Trends in occupational exposure to styrene in the European glass fibre-reinforced plastics industry.

AIM: This study presents temporal trends of styrene exposure for workers in the European glass fibre-reinforced plastics (GRP) industry during the period 1966-2002. METHODS: Data of personal styrene exposure measurements were retrieved from reports, databases and peer-reviewed papers. Only sources with descriptive statistics of personal measurements were accepted. The styrene exposure data cover personal air samples and biological monitoring data, that is, urinary styrene metabolites (mandelic acid and/or phenylglyoxylic acid) and styrene in blood. Means of series of measurements were categorized by year, country, production process, job and sampling strategy. Linear mixed models were used to identify temporal trends and factors affecting exposure levels. RESULTS: Personal exposure measurements were available from 60 reports providing data on 24145 1-8-h time-weighted average shift personal air samples. Available data of biological exposure indicators included measurements of mandelic acid in post-shift urine (6361 urine samples being analysed). Trend analyses of the available styrene exposure data showed that the average styrene concentration in the breathing zone of open-mould workers in the European GRP industry has decreased on average by 5.3% per year during the period 1966-1990 and by only 0.4% annually in the period after 1990. The highest exposures were measured in Southern Europe and the lowest exposures in Northern Europe with Central Europe in between. Biological indicators of styrene (mandelic acid in post-shift urine) showed a somewhat steeper decline (8.9%), most likely because urine samples were collected in companies that showed a stronger decrease of styrene exposure in air than GRP companies where no biological measurements were carried out.

Effects of dioxins and furans on liver enzymes, lipid parameters, and thyroid hormones in former thermal metal recycling workers.

A cross-sectional study was performed to examine the internal exposure of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDF) in former workers in a nonferrous metal recycling facility. Liver enzymes, lipid parameters, and thyroid hormones were measured to check possible biologic effects. Compared to background levels, the international toxicity equivalent levels of exposed workers were slightly elevated (median 42 ppt, range 13-281 ppt). The workers also had higher total PCDF concentrations (median 128 ppt, range 30-1138 ppt). Correlation analyses demonstrate significant associations with only one liver enzyme, alanine aminotransferase. There were no such associations with serum cholesterol levels or with serum thyroid hormones. Because of the cross-sectional design of the study, firm conclusions cannot be drawn. For further evaluation, a follow-up examination appears necessary.

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.

Neuropsychiatric symptoms in active construction painters with chronic solvent exposure.

A cross-sectional study was performed to assess whether chronic solvent exposure of painters is associated with increased neuropsychologic symptoms. 401 painters and 209 construction workers without solvent exposure, both groups with at least 10 years of employment, were subjected to extensive clinical examinations. Standardized questionnaires were used for medical and occupational history. Painters reported an excess of specific symptoms that could be assigned to mood and behaviour. The differences between specific and unspecific questionnaire outcomes as well as the positive correlation between chronic exposure index and symptom scores support the hypothesis of solvent induced effects. These symptoms are related to life-long solvent exposure rather than current exposure levels. At present the questions of time course and reversibility or irreversibility of symptoms cannot be answered. The predictive value of these symptoms for subsequent neuropsychiatric morbidity remains to be elucidated in a future follow-up study.

Chlorinated dibenzo-p-dioxins and dibenzofurans and the human immune system: 3. Plasma immunoglobulins and cytokines of workers with quantified moderately-increased body burdens.

