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Biomedical subjects

K H Schaller

Publications and source records attributed to K H Schaller.

At least 19 recordsLinked to original sources

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.

Adult↗

In vitro predictions of skin absorption of caffeine, testosterone, and benzoic acid: a multi-centre comparison study.

To obtain better insight into the robustness of in vitro percutaneous absorption methodology, the intra- and inter-laboratory variation in this type of study was investigated in 10 European laboratories. To this purpose, the in vitro absorption of three compounds through human skin (9 laboratories) and rat skin (1 laboratory) was determined. The test materials were benzoic acid, caffeine, and testosterone, representing a range of different physico-chemical properties. All laboratories performed their studies according to a detailed protocol in which all experimental details were described and each laboratory performed at least three independent experiments for each test chemical. All laboratories assigned the absorption of benzoic acid through human skin, the highest ranking of the three compounds (overall mean flux of 16.54+/-11.87 microg/cm(2)/h). The absorption of caffeine and testosterone through human skin was similar, having overall mean maximum absorption rates of 2.24+/-1.43 microg/cm(2)/h and 1.63+/-1.94 microg/cm(2)/h, respectively. In 7 out of 9 laboratories, the maximum absorption rates of caffeine were ranked higher than testosterone. No differences were observed between the mean absorption through human skin and the one rat study for benzoic acid and testosterone. For caffeine the maximum absorption rate and the total penetration through rat skin were clearly higher than the mean value for human skin. When evaluating all data, it appeared that no consistent relation existed between the diffusion cell type and the absorption of the test compounds. Skin thickness only slightly influenced the absorption of benzoic acid and caffeine. In contrast, the maximum absorption rate of testosterone was clearly higher in the laboratories using thin, dermatomed skin membranes. Testosterone is the most lipophilic compound and showed also a higher presence in the skin membrane after 24 h than the two other compounds. The results of this study indicate that the in vitro methodology for assessing skin absorption is relatively robust. A major effort was made to standardize the study performance, but, unlike in a formal validation study, not all variables were controlled. The variation observed may be largely attributed to human variability in dermal absorption and the skin source. For the most lipophilic compound, testosterone, skin thickness proved to be a critical variable.

Adolescent↗

Longitudinal study examining the neurotoxicity of occupational exposure to aluminium-containing welding fumes.

OBJECTIVES: The neurotoxicity of occupational exposure to aluminium (Al)-containing welding fumes has been discussed with controversial results. The aim of the longitudinal study was to examine a group of Al welders for significant central nervous changes in comparison with a non-exposed cohort. METHODS: A group of 98 Al welders (mean age 37 years) in the car-body construction industry, with a median of 6 years of occupational exposure to Al welding fumes, and an education-matched, gender-matched, age-matched control group of 50 car-production workers (mean age 36 years) at the same plant, were included in this longitudinal study. Two cross-sectional studies were done in 1999 and 2001. In the second cross-sectional study 97 welders and 50 controls could be examined. The examination programme consisted, for example, of a standardised anamnesis, focussing on occupational history, education, illnesses, medication, accidents and current alcohol consumption, a physical examination that included neurological status, and the assessment of Al concentration in plasma and urine. The neurobehavioral methods included a symptom questionnaire, modified Q16, and computerised and non-computerised tests: psychomotor performance (steadiness, line tracing, aiming, tapping), verbal intelligence (WST), simple reaction time, digit span, block design (HAWIE), symbol-digit substitution, digit span, switching attention (European neurobehavioral evaluation system, EURO-NES), and standard progressive matrices. The data were analysed by multivariate analysis of covariance (MANCOVA) for repeated measurements with covariates age, education, and carbohydrate-deficient transferrin in plasma (CDT). RESULTS. The median Al urine concentration (mean preshift/postshift) was 52.4 microg/g creatinine (2001) and 57.6 microg/g creatinine (1999). Median respirable air dust was 0.67 mg/m(3) (2001) and 0.47 mg/m(3) (1999). Welders and controls did not report significantly more symptoms in the modified Q16. Furthermore, no significant differences in psychomotor performance and other neurobehavioral tasks, except for reaction time, were seen between welders and non-welders. Regression analyses reveal a significant relationship between reaction time and Al excretion in urine that was confounded by other factors. CONCLUSIONS: At present the outcome for reaction time has to be interpreted as a single result. However, as the modified Q16 questionnaire and the rest of the psychomotor performance showed no significant changes, the next cross-sectional study, in 2003, will provide further information on which a final conclusion can be based.

