Helmut Valentin

Cross-sectional epidemiological study on neurotoxicity of solvents in paints and lacquers

SummaryIn a multi-disciplinary retrospective study we examined 105 house painters employed for at least ten years (median 27 years, range 10–36 years). Fifty-three workers from various professions (non-painters), who were matched with regard to age, occupational training and socio-economic status served as the control group. In both groups no cases of a clinically manifest polyneuropathy or encephalopathy were found. The neurophysiological examinations (EEG and NCV-measurement) showed no differences in painters and controls that would indicate adverse effects of organic solvents. There were no cases with neuroradiological findings of a diffuse cerebral atrophy. Furthermore the evaluation of certain brain structures (ventricular diameter, cella media index) of the CAT films did not reveal any significant differences. In the neurobehavioral tests significant differences in the results were only found in the subtests “change of personality” and “short term memory capacity” in a subgroup of painters with repeated prenarcotic symptoms at the workplace. Ambient air monitoring measurements at 30 representative work-places showed that the concentrations of the main components of the solvent-mixtures were well below the MAK-values. The results of the “Erlangen Painter Study” does not confirm former epidemiologic findings from other countries, mainly Denmark. However, there are some aspects, such as minor solvent exposure in German house painters, insufficient diagnostic and etiological procedures as well as mis-classifications which may explain the different experiences.

Investigations on neurotoxicity of chemical substances at the workplace

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) δ-Aminolevulinic acid dehydratase (ALA-D) and (4) δ-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 μg/dl (54 μg/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 μg//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 μg/dl. From our study it is concluded that chronic lead exposure resulting in blood-lead levels of below 70 μg/dl is no occupational risk causing a functionally significant slowing of nerve conduction velocities.SummaryA longitudinal study was performed on eleven persons, who had been chronically exposed to mercury (Hg) (3 to 31 years, median 5 years) in 1977, 1980 resp., and 1982. During their work in a chemical plant they had had contact to elemental Hg and various inorganic as well as organic mercury compounds. The main purpose of the investigation was the evaluation of possible adverse effects to the nervous system caused by mercury. The internal Hg-exposure was measured by mercury analysis in blood (Hg-B) and in urine (Hg-U). Furthermore ldtime-weighted average” levels were calculated on the basis of former Hg-determinations from 1974 to 1982. For Hg-B these values ranged between 26 and 104 μg/dl (median 42 μg/l) and for Hg-U between 73 and 434 μg/g creatinine (median 233 μg/g creatinine) (upper normal levels: Hg-B: 5 μg/l; Hg-U: 5 μg/g creatinine). The determination of the peripheral nerve conduction