D. Weltle

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.

External and internal antimony exposure in starter battery production

In the production of lead batteries two antimony compounds occur: in the casting of grids antimony trioxide (Sb2O3), and in the formation of lead plates stibine (SbH3). Seven workers from the gridcasting area and 14 workers from the formation area were examined with regard to the antimony concentration in blood (Sb-B) and urine (Sb-U). Antimony air concentrations (Sb-A) were measured by means of personal air samplers. Urine samples were collected at the end of the working week, at the beginning (U1) and the end (U2) of the shift, and at the beginning of work following a weekend without Sb exposure (U3). At U2 among the casters the median Sb-A exposure was 4.5 (1.18–6.6) μg Sb/m3 and among the formation workers, 12.4 (0.6–41.5) μg Sb/m3. The exposure in both groups is more than 10 times lower than the present threshold limit values. The median Sb-B concentrations in the preshift samples was 2.6 (0.5–3.4) μg Sb/l for the casters and 10.1 (0.5–17.9) μg Sb/l for the formation workers. The average Sb-U values (U2) were 3.9 (2.8–5.6) μg Sb/g creatinine in the casting area and 15.2 (3.5 23.4) μg Sb/g creatinine in the forming area. Our investigation indicates that the two antimony compounds show virtually equal pulmonary absorption and renal elimination. The statistically significant correlations between Sb-A/Sb-B and Sb-A/Sb-U form the basis for proposals regarding appropriate biological exposure limits for occupational antimony exposure.

Determination of environmental caused chlorophenol levels in urine of the general population

SummaryA sensitive, specific and analytically reliable method for the determination of mono-, di-, tri- and tetrachlorophenols in human urine has been elaborated. After acid hydrolysis and a simultaneous steam distillation of the urine samples, spiked with an internal standard, the chromatographically concentrated chlorophenols have been derivatized with pentafluorobenzoylchloride and analyzed by capillary gas chromatography/mass spectrometry. The detection limits for the chlorophenols ranged from 0.2 to 2.5 μg/l. Using this method we were able to detect 4-MCP, 2,4-+2,5-DCP, 2,4,6-TCP, 2,4,5-TCP and 2,3,4,6-+2,3,5,6-TeCP in urine samples of a group of 258 men and women which had no known occupational contact to hazardous chemical substances. The 95 percentiles for the concentrations of these substances in the urine samples under investigation were 7.5 (4-MCP); 33.6(2,4-+2,5-DCP); 4,7 (2,4,6-TCP); 4,5 (2,4,5-TCP) and 22.2 (2,3,4,6-+2,3,5,6-TeCP) μg per liter. That means, that these chlorophenols are constituents of urine of the normal population in concentrations which in part are greater than that of pentachlorophenol (PCP).

Neurotoxicity of solvent mixtures in spray painters

SummaryA multidisciplinary cross-sectional study was carried out in 105 spray painters with long-term solvent exposure (10–44 years) and in 58 control subjects not exposed to solvents. By means of air monitoring the solvent concentrations in the ambient air during spray painting were determined using charcoal and silicagel tubes with pumps and passive samplers. In general, the air concentrations of the individual compounds did not exceed the current limit values (MAK values). Aromatic hydrocarbons like toluene, xylene, ethylbenzene, trimethylbenzene, aliphatic hydrocarbons (e.g., heptane) and acetates (ethylacetate, butylacetate) were determined to be important components of paint solvents. However, in unfavorable work conditions the “exposure index” could exceed the permissible limits two or three times. To assess the body solvent load at the time of examination, biological monitoring (BM) was performed. The main finding was that there was no evidence of neuro-toxicologically relevant solvent exposure. Only in the case of methyl hippuric acid in urine spot samples did the spray painters show a higher mean value (80 mg/l) than control subjects (below 20 mg/l), indicating recent xylene exposure. Elevated urinary chromium concentrations (maximum value 29 μg/l) were found in 28 spray painters as a result of using zinc chromate-containing wash primers without taking protective measures. To assess the degree of past solvent exposure a special questionnaire was used. This included variables like duration and amount of solvent exposure, the presence of a technical ventilation system, health complaints during painting, etc. Additionally, three “solvent exposure indices” (SEI) were calculated and used for evaluation of “dose-effect relationships.” In summary, the responses to the questionnaire did not show a characteristic pattern of symptoms. The frequency of symptoms is more likely to be determined by age than by chronic solvent exposure. Health complaints like increased tiredness, deterioration in short-term memory, and headache were equally frequent in spray painters and controls. In correlation analyses no hints of a dose-response relationship could be found.

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.

