Medical surveillance in biotechnology research laboratories: is there a need for special medical check-ups?
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Adult↗
Biomedical subjects
Hans Drexler
Publications and source records attributed to Hans Drexler.
Prevention of work-related decompression illness events by detection of a cardiac right-to-left shunt.
A 44-year-old tunnel worker was studied who suffered from several unexplained decompression illness events for almost 15 years. This caisson worker was affected after standard pressure profiles that did not cause symptoms of decompression illness in his colleagues on the same shift. Transesophageal echocardiography revealed an atrial septal defect (grade II) in this otherwise healthy man. Cranial magnetic resonance imaging showed ischemic brain lesions. Among divers, patent foramen ovale, the most common cause of cardiac right-to-left shunts, was shown to increase the risk for decompression illness events by a factor of 4.5 and to double the risk of ischemic brain lesions. Hyperbaric workers with symptoms of unexplained decompression illness, even if they are only slight, should immediately be transferred to a cardiologist so that a cardiac right-to-left shunt will not be overlooked.
Adult↗
Current internal exposure to pesticides in children and adolescents in Germany: urinary levels of metabolites of pyrethroid and organophosphorus insecticides.
AIM: Pesticides are widely used throughout the world, in agriculture to protect crops and in public health to control diseases transmitted by vectors or intermediate hosts. After the prohibition of organochlorines such as DDT, today, mainly pyrethroids and organophosphorus insecticides are used. Whereas many studies have been published on background exposure of the population to organochlorines, data on internal exposure of the population to pyrethroids and organophosphorus insecticides are scarce. Here, we report on internal exposure of children and young people, in an urban area in Germany, to pyrethroids and organophosphorus acids, assessed by the analysis of urinary levels of their corresponding specific metabolites. METHODS: Approximately 673 children and adolescents took part in this voluntary investigation, including 331 children <6 years of age. Their parents stated that they and their children had never used pyrethroids or organophosphorus acids in their homes or for medical reasons. We analysed their spot urine samples for six metabolites of organophosphorus insecticides [dimethyl-phosphate (DMP), diethyl-phosphate (DEP), dimethyl-thiophosphate (DMTP), diethyl-thiophosphate (DETP), dimethyl-dithiophosphate (DMDTP) and diethyl-dithiophosphate (DEDTP)] and for four metabolites of pyrethroids [cis-3-(2,2-dibromo-vinyl)-2,2-dimethyl-cyclopropane carboxylic acid (Br2CA), cis-3-(2,2-dichloro-vinyl)-2,2-dimethyl-cyclopropane carboxylic acid (cis-Cl2-CA ), trans-3-(2,2-dichloro-vinyl)-2,2-dimethyl-cyclopropane carboxylic acid (trans-Cl2-CA) and 4-fluoro-3-phenoxy-benzoic acid (F-PBA)] using gas chromatographic methods with mass-selective detection. The limit of detection was 0.1-0.2 microg/l for pyrethroid metabolites and 1 microg/l for metabolites of organophosphorus acids; in DMP it was 5 microg/l. RESULTS: The 95th percentiles of the urinary metabolite concentrations were, in microgrammes per litre, DMP 158, DMTP 180, DMDTP 12, DEP 17, DETP 8, DEDTP <1; Br2CA 0.30, cis-Cl2-CA 0.44, trans-Cl2-CA 1.22, F-PBA 0.30. There were no correlations between urinary metabolite levels and the age of the children. CONCLUSION: Current background levels of internal exposure to pyrethroids and organophosphorus insecticides in children and adolescents in Germany are shown. Exposure to these substances in the general population is thought to occur mainly via residues in the diet. The level of background internal pyrethroid exposure in the children is orders of magnitude lower than the corresponding acceptable daily intake (ADI) values published, but the level of internal organophosphate exposure may reach and even exceed ADI values. This observation demands further investigation.
Adolescent↗
Naphthalene--an environmental and occupational toxicant.