velocities (NLG) of motor and sensory fibers as well as the registration of somatosensory-evoked potentials (SEP) revealed no pathological results, except one borderline case. The NLG- and SEP-values did not significantly differ from those of non exposed persons or from those of former NLG-determinations. No correlations were found between indicators of Hg-exposure and neurophysiological parameters regarding dose-effect-relationship. Statistical differences resulted in the time-dependent test of the psychological test battery performed in comparison to age-matched control persons of equal socio-economous status. In additional, significant relationships were calculated between Hg-exposure and these tests. Considering the inter- and intraindividual variations of the psychological test results, there were no substantial alterations in the total findings over the observed period except for one case. Workers with Hg-exposure below the current BAT-values (Hg-B 50 μg/l, Hg-U 200 μg/l) showed no pathological findings in the neurological, neurophysiological and neuropsychological examinations.ZusammenfassungIm Rahmen einer Längsschnittstudie haben wir 1977 bzw. 1980 and 1982 elf Beschaftigte einer chemischen Fabrik mit langjähriger, beruflicher Quecksilber(Hg)-Exposition (3 bis 31 Jahre, Median 5 Jahre) hinsichtlich neurologischer Störungen untersucht. Beruflich bestand vor allem Umgang mit metallischem Quecksilber, aber auch mit verschiedenen anorganischen sowie organischen Hg-Verbindungen. Zur Objektivierung der Schwermetall-Belastungen wurde der Quecksilbergehalt in Blutund Urinproben analysiert. Zur Berechnung „zeitgewichteter” Werte standen die Hg-Befunde der Jahre 1974 bis 1982 zur Verfügung. Insgesamt ergaben sich hiernach deutliche Hg-Belastungen: Hg-B 26 bis 104 μg/l (Median 42 μg/1), Hg-U: 73 bis 434 μg/g Kreatinin (Median 233 μg/g Kreatinin). Die geprüften Nervenleitgeschwindigkeiten (NLG) des N. ulnaris und N. medianus sowie die somatosensorisch evozierten Potentiate (SEP) des N. medianus zeigten mit Ausnahme eines grenzwertigen Befundes keine pathologischen Meßwerte. Im Vergleich zu Kontrollpersonen and gegenüber den Vorbefunden ergaben sich keine signifikanten Unterschiede. Ferner waren auf statistischer Basis keine Hinweise auf das Vorliegen von “Dosis-Wirkungs-Beziehungen” festzustellen. Die testpsychologischen Untersuchungen erbrachten gegenüber Kontrollpersonen gleichen Alters und mit ähnlichem sozioökonomischen Status statistisch gesicherte Unterschiede in den zeitabhängigen Tests, die fur eine psychomotorische Verlangsamung sprechen. Zudem resultierten korrelationsanalytisch Zusammenhänge zwischen dem Ausmaß der Hg-Belastungen and diesen Testergebnissen. Bei der Beurteilung der testpsychologischen Einzelbefunde im Längsschnitt sind unter Beriicksichtigung der inter- und intraindividuellen Streubreiten keine wesentlichen Anderungen im Gesamtergebnis festzustellen, wenn man von einer Ausnahme absieht. Beschaftigte mit BAT-Wert-Unterschreitungen (Hg-B 50 μg/1, Hg-U 200 μg/l) zeigten insgesamt keine pathologischen Befundmuster bei den neurologischen, neurophysiologischen und neuropsychologischen Untersuchungen.