Adult↗

In vitro evaluation of the efficacy of skin barrier creams and protective gloves on percutaneous absorption of industrial solvents.

OBJECTIVES: The aim of the experiments was to evaluate the efficacy of skin barrier creams (SBCs) and protective gloves and its potential for reduction of percutaneous absorption of industrial solvents. METHODS: We assessed percutaneous absorption of ethylene glycol (EG), isopropyl alcohol (IA) and 1,2,4-trimethylbenzene (TMB), using static diffusion cells. These solvents were applied neat (EG, TMB) as well as in 10% and 50% aqueous solution (EG, IA) or in 10% and 50% ethanol-diluted solution (TMB). Furthermore, we tested the percutaneous absorption of IA mixed in one cleaning agent (CA), used in newspaper printing shops to clean the rollers of printing machines. Additionally, the penetration behaviour of 10% and 50% solutions of EG, IA and TMB was tested. The experiments were carried out on untreated and on SBC-treated excised human skin from one donor, and on protective gloves. Saline was used as receptor fluid for EG and IA, and neat ethanol for TMB. RESULTS: The penetration of 50% EG, IA and TMB solutions through SBC-treated skin was higher than in untreated skin (factor 3.9 for EG, 0.32 for IA and 0.06 for TMB). The penetration of IA in the IA-CA mixture was five-times higher through untreated skin as for the single compound in 10% aqueous solution. In skin, treated with SBC, we found a 17-fold penetration enhancement of IA in the IA-CA mixture. No appreciable penetration of EG and IA was observed through nitrile rubber gloves. CONCLUSIONS: Our in vitro experiments could not demonstrate an efficacy of SBC to protect skin penetration for the tested solvents. The percutaneous absorption of all solvents in 50% solution was increased through skin treated with SBCs. Furthermore, SBCs enhance the penetration rates of solvents from complex mixtures compared with the single solvents. The tested gloves showed sufficient protection for the hydrophilic solvents, but not for TMB.

2-Propanol↗

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

Chromatography↗

Urinary beryllium--a suitable tool for assessing occupational and environmental beryllium exposure?

OBJECTIVES: The reasons for the slow progress and lack of new knowledge in the biological monitoring of beryllium (Be) are to be found in the presumed small number of working activities involving exposure to the metal, and the lack of adequate analytical methods. The reference values for urinary Be reported earlier in the literature appear to be too high, due to the poor specificity and sensitivity of the adopted methods. The aim of this study was to correlate Be air concentrations and Be urinary levels to ascertain whether the biological indicator was suitable for assessing occupational exposure to the metal. METHODS: To investigate the relationship between the Be concentrations in air and those excreted in urine, we examined 65 metallurgical workers exposed to very low levels of the metal, and 30 control subjects. The exposed workers were employed in two electric steel plants and two copper alloy foundries. The alloys were produced in electric furnaces, starting with scrap containing Be as an impurity. The Be concentrations in the air were monitored by area samplers and the levels of Be in the urine of the workers were determined in samples taken at the end of the shift. Both determinations were carried out by ICP-MS. RESULTS: The median airborne Be concentrations in the copper alloy plants were 0.27 microgram/m3 in the furnace area and 0.31 microgram/m3 in the casting area. Median values of 0.03 to 0.12 microgram/m3 were determined in the steel plants, the relatively wide range probably due to differing amounts of Be in the scrap. Regression analysis was performed on the median values from four work areas and the corresponding urinary samples. A significant correlation was found for the relationship between external and internal exposure. The urinary Be levels were in the range between 0.12 and 0.15 microgram/l with observation of the recommended TLV-TWA for inhalable dust of 0.2 microgram/m3 (0.2 microgram/l at the upper 95th percentile). CONCLUSIONS: Sufficient data are not currently available to be able to propose a BEI for urinary Be. Our results show that new investigations are necessary to improve the evaluation of dose indicators and the relationship between external and internal exposure to Be.

Adult↗

Exposure assessment in the hard metal manufacturing industry with special regard to tungsten and its compounds.

