, hitzebelasteten Arbeitnehmern eines Stahlwerkes wurden Mineral- und Spurenelementanalysen im Blut durchgeführt. Als Vergleichskollektiv dienten 20 Schwerarbeiter des gleichen Betriebes, die nicht hitzeexponiert waren. Die Untersuchungen ergaben für die Hitzearbeiter (für das Vergleichskollektiv) folgende Mittelwerte und Standardabweichungen: Natrium: 327,50±14,98 mg- % (323,98±5,28 mg-%) Kalium: 13,29±1,49 mg-% (15,31±1,10 mg-%) Calcium: 7,91±0,74 mg-% (9,25±1,19 mg-%) Magnesium:1,91±0,28 mg-% (1,60 ± 0,28 mg-%) Blei: 24,31±8,40 g-% (14,37±3,26 g-%) Nickel: 1,56± 1,27 g-% (2,28±0,67 g-%)Die Differenzen zwischen beiden Gruppen sind, mit Ausnahme von Natrium, für alle untersuchten Elemente statistisch signifikant. Sie lassen sich mit einem durch Hypovolumämie des Körperkerns ausgelösten kompensatorischen Hyperaldosteronismus erklären. Dieser Schutzmechanismus betrifft nur den Natriumhaushalt. Die hohen Kaliumverluste werden selbst durch kaliumreiche Getränke nicht voll ausgeglichen.

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Cybernetic problems of industrial medicineIII. Analyses of minerals and trace elements in the blood of heavy workers chronically exposed to heat

Summary Good health and productivity of men are essentially dependent of climatic factors. Mainly in iron- and steel-industry a broad spectrum of oppressing environmental circumstances is to be found. Changes in the household of minerals and trace minerals, concerning the adaptation of human organism to high environmental temperatures play an important part, especially because these changes effect the bodily charge. Aim of this work was to show the effects of chronical, thermic stress at the place of employment on the household of minerals and trace minerals.With blood of 35 healthy, heatexposed workers of a steel factory mineral and trace mineral analyses were performed. As a comparison 20 heavy workers of the same factory were chosen who were not heatexposed. The results of the analysis gave the following mean ratios and standard deviation for the heatworkers (for the compared collective): sodium: 327.50±14.98 mg-% (323.98±5.28 mg-%) potassium: 13.29±1.49 mg-% (15.31±1.10 mg-%) calcium: 7.91±0.74 mg-% (9.25±1.19 mg-%) magnesium: 1.91 ±0.28 mg-% (1.60±0.28 mg-%) lead: 24.31±8.40 g-% (14.37±3.26 g-%) nickel: 1.56±1.27 g-% ( 2.28±0.67 g-%)The differences between both groups are statistically significant for all analysed elements, except sodium. This could be explained by a compensatoric hyperaldosteronism, caused by a hypovolumia of the body nucleus. This protective mechanism only concerns the household of sodium. The high losses of potassium are not fully compensated even not by drinks being rich with potassium.

     

Behaviour of some indicators of biological effect in female lead workers

Summary The relationships between certain indicators of internal dose and of biological effect were studied in 93 adult women with varying degrees of exposure to lead (PbB levels ranging from 8 to 74 g/ 100 ml). The results were compared with those obtained in a group of 95 males with more of less similar exposure. In both groups a good correlation was found between PbB and ALAD, EP, CPU taken singularly and the trend of the indicators of effect, depending on PbB levels, was similar: the decrease in ALAD values was already clear at PbB levels which do not cause an elevation of EP and the erythrocyte metabolite increased earlier than CPU. Considering the same levels of internal lead load (measured by both PbB and PbU-EDTA) in women, EP values were higher than in the men. No significant difference was established between the two sexes regarding ALAD and CPU values, when considered at the same PbB levels. Validity of ALAD and EP in the females, as already shown in our previous studies on males, was moderate in predicting PbB levels 40 g/100 ml, while it clearly improved at PbB levels 50–60 g/ 100 ml. This indicates that for screening women of child-bearing age the two indicators of effect must be used with caution, since a value of 40 g/100 ml has been proposed as the permissible PbB limit.Abbreviations PbB blood lead (g/100 ml) - PbU-EDTA amount of chelatable lead excreted with 24 hours urine after administration of CaNa₂ EDTA (1 g intravenously) - ALAD -aminolevulinic acid dehydratase activity of erythrocytes (mU/ml RBC) - EP erythrocyte protoporphyrin (g/100 ml RBC) - ALAU urinary -aminolevulinic acid (mg/1) - CPU urinary coproporphyrin (g/1)     

Relationship between inhibition of erythrocyte pyrimidine 5′-nucleotidase activity and biological response for porphyrin metabolism in workers occupationally exposed to lead