For many years naphthalene had been considered as a non-carcinogenic polycyclic aromatic hydrocarbon (PAH). Airborne naphthalene concentrations have always been observed to be below the limit values of various national committees, such as the threshold limit value (TLV) of the American Conference of Governmental Industrial Hygienists (ACGIH) and the MAK of the Deutsche Forschungsgemeinschaft (DFG) (10 ppm). Since 2000, when the US National Toxicology Program revealed clear evidence of the carcinogenic activity of naphthalene in rats, international agencies [the International Agency for Research on Cancer (IARC), the US Environmental Protection Agency (US EPA), DFG] have reclassified naphthalene as a potential human carcinogen, and the European Union (EU) is currently preparing a new risk assessment report. It is presently unknown how to protect humans from health risks resulting from occupational and environmental naphthalene exposure. Knowledge about the external and internal exposure of humans serves as the key determinant in a comprehensive risk assessment. We review here ambient monitoring studies concerning the external naphthalene exposure that results from ubiquitous environmental sources (indoor and outdoor air, water, soil, food) and from a variety of critical workplaces (coking plants, creosote impregnation, distillation of coal tar and naphthalene, manufacture of refractories, graphite electrodes, aluminium and mothballs). Based on results of ambient monitoring studies published so far, a new hygiene-based exposure limit of 1.5 mg naphthalene per cubic metre of air (0.3 ppm) is proposed. Furthermore, results from biological monitoring studies are summarised in this article. The internal burden was almost exclusively determined by means of the urinary metabolites 1-naphthol and 2-naphthol, but it is currently not possible for one to evaluate a biological tolerance level (BAT) or a biological exposure index (BEI). Based on the toxicokinetics and metabolism of naphthalene, the central question on its carcinogenicity is briefly sketched. Naphthoquinones play an important role in this context. Their adducts with macromolecules may be the parameters of choice for the estimation of effects to human health.
Environmental Exposure↗
Effectiveness of skin protection creams as a preventive measure in occupational dermatitis: a critical update according to criteria of evidence-based medicine.
OBJECTIVES: This study attempts to assess the evidence of the generally recommended three-step programme of skin protection in the prevention of occupational skin disease. METHODS: The following clinical questions, representative of critical appraisal of this preventive measurement, were generated: (1) Can a skincare regimen effectively reduce or eliminate work-related poor skin conditions? (2) Do protective creams prevent harmful substances from penetrating and adhering to the skin? (3) Is the differentiation between pre-exposure and post-exposure products justified by reliable data? Answers were generated according to the method used in evidence-based medicine by searching the literature, critically appraising the results and applying the results to the clinical questions. For our search we decided to use PubMed as the most convenient access to Medline and because, in contrast to other databases, this access is available free of charge. RESULTS: To investigate the efficacy of barrier creams as pre-exposure skin protectors various in vitro and in vivo test methods have been developed. Over the past years the test techniques have been improved in order to adopt a real workplace situation. Efforts for standardisation of evaluation criteria have been made, too. Nevertheless, there is a lack of placebo-controlled, randomised clinical trials evaluating the benefit of these products in the prevention of occupational contact dermatitis under real workplace conditions. The literature data are conflicting; some publications report on the positive aspects of skin protection, whereas others stress the negative ones. CONCLUSION: Not enough data have been accumulated for one to prove the benefit of skin protection measures under real workplace condition. Up to now, it is almost unclear if the various in vitro and in vivo methods used are suitable to simulate real workplace conditions and if these test results can be related to real occupational exposure. For the evidence-based recommendation of skin protection, further studies, especially under daily working conditions evaluating the contribution of each single element of skincare programme (products, frequency of application and education programme) are needed.
Clinical Trials as Topic↗
Internal exposure of the general population to DEHP and other phthalates--determination of secondary and primary phthalate monoester metabolites in urine.
A number of phthalates and their metabolites are suspected of having teratogenic and endocrine disrupting effects. Especially the developmental and reproductive effects of di(2-ethylhexyl)phthalate (DEHP) are under scrutiny. In this study we determined the concentrations of the secondary, chain oxidized monoester metabolites of DEHP, mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP) and mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) in urine samples from the general population. The utilization of the secondary metabolites minimized any risk of contamination by the ubiquitously present phthalate parent compounds. Included in the method were also the simple monoester metabolites of DEHP, dioctylphthalate (DOP), di-n-butylphthalate (DnBuP), butylbenzylphthalate (BBzP) and diethylphthalate (DEP). Automated sample preparation was performed applying a column switching liquid chromatography system enabling online extraction of the urine on a restricted access material (RAM) and separation on a reversed phase analytical column. Detection was performed by negative ESI-tandem mass spectrometry in multiple reaction monitoring mode and quantification by isotope dilution. The excretion of DEHP and the other phthalates was studied by analyzing first morning urine samples from 53 women and 32 men aged 7-64 years (median: 34.2 years) living in northern Bavaria (Germany) who were not occupationally exposed to phthalates. Phthalate metabolites, secondary and primary ones, were detected in all specimens. Concentrations were found to vary strongly from phthalate to phthalate and subject to subject with differences spanning more than three orders of magnitude. Median concentrations for excretion of DEHP metabolites were 46.8 microg/L for 5OH-MEHP (range 0.5-818 microg/L), 36.5 microg/L for 5oxo-MEHP (range 0.5-544 microg/L), and 10.3 microg/L for MEHP (range:<0.5 (limit of quantification, LOQ) to 177 microg/L). A strong correlation was found between the excretion of 5OH-MEHP and 5oxo-MEHP with a correlation coefficient of r=0.991, indicating close metabolic proximity of those two parameters but also the absence of any contaminating interference. Median concentrations for the other monoester metabolites were for mono-n-butylphthalate (MnBuP) 181 microg/L, for monobenzylphthalate (MBzP) 21.0 microg/L, for monoethylphthalate (MEP) 90.2 microg/L and for mono-n-octylphthalate (MOP)<1.0 microg/L (LOQ). These results will help to perform health risk assessments for the phthalate exposure of the general population.
