Prevalence of Back Pain among German Ophthalmologists.

INTRODUCTION: The aim of this study was to evaluate the prevalence of back pain among German ophthalmologists, to investigate the relationship towards age, gender, various profession-related factors, to correlate localization of pain to subspecialties, and to explore individual therapeutic and coping strategies. METHODS: In this prospective, cross-sectional survey, a 9-item questionnaire was sent via mail to all members of the German professional association of ophthalmologists "Berufsverband der Augenärzte Deutschlands e.V. (BVA)." Responses were analyzed according to a pre-specified analysis plan. RESULTS: From a total of 5,954 members contacted, 1,861 copies (31%) were received back, of which 1,807 (30%) were suitable for analysis. 913 (51%) participants were female and 876 (48%) were male, with a median age of 50 years (interquartile range: 44; 57). 1,464 ophthalmologists (81%) reported current back problems, considerably more than had been reported in the general population or in other medical specialties. Older age, female gender, and higher number of professional years appeared to be risk factors for developing back pain. Overall, neck pain was the leading symptom in 951 attendees (65%) but differed between ophthalmologists who primarily performed conservative treatment (cervical spine) and those who performed surgery (mainly lumbar spine). 1,037 participants (71%) link their complaints to their occupational activity. Exercising and back training were reported as common strategies for prevention and coping with the problem. Recommendations for improvement were mainly ergonomic optimization of the working place. CONCLUSIONS: The prevalence of back pain complaints in German ophthalmologists is high. Neck pain (65%) was the leading localization, followed by low back pain (53%) and shoulder (38%) problems, which might emphasize a special back pain complaint profile in ophthalmologists. Low back pain seems to be more common in ophthalmologists with surgical specialization than in those with mainly medical tasks. The high prevalence of back pain in ophthalmologists should be communicated with employers, the industry, and professional societies to develop and implement a strategy to prevent occupational-related musculoskeletal disorders and preserve the ability to work and the quality of life.

Combusting vegetable oils in diesel engines: the impact of unsaturated fatty acids on particle emissions and mutagenic effects of the exhaust.

High particle emissions and strong mutagenic effects were observed after combustion of vegetable oil in diesel engines. This study tested the hypothesis that these results are affected by the amount of unsaturated or polyunsaturated fatty acids of vegetable oils. Four different vegetable oils (coconut oil, CO; linseed oil, LO; palm tree oil, PO; and rapeseed oil, RO) and common diesel fuel (DF) were combusted in a heavy-duty diesel engine. The exhausts were investigated for particle emissions and mutagenic effects in direct comparison with emissions of DF. The engine was operated using the European Stationary Cycle. Particle masses were measured gravimetrically while mutagenicity was determined using the bacterial reverse mutation assay with tester strains TA98 and TA100. Combustion of LO caused the largest amount of total particulate matter (TPM). In comparison with DF, it particularly raised the soluble organic fraction (SOF). RO presented second highest TPM and SOF, followed by CO and PO, which were scarcely above DF. RO revealed the highest number of mutations of the vegetable oils closely followed by LO. PO was less mutagenic, but still induced stronger effects than DF. While TPM and SOF were strongly correlated with the content of polyunsaturated fatty acids in the vegetable oils, mutagenicity had a significant correlation with the amount of total unsaturated fatty acids. This study supports the hypothesis that numbers of double bounds in unsaturated fatty acids of vegetable oils combusted in diesel engines influence the amount of emitted particles and the mutagenicity of the exhaust. Further investigations have to elucidate the causal relationship.

Work-related outcomes in randomised placebo-controlled pain trials: a systematic review and meta-analysis.

