Biological monitoring of exposure and effects in workers employed in a selenium-processing plant.

PURPOSE: The aim of the study was to assess external and internal selenium exposure and potential biological effects in employees working in a selenium-processing plant. METHODS: Twenty male employees of a selenium-processing plant (exposed) and 20 age-matched male individuals without occupational selenium exposure (controls) participated in the study. Exposure to selenium at the workplace was determined by personal air sampling. Internal exposure was assessed by measuring total selenium concentration in plasma after a workshift and after holidays as well as by measuring the selenium concentration in urine before and after shift and after holidays. The activity of glutathione peroxidase (GPx) in blood and the prothrombin time were determined as biological effect parameters. RESULTS: The exposure to selenium in the workplace air ranged from 8 to 950 µg/m(3) and exceeded in a large part current occupational exposure limits. The selenium levels in plasma samples of the exposed ranged from 49 to 182 µg/L during exposure and were significantly higher than the plasma levels observed after holidays as well as in the control group. The selenium concentration in pre- and post-shift urine samples did not differ significantly, and the average urinary selenium levels of the employees (18-1,104 µg/g creatinine) were significantly higher than those measured after holidays or determined in controls. Both the concentration of selenium in plasma and in urine did not correlate with the current external exposure of the employees at the workplace. However, we found a strong and significant association between the two biomonitoring parameters. In spite of the considerable high external exposure to elemental selenium, we did not find any effect on the GPx activity in blood as well as on the prothrombin time. CONCLUSIONS: Both the selenium levels in plasma and urine may be used as biological monitoring parameters for the assessment of chronic occupational exposure to selenium. Nevertheless, the toxicokinetics of the urinary excretion of selenium remain still unclear and require further investigations. Moreover, our findings emphasise the necessity of a re-evaluation of occupational exposure limits for elemental selenium and inorganic selenium compounds.

Longitudinal study on potential neurotoxic effects of aluminium: II. Assessment of exposure and neurobehavioral performance of Al welders in the automobile industry over 4 years.

OBJECTIVES: This is the second of two parallel longitudinal studies investigating Al exposure and neurobehavioral health of Al welders over 4 years. While the first published study in the trail and truck construction industry examined the neurobehavioral development of Al welders from age 41-45 in the group mean (Kiesswetter et al. in Int Arch Occup Environ Health 81:41-67, 2007), the present study in the automobile industry followed the development from 35 to 39. Although no conspicuous neurobehavioral developments were detected in the first study, which furthermore exhibited the higher exposure, it cannot be excluded that exposure effects appear in earlier life and exposure stages. METHODS: The longitudinal study is based on a repeated measurement design comprising 4 years with three measurements in 2 years intervals. 92 male Al welders in the automobile industry were compared with 50 non-exposed construction workers of the same industry and of similar age. The repeated measurements included total dust in air, and Al pre- and post-shift plasma and urine samples. Neurobehavioral methods comprised symptoms, verbal intelligence, logic thinking, psychomotor behavior, memory, and attention. The computer aided tests came from the Motor Performance Series and the European Neurobehavioral Evaluation System. The courses of neurobehavioral changes were analyzed with multivariate covariance-analytical methods considering the covariates age, indicators of 'a priori' intelligence differences (education or markers of 'premorbid' intelligence), and alcohol consumption (carbohydrate-deficient transferrin in plasma). Additionally, the interrelationship, reliability and validity of biomonitoring measures were examined. RESULTS: The mean environmental dust load during welding, 0.5-0.8 mg/m(3), and the mean internal load of the welders (pre-shift: 23-43 microg Al/g creatinine in urine; 5-9 microg Al/l plasma) were significantly lower than in the parallel study. Under low exposure, the stability of biomonitoring measures was reduced, but the Al load differed significantly between Al welders and referents. It could not be shown that the development of neurobehavioral performances over the 4-year period differed between both groups. Mainly, markers of premorbid intelligence and age were related to neurobehavioral performance differences but not Al exposure. CONCLUSIONS: The biomonitoring and neurobehavioral results are in line with the results of the first published study. The repeated measurement models of both studies showed no adverse neurobehavioral effects of Al welding. A modular lifetime-oriented research concept is outlined aiming at the investigation of sequential periods of exposure life with special focus on the biologically most sensitive phases like first exposure and old age.