Investigations of thallium-exposed workers in cement factories

SummaryThallium and its compounds have a high toxic potency. For the production of particularly resistant sorts of cement, additives containing thallium, among other things, are employed. In conformity with our present toxicological knowledge, the determination of the concentration of thallium in the urine must be considered a suitable parameter for the assessment of the presence of thallium in the body. Occupational-medical preventive examinations were carried out in a total of 128 male employees from all areas of production in three cement factories. An exposure of these employees to thallium was objectified by analyses of the roasted pyrites employed and the dust from the electric filter. The study included the questioning of the employees with respect to their previous history of health, and also a physical examination aimed at detecting clinical symptoms of a possible effect of thallium. The analysis of thallium was carried out in samples of “spontaneous” urine. The analytical method employed was flameless atomic absorption spectroscopy (carbon-rod atomizer).In part, the group of persons investigated revealed excretions of thallium slightly or moderately above the normal level (range: < 0.3-6.3 μg/g creatinine). As the upper normal limit of thallium excretion, we computed a value of 1.1 μg/g creatinine.In no case, however, did the case history data or the findings of the physical examination reveal any indication of the symptoms characteristic of thallium poisoning.

Untersuchungen zur Neurotoxizität von Arbeitsstoffen

SummaryWe studied 31 employees (26 men, five women) from three firms, between the ages of 16 and 56 years, who had been exposed to trichloroethylene (TRI) from 1 month to 35 years, mean 7 years.To objectify the actual solvent-exposure we performed “biological monitoring” and determined TRI- and the metabolites trichloroethanol (TCE) and trichloroacetic acid (TCA) in blood- and/or urine-samples. The following concentrations were found in the urine-samples: TCE 19.0-357.0 mg/g creatinine, median 90.0; TCA 2.0-201.0 mg/g creatinine, median 48.0; TTC (TCE + TCA) 31.0-416.0 mg/g creatinine, median 112.5.Additionally three results of former urine-analyses in the period 1978–1980 from 10 workers were obtained to calculate “time-weighted-average (TWA)”-levels (TWA-TTC in urine: 53–640 mg/g creatinine).Nerve conduction velocity (NLG)-measurements of motor and/or sensory fibers of the ulnar and median nerve were performed to test peripheral nerve function. Seven employees were excluded. They had possible competitive risks of peripheral neuropathy, or were of less than 10 months exposed.For controls we examined 24 healthy persons of identical sex and age (matched pairs), but without known risks of a peripheral neuropathy.In comparing the nerve conduction velocities there were no significant differences between TRI-exposed and non-exposed persons.Correlation analyses and the individual assessment of the data concerning exposure/dose and effect revealed no signs of a “dose-effect-relationship”.ZusammenfassungWir untersuchten 31 Beschäftigte aus drei Betrieben (26 Männer, 5 Frauen) im Alter von 16 his 56 Jahre, die beruflich zwischen 1 Monat und 35 Jahren, im Mittel 7 Jahre, Trichloräthylen (TRI)-exponiert waren. Die Objektivierung der aktuellen Lösemittel-Belastung erfolgte im Rahmen des „Biological Monitoring” anhand der TRI-bzw. Metaboliten- (Trichloräthanol (TCE), Trichloressigsäure (TCA))-Spiegel in Blut und/oder Urinproben. Im Urin wurden folgende Konzentrationen gemessen: TCE 19,0–357,0 mg/g Kreatinin, Median 90,0, TCA 2,0–201,0 mg/g Kreatinin, Median 48,0, und TTC (TCE + TCA) 31,0–416,0 mg/g Kreatinin, Median 112,5.Bei zehn Beschäftigten standen zusätzlich drei Ergebnisse von Urinuntersuchungen der Jahre 1978 bis 1980 zur Verfügung, die zur Berechnung „zeitgewichteter (TWA)”-Belastungswerte herangezogen wurden (TWA-TTC im Urin: 53–640 mg/g Kreatinin).Zur Prüfung der peripheren Nervenfunktion bestimmten wir elektromyographisch die motorische und sensorische Nervenleitgeschwindigkeit (NLG) des N. ulnaris und N. medianus. Sieben Beschäftigte blieben wegen möglicher konkurrierender außerberuflicher Risiken einer peripheren Neuropathie oder einer Expositionsdauer von weniger als 10 Monaten von der neurophysiologischen Beurteilung ausgeschlossen. Als Kontrollen standen für das verbleibende TRI-exponierte Kollektiv 24 Personen gleichen Geschlechts und Alters (matched pairs) zur Verfügung, bei denen anamnestisch keine Risiken einer peripheren Neuropathie vorlagen.Beim Vergleich der mittleren Nervenleitgeschwindigkeiten resultierten keine statistisch gesicherten Unterschiede. Korrelationsanalytisch und bei der Beurteilung der individuellen Belastungs- und Beanspruchungsparameter ergaben sich keine konkreten Hinweise für das Vorliegen einer Dosis-Wirkungs-Beziehung.

External quality control programmes in the toxicological analysis of biological material in the field of occupational medicine — experiences from three round-robins in the Federal Republic of Germany

SummaryDue to the technical rule for dangerous agents (TRgA 410) “statistical quality control” from the German Society of Occupational Medicine three intercomparison programmes on toxicological analysis in blood and urine were organized. In 1982 35 laboratories participated in the analysis of twelve parameters in two urine samples. The round-robin 1983 considered blood analysis (3 metals) as well as determinations in urine samples (15 components) by 51 laboratories. In the third intercomparison programme in 1985 determinations of 4 metals in blood samples as well as 10 inorganic and 8 organic substances in urine specimens were carried out (75 laboratories). Two samples with two concentration adjustments were used. A successful participation was certified, if both results of one parameter are in the tolerance range (assigned value±3s). For the round robin 1982 the percental rate of accurate results was 42%, in 1983 64%. In 1985 62% of the results were located within the 3s-range.