BACKGROUND: Chronic painful conditions have an important influence on the ability to work. Work-related outcomes, however, are not commonly reported in publications on trials investigating the treatment of chronic painful conditions. We aim to provide an overview of the reporting of work-related outcomes in such trials and investigate the relationship between work-related outcomes and pain outcomes. METHODS: We conducted a systematic literature search in PubMed with the aim of identifying randomised placebo-controlled clinical trials investigating treatments for chronic painful conditions or rheumatic diseases that also reported on work-related outcomes. Methodological study quality was assessed with the Oxford Quality Scale (OQS). Meta-analyses were conducted for the outcomes of interference with work and number of patients with at least 30% reduction in pain intensity (30% pain responders). The correlation between work-related and pain outcomes was investigated with regression analyses. RESULTS: We included 31 publications reporting on 27 datasets from randomised placebo-controlled trials (with a total of 11,434 study participants) conducted in chronic painful or rheumatic diseases and reporting on work-related outcomes. These 31 publications make up only about 0.2% of all publications on randomised placebo-controlled trials in such conditions. The methodological quality of the included studies was high; only nine studies scored less than four (out of a maximum five) points on the OQS. Sixteen different work-related outcomes were reported on in the studies. Of 25 studies testing for the statistical significance of changes in work-related outcomes over the course of the trials, 14 (56%) reported a significant improvement; the others reported non-significant changes. Eight studies reported data on both interference with work and 30% pain responders: meta-analyses demonstrated similar, statistically significant improvements in both these outcomes with active therapy compared to placebo and regression analysis showed that these outcomes were correlated. CONCLUSIONS: Despite the importance of pain as a reason for decreased ability to work, work-related outcomes are reported in substantially less than 1% of publications on placebo-controlled trials in chronic painful and rheumatic diseases. Work-related outcomes and pain responder outcomes are closely related.

Systematic review and quantification of respiratory cancer risk for occupational exposure to hexavalent chromium.

AIM: To investigate the exposure-risk relationship for occupational chromium (VI) exposure and lung cancer in order to establish exposure limits. METHODS: We systematically searched for studies reporting on occupational Cr(VI) exposure and cancers of the respiratory tract. To be included, studies needed to provide data for more than one level of occupational Cr(VI) exposure, adequately consider the confounder smoking and be of adequate methodological quality. Because direct genotoxicity was considered the predominant mechanism of carcinogenesis of Cr(VI), linear models were applied in order to fit risk data. Relative risks were calculated based on these linear regression models and then used to estimate excess absolute risks. RESULTS: Five studies of two cohorts of chromium production workers in Baltimore, Maryland, and Painesville, Ohio, were included. Based on different estimates for the exposure effect, the absolute excess risk was found to be "acceptable" (less than 4 per 10,000 according to the German Committee on Hazardous Substances, "AGS") at a Cr(VI) concentration of 0.1 µg/m(3), and became "intolerable" (more than 4 per 1,000) beyond a Cr(VI) concentration of 1 µg/m(3). CONCLUSION: Occupational exposure limits for Cr(VI) based on excess absolute risks can be derived from published data identified by a systematic literature review.

Mutagenicity of diesel engine exhaust is eliminated in the gas phase by an oxidation catalyst but only slightly reduced in the particle phase.

Concerns about adverse health effects of diesel engine emissions prompted strong efforts to minimize this hazard, including exhaust treatment by diesel oxidation catalysts (DOC). The effectiveness of such measures is usually assessed by the analysis of the legally regulated exhaust components. In recent years additional analytical and toxicological tests were included in the test panel with the aim to fill possible analytical gaps, for example, mutagenic potency of polycyclic aromatic hydrocarbons (PAH) and their nitrated derivatives (nPAH). This investigation focuses on the effect of a DOC on health hazards from combustion of four different fuels: rapeseed methyl ester (RME), common mineral diesel fuel (DF), SHELL V-Power Diesel (V-Power), and ARAL Ultimate Diesel containing 5% RME (B5ULT). We applied the European Stationary Cycle (ESC) to a 6.4 L turbo-charged heavy load engine fulfilling the EURO III standard. The engine was operated with and without DOC. Besides regulated emissions we measured particle size and number distributions, determined the soluble and solid fractions of the particles and characterized the bacterial mutagenicity in the gas phase and the particles of the exhaust. The effectiveness of the DOC differed strongly in regard to the different exhaust constituents: Total hydrocarbons were reduced up to 90% and carbon monoxide up to 98%, whereas nitrogen oxides (NO(X)) remained almost unaffected. Total particle mass (TPM) was reduced by 50% with DOC in common petrol diesel fuel and by 30% in the other fuels. This effect was mainly due to a reduction of the soluble organic particle fraction. The DOC caused an increase of the water-soluble fraction in the exhaust of RME, V-Power, and B5ULT, as well as a pronounced increase of nitrate in all exhausts. A high proportion of ultrafine particles (10-30 nm) in RME exhaust could be ascribed to vaporizable particles. Mutagenicity of the exhaust was low compared to previous investigations. The DOC reduced mutagenic effects most effectively in the gas phase. Mutagenicity of particle extracts was less efficiently diminished. No significant differences of mutagenic effects were observed among the tested fuels. In conclusion, the benefits of the DOC concern regulated emissions except NO(X) as well as nonregulated emissions such as the mutagenicity of the exhaust. The reduction of mutagenicity was particularly observed in the condensates of the gas phase. This is probably due to better accessibility of gaseous mutagenic compounds during the passage of the DOC in contrast to the particle-bound mutagens. Concerning the particulate emissions DOC especially decreased ultrafine particles.