The concentrations of immunoglobulins (IgA, IgD, IgG, IgM) and of several cytokines were measured in the plasma of volunteers with clearly, but moderately, increased body burdens of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDF), using monoclonal antibodies and an enzyme-linked immuno-sorbant assay. Two groups of workers with different body burdens of PCDD/PCDF were studied: (trial I) persons with mainly 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and (trial II) persons with mainly penta- and hexachlorinated dibenzofurans (P5CDF/H6CDF) in their blood fat. Including the reference group, 158 volunteers were investigated. A slight but statistically significant decrease was observed in the plasma concentration of IgG1 in persons exposed to TCDD, but not in persons exposed to P5CDF/H6CDF. When the data of both groups were pooled and a multi-regression analysis against international TCDD toxicity equivalencies (I-TEq, NATO/CCMS) was performed, taking several confounding factors into account, no influence of the dioxin exposure could be revealed. There were no changes in the plasma concentrations of the other immunoglobulins studied. In the same volunteers, no deviation from the reference range was found for the concentrations of the cytokines: IL-1alpha, IL-1beta, IL-6 and TNFalpha in blood plasma.

Occupational neurotoxicology of organic solvents and solvent mixtures.

The results of two field studies in painters and spray painters, the outcomes of examinations of workers with suspected work-related disease due to solvents, as well as data from an evaluation of an epidemiologic study in painters with confirmed occupational disease, are presented and discussed. The results of these studies and the experiences in occupational medicine in the Federal Republic of Germany do not support the assumption of high neurotoxic risks in solvent-exposed workers, which can be postulated from various epidemiologic studies from Scandinavian countries. Several factors may explain the different conclusions: 1) lower solvent exposures of German painters in the past decades; 2) false positive diagnosis of a toxic encephalopathy; 3) aetiological misclassification; 4) differences in legislation relevant for the acknowledgement of occupational diseases. In conclusion, there is a need for further well-designed epidemiologic studies in occupationally solvent-exposed workers. Suggestions regarding assessment of exposure and neurobehavioral tests are given.

Intervention study on acquired color vision deficiencies in styrene-exposed workers.

The main aim of the study was to examine the possible effects of occupational exposure to styrene on color vision function and the course after reduction of exposure. Color vision function was examined in 22 styrene-exposed laminators and 11 control subjects at a boat manufacturing plant. The Lanthony D-15 desaturated panel was used to test acquired dyschromatopsia. In all, six examinations were performed: Monday morning and Thursday afternoon of the same week, before and immediately after a vacation of 4 weeks (altogether, phase 1), and approximately 10 months later (phase 2), after the exposure level of styrene had been reduced. Styrene uptake was objectified by biological monitoring measuring the metabolites mandelic acid and phenylglyoxcylic acid in urine samples taken on Thursday afternoon. In both Thursday examinations, styrene-exposed workers had higher color confusion index (CCI) values compared with controls, which indicated quantitative color vision loss. After an exposure-free period of 4 weeks, a significant decrease of CCI values to normal range was found in laminators. Reexamination 10 months later showed also lower CCI values in exposed workers, indicating a dose-effect relationship. Abnormal CCI values occurred primarily in subjects with an excretion of approximately 500 to 600 mg mandelic acid plus phenylglyoxcylic acid per gram creatinine or more. We concluded that styrene-induced color vision dysfunction is reversible after an exposure-free interval of 4 weeks. The current Biological Tolerance Value of 600 mg mandelic acid plus phenylglyoxcylic acid per gram creatinine, as used in Germany, protects styrene-exposed workers from this subclinical effect.

[Magnetic resonance tomography of the brain in workers with chronic occupational manganese dioxide exposure]. / Magnetresonanztomographie des Gehirns bei Beschäftigten mit chronischer beruflicher Mangandioxide-Exposition.