[Nickel levels in female dermatological patients]. / Innere Nickelbelastung von dermatologischen Patientinnen.

Nickel levels in urine were determined among 163 female dermatological patients aged 18 to 46 years. Data on life-style factors were collected in parallel via a questionnaire. Urinary nickel excretion was in the normal range of the German female population (0.2-46.1 microg Ni/g creatinine). The 95th percentile (3.9 microg Ni/l urine) exceeded the German reference value (3.0 microg Ni/l urine). In the multivariate regression analyses we found a statistically significant increase of ln-transformed nickel levels with increase in age and in women using dietary supplements. The following variables were not associated with Nickel urine levels: suffering from nickel eczema, smoking, drinking stagnated water, eating foods with high nickel contents and using nickel-containing kitchen utensils as, for example, an electric kettle with an open heater coil. We conclude that personal urinary levels should be assessed with simultaneous consideration of habits and life-style factors. A German national survery would be useful. Those patients who experience the exacerbation of their eczema in cases of oral provocation, for example, by a high nickel diet should be aware of potential sources of nickel, such as supplements.

Percutaneous absorption of aromatic amines - a contribution for human health risk assessment.

Several aromatic amines (AA) are human carcinogens. AA are widely-used, e.g., in the rubber industry. The uptake of AA at the workplace occurs by inhalation and percutaneous absorption. At present there are no risk assessment studies for percutaneous AA absorption using occupationally relevant concentrations. We conducted diffusion cell experiments for aniline (ANI), o-toluidine (OT), 4,4'-methylenedianiline (MDA) and N-phenyl-2-naphthylamine (PBNA). Excised human skin was exposed to different AA concentrations in vehicles containing water and solvents. Recovery for ANI in receptor fluid was about 20-38% and for MDA 15% over 24h. PBNA could not be detected in the receptor fluid. Further data for OT and beta-naphthylamine (BNA) were considered from our recent study. A semi-quantitative percutaneous absorption ranking for AA was derived: BNA>OT>ANI>MDA>PBNA. For aqueous ANI solutions up to saturation a linear relationship of exposed dose and penetrated amount was observed. However, a linear extrapolation of the flux of neat compounds, as often recommended for risk assessment policies, underestimates considerably the percutaneous uptake. The in vitro data support our recent findings in rubber industry workers that the percutaneous absorption may significantly contribute to overall exposure of AA.

Percutaneous absorption of aromatic amines in rubber industry workers: impact of impaired skin and skin barrier creams.

BACKGROUND: Several aromatic amines (AA) could cause bladder cancer and are an occupational hygiene problem in the workplace. However, little is known about the percutaneous absorption of chemicals via impaired skin and about the efficacy of skin protection measures to reduce internal exposure. AIMS: To determine the impact of skin status and of skin protection measures on the internal exposure to AA in workers manufacturing rubber products. METHODS: 51 workers occupationally exposed to aniline and o-toluidine were examined. The workplace conditions, risk factors for skin and the use of personal protective equipment were assessed by means of a self-administered questionnaire. The skin of hands and forearms was clinically examined. Exposure to aniline and o-toluidine was assessed by ambient air and biological monitoring (analyses of urine samples and of haemoglobin adducts). RESULTS: Haemoglobin-AA-adduct levels in workers with erythema (73%) were significantly higher (p<0.04) than in workers with healthy skin (mean values: aniline 1150.4 ng/l vs 951.7 ng/l, o-toluidine 417.9 ng/l vs 118.3 ng/l). The multiple linear regression analysis showed that wearing gloves significantly reduced the internal exposure. A frequent use of skin barrier creams leads to a higher internal exposure of AA (p<0.03). However, the use of skincare creams at the workplace was associated with a reduced internal exposure (p<0.03). From these findings we assume that internal exposure of the workers resulted primarily from the percutaneous uptake. CONCLUSIONS: The study demonstrates a significantly higher internal exposure to AA in workers with impaired skin compared with workers with healthy skin. Daily wearing of gloves efficiently reduced internal exposure. However, an increased use of skin barrier creams enhances the percutaneous uptake of AA. Skincare creams seem to support skin regeneration and lead to reduced percutaneous uptake.