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.

Health hazards from fine asbestos dusts

SummaryFor the period from 1973 to the end of 1986, 70656 data sets on occupational preventive medical examinations in employees exposed occupationally to asbestos dust (G 1.2) were made available to us by the Central Registry for Employees Exposed to Asbestos Dust (ZAS). On the basis of this data, an analysis of asbestosis risk was to be made in relation to specific areas of work, taking into consideration the beginning and duration of exposure. Proceedings for declaratory appraisal in accordance with occupational disease no. 4103 were instituted in 1760 cases in the report period. In accordance with the character of the available data, the X-ray findings in the lungs were available from the persons investigated as parameters of possible asbestosis risk on the basis of coding consistent with the International Pneumoconiosis Classification (ILO U/C 1971 and/or ILO 1980 West Germany). The major result of the statistical analyses on the mainframe macrocomputer of the University of Erlangen-Nuremberg was that the relatively highest risk of asbestosis was present in persons whose exposure began before 1955. On the other hand, with increasing duration of exposure, an unequivocal rise of the asbestosis risk could not be detected on the basis of the overall population. In relation to the individual fields of work, the relatively highest risk of asbestosis was shown to be in the asbestos textile and paper industry, as well as in the asbestos cement industry. No detectable risk of asbestosis was present in the fields of mining, traffic and health service and for women in the industrial sectors of building material, gas and water, catering trade, building, commerce as well as banking and insurance. Accordingly, it can be assumed that certain fields of work are or were exposed to such a small extent or not at all that a risk of asbestosis which is relevant in terms of occupational medicine is no longer to be assumed or was not to be assumed. This applies above all to certain work in the frictional coating (brake lining) and asbestos paper industry. Furthermore, the analysis of the data material did not provide any unequivocal indications that inhalative smoking habits have a negative effect on the risk of asbestosis. In prinicple, it can be stated that the occupational preventive medical investigations according to G 1.2 are effective. However, irrespective of this, the analysis has shown that a regular exchange of experience on the part of authorized physicians should be institutionalized and the second X-ray appraisal should be retained in order to ensure a high measure of reliability and diagnostic relevance of the available investigation data. Besides this, all expert appraisal results from patients with recognized occupational diseases according to subparagraphs, 4103, 4104 and 4105 BeKV (no. 4103: asbestosis, no. 4104: asbestosis in connection with lung cancer, no. 4105: mesothelioma of the pleura or peritoneum) should be centrally registered both in persons exposed to asbestos dust and in persons with asbestosis and accompanying malignant diseases, would then be possible.

Zur Frage von Bronchialspasmen bei Silikose, Emphysem und chronischer Bronchitis und deren Beeinflussung durch Aerosolinhalation