AIM: Changes within the brain detected by MRI after chronic manganese poisoning raised the question whether morphological changes of the basal ganglia, particularly of the globus pallidus, could be detected after chronic occupational exposure to manganese dioxide. METHOD: In a cross-sectional study, healthy workers (48 male and 27 female) at a dry cell battery factory were examined. Actual internal exposure was quantified by the analysis of manganese in the blood using atomic absorption spectrometry. Chronic exposure was defined as a cumulative index (CBI) including duration of exposure, individual workplace factors, and previously measured concentrations of MnO2 in dust samples. A Philips Gyroscan T5-II (0.5 T) was used for the MRI of the brain. The following indicators were taken to ascertain possible manganese-induced changes; Pallidum-Index (PI), width of 3rd ventricle and cella media index in addition to clinical examinations. RESULTS: No cases of parkinsonism were detected in clinical examinations or by other means. The mean manganese concentration in blood was 12 micrograms/l (range: 3.9-23.3 micrograms/l). In comparison to the upper reference value of 10 micrograms/l, 42 workers (56%) had a higher body burden. A significant positive correlation between manganese levels in blood and the PI (indicated by T1-shortening) was observed as well as between the CBI and workplace-specific exposure. Brain atrophy was not detected in any of the observed cases. CONCLUSIONS: Long-term exposure to manganese dioxide dust correlates with the Pallidum-Index in MRI scans. Although the MRI findings have no current clinical relevance for individuals, further studies are necessary to evaluate specificity and potential prognostic value.

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.

Exposure study on chemosensory effects of epsilon-caprolactam in the low concentration range.

OBJECTIVE: Aim of the study was to examine possible chemosensory effects of epsilon-caprolactam in the low concentration range relevant to indoor environmental conditions. METHODS: Twenty healthy subjects (10 male, 10 female) aged from 21 to 38 years were exposed for 6 h, respectively, to 0, 0.15, 0.5 and 5 mg/m3 epsilon-caprolactam vapours in a randomized and double-blind method. As a measure of trigeminal stimulation of the eye, blink frequency was video-recorded four times per day and evaluated by using a new semi-automatic, computer-assisted method compared to baseline recording and manual counting. Digital slit lamp photographs were taken at the same time to examine conjunctival hyperaemia. A standardized ophthalmologic grading scale was used to measure redness of the eyes objectively. Active anterior rhinomanometry compared nasal resistance before and after exposure. Subjective ratings of discomfort and mental orientation were assessed using the German version of the Swedish Performance Evaluation system (SPES). As a measure of personality traits, positive and negative affectivity was determined (PANAS). RESULTS: Six hour exposures to epsilon-caprolactam revealed no significant dose-response relationship concerning blink frequency, nasal resistance and redness of the bulbar conjunctiva. Subjective ratings of discomfort (sum scores) significantly increased only at the highest concentration of 5 mg/m3. However, the increase in discomfort was only moderate, ranging between "not at all" and "somewhat". Significant increases of the subjective detection of malodour (subscore) already occurred at 0.15 mg/m3, showing no adaptation over time. Irritation of the eyes or upper airways was not reported. CONCLUSIONS: Exposure to epsilon-caprolactam vapour did not elicit any acute health effects in a concentration range up to 0.5 mg/m3. Even at the highest concentration of 5 mg/m3, we could only find a slight increase in subjective symptoms, mainly due to an unincisive increase of perception of malodour.

The ototoxicity of styrene: a review of occupational investigations.

OBJECTIVES: The objective of this study was to review critically a number of occupational investigations of the exposure and effect relation between inhaled styrene vapour and hearing loss. There is concern that workers' hearing may be impaired by exposure to styrene, as used in industries making plastics and fibreglass-reinforced products. METHODS: Seven occupational studies, each dealing with the ototoxicity of styrene, were examined. Factors assessed included the experimental design and number of subjects within exposure groups, measurement of the styrene-in-air concentration, confirmation of the styrene exposure by blood or urine analysis, determination of the hearing threshold levels for the exposure and control groups, and measurement of any occupational noise in the subjects' workplaces. Consideration was also given to statistical relations between high-frequency hearing loss and lifetime exposure indices for styrene and noise. RESULTS: The results are equivocal. Four investigations failed to find any effect of styrene on hearing thresholds. In contrast, other investigations claimed to have demonstrated styrene-induced hearing loss in industrial populations, with synergism between styrene and noise. However, these reports exhibited shortcomings of experimental design and data analysis. CONCLUSIONS: Considering the body of evidence as a whole, hearing deficits due to occupational exposure to styrene at low concentrations have not been demonstrated by scientifically reliable argument. There is some suggestion of an association between styrene exposure, occupational noise, and hearing dysfunction. Further studies in humans are necessary to clarify this question.