Summary A rapid determination of erythrocyte pyrimidine 5-nucleotidase (P5N) activity in lead workers was carried out using a high-performance liquid chromatograph (HPLC). The P5N activity had a good negative correlation with the concentration of lead in blood (PbB) ranging from 16 to 96 g/dl (r = -0.82, n = 77). Further, the P5N was compared with other biological parameters: erythrocyte -aminolevulinic acid dehydratase (ALAD) activity, erythrocyte protoporphyrin (PROTO), urinary -aminolevulinic acid (ALA) and urinary coproporphyrin (COPRO).The correlation coefficients between P5N and ALAD, log PROTO, log ALA, and log COPRO were 0.59, –0.72, –0.65, and –0.61, respectively. On the other hand, the normal value of P5N obtained from 72 healthy subjects was 11.9 ± 2.1 units; ol uridine/h/g Hb (mean ± SD), indicating that the lower limit of 95% confidence interval for normal P5N was about 8 units. When P5N was cut off at 8 units in 77 lead workers, the validity (sensitivity + specificity) for PbB 40 g/dl, PbB 60 gg/dl, erythrocyte PROTO 150 g/dl RBC, urinary ALA 6 mg/l, and urinary COPRO 150 g/l was 1.66, 1.76, 1.57, 1.68, and 1.60, respectively. From these results, it was confirmed that the erythrocyte P5N test is suitable for the biological monitoring of exposure to lead in a wide range, and its activity is useful in predicting the disturbance of porphyrin metabolism induced by lead.     

Determination of the urinary metabolites of styrene: estimation of the method evaluation function and evaluation of reference values in Danish subjects

Summary A European study on styrene exposure was initiated in 1989 to evaluate the health effects of environmental and occupational exposure. A part of this study included the development of an analytical method for use in a biological monitoring program. The urinary metabolites of styrene, mandelic acid (MA) and phenyl-glyoxylic acid (PGA) were quantitated by a direct and convenient high-performance liquid chromatography method. Urine samples were diluted with eluent and analysed by HPLC with a C₈ reversed-phase column and a buffer to acetonitrile (9:1) eluent with a counterion added. The detector used was a variable UV dectector and the wavelength was = 210 nm. The method was statistically evaluated by a method evaluation demonstrating no systematic error. The uncertainty was 23.8 mol/l and 11.5 mol/l for MA and PGA, respectively. The limit of detection (LOD) of MA is 71.4 mol/l and the LOD of PGA is 34.5 mol/l, sufficiently low for the measurement of styrene exposure at a low exposure level. The present study indicates that reference values for MA and PGA are low. The fraction of reference values below LOD was 0.80 for MA and 0.66 for PGA; consequently, the reference values were described by a non-parametric one-sided tolerance interval. The 95% one-sided upper tolerance limits calculated for MA and PGA were 31.0 mol/mmol creatinine and 20.1 mol/mmol creatinine, respectively, with the coverage 0.95 ±0.045 for both metabolites. The method has been used for biological monitoring in several studies of environmentally and occupationally exposed subjects in concentrations up to 200 mol/mmol creatinine for MA and 150 mol/mmol creatinine for PGA.     

Changes in external and internal lead load in different working areas of a starter battery production plant in the period 1982 to 1991

Summary Our investigation was based on routine ambient and biological monitoring data in a starter battery production plant from 1982 to 1991. This retrospective longitudinal study included 134 blue collar workers in seven main production areas (casting, lead oxide production, bunker, pasting, formation, plate stacking, assembly). Over the whole period a statistically significant decrease in blood lead concentration in the whole sample, from 48.92 g/dl (1982) to 22.99 g/dl (1991), could be ascertained. This positive trend could also be proven for the most important production areas. The highest internal lead load was present in employees from the formation and adjoining production areas, followed by pasting, casting and assembly. In comparison to other battery factories our results are in the lower range. Furthermore, we carried out a data linkage between air and blood lead concentrations. We were able to demonstrate a decrease in external lead load in most of the production areas, but this reduction was not so distinct as that in the blood lead concentration. These results indicate the efficiency of preventive efforts in technical work protection and especially in intensive medical supervision of the exposed workers. Influencing personal hygienic behaviour and intervention at blood lead levels of 50 g/dl promises the best success in worker protection.     

Biochemical and physiological aspects of 2,5-hexanedione: endogenous or exogenous product?