Interference with work in fibromyalgia: effect of treatment with pregabalin and relation to pain response.

BACKGROUND: Clinical trials in chronic pain often collect information about interference with work as answers to component questions of commonly used questionnaires but these data are not normally analysed separately. METHODS: We performed a meta-analysis of individual patient data from four large trials of pregabalin for fibromyalgia lasting 8-14 weeks. We analysed data on interference with work, inferred from answers to component questions of Fibromyalgia Impact Questionnaire (FIQ), Short Form 36 Health Survey, Sheehan Disability Scale, and Multidimensional Assessment of Fatigue, including "How many days in the past week did you miss work, including housework, because of fibromyalgia?" from FIQ. Analyses were performed according to randomised treatment group (pregabalin 150-600 mg daily or placebo), pain improvement (0-10 numerical pain rating scale scores at trial beginning vs. end), and end of trial pain state (100 mm visual analogue pain scale [VAS]). RESULTS: Comparing treatment group average outcomes revealed modest improvement over the duration of the trials, more so with active treatment than with placebo. For the 'work missed' question from FIQ the change for patients on placebo was from 2.2 (standard deviation [SD] 2.3) days of work lost per week at trial beginning to 1.9 (SD 2.1) days lost at trial end (p < 0.01). For patients on 600 mg pregabalin the change was from 2.1 (SD 2.2) days to 1.6 (SD 2.0) days (p < 0.001). However, the change in days of work lost was substantial in patients with a good pain response: from 2.0 (SD 2.2) days to 0.97 (SD 1.6) days (p < 0.0001) for those experiencing >/= 50% pain improvement and from 1.9 (SD 2.2) days to 0.73 (SD 1.4) days (p < 0.0001) for those achieving a low level of pain at trial end (<30 mm on the VAS). Patients achieving both >/= 50% pain improvement and a pain score <30 mm on the VAS had the largest improvement, from 2.0 (SD 2.2) days to 0.60 (SD 1.3) days (p < 0.0001). Analysing answers to the other questions yielded qualitatively similar results. CONCLUSIONS: Effective pain treatment goes along with benefit regarding work. A reduction in time off work >1 day per week can be achieved in patients with good pain responses.

Testing for cattle allergy: modified diagnostic cutoff levels improve sensitivity in symptomatic claw trimmers.

BACKGROUND: The diagnosis of cattle-related sensitization is complicated by the variability and complexity of cattle allergen extracts. OBJECTIVE: To evaluate a modified diagnostic procedure leading to more accurate results especially in the early phase of sensitization. METHODS: We tested 27 claw trimmers with and 65 without cattle-related symptoms using two commercially available cattle allergen extracts. We also used a self-prepared cattle allergen mix designed to represent the full spectrum of cattle allergens from a typical agricultural workplace. RESULTS: More than 50% of symptomatic claw trimmers showed negative test results with commercial extracts and a sensitization cutoff point of 0.35 kU/l. In contrast, with the self-prepared cattle allergen mix, positive results were observed for almost all of them. Evaluating the results of the commercial test kits at different cutoff levels, we found an ideal cutoff point to improve the sensitivity at 0.2 kU/l. CONCLUSION: Additional tests with self-made cattle hair extracts can help to bridge the diagnostic gap seen in patients showing cattle-related symptoms, but negative results in commercially available tests. For early-stage sensitization screening, we propose to lower the cutoff level indicating sensitization to 0.2 kU/l.