Longitudinal study of neurotoxicity with occupational exposure to aluminum dust.

Two cross-sectional studies were conducted at a German aluminum (Al) powder plant to evaluate possible nervous system effects from occupational Al exposure. The investigation included biological monitoring, a neuropsychological test battery, and event-related P300 potentials. Neurophysiologic findings in workers chronically exposed to Al dust did not differ from non-Al-exposed controls from the same plant. The authors suggest that chronic exposure to Al dust, at the levels documented in this study, does not induce measurable cognitive decline.

A simple and reliable enzymatic assay for the determination of formic acid in urine.

A simple, reliable and efficient enzymatic assay for the analysis of formic acid in urine is described. The principle of the method is the quantitative oxidation of the acid with the enzyme formate dehydrogenase (FDH) in the presence of NAD. The detection limit was 0.5 mg/l, the recovery rates ranged from 66% to 74% and the coefficient of variation was 5%. The results obtained with this method correlated well with the values measured with two different gas chromatographic procedures. Normal formic acid excretion in urine is between 2.0 and 30.0 mg/l, with a mean of 13.0 +/- 7.4 mg/l and between 1.2 and 17.5 mg/g creatinine, the mean being 7.7 +/- 4.0 mg/g creatinine. The determination of formic acid concentration in urine may be an important means to quantify the degree of exposure to or intoxication of persons with methanol, formaldehyde and acetone.

[Quantitative determination of hippuric acid in urine using high pressure liquid chromatography (author's transl)]. / Quantitative Bestimmung von Hippursäure im Urin mit der Hochdruck-Flussigkeits-Chromatographie.

A simple method to determine hippuric acid in urine by high pressure liquid chromatography is described. An ion exchange column is used for the separation. The detection is carried out with a photometer. The analytical criteria of the reliability of the method are tested. The results for the precision and the accuracy of the method meet the guidelines of the statistical quality control. 34 urinary constituents were tested for their interference in order to examine the specificity. Measuring urine samples from 46 normal persons yielded hippuric acid concentrations between 160 and 2010 mg/1. The median was 400 mg/1, equivalent to 357 mg/g creatinine. These results are compared to those given in the literature. Comparative investigations of those urine samples by a gas chromatographic method matched well, with a coefficient of regression of 0.86.

Cadmium and renal hypertension.

In our study we investigated 36 patients with renal disease, 22 of whom were hypertensive. In all proteinuria was present (4.30 +/- 5.05 g protein/day) and renal lesions were proved by renal biopsy. Blood cadmium in non-smokers was significantly (P less than 0.05) lower than in smokers. We found a positive correlation between cadmium concentrations in blood and urine (P less than 0.01, r = 0.44) and between cadmium concentration in blood and serum uric acid levels (P less than 0.01, r = 0.44). Proteinuria was weakly correlated with cadmium concentration in urine (P less than 0.05, r = 0.35). Patients with hypertension showed a significantly higher (P less than 0.05) urine cadmium excretion per day (1.60 +/- 1.12 micrograms/day compared with normotensives with disease of the kidney (1.14 +/- 1.47 micrograms/day). Our results indicate that cadmium may be involved in the development of hypertension in patients with renal disease.

Quality assurance of biological monitoring in occupational and environmental medicine.