Summary This article reports results regarding two different physiological aspects of 2,5-hexanedione (2,5-HD). The first is the relationship between free 2,5-HD (the fraction of real 2,5-HD) and total 2,5-HD (2,5-HD obtained from acid hydrolysis) in urine and blood of workers exposed ton-hexane. The second part of the study is an attempt to clarify physiological excretion of 2,5-HD in subjects not occupationally exposed ton-hexane. The concentration of free 2,5-HD in urine of workers exposed ton-hexane is about 8% of total urinary 2,5-HD. In blood, free 2,5-HD is about 50% of the total. The serum concentration range of total and free 2,5-HD in workers from whom blood was taken was 33–418 g/l and 14–283 g/l respectively. In subjects not exposed ton-hexane, urinary concentration of 2,5-HD ranged between 0.17 and 0.98 mg/1, the urinary excretion rate between 0.23 and 0.57g/min, and renal clearance between 14 and 66 ml/min. The blood concentration of 2,5-HD in nonexposed subjects was 6–30g/1. Fluctuations typical of a circadian rhythm were not observed for 2,5-HD in blood or urine. We think that 2,5-HD is mainly a product of intermediate metabolism in the human body. Only a minimal part could derive fromn-hexane as a ubiquitous micropollutant.     

Increase in the amount of erythrocyte δ-aminolevulinic acid dehydratase in workers with moderate lead exposure

Summary The amount of ALA-D in human erythrocytes was determined directly by radioimmunoassay or calculated from the restored activity assayed in the presence of zinc and dithiothreitol, and a good correlation was observed between the RIA-based and the restored activity-based amounts.The RIA-based amount of ALA-D in the blood of 10 normal individuals (blood lead levels of 5.6 ± 2.3 g/100 ml: mean ± SD) and 19 lead-exposed workers (blood lead levels of 41.2 ± 10.2 g/100 ml) was 54.1 ± 11.8 g/ml blood and 92.3 ± 20.6 g/ml blood, respectively, indicating an apparent increase of the enzyme amount in lead-exposed workers.A significant increase in the amount of erythrocyte ALA-D calculated from the restored activity in lead-exposed workers was observed even in the low blood lead level of 10–20 g/100 ml, resulting in the range of blood lead level 20–40 g/100 ml. No significant difference was observed in hematocrit and hemoglobin content between lead-exposed and non-exposed groups. These observations suggested that the increase of erythrocyte ALA-D in lead exposure was not due to anemia, which might result in the increase of young erythrocytes in peripheral blood.This increase in the amount of ALA-D in human erythrocytes might be a result of the function to overcome the inhibition of the enzyme in bone marrow cells during lead exposure, and these findings may throw light on the danger to human health of low-level lead toxicity.Abbreviations ALA-D -Aminolevulinic acid dehydratase or 5-Amnoevulinic acid hydro-lyase, EC 4.2.1.24 - ALA -Aminolevulinic acid - Rc Reticulocyte - RIA Radioimmunoassay - DTT Dithiothreitol Supported in parts by Science Research Fund of the Ministry of Education, Science and Culture of Japan and by Research Grant of Fujiwara Foundation of Kyoto University     

In vitro susceptibility of mycelial and yeast forms of Penicillium marneffei to amphotericin B,fluconazole, 5-fluorocytosine and itraconazole

The mycelial (25°C) and yeast-like (37°C) forms of Penicillium marneffei clinical and type strains were investigated for their in vitro susceptibility to amphotericin B (AmB), 5-fluorocytosine (5-FC), fluconazole (FLU) and itraconazole (ITZ), using Bacto antibiotic medium 3, yeast-nitrogen, Sabouraud's dextrose (pH 5.7) and high resolution (pH 7.1) broth media (1ml/tube), respectively. Results indicated that the minimal inhibitory and minimal fungicidal concentrations (MICs and MFCs) for the mycelial cultures of P. marneffei to AmB were in the range 0.78–1.56 and 0.78–3.125 g/ml, respectively, as against 3.125–25 g (MICs) for the yeast form cultures. The MFCs to AmB for the yeast form were one dilution higher. The MICs to FLU were generally lower for the yeast form (6.25–25 g) than the mycelial form (25–50 g/ml), whereas MFCs for the mycelial cultures were > 100 g as compared to 6.25–100 g for their yeast form. The MICs for the mycelial form to 5-FC ranged from < 0.195–0.39 g. Higher MICs (6.25 g) were recorded for their yeast form. The MFCs to 5-FC for the yeast form were 25–100 g/ml. The MICs for the mycelial form to ITZ ranged from < 0.195 to 3.125 g/ml. Higher values (< 0.195–50 g) were recorded for their yeast-like form. The MFCs to ITZ for mycelial and yeast forms ranged from < 0.195–0.39 and 25–100 g/ml, respectively. Results indicate that P. marnefei's yeast form is more sensitive to FLU and ITZ (8 of 10 strains) while the mycelial form displayed greater susceptibility to AmB and 5-FC. The MICs for ITZ remained steady in SD medium, pH 5.7 to 7.1. However, some strains gave higher MIC values (0.39–1.56 g/ml) when tested in the HR.     