Investigation of the association of Apgar score with maternal socio-economic and biological factors: an analysis of German perinatal statistics.

PURPOSE: To examine the relationship of 5-min Apgar score with maternal socio-economic and biological factors. METHODS: We analyzed data from 465,964 singleton pregnancies (37-41 weeks' gestation) from the German perinatal statistics of 1998-2000. Using a logistic regression model we analyzed the incidence of low (0-6) 5-min Apgar scores in relation to these maternal factors: body mass index (BMI), age, previous live births, country of origin, occupation, single mother status, working during pregnancy, and smoking. RESULTS: A low Apgar score was more common in overweight [adjusted odds ratio (OR) 1.24; 95% confidence interval (CI) 1.10-1.40; P < 0.001] and obese [OR 1.92 (95% CI 1.67-2.20); P < 0.001] compared to normal weight women. A low Apgar score was also more common for women aged >35 years compared to those aged 20-35 years [OR 1.35 (95% CI 1.16-1.58); P < 0.001]. Furthermore, odds of a low Apgar score were higher for women with no previous live births compared to those with one or more previous live births [OR 1.52 (95% CI 1.37-1.70); P < 0.001]. Socio-economic factors did not convincingly influence Apgar scores. CONCLUSIONS: There was an influence of the biological maternal factors age, BMI, and parity on the 5-min Apgar score. There was no convincing effect of socio-economic factors on Apgar score in our study population. Possible reasons for this are discussed.

Vitamin d and chronic pain in immigrant and ethnic minority patients-investigation of the relationship and comparison with native Western populations.

Vitamin D deficiency has been implicated in chronic pain. Immigrant and ethnic minority populations have been shown to have lower vitamin D levels than native Western populations and often to be vitamin D deficient. This systematic review investigates the relationship between vitamin D and chronic pain in immigrant and ethnic minority populations. Included were studies reporting on 25-OH vitamin D levels in immigrant/ethnic minority populations affected by chronic pain, and/or reporting on the treatment of chronic pain with vitamin D preparations in such populations. We found that 25-OH vitamin D levels were low and often deficient in immigrant/ethnic minority populations. Vitamin D levels depended on the latitude of the study location and hence sunlight exposure. There was insufficient evidence to reach a verdict on the value of treating chronic pain in immigrant/ethnic minority patients with vitamin D preparations because the studies were few, small, and of low quality.

The benzene metabolite para-benzoquinone is genotoxic in human, phorbol-12-acetate-13-myristate induced, peripheral blood mononuclear cells at low concentrations.

Benzene is one of the most prominent occupational and environmental pollutants. The substance is a proven human carcinogen that induces hematologic malignancies in humans, probably at even low doses. Yet knowledge of the mechanisms leading to benzene-induced carcinogenesis is still incomplete. Benzene itself is not genotoxic. The generation of carcinogenic metabolites involves the production of oxidized intermediates such as catechol, hydroquinone and para-benzoquinone (p-BQ) in the liver. Further activation to the ultimate carcinogenic intermediates is most probably catalyzed by myeloperoxidase (MPO). Yet the products of the MPO pathway have not been identified. If an oxidized benzene metabolite such as p-BQ was actually the precursor for the ultimate carcinogenic benzene metabolite and further activation proceeds via MPO mediated reactions, it should be possible to activate p-BQ to a genotoxic compound in vitro. We tested this hypothesis with phorbol-12-acetate-13-myristate (PMA) activated peripheral blood cells exposed to p-BQ, using the cytokinesis-block micronucleus test. Addition of 20-28 ng/ml PMA caused a significant increase of micronuclei at low and non-cytotoxic p-BQ concentrations between 0.04 and 0.2 microg/ml (0.37-1.85 microM). Thus with PMA or p-BQ alone no reproducible elevation of micronuclei was seen up to toxic concentrations. PMA and p-BQ induce micronuclei when administered jointly. Our results add further support to the hypothesis that MPO is a key enzyme in the activation of benzene.

Exposure to allergens of different cattle breeds and their relevance in occupational allergy.