Adolescent↗
A first approach to estimate the internal exposure to acrylamide in smoking and non-smoking adults from Germany.
Since the formation of acrylamide (AA) in the heating process of starch-containing food could be demonstrated and high contents of this substance were found in commercial food products, there is a great discussion about the possible human health risks connected with this dietary exposure. In order to determine the body burden of the general population in Germany caused by this uptake, we investigated the internal exposure to acrylamide and acrylonitrile in a group of 72 persons using haemoglobin adducts as parameters of biochemical effects. The collective was subdivided into non-smokers and smokers basing on the results of the smoking-specific acrylonitrile adduct (N-cyanoethylvaline, CEV). The median value for the adduct of AA (N-2-carbamoylethylvaline, AAV) in 25 non-smokers was 21 pmol/g globin (approximately 0.6 microgram/l blood) with a 95 percentile of 46 pmol/g globin (approximately 1.3 micrograms/l) (LOD: 12 pmol/g globin). The median level for AAV in smokers (n = 47) was found to be 85 pmol/g globin (approximately 2.3 micrograms/l blood) with a 95 percentile of 159 pmol/g globin (approximately 4.3 micrograms/l blood). Based on these results about 60 micrograms AA/d are taken up by adult non-smoking persons. According to calculations of WHO and US EPA this background exposure would lead to a cancer risk between 6 x 10(-4) and 3.6 x 10(-3). Our results confirm a body burden to AA even in persons from the non-smoking general population in Germany that is most probably caused by dietary uptake. Smoking habits considerably contribute to the level of this adduct.
Acrylamide↗
An estimation of the daily intake of di(2-ethylhexyl)phthalate (DEHP) and other phthalates in the general population.
We analyzed 85 urine samples of the general German population for human specific metabolites of phthalates. By that we avoided contamination with the parent phthalates being omnipresent in the environment and for the first time could deduce each individual's internal exposure to phthalates without contamination. Determined were the secondary metabolites mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP) and mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) of di(2-ethylhexyl)phthalate (DEHP) and the primary monoester metabolites of DEHP, di-noctylphthalate (DnOP), di-n-butylphthalate (DnBP), butylbenzylphthalate (BBzP) and diethylphthalate (DEP). Based on these internal exposure values we calculated the daily intake of the parent phthalates using urinary metabolite excretion factors. For DEHP we determined a median intake of 13.8 micrograms/kg body weight/day and an intake at the 95th percentile of 52.1 micrograms/kg body weight/day. The tolerable daily intake (TDI) value settled by the EU Scientific Committee for Toxicity, Ecotoxicity and the Environment (CSTEE) is 37 micrograms/kg body weight/day. Twelve percent of the subjects (10 out of 85 samples) within our collective of the general population are exceeding this value. Thirty-one percent of the subjects (26 out of 85 samples) had values higher than the reference dose (RfD) of 20 micrograms/kg body weight/day of the U.S. Environmental Protection Agency (EPA). For DnBP, BBzP, DEP and DnOP intake values at the 95th percentile were 16.2, 2.5, 22.1 and 0.42 micrograms/kg body weight/day respectively. Our results unequivocally prove that the general German population is exposed to DEHP to a much higher extent than previously believed. This is of greatest importance for public health since DEHP is not only the most important phthalate with respect to its production, use, occurrence and omnipresence but also the phthalate with the greatest endocrine disrupting potency. DEHP is strongly suspected to be a developmental and reproductive toxicant. We are not aware of any other environmental contaminant for which the TDI and RfD are exceeded to such an extent within the general population. The transgressions of the TDI and RfD for DEHP are accompanied by considerable ubiquitous exposures to DnBP and BbzP, two phthalates under scrutiny for similar toxicological mechanisms.