Measurement of manganese amelioration of cadmium toxicity inChlorella pyrenoidosa using turbidostat culture

Cadmium (Cd) toxicity and amelioration of Cd toxicity by Mn were measured inChlorella pyrenoidosa, using turbidostat culture. The responses were measured in terms of the maximum specific growth rate, _max, of the populations. In turbidostat culture _max is a dependent variable that can be measured continuously. Cd (as CdCl₂· 2.5 H₂O) was added to control populations at a concentration of 1.8 M Cd. Toxicity was expressed after a 5 generation lag and resulted in a _max steady state 62% lower than the initial control after 2 generations. With continued Cd exposure, Mn (as MnCl₂ · 6H₂O) was then added stepwise to a concentration of 10.4 M Mn which caused a rapid, immediate increase in _max followed by linear increase until a steady-state plateau was reached at a _max 90% of control. The ameliorative response spanned 20 culture generations. After addition of Mn (10.4 M), cellular Cd concentration did not change and cellular Mn concentration increased. Increase in mean cell size accompanied Cd exposure and was significantly decreased when supplemented with 10.4 M Mn. Possible mechanisms of the amelioration are discussed.     

Cytogenetic studies of herbicide interactions in vitro and in vivo using atrazine and linuron

The herbicides atrazine and linuron, found in Wisconsin's groundwater, were tested alone and in combination, both in vivo and in vitro, to determine their individual and combined genotoxic effects. Human lymphocytes exposed in vitro to either 1 g/ml linuron or 0.001 g/ml atrazine showed little chromosome damage, whereas significant chromosome damage was observed in lymphocytes simultaneously exposed to 0.5 g/ml linuron and 0.0005 g/ml atrazine, suggesting at least an additive model. In another experiment, mice were fed 20 g/ml atrazine, 10 g/ml linuron, or a combination of 10 g/ml atrazine and 5 g/ml linuron in their drinking water for 90 days, after which bone marrow cells and cultured splenocytes were examined for chromosomal damage. None of the treatment groups showed chromosome damage in bone marrow, whereas the cultured splenocytes demonstrated damage in all treatment groups. These experiments suggest that, prior to assessing the risk of a herbicide, it may be necessary to test it in combinations which mimic the mixtures which would occur under field conditions, such as in contaminated groundwater.     

Studies on erythrocyte pyrimidine 5′-nucleotidase (P5N) test and its evaluation in workers occupationally exposed to lead

Summary An erythrocyte pyrimidine 5-nucleotidase (P5N) test was performed for 171 workers occupationally exposed to lead. Erythrocyte P5N activity was markedly inhibited by exposure to lead. Among several biological indicators (erythrocyte P5N, -aminolevulinic acid dehydratase (ALAD), protoporphyrin (PROTO), urinary -aminolevulinic acid (ALA), coproporphyrin (COPRO)), the P5N activity had the highest correlation with the concentration of lead in blood (r = – 0.77). A significant inhibition of erythrocyte P5N was found in groups of lead workers with blood-lead levels of more than 10 to 19 g/dl. This P5N inhibition started before any changes occurred in urinary ALA and COPRO. A 45 to 50% inhibition of P5N corresponded to the blood-lead value (50 g/dl) of the BEI recommended by ACGIH. In some lead workers, erythrocyte nucleotides (mainly CTP and UTP) were determined. The data indicated that a marked accumulation of these nucleotides had occurred, and their levels correlated negatively with P5N activity and positively with blood lead.     

Blood acetone concentration in “normal people” and in exposed workers 16 h after the end of the workshift

Summary Acetone levels were measured by gas chromatography mass spectrometry (GC-MS) in environmental and alveolar air, blood and urine of 89 non-occupationally exposed subjects and in three groups of workers exposed to acetone or isopropanol. Acetone was detected in all samples from non-exposed subjects, with mean values of 840 g/l in blood (Cb), 842 g/l in urine (Cu), 715 ng/l in alveolar air (Ca) and 154 ng/l in environmental air (Ci). The ninety-fifth percentiles were 2069 g/l in Cb, 2206 g/l in Cu and 1675 ng/l in Ca. The blood/air partition coefficient of acetone was 597. Correlations were found in Cb, Cu and Ca. In specimens sampled at the end of the workshift from subjects occupationally exposed to acetone, a correlation was found in the blood, urine, alveolar and environmental air concentrations. The blood/air partition coefficient of acetone was 146. On average, the blood acetone levels of workers were 56 times higher than the environmental exposure level, and the concentration of acetone in alveolar air was 27% more than that found in inspiratory air. The half-life for acetone in blood was 5.8 h in the interval of 16 h between the end of the workshift and the morning after. The morning after a workshift with a mean acetone exposure of 336 g/l, blood and urinary levels were 3.5 mg/l and 13 mg/l, respectively, which were still higher than those found in normal subjects. It can be concluded that endogenous production of acetone and environmental exposure to acetone or isopropanol do not affect the reliability of biological monitoring of exposed workers, even 16 h after low exposure.