INTRODUCTION: Cattle are an important source of allergens in the working area of farmers. Asthma caused by cow allergens is a significant occupational problem. Yet in allergological testing, the results of in vivo and in vitro diagnostic tests are often inconsistent even in cases with clearly cattle-related symptoms. OBJECTIVES AND METHODS: The aim of this study was to investigate four different commercial cow allergen extracts and to compare them with self prepared extracts of different cattle breeds by means of SDS-PAGE and immunoblotting using the sera of 42 German farmers with asthma and rhino-conjunctivitis caused by cattle contact. RESULTS: The commercial extracts investigated in this study showed only minor differences in protein pattern. Using sera in immunoblotting experiments distinct bands were found for all symptomatic farmers, even in 13 farmers with a negative result in commercially available serological allergy tests. Bands with molecular weights in the range between about 11 and 67 kDa were observed; reactivity with the major allergen Bos d 2 at about 20 kDa was detected in all farmers, although it was not the strongest band in all cases. CONCLUSIONS: We demonstrate for the first time the allergenic relevance of additional proteins with molecular weights of 14, 30, 55 and approx. 67-97 kDa in more than 50% of farmers with cattle related symptoms. One of our most striking results was that 32% of the investigated farmers with cattle related symptoms showed negative results with commercial serological tests but distinct reactions with cow allergen in immunoblotting experiments. The Bos d 2 content in hair showed differences between certain breeds whereas German Brown and Simmental had particularly higher quantities of Bos d 2 in their hair than breeds such as Holstein-Friesian. These results strongly support the following recommendation: test results with commercial extracts that are contradictory to the clinical symptoms should be supplemented by skin tests using extracts of the hair of the farmers' own cattle.

Environmental exposure to allergens of different dog breeds and relevance in allergological diagnostics.

In our environment, dogs are a relevant source of allergens, but diagnosing dog-related allergies may present difficulties, as in diagnostic tests with commercial dog allergens, some patients show only slight positive or negative results, even though they suffer from dog-related symptoms. Occasionally, allergy tests with extracts of dog hair belonging to patients' dogs or from dogs of the same breed were found to yield more reliable results, possibly due to breed-specific allergen components. The purpose of this study was to determine breed-specific differences or possibly hypo- or hyperallergenic dog breeds. The dog allergen content and protein patterns of different commercial and self-prepared dog allergen extracts were compared. Protein extracts were separated using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and stained with silver. The major allergen Can f 1 was quantified using the commercially available enzyme-linked immunosorbent assay (ELISA) technique. The majority of the bands in the self-prepared extracts of different breeds had a molecular mass lower than 30 kD. Notably, the self-prepared extracts of hair of common breeds showed distinct protein bands with a molecular mass lower than 14 kD, which the commercial extracts did not. With regard to Can f 1 content, a marked variability occurred. Factors related to individual dogs seem to influence the allergenicity more than breed or gender. This is the first report to describe allergens with low molecular mass that are absent in extracts of commercial test kits. Consequently, skin tests with self-prepared dog allergen extracts need to be performed in case of inconsistent test results with commercial extracts.

German cattle allergy study (CAS): public health relevance of cattle-allergic farmers.

INTRODUCTION: Allergic reactions caused by animals are a common and significant occupational health concern. In a large population-based study on occupational asthma in Europe, farming has been among the occupations with the highest risk. OBJECTIVES: Characteristics of cattle-allergic farmers are described in a retrospective observational design. METHODS: The study covers farmers from all regions of Germany which were reported to the Agricultural Institutions for Statutory Accident Insurance and Prevention (Landwirtschaftliche Berufsgenossenschaften, LBGs) between 1990 (January) and 2002 (December) with a suspected occupational cattle-allergic airways disease. For these farmers, the following parameters were considered: age, gender, onset of airways symptoms related to contact with cattle, begin of employment disability, total and specific Immunoglobulin E (IgE) against cattle allergens, and results of lung function measurements. RESULTS: A total of 513 patients (age 14-74, mean 40.7 years; 45.6% women, 54.4% men) had been reported for a suspected occupational cattle-allergic airways disease. Of these patients 24.8% showed cattle-related symptoms of asthma, 11.7% of rhinitis, and 60% of both asthma and rhinitis, while only 34.5% of all reported patients showed an airways obstruction in the first documented lung function test. A total of 62.5% out of the group of patients with an officially recognized occupational disease (42.1%, n=216) have an initial employment disability with a rating of 20% or above. CONCLUSIONS: Our results underline the high public health relevance of cattle allergy in farmers, especially in the light of the large number of young patients. Considering the known difficulties in diagnosing cattle allergy due to the number of false negative test results, we are convinced that its relevance is even higher than the number of reported cases suggests. The high rate of initial employment disability among the affected patients underlines the need for improved preventive measures.