ZusammenfassungDas Vorkommen von generalisierten Bronchialspasmen mit funktionsmindernder Rückwirkung auf den Atemtrakt bei chronischen Lungenkrankheiten, insbesondere bei der Silikose, wird einer kritischen Betrachtung unterzogen.Mit Hilfe des Ergospirographen nach Knipping und eines im Nebenschluß angebrachten Aerosolgerätes wurde die fortlaufende, un-unterbrochene Registrierung der Ruheatmung, der Atemmittellage und der Lungenvolumina vor, während und nach der Aerosol-Inhalation mit bronchoaktiven Pharmaka ermöglicht. Bei verschiedenen chronischen Lungenkrankheiten (Emphysem, Bronchitis, Silikose verschiedener Schweregrade) war in insgesamt 56 Fällen unter einer kurzzeitigen Inhalation von Bronchovydrin-Aerosol eine meßbare Änderung respiratorischer Größen und somit ein generalisierter Bronchospasmus nicht zu objektivieren. Daß aber spastische Bronchialreaktionen durch die von uns angewandte Bronchovydrin-Medikation gelöst und aufgezeigt werden können, ließ sich durch die eindrucksvolle Registrierung eines Anfalles von Asthma bronchiale nachweisen. Die Indikation zur Aerosol-Therapie mit bronchodilatatorischen Mitteln läßt sich daher nur von Fall zu Fall entscheiden.Einzelbeobachtungen mit Inhalationen eines bronchokonstriktorischen Aerosols (1%iges Acetylcholinchlorid) zeigten bei den oben angeführten Krankheitszuständen keinen signifikanten Effekt.

Hat die Inhalation von Feinstäuben einen unmittelbaren Einfluß auf die Atmung und den Gasstoffwechsel

ZusammenfassungZur fortlaufenden Registrierung der Atmung, der Thoraxruhelage und der Sauerstoffaufnahme in Ruhe und unter Arbeit im zeitweiligen Staubmilieu haben wir den ergospirographischen Apparat nach Knipping durch einen im Nebenschluß angebrachten Wrightschen Staubentwickler erweitert. Unter kurzzeitiger Einwirkung von hochkonzentrierten Feinstäuben aus Aluminium (durchschnittliche lichtmikroskopische Teilchengröße 2 μ) und Ruß (durchschnittlicher Teilchendurchmesser 0,08 μ) bei Teilchenzahlen bis zu 45400/cm3 in der Atemluft ließen sich in 29 Versuchen an 17 Personen keinerlei Änderungen der respiratorischen Funktion im Vergleich zu der Ausgangslage unter staubfreier Atemluft erkennen. Atemfrequenz, Atemvolumen, Atemminutenvolumen, Sauerstoffaufnahme je Minute, Atemmittellage und — soweit untersucht — auch Vitalkapazität, Atemstoß und Atemgrenzwert blieben praktisch konstant. Infolgedessen wurde auf die Applikation bronchodilatatorischer Aerosole verzichtet.

Investigations on neurotoxicity of chemical substances at the workplace@@@Untersuchungen zur neurotoxizitt von arbeitsstoffen: IV. Determination of the Motor and Sensory Nerve Conduction Velocity in Persons Occupationally Exposed to a Mixture of Organic Solvents@@@IV. Messung der motorischen und sensorischen Nervenleitgeschwindigkeit bei beruflicher Exposition gegenber Lsemittelgemischen

SummaryA cross-sectional study was performed on 112 workers with longterm exposure (mean 5 years) to a mixture of organic solvents (aliphatic and aromatic hydrocarbons, halogenated hydrocarbons). The purpose of the study was to examine whether this exposure had caused impairment of the peripheral nervous function. Forty-six workers with non-occupational risks of peripheral neuropathy (previous diseases, alcohol abuse, medication) were excluded. As a basis for the evaluation of solvent exposure, we carried out “environmental and biological monitoring” for some solvents. In no case did a hint of a manifest disorder of the nervous system exist. By comparison with age-matched controls, the mean sensory conduction velocity (NCV) of the N. ulnaris of the exposed persons was significantly reduced by 1.5 m/s. The maximal motor NCV of the N. ulnaris and the sensory NCV of the N. medianus did not differ significantly. The differentiation of the workers relating to short-(7–24 months), middle-(25–60 months)- and long-(more than 60 months) term exposure showed that the sensory NCV of the N. ulnaris was slowed only for persons with middle- and long-term histories of solvent exposure. Assessing the individual neurophysiological status the frequency of pathological NCV improved from 12 to 36% in relation to increasing time of exposure. Overall 15 of 66 workers (23%) had abnormal NCVs. The findings are discussed according to data given in literature.