Biological monitoring of chemical exposure in the workplace has become increasingly important in the assessment of health risk as an integral part of the overall occupational health and safety strategy. In environmental medicine biological monitoring plays also an important role in the assessment of excessive, acute or chronic exposure to chemical agents. To guarantee that the results obtained in biological monitoring are comparable with threshold limit values and results from other laboratories, the analysis must be carried out with tested and reliable analytical methods and accompanied by a quality assurance scheme. Confounding influences and interferences during the pre-analytical phase can be minimised by recommendations from experienced laboratories. For internal quality control commercially available control samples with an assigned concentration are used. External quality control programs for biological monitoring are offered by several institutions. The external quality control program of the German Society of Occupational and Environmental Medicine has been organised since 1982. In the meantime the 27th program has been carried out offering 96 analytes in urine, blood and plasma for 47 substances. This program covers most of the parameters relevant to occupational and environmental medicine. About 350 laboratories take part in these intercomparison programs. At present, ten German and 14 international laboratories are commissioned to determine the assigned values. The data evaluated from the results of the intercomparison programs give a good overview of the current quality of the determination of analytes assessed in occupational and environmental toxicological laboratories. For the analysis of inorganic substances in blood and urine the tolerable variation ranges from 7.5 to 43.5%. For organic substances in urine the tolerable variation ranges from 12 to 48%. The highest variations (36-60%) were found for the analysis of organochlorine compounds in plasma. The tolerable variations for the determination of solvents in blood by head space gas chromatography range from 26 to 57%. If the recommendations for the pre-analytical phase, the selection of reliable analytical methods by the laboratory and the carrying out of adequate quality control are observed, the pre-requisites for reliable findings during biological monitoring are fulfilled

Current status of the external quality assurance programmes of the German Society for Occupational and Environmental Medicine.

Due to a technical rule issued by the Ministry of Labour, in Germany toxicological analysis in blood and urine for biological monitoring must be carried out under quality assurance. Since 1982 the German Society for Occupational and Environmental Medicine has offered 13 intercomparison programmes. The 1994 round robin considered 7 metals and 5 solvents in blood, 12 organochlorine compounds in plasma and 14 inorganic, as well as 11 organic, compounds in urine in the occupational and in the environmental exposure range. Reference values and tolerance ranges are established by reference laboratories. Successful participation was certified if the results for 2 concentration adjustments were in tolerance range (assigned value +/- 3 S.D.). In 1994 in 119 laboratories the percentage rate of accurate results was 59%. This mean success rate is in agreement with the last 12 round robins.

Quantitative determination of chromium and nickel in tumour and tumour-free human tissue.

Environmental pollution with carcinogenic substances, in addition to individual abuse, are discussed as important factors causing development of cancer. We must assume that certain nickel and chromium compounds, which are ubiquitous in our ecosystem, must have carcinogenic effects on humans too. The aim of this study is therefore to examine the extent to which the accumulation of the potentially carcinogenic metal ions nickel and chromium could be measured in tissue from tumour patients. We examined tumour and tumour-free tissue obtained from a total of 48 patients who had carcinomas of the stomach, bowel, or kidney. We also analyzed nickel and chromium content in whole blood and urine samples from these persons. The quantitative metal estimations were done using atomic absorption spectrophotometry. Differences between chromium and/or nickel content in tumour or tumour-free tissue were not observed. An accumulation of these metal ions in tumour tissue is therefore improbable. We were also unable to find differences in metal content with regard to chromium and nickel as related to the appearance of tumour in the organ. In contrast, tumour patients had a 5- to 7-fold increase over normal values for chromium and nickel in blood and urine. This was attributable to unavoidable contamination of tissue and body fluids with chromium- and nickel-containing instruments during major surgical procedures.

Increased content of chromium and nickel in lung tissues from patients with bronchial carcinoma.

Epidemiological studies have shown that occupational exposure to certain chromium and nickel compounds is followed by an increased lung cancer incidence. However, few data exist on the content of these metals in lung cancer patients in general. In the present study, central and peripheral lung tissue, bronchial tissue and hilar lymph nodes were collected from 20 patients with bronchial carcinoma and 21 control individuals, and the tissue concentration of chromium and nickel was measured by use of atomic absorption analysis. Increased levels of both metals were found in cancer patients as compared to controls. Lung tissue concentration of chromium was two-fold increased, while the bronchial wall content of nickel was three times the level in control individuals. Smokers showed a dose-related increase in the deposition of both chromium and nickel. Furthermore, in cancer patients an inverse relationship between smoking and the tissue level of chromium in regional lymph nodes was found, possibly indicating a depressive effect on pulmonary clearance mechanisms. Our results emphasize the possible role of small amounts of chromium and nickel as agents in bronchial carcinogenesis, unrelated to occupation and probably related to tobacco smoking.