OBJECTIVES: To assess the exposure to tungsten, cobalt, and nickel in a plant producing hard metals. The main components of hard metals are tungsten carbide and cobalt metal. According to recent studies, these two components may be responsible for both fibrogenic and carcinogenic effects. METHODS: 87 workers were investigated (86 male, one female) with a median age of 42 (range 22-58) and a mean duration of exposure of 13 years (range 1-27 years). Stationary and personal air sampling, and biological monitoring were carried out. RESULTS: Ambient monitoring yielded maximum tungsten concentrations of 417 microg/m3 in the production of heavy alloys. A maximum cobalt concentration of 343 microg/m3 and a maximum nickel concentration of 30 microg/m3 were found at the sintering workshop. The highest urinary cobalt concentrations were found in the powder processing department. The mean concentration was 28.5 microg/g creatinine and the maximum value was 228 microg/g creatinine. The maximum nickel concentration in urine of 6.3 microg/g creatinine was detected in the department producing heavy alloys. The highest tungsten concentrations excreted in urine were found in grinders and had a mean value of 94.4 microg/g creatinine and a maximum of 169 microg/g creatinine. Due to the different solubility and bioavailability of the substance, there was no correlation between the tungsten concentrations in air and urine on a group basis. CONCLUSIONS: Despite its low solubility, tungsten carbide is bioavailable. The different bioavailability of tungsten metal and tungsten compounds has to be considered in the interpretation of ambient and biological monitoring data in the hard metal producing industry. The bioavailability increases in the order: tungsten metal, tungsten carbide, tungstenate. Only if both monitoring strategies are considered in combination can a valid and effective definition of high risk groups be derived.

Adult↗

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.

Adult↗

Aluminium dust-induced lung disease in the pyro-powder-producing industry: detection by high-resolution computed tomography.

OBJECTIVE: The aim of this case study was to investigate the suitability of high-resolution computed tomography (HRCT) for detecting early stages of lung fibrosis induced by aluminium (Al) dust. METHODS: A 40-year-old worker was studied who had worked as a stamper for 14 years in a plant producing aluminium powder and had been exposed to high levels of aluminium dust during this time. The investigation included the collection of general data on health and details on occupational history, immunological tests, a physical examination, lung function analysis, biological monitoring of Al in plasma and urine, chest X-rays and HRCT. RESULTS: For many years the man has suffered from an exercise-induced shortness of breath. Lung function analysis revealed a reduction of the vital capacity to 57.5% of the predicted value. The Al concentration in plasma was 41.0 micrograms/l (upper reference value 10 micrograms/l) and in urine 407.4 micrograms/l upper reference value 15 micrograms/l, biological tolerance (BAT) value 200 micrograms/l[ at the time of diagnosis. Chest X-ray showed unspecific changes. HRCT findings were characterised by small, centrilobular, nodular opacities and slightly thickened interlobular septae. Exposure to other fibrotic agents could be excluded. CONCLUSIONS: HRCT was more sensitive than chest X-rays for detecting this early stage of Al-dust-induced lung disease. The suitability of HRCT in the surveillance of workers highly exposed to aluminium powder should be evaluated in further studies. Biological monitoring can be used to define workers at high risk.

Adult↗

Analytical validity of the determination of mercury in whole blood and urine--results of the German external assurance programme for toxicological analysis in biological materials.

The determination of mercury concentrations in blood and urine is currently the best way of monitoring individual uptake of organic and inorganic mercury. In Germany these determinations must be carried out under the conditions of an external quality assurance programme. The German performance evaluation, based on reference values established by reference laboratories yields success rates in percent for the participants in the intercomparison programme of about 60%. A Canadian evaluation system based on two evaluations scores, yields success rates of 25-50% for "good performance" and of 65-80% for "acceptable performance". The determination of mercury in blood and urine is at present not carried out with the necessary reliability.

Germany↗

Normal values for arsenic and selenium concentrations in human lung tissue.