Strong mutagenic effects of diesel engine emissions using vegetable oil as fuel.

Diesel engine emissions (DEE) are classified as probably carcinogenic to humans. In recent years every effort was made to reduce DEE and their content of carcinogenic and mutagenic polycyclic aromatic compounds. Since 1995 we observed an appreciable reduction of mutagenicity of DEE driven by reformulated or newly designed fuels in several studies. Recently, the use of rapeseed oil as fuel for diesel engines is rapidly growing among German transportation businesses and agriculture due to economic reasons. We compared the mutagenic effects of DEE from two different batches of rapeseed oil (RSO) with rapeseed methyl ester (RME, biodiesel), natural gas derived synthetic fuel (gas-to-liquid, GTL), and a reference diesel fuel (DF). The test engine was a heavy-duty truck diesel running the European Stationary Cycle. Particulate matter from the exhaust was sampled onto PTFE-coated glass fibre filters and extracted with dichloromethane in a soxhlet apparatus. The gas phase constituents were sampled as condensates. The mutagenicity of the particle extracts and the condensates was tested using the Salmonella typhimurium/mammalian microsome assay with tester strains TA98 and TA100. Compared to DF the two RSO qualities significantly increased the mutagenic effects of the particle extracts by factors of 9.7 up to 59 in tester strain TA98 and of 5.4 up to 22.3 in tester strain TA100, respectively. The condensates of the RSO fuels caused an up to factor 13.5 stronger mutagenicity than the reference fuel. RME extracts had a moderate but significant higher mutagenic response in assays of TA98 with metabolic activation and TA100 without metabolic activation. GTL samples did not differ significantly from DF. In conclusion, the strong increase of mutagenicity using RSO as diesel fuel compared to the reference DF and other fuels causes deep concern on future usage of this biologic resource as a replacement of established diesel fuels.

A 5-year follow-up study on respiratory disorders and lung function in workers exposed to organic dust from composting plants.

OBJECTIVES: To evaluate acute and chronic effects of long-term exposure to organic dust on respiratory disorders and lung function among employees at 41 composting facilities in Germany. METHODS: A total of 218 compost workers and 66 control subjects were enrolled in the cohort. They were evaluated using a standardized questionnaire, a clinical examination, and spirometric measurements. Changes of symptoms, respiratory disorders, and lung function were determined in a first survey after 5 years of exposure in 123 compost workers and 48 controls. Exposure measurements were performed at six composting facilities for respirable dust, cultivable microorganisms, and endotoxins. RESULTS: Exposure measurements revealed high concentrations of thermo-tolerant/thermophilic actinomycetes and filamentous fungi in the bio-aerosols at the composting sites. A significantly higher job fluctuation was observed among the compost workers compared to control subjects (95 vs. 18; p < 0.05). Compost workers reported a significantly higher prevalence of mucosal membrane irritation (MMI) of the eyes and upper airways than control subjects. Conjunctivitis was diagnosed significantly more often in compost workers. Forced vital capacity in percent of predicted (FVC%) of the non-smoking compost workers declined significantly (-5.4%) during the observation period compared to control subjects. The decline of FVC% in 16 compost workers exceeded 10% of initial values. A significant increase was observed in the number of compost workers suffering from chronic bronchitis (RR = 1.41; 95% CI = 1.28-1.55). Allergic alveolitis was diagnosed clinically in two compost workers. CONCLUSIONS: The exposure to organic dust at workplaces of composting facilities is associated with adverse acute and chronic respiratory health effects, including MMI, chronic bronchitis, and an accelerated decline of FVC%. The pattern of health effects differs from those at other workplaces with exposures to organic dust possibly due to high concentrations of thermo-tolerant/thermophilic actinomycetes and filamentous fungi at composting plants.