Neurotoxicity of solvent mixtures in spray painters. II: Neurologic, psychiatric, psychological, and neuroradiologic findings

SummaryA multidisciplinary cross-sectional study was performed to examine the chronic neurotoxicity of organic solvents. Participating in the study were 105 persons employed as spray painters and having long-term solvent exposure (10–44 years) and a control group consisting of 58 construction workers, electricians, and plumbers without occupational contact to solvents. Samples were matched for age, preexposure intelligence level, occupation, and socioeconomic status. After controlling for potentially non occupational confounding factors (neuropsychiatric diseases, metabolic disorders, high blood pressure, alcohol intake) 83 spray painters and 42 controls were entered finally into the study. The evaluation included work history, self-rating questionnaire, neurologic investigation, psychiatric analysis using the Present State Examination (PSE), psychological testing, and computerized axial tomography (CAT) of the brain. Physical and neurologic examinations demonstrated no case of overt disorders of the central or peripheral nervous system. An important result of the psychiatric analysis was that the syndromes “special features of depression” and “loss of interest and concentration” occurred significantly more frequently among spray painters than among controls. Further analyses demonstrated an association with chronic exposure over 30 years and repeated acute neurotoxic effects during solvent exposures. Neither psychological nor performance tests demonstrated any statistically significant differences in the performance sets after adjustment according to premorbid intelligence level; this finding supports the presumption of only a low grade of mental dysfunction. Correlation analyses indicated a relationship between subjective health complaints and long-term solvent exposure; however, the effect of age cannot be completely ruled out. Visual evaluation of CAT scans of the brain demonstrated significantly higher values for spray painters on the Cella media index, a measure of the inner liquor system of the brain. None of the other CAT parameters of inner or external brain atrophy showed significant differences. The rate of diffuse cerebral atrophy was not increased in spray painters. No statistical relationship between the solvent exposure index and CAT parameters was found by correlation analysis. In summary, the results do not support the hypothesis of an increased risk of solvent-induced encephalopathy among spray painters. It is not possible to establish a typical picture of central nervous system dysfunction due to chronic solvent exposure. Differences in the frequency of PSE symptoms “special features of depression” and “loss of interest and concentration” could be considered solvent related only if long-term (on average 30-year) exposure in combination with repeated acute neurotic effects had occurred. Cerebral atrophy beyond that of normal aging was not found in long-term exposed spray painters.

The influence of passive smoking on pulmonary function—A study of 1,351 office workers

Until now it has been difficult to ascertain how much passive inhalation of tobacco smoke affects bronchopulmonary function. To answer this question, an investigation involving 1,351 white collar workers was carried out. Information about active and passive tobacco smoke exposure was obtained by a standardized questionnaire. This made it possible to subdivide the overall group into five subgroups: Never smokers, passive smokers, ex-smokers, current smokers, and other smokers. Forced expiratory vital capacity (FVC) and maximal expiratory flow-volume (MEFV) curves were used for lung function analysis. From these curves FVC, forced mid-expiratory flow (FEF 25/75), forced end-expiratory flow (FEF 75/85), and maximal mid-expiratory flow (MEF 25/75) were determined and standardized for sex, age, height, and body weight. Passive smokers evaluated by this method showed essentially no decrease in parameters describing ventilatory function. It is concluded from the dose-and time-effect relationships obtained in active smokers between the lung function parameters and the duration of tobacco smoke exposure on the one hand and the daily consumption of cigarettes on the other that passive smoking in small doses may have no essential effect on pulmonary function.

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.

Exposure to soluble barium compounds: an interventional study in arc welders

SummarySoluble barium (Ba) compounds are well-known toxicants. Intoxications are mainly known in an acute form from casual or suicidal oral ingestion. No scientifically based data are available on possible health effects of inhalative exposure to soluble Ba salts at the workplace. Therefore, we investigated 18 welders in an interventional study over 1 week. They performed welding of Ba-containing stick electrodes and self-shielded flux cored wires under conditions similar to real working conditions. The welding fumes contained 31%–37% Ba, more than 90% of which was soluble in acids. Without appropriate preventive measures, a high rate of measurements exceeded the TLV values for total welding fumes of 5 mg/m3 and for soluble Ba of 0.5 mg/m3. The median fume concentrations were 13.2 mg/m3 in stick electrode welding and 12.3 mg/m3 in flux cored wire welding. The median Ba concentrations were 4.4 and 2.0 mg/m3 respectively. An integrated exhaust system built into the gun proved to be efficient in flux cored wire welding. The internal exposure to Ba reached median urine levels up to 101.7 μg/l (normal: below 20 μg/l) and median plasma concentrations of up to 24.7 μg/l (normal: below 8 μg/l). No health impact on the welders could be proven, but hypokalemia may have occurred as a result of the Ba exposure.

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.