Normal values and ranges were determined for arsenic and selenium concentrations in lung and hilus tissue. The study group consisted of 50 deceased persons, who were examined by autopsy at the Institute for Pathology of the University of Erlangen-Nuremberg. Taking into consideration topographic-anatomical criteria, samples were taken of each lung lobe and the hilar lymph nodes. The dried tissue was analyzed using by means of hydride atomic absorption spectrometry after wet-oxidative digestion. Normal values ranged for the arsenic concentrations from <1-74 ng/g dry weight and for the selenium concentrations from <3-574 ng/g dry weight. Arsenic was found to accumulate in the hilus tissue, whereas selenium did not. Considerable intraindividual and interindividual variation was found for both arsenic and selenium. There were no statistically significant differences regarding age, smoking habits, and lung diseases. Lung tissue samples from three deceased persons from Houston, Texas, contained lower arsenic concentrations and somewhat higher levels of selenium compared to the German autopsies; these levels were, however, still within the indicated normal ranges. The following conclusions can be drawn from the results available at present: Intraindividual and interindividual variation is high for the arsenic and selenium concentrations in human lung tissue, so that only relatively wide normal ranges can be given for the general population. Smoking habits, age, and lung diseases do not seem to affect the indicated normal ranges. Postmortem determination of arsenic and selenium concentrations in human lung tissue can provide important information on former occupational or environmental exposure.

Adult↗

Occupational exposure to polycyclic aromatic hydrocarbons in a fireproof stone producing plant: biological monitoring of 1-hydroxypyrene, 1-, 2-, 3- and 4-hydroxyphenanthrene, 3-hydroxybenz(a)anthracene and 3-hydroxybenzo(a)pyrene.

OBJECTIVES: Assessment of external and internal exposure to polycyclic aromatic hydrocarbons (PAH) in a fireproof stone producing plant. METHODS: Five personal and four stationary air measurements were performed to determine the concentrations of benz(a)anthracene, benzo(a)pyrene, benzo(b)fluoranthene, chrysene, dibenz(a,h)anthracene, fluoranthene, phenanthrene and pyrene, in air. To estimate internal exposure, we determined the urinary excretion of 1-hydroxypyrene, 1-, 2-, 3-, and 4-hydroxyphenanthrene, 3-hydroxybenz(a)anthracene and 3-hydroxybenzo(a)pyrene in 19 workers, using a sensitive and reliable high-performance liquid chromatographic method with fluorescence detection. RESULTS: During the production of fireproof stones, the German technical exposure limit (TRK) for benzo(a)pyrene of 2 microg/m3 was exceeded in two cases. The mean values of the sum of eight PAHs were 12.6 microg/m3 (stationary air measurement) and 22.2 microg/m3 (personal air measurement). Urinary 1-hydroxypyrene excretion predominated, with a median of 11.1 microg/g creatinine (creat.), followed by 3-hydroxyphenanthrene (median 2.2 microg/g creat.), 1-hydroxyphenanthrene (median 1.9 microg/g creat.) and 2-hydroxyphenanthrene (median 1.6 microg/g creat.). 4-Hydroxyphenanthrene (median 0.3 microg/g creat.) and 3-hydroxybenz(a)anthracene (median 0.17 microg/g creat.) were found in far lower concentrations, while 3-hydroxybenzo(a)pyrene was found only in very low concentrations (median 0.014 microg/g creat.). No correlations could be detected for a relationship between external and internal exposure. A significant correlation between urinary metabolite concentrations could be calculated only for 3-hydroxybenz(a)anthracene and 1-hydroxypyrene. CONCLUSIONS: In comparison with other industries, the internal PAH exposure at workplaces in a fireproof stone producing plant is high. This is probably caused by dermal PAH-absorption. Therefore, biological monitoring must be performed in the health surveillance of fireproof stone producing workers. The urinary PAH metabolites should be determined: 3-hydroxybenz(a)anthracene could probably be used as a biomarker representing the group of carcinogenic PAH.

Adult↗

An analysis of criteria for biological limit values developed in Germany and in the United States.

The biological tolerance values established by the German Research Foundation and the biological exposure indices developed by the American Conference of Governmental Hygienists represent two extensive lists of occupational exposure guidelines for use in biological monitoring. Although there is substantial agreement between the two organizations on most points, there are several important differences in the approaches taken in setting of the guideline values. Analysis of these distinctions serves to focus attention on the current issues impeding international agreement over occupational exposure guidelines. Among these issues are (1) the specification of the biological monitoring guidelines as ceiling or average values; (2) whether carcinogenic substances should be treated differently from agents with other toxic outcomes; (3) the method of accounting for variability among individual workers; and (4) the extent to which these guidelines should be extended to include genetic markers, indicators of susceptibility, or indicators of early biological response.