[New aspects for the evaluation of health effects caused by exposure against halogenated hydrocarbons at the working place. A literature review (author's transl)]. / Neue Aspekte zur Beurteilkung einer Einwirkung von Halogenkohlenwasserstoff-Lösemitteln am Arbeitsplatz Eine Literaturübersicht.

Halogenated hydrocarbons with over 150 toxicological relevant substances represent a considerable group among the numerous noxes at the working-places. Tri- and perchloroethylene are industrially widely used solvents for cleaning, degreasing and extraction. At the workplace the main amount of intake occurs via lung. Hepato-, nephro-, neuro- and cardiotoxicological effects are important solvent-induced health impairments. If the valid maximum concentrations in the work area (MAK-value) for the specific substance is not exceeded, altogether health hazards are impropable. With information of the "Unfallverhütungsbericht" only 23 cases of intoxications at the workplace were indemnified in 1977 for the first time. The causes for this low number are: installation of closed equipments, automation of the procedures and improvement of the personal hygiene. However praxis in occupational medicine shows, that there is a great number of persons in small firms that has contact with these solvents. For the surveillance and judgement of these solvent-exposed persons exist two methods. First the airborne concentration of the chemical compound can be determined at the working area. Second the solvent and/or its metabolites can be quantitative analyzed in the biological material. This method, called "biological Monitoring (BM)" has important advantages. BM should be prefered in cases of non-continuous, short-term exposures to concentrations of high degree. The judgement has to be done in relation to biological permissible limits (Biologische Arbeitsstoff-Toleranz-Werte, BAT, biological threshold limit values, BTLV's). Based on our longtime experience this specific and sensitive method should be used with priority.

[Carcinogenic industrial substances--a review of the present information]. / Krebserzeugende Arbeitsstoffe--eine Ubersicht zum aktuellen Kenntnisstand.

The potential carcinogenic risks of chemical substances at the workplace show increasing importance in occupational and environmental medicine, but the problems are also discussed controversially. Based on national and international literature estimations according the portions of occupational cancer are given. In accordance with former estimations from our institute, it is concluded, that 1-2% of all cancer deaths are caused by work and profession. A review of data from newer literature shows, that the numbers of chemicals with carcinogenic potency vary considerably. This is mainly due to the largely unknown mechanism of carcinogenesis, aspects of syncarcinogenesis and cocarcinogenesis as well as the different evaluation of mutagenicity-, short-term- and animal-tests on the one hand and of epidemiologic as well as casuistic studies on the other hands regarding carcinogenicity of chemicals for humans. In this context, the importance of epidemiologic studies for detecting unknown cancerogenic risks for humans is emphasized. In the field of occupational medicine it is relevant to differ between compensation and prevention. According to this aspects, for compensation of a malignant tumor as an occupational disease, more strict criterias must be fulfilled to objectify the carcinogenicity of a substance for humans than for preventive measures. On the basis of the monographs as well as reviews of the International Agency for Research on Cancer (IARC) the single substances, mixture of substances and industrial processes with proven or probably carcinogenicity for humans are given. In comparison to the monograph of Hueper from 1963 it is concluded, that until now no critical increase of carcinogenic substances at the workplace has occurred. For preventive efforts at the workplace, the medical examinations are important. These are based on various regulations by law or by German Employers Liability Insurance. In conclusion, recommendations and demands are given regarding prevention, evaluation and compensation of malignant diseases as well as detection of unknown carcinogenic risks for humans at the workplace.

[Severe lead polyneuropathy. Clinical course and prognosis--case report]. / Schwere Blei-Polyneuropathie. Verlauf und Prognose--Ein kasuistischer Beitrag.