External quality assurance program for biological monitoring in occupational and environmental medicine.

Biological monitoring of chemical exposure in the workplace and in the environment has become increasingly important in assessing health risk. The analysis must be carried out under a quality assurance scheme to guarantee that the results obtained in biological monitoring are comparable with the threshold limit values and results from other laboratories. Since 1982, the German Society for Occupational and Environmental Medicine has offered 28 intercomparison programs. These programs cover 96 analytes in urine, blood, and plasma for 47 substances and cover most parameters that are relevant in occupational and environmental medicine. The data obtained in these programs provide a good overview of the current quality of the determination of analytes that are assessed in occupational and environmental toxicological laboratories. For the analyses of inorganic substances in blood and urine, the tolerable variation ranges from 7.5% to 43.5%. For organic substances in urine, the tolerable variation ranges from 12% to 48%. For organic substances in urine, the tolerable variation ranges from 12% to 48%. The highest variations (36% to 60%) were found for the analysis of organochlorine compounds in plasma. The tolerable variations for determining solvents in blood by head space gas chromatography range from 26% to 57%. The overall average success rates for the participants of the external quality programs range from 65% to 75%.

Organochlorine compounds in breast-fed vs. bottle-fed infants: preliminary results at six weeks of age.

BACKGROUND: Polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) are ubiquitous compounds with carcinogenic and teratogenic properties. They are chemically very stable and lipophilic and, therefore, accumulate in our food-chain. They are prenatally transmitted from mother to foetus, and mother's milk due to its high lipid content is an elimination pathway of special importance. Therefore, breast-feeding has been held responsible for elevated concentrations of these organochlorine compounds as well as for harmful effects in children later in life. METHODS: Blood samples (2.5 ml) were taken from each 10 breast-fed and bottle-fed infants at 6 weeks of age. Blood specimens were immediately centrifuged, and serum was stored in glass tubes at -20 degrees C until analysis. Three higher chlorinated PCB congeners (IUPAC nos. 138, 153 and 180), HCB, and the organic metabolite of DDT, p,p << -DDE, were analysed with capillary gas chromatography with electron capture detection. Reliability was tested with gas chromatography-mass spectrometry. RESULTS: There were no differences between the study groups of breast-fed and bottle-fed infants with regard to sex distribution, gestational age, birth-weight, age of the mothers, and smoking behaviour of the parents. In contrast, serum concentrations of all organochlorine compounds were significantly higher (P < 0.0001) in breast-fed than in bottle-fed infants (mean): PCB 138, 0.38 vs. 0.10 microg/l; PCB 153, 0.49 vs. 0.1 microg/l; PCB 180, 0.31 vs. 0.04 microg/l; SigmaPCB, 1.19 vs. 0.29 microg/l; HCB, 0.13 vs. 0.04 microg/l; p,p << -DDE, 1.05 vs. 0.18 microg/l. CONCLUSIONS: Breast-feeding significantly increases the pollution of our infants with different organochlorine compounds as early as at 6 weeks of age. The progress of the present study will show whether this pollution will further increase with longer duration of breast-feeding, and whether breast-feeding bears any health risks for our offspring.

Formaldehyde exposure at various workplaces.

The results of formaldehyde determinations in the air at various workplaces in the period 1980-1988 are presented. The airborne concentrations varied between less than 0.01 and 10.9 mg m-3 (mean 0.7 mg m-3). For ambient air monitoring, active sampling and capillary gas chromatography are reliable and sensitive methods. Formic acid excretion in urine is an unspecific and insensitive biological indicator for monitoring low-dose formaldehyde exposure.