Disabling work-related persistent photosensitivity following photoallergic contact dermatitis from chlorpromazine and olaquindox in a pig breeder.

The use of veterinary medicines and medicated feed has a potential for the exposure of agricultural workers to pharmaceuticals with phototoxic and photoallergic side-effects. We present a 67-year-old self-employed farmer and pig breeder with a 22-year history of severe persistent photosensitivity following photoallergic contact dermatitis due to direct occupational dermal and airborne contact to chlorpromazine (sedative) and olaquindox (antibiotic and animal growth promoter, AGP). His first dermatitis symptoms appeared at the age of 45 when the pig breeding was intensified. He showed erythematous, scaly, and pruritic plaques localized symmetrically on the sun-exposed backs of his hands, fingers, and forearms, spreading to his face and other sun-exposed body sites. Without protective measures, he injected the animals with chlorpromazine. Besides, for several years he mixed by hand a powder containing olaquindox into the pigs' dry food. Epicutaneous and photo-patch tests showed positive reactions to promethazine, chlorpromazine, and olaquindox. In spite of the complete avoidance of the identified photoallergens for several years, his life is still extremely disabled due to the persistent photosensitivity. Our case report stresses the observation that olaquindox and chlorpromazine as phototoxic agents and photoallergens are capable of inducing a persistent and severe photosensitivity for many years, even after termination of exposure. Although the use of phenothiazine derivates and APGs for animals has meanwhile been banned in the European Union (EU), AGPs are still widely used in Asia. Physicians, especially occupational physicians, should be still aware of these phototoxic and photoallergic agents to reduce the burden of skin disease at work.

Mutagenicity of cytochrome P450 2E1 substrates in the Ames test with the metabolic competent S. typhimurium strain YG7108pin3ERb5.

UNLABELLED: Poor metabolic competence of in vitro systems was proposed to be one of their major shortcomings accounting for false negative results in genotoxicity testing. For several "low molecular weight cancer suspects" this was specifically attributed to the lack of cytochrome P450 2E1 (CYP2E1) in conventional in vitro metabolising systems. One promising attempt to overcome this problem is the transfection of "methyltransferase-deficient"S. typhimurium strains with the plasmid pin3ERb5. This plasmid contains DNA encoding for a complete electron transport chain, comprising P450 reductase, cytochrome b5 and cytochrome P450 2E1. In order to answer the question if CYP2E1 substrates that yield negative or inconclusive results in the Ames test can be activated by metabolic competent bacterial strains, we used YG7108pin3ERb5 to investigate the following compounds: acetamide, acrylamide, acrylonitrile, allyl chloride, ethyl acrylate, ethyl carbamate, methyl-methacrylate, vinyl acetate, N-nitrosopyrrolidine, trichloroethylene and tetrachloroethylene. N-Nitrosodiethylamine served as a positive control. In addition to these known or proposed CYP2E1 substrates, we investigated the polycyclic aromatic hydrocarbon benzo[alpha]pyrene and the heterocyclic aromatic amines 2-aminofluorene and 2-aminoanthracene. RESULTS: The extensive metabolic competence of the transformed strain is underlined by results showing strong mutagenicity between 10 and 500 micro g N-nitrosopyrrolidine per plate. Unexpectedly, 2-aminoanthracene was mutagenic at a concentration range between 25 and 250 micro g per plate using YG7108pin3ERb5. Moreover, we demonstrate for the first time a clear response of sufficiently characterised allyl chloride in the Ames test at a reasonably low concentration range between 300 and 1500 micro g per plate. We achieved similar results in the parent strain YG7108 with conventional metabolic activation. Without metabolic activation less pronounced mutagenicity occurred, suggesting a contribution of a direct alkylating effect. Propylene oxide is usually contained in allyl chloride as stabilizer at amounts up to 0.09%. Though YG7108 revealed to be very sensitive towards propylene oxide, allyl chloride dissolved in water was not mutagenic, showing that no water soluble compounds contribute to its mutagenicity. None of the remaining compounds showed mutagenic effects using YG7108pin3ERb5. CONCLUSION: YG7108pin3ERb5 and its parent strain YG7108 are sensitive for compounds which are negative in conventional tester strains including N-nitrosodiethylamine, N-nitrosopyrrolidine, propylene oxide and allyl chloride.