Adolescent↗
Hemoglobin adducts of ethylene oxide, propylene oxide, acrylonitrile and acrylamide-biomarkers in occupational and environmental medicine.
In a chemical plant, ethylene oxide (EO) and propylene oxide (PO) were used for the production of surfactants for the textile industry. Within health supervision, we investigated the internal exposure of the workers using hemoglobin adducts as parameters of biochemical effects. The 95th percentile for N-2-hydroxyethylvaline (HEV) was 1280 pmol/g globin (=29.4 microg/l blood) in blood from exposed workers compared with 100 pmol/g globin (or 2.3 microg/l) in controls. N-(R,S)-2-hydroxypropylvaline (HPV) both in workers and controls was below the detection limit (80 pmol/g globin or 2 microg/l). The levels of the adducts of acrylonitrile (ACN) and acrylamide (AA) were also determined, though they were mainly accounted for by smoking and diet. Median values of N-2-cyanoethylvaline (CEV) were below 4 pmol/g globin (or 0.1 microg/l) in non-smokers (n=24) and 131 pmol/g globin (or 3.3 microg/l) in smokers (n=38). Median values of N-2-carbamoylethylvaline (AAV) were 22 pmol/g globin (or 0.6 microg/l) in non-smokers compared with 89 pmol/g globin (or 2.4 microg/l) in smokers. Correlations were found between smoking habits and adduct levels of CEV and AAV.
Acrylamide↗
Analysis of ethenoguanine adducts in human urine using high performance liquid chromatography-tandem mass spectrometry.
Several chemical carcinogens, such as vinyl chloride and ethyl carbamate, can react with DNA to form etheno-adducts in vitro and in vivo, which can be repaired through the base excision repair pathway, and then excreted with the urine. A specific and sensitive method, based on high performance liquid chromatography electrospray ionization tandem mass spectrometry, was developed for the detection of ethenoguanines (1,N2-ethenoguanine and its isomer N2,3 ethenoguanine) in urine. Urine samples were obtained from 13 healthy subjects not occupationally exposed to industrial chemicals. A confirmatory GC/MS method was also applied. Ethenoguanine isomers excreted with the urine were in the low nmol/l range (<0.3-8 nmol/l). Since occupational exposure to chemicals that may form etheno-adducts can be ruled out, endogenously produced intermediates, such as 2,3-epoxy-4-hydroxynonanal, may be responsible for the formation of etheno-adducts in human DNA. The background level of the general population has to be taken into account, especially in the investigation of persons occupationally exposed to etheno-adduct forming chemicals.
Adult↗
Pyrethroid exposure of the general population-is this due to diet.
Inhabitants (1177) of a residential area in Frankfurt/Main have been investigated with respect to internal exposure to pyrethroids. Biological monitoring revealed a body burden of pyrethroids. The 95th per thousand for the urinary metabolites of pyrethroids, such as permethrin and cypermethrin, cis and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cis-DCCA and trans-DCCA), was determined to be 0.5 and 1.4 microg/l, respectively. 95th per thousand for cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA), a specific metabolite of deltamethrin, and 4-fluoro-3-phenoxybenzoic acid (F-PBA), a metabolite of cyfluthrin, were 0.3 and 0.27 microg/l, respectively. The metabolic pattern found for these samples points out that pyrethroids are probably ingested orally with daily diet.
Adolescent↗
Butoxyethoxyacetic acid, a biomarker of exposure to water-based cleaning agents.
The aim of the study was to investigate the suitability of butoxyethoxyacetic acid (BEAA) as a biomarker of exposure to water-based cleaning agents containing diethylene glycol mono butyl ether (DEGBE). The study was performed in two printing plants where water-based products containing 10-15% DEGBE were used for rubber and blanket washes. Thirty nine newspaper pressroom workers (exposed) and 19 employees of newspaper despatch departments (controls) were investigated. By questionnaire, the workers were asked about the use of personal protective measures. BEAA was determined in post-shift urine using GC-MS. The BEAA concentration in the urine of exposed workers ranged up to 75.1 mg/l (median 6.3 mg/l), whereas in urine samples of the controls the BEAA level was below or around the determination limit of 0.5 mg/l. A protective effect on DEGBE uptake was observed with the use of protective gloves. This observation implies that dermal penetration of DEGBE may be important in exposure monitoring.