The case of a 46 years old bricklayer is described, who developed a severe lead-polyneuropathy. The cause of the neurological disease was the dermal application of leadacetate -solutions because of chronic eczema of the hands over several years. There was a delayed manifestation of the peripheral neuropathy. Besides the typical pareses of the N. radialis also a slowing of nerve conduction velocities of sensible fibers were objectified by neurophysiological measurements. After decorporation -treatment with CaNa2EDTA there was a clear improvement ten months later. The anemia caused by lead had recovered completely. The aspects and course of the disease are discussed regarding results in literature. It is concluded, that during a severe lead polyneuropathy besides motor also sensory nerve fibers can be involved.

[Current aspects of hepatotoxicity in occupational medicine]. / Aktuelle arbeitsmedizinische Aspekte zur Hepatotoxizität von Arbeitsstoffen.

A large number of chemical agents encountered occupationally are known as potential hepatotoxins. The practical relevance of these results should be considered critically for the individual case and under usual work layout. In this paper the current state of knowledge for hepatotoxicity in occupational medicine is described. Different diagnostical methods and criteria for suspected chemical-induced liver injury are shown. The paper focuses on the potential hepatotoxic effects of chronic exposures to solvents, since these substances are used in a large variety of modern places of work. On the basis of field studies in occupationally exposed workers the potential hepatotoxical effects of mixtures of solvents are discussed. Recommendations for medical surveillance places of work are proposed.

Brain imaging techniques applied to chronically solvent-exposed workers: current results and clinical evaluation.

The application of neuroimaging techniques such as cerebral blood flow (CBF), single photon emission tomography (SPECT), X-ray computed tomography (CAT), and magnetic resonance imaging (MRI) on solvent-exposed workers and patients with toxic encephalopathy results in different and somewhat inconclusive pictures. The aim of this paper is to therefore critically review the current knowledge on chronic neurotoxicity of solvent exposures with respect to neuroimaging technique. CAT measurements of 86 house or construction painters, 82 spray painters, and 81 nonpainters showed no abnormal diffuse brain atrophy due to chronic solvent exposure after controlling for confounding variables such as age, alcohol consumption, or former disease. Correlation analyses did not show any consistent, biologically plausible exposure-effect relationship. Neuropsychologic test results did not correlate significantly with CAT parameters, whereas a strong age dependency exists. It is concluded that long-term exposure to solvent concentrations not exceeding permissible occupational limit values does not cause increased brain atrophy.

Survey of solvent related chronic encephalopathy as an occupational disease in European countries.

OBJECTIVES: To obtain information about solvent related chronic encephalopathy (SRCE) in the countries of the European Union (EU). METHOD: A survey was conducted in 1998 and 1999 among medical experts, authorities for health and safety, and social security institutions. RESULTS: SRCE is an acknowledged occupational disease in most of the participating countries. However, the numbers of compensated cases differ considerably. This is mainly a consequence of national social law rather than of differences in the criteria of diagnosis. In countries with relatively high reported incidences-such as Denmark, Finland, Norway, and Sweden-the number of acknowledged cases has declined over the past 5-10 years, although the most important criteria of diagnosis and causality, according to expert opinion, equivalent diagnostic procedures, and measures for prevention within the EU are not comparable. CONCLUSIONS: There is a need for common guidelines for early diagnosis and the evaluation of causality. Actual figures of SRCE are not suitable to estimate prospective numbers of cases. For this reason a multicentre study in EU states is necessary after a consensus of diagnostic procedure. It is likely that the number of cases will decrease as a result of changes in legislation and preventive measures-such as substitution or reduction of solvents in the products, improvement of technical equipment, and regular health surveillance. Future research activities should focus on follow up studies of prognosis, randomised clinical trials of treatment, investigation of neurotoxic mechanisms, and of the interaction of solvent mixtures.