Germany↗

Efficacy of measures of hygiene in workers sensitised to acid anhydrides and the influence of selection bias on the results.

OBJECTIVES: Organic acid anhydrides are potential sensitisers and cause occupational airway diseases. In an intervention study the efficacy of measures of hygiene at the workplace and possible selection bias were investigated. METHODS: A first investigation with 110 workers exposed to hexahydrophthalic acid anhydride (HHPA) and methyltetrahydrophthalic acid anhydride (MTHPA) was carried out in July 1991. The results (skin prick test, specific serum IgE) showed that 20 people were sensitised, and in a challenge test the clinical relevance of the sensitisation was confirmed in six subjects. In December 1991, the hygiene conditions at the plant were improved. In November 1995 a second investigation of 84 people was performed (anamnesis, skin prick test, specific IgE, spirometry, and ambient and biological monitoring). The 27 people who had left the plant in the meantime were asked their reasons for leaving. RESULTS: The relative risk of people sensitised in 1991 of leaving the plant between 1991 and 1995 was 2.6 (95% confidence interval (95% CI) 1.4 to 4.9) compared with people without any sign of sensitisation. The percentage of people identified as sensitised in 1991, who were still working at the plant and came to the second investigation, was higher than for people without evidence of sensitisation (10/10 v 47/73; p < 0.05). In all the 10 sensitised people in 1991 the findings of the first investigation were confirmed in 1995. The rate of sensitisation in 1995 was 21%. None of the six people employed after 1991 showed evidence of sensitisation. Of the six people with clinically relevant sensitisation confirmed by a challenge test in 1991, five were still at their workplace. From 1991 they were only exposed to MTHPA at a reduced concentration (< 0.5-36 micrograms/m3 in 1995). All of them reported fewer symptoms than in 1991. No signs of bronchial obstruction were detected by spirometry at the workplace. CONCLUSIONS: In cross sectional studies there is a selection bias with a risk of underestimating the incidence of allergic diseases. The results further suggest that the improved hygiene conditions probably had a positive effect on the symptoms in sensitised people.

Adult↗

Lead induced anaemia due to traditional Indian medicine: a case report.

Lead intoxication in adults without occupational exposure is a rare and unexpected event. The case of a western European is reported who had severe anaemia after ingestion of several ayurvedic drugs, obtained during a trip to India. Laboratory findings showed high blood lead concentrations, an increased urinary lead concentration, and an increased urinary excretion of delta-aminolaevulinic acid. Also, slightly increased urinary concentrations of arsenic and silver were found. Physicians should be aware that with growing international travel and rising self medication with drugs from uncontrolled sources the risk of drug induced poisoning could increase in the future.

Adult↗

The mercury concentration in breast milk resulting from amalgam fillings and dietary habits.

Health risks from amalgam fillings are a subject of controversy. In Germany it is not advised to use amalgam fillings during breast feeding. Objectives of this study were to examine the concentration of mercury in human breast milk and the confounders which may modify the mercury levels. Women who gave birth between August 1995 and May 1996 in a district hospital were asked to participate in the study. The examination included a standardized anamnesis and an inspection of the teeth by an dentist. Blood and urine samples of 147 women and breast milk samples of 118 women were collected in the first week after birth. After 2 months of breast feeding a second breast milk sample was collected from 85 of women. Mercury was measured by cold-vapor atomic absorption spectrometry. The concentration of mercury in the breast milk collected immediately after birth showed a significant association with the number of amalgam fillings as well as with the frequency of meals. Urine mercury concentrations correlated with the number of amalgam fillings and amalgam surfaces. In the breast milk after 2 months of lactation, the concentrations were lower (mean: <0.25 microg/L; range <0.25-11.7 microg/L) compared with the first sample (mean: 0.90 microg/L; range <0.25-20. 3 microg/L) and were positively associated with the fish consumption but no longer with the number of the amalgam fillings. Accordingly, the additional exposure to mercury of breast-fed babies from maternal amalgam fillings is of minor importance compared to maternal fish consumption.

Adult↗