Acetates↗
Latex sensitization in dental students using powder-free gloves low in latex protein:a cross-sectional study.
In Germany, employers must provide low-protein, powder-free gloves. This study was carried out to determine the current prevalence of latex sensitization in dental students using these gloves and to compare our results with a study of the same design dating from 1990/1991 at our university. A cross-sectional study was performed by questionnaire, prick testing and determination of specific IgE antibodies. 226 of 403 dental students underwent prick testing with a panel of 8 aero-allergens, 1 commercially available latex extract and 5 high-ammonia accelerator-free latex fluids. 39 of 226 dental students (17.3%) had a positive prick test response to at least 1 of the 6 latex substances tested. The prick test positivity was similar in preclinical education (semester 1-6) and in clinical education (semester 7-10), at 17.1% and 17.4%, respectively. In 9 of 32 persons with positive prick tests, specific IgE antibodies to latex could be detected. Within the past 10 years, prick test positivity increased from 8.7% to 17.3%. 14 students (6.2%) reported a history of glove intolerance, 3 of them (1.3%) showing a positive prick test to latex. By the use of low-protein, powder-free gloves less students with glove intolerance were observed. The observed reactions to between 1 and 3 of 6 latex substances tested may indicate a decrease in intensity and spectrum of sensitization. Additionally non-occupational sensitization may be of importance.
Adult↗
Atropine and Cognitive Performance After Electroconvulsive Therapy.
Two groups of patients receiving bilateral, moderately suprathreshold electroconvulsive therapy (ECT) were compared in their cognitive functions after receiving either 0.5 mg atropine i.v. or no atropine before ECT. The patients were tested for cognitive functions after four treatments using various measures, including orientation; retrograde (verbal and visuospatial) memory for information acquired about 15 minutes pretreatment and tested for about 1 hour posttreatment; anterograde (verbal and visuospatial) memory for information acquired about 1 hour, 30 minutes posttreatment and tested for both immediately after learning and 20 minutes later; and retrieval from semantic memory as assessed by word fluency. We found no effect of 0.5 mg atropine on cognitive performance, even though anticholinergic drugs that cross the blood brain barrier might be expected to affect cognition after ECT.
Journal Article↗
NTP center for the evaluation of risks to human reproduction reports on phthalates: addressing the data gaps.
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Animals↗
Polychlorinated biphenyls in the blood plasma: current exposure of the population in Germany.
UNLABELLED: Until the 1970s, polychlorinated biphenyls (PCB) were used as industrial chemicals for diverse commercial applications, leading to a ubiquitous contamination of nature and man. In the 1980s, PCBs were prohibited by law in many industrialized countries. Hence, in recent years a steady decline in PCB levels has been seen. Here we report on PCB plasma levels in children and adults in Germany in 1998. PARTICIPANTS AND METHODS: 130 children/youth (0 to <18 y) and 494 adults (18 to 65 y) living in an urban environment participated in this study. Occupational exposure to PCBs was excluded by questionnaire. Gas chromatography/electron capture detection was used to analyze blood plasma samples. RESULTS: In all blood specimens, PCB congeners 28, 52, and 101 were below the limit of quantification (<0.1 microg/L) and only the congeners 138, 153, and 180 were detected. The 95th percentiles in the age groups 0 to <6 y, 6 to <12 y, 12 to <18 y, 18 to 25 y, 26 to 35 y, 36 to 45 y, 46 to 55 y, and >55 y were as follows: PCB 138: 1.02; 1.05; 0.61; 1.01; 1.22; 1.44; 2.23; 2.94 microg/L plasma; PCB 153: 1.47; 1.23; 0.59; 1.26; 1.53; 2.11; 3.27; 3.98 microg/l plasma; PCB 180: 0.88; 1.23; 0.39; 0.88; 1.16; 1.71; 2.16; 3.31 microg/L. DISCUSSION: In adults, plasma levels of PCBs increased with age. In comparison with published reference values on internal PCB exposure in the population in Germany, based on data obtained in 1991/4 and 1994/5, the steady decline in PCB levels reflects the falling external and internal PCB exposure after the ban on PCB. For the first time, current PCB exposure during childhood and adolescence in Germany is provided here. In childhood, internal PCB exposure declined with age, especially in children who had been breastfed. An impact of breastfeeding on internal PCB exposure was found in age groups up to 12 years old.
Adolescent↗