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J Angerer

Publications and source records attributed to J Angerer.

At least 55 records · Page 3Linked to original sources

High-performance liquid chromatographic method with fluorescence detection for the determination of 3-hydroxybenzo[a]pyrene and 3-hydroxybenz[a]anthracene in the urine of polycyclic aromatic hydrocarbon-exposed workers.

The described high-performance liquid chromatographic method with fluorescence detection (HPLC-FD) permits the simultaneous determination of 3-hydroxybenzo[a]pyrene and 3-hydroxybenz[a]anthracene as the most important metabolites of the carcinogenic polycyclic aromatic hydrocarbons (PAHs) benzo[a]pyrene and benz[a]anthracene in human urine. After enzymatic hydrolysis, to release the conjugated metabolites, the analytes are separated from the matrix by means of a liquid-solid extraction step which is followed by a coupled column HPLC procedure using an enriching precolumn consisting of silica modified with copper phthalocyanine. This special precolumn selectively adsorbs PAHs with at least three condensed rings and thus separates them from the urine matrix. The quantitative analysis was carried out using a switchable fluorescence detector. The detection limits were 6 ng/l urine (3-hydroxybenzo[a]pyrene) and 8 ng/l urine (3-hydroxybenz[a]anthracene). The relative standard deviations of the within-series imprecision ranged between 4.0% and 9.0%. The between-day imprecision was 7.7% (3-hydroxybenz[a]anthracene) and 12.9% (3-hydroxybenzo[a]pyrene). The recovery rates ranged between 102% and 124%. Using this analytical method we determined PAH metabolites in post shift urine samples from 19 workers engaged in the production of fire-proof materials. The urinary concentrations ranged from 3 to 198 ng 3-hydroxybenzo[a]pyrene per g creatinine and from 15 to 1871 ng 3-hydroxybenz[a]anthracene per g creatinine.

Adsorption↗

Percutaneous penetration studies for risk assessment.

During the last few years the general interest in the percutaneous absorption of chemicals has increased. It is generally accepted that there is very few reliable quantitative and qualitative data on dermal exposure to chemicals in the general population and in occupationally exposed workers. In order to predict the systemic risk of dermally absorbed chemicals and to enable agencies to set safety standards, data is needed on the rates of percutaneous penetration of important chemicals. Standardization of in vitro tests and comparison of their results with the in vivo data could produce internationally accepted penetration rates and/or absorption percentages very useful for regulatory toxicology. The work of the Percutaneous Penetration Subgroup of EC Dermal Exposure Network has been focussed on the standardization and validation of in vitro experiments, necessary to obtain internationally accepted penetration rates for regulatory purposes. The members of the Subgroup analyzed the guidelines on percutaneous penetration in vitro studies presented by various organizations and suggested a standardization of in vitro models for percutaneous penetration taking into account their individual experiences, literature data and guidelines already in existence. During the meetings of Percutaneous Penetration Subgroup they presented a number of short papers of up to date information on the key issues. The objective was to focus the existing knowledge and the gaps in the knowledge in the field of percutaneous penetration. This paper is an outcome of the meetings of the Percutaneous Penetration Subgroup and reports the presentations on the key issues identified throughout the 3-year duration of the Dermal Exposure Network (1997-1999).

Journal Article↗

Aluminium dust-induced lung disease in the pyro-powder-producing industry: detection by high-resolution computed tomography.

OBJECTIVE: The aim of this case study was to investigate the suitability of high-resolution computed tomography (HRCT) for detecting early stages of lung fibrosis induced by aluminium (Al) dust. METHODS: A 40-year-old worker was studied who had worked as a stamper for 14 years in a plant producing aluminium powder and had been exposed to high levels of aluminium dust during this time. The investigation included the collection of general data on health and details on occupational history, immunological tests, a physical examination, lung function analysis, biological monitoring of Al in plasma and urine, chest X-rays and HRCT. RESULTS: For many years the man has suffered from an exercise-induced shortness of breath. Lung function analysis revealed a reduction of the vital capacity to 57.5% of the predicted value. The Al concentration in plasma was 41.0 micrograms/l (upper reference value 10 micrograms/l) and in urine 407.4 micrograms/l upper reference value 15 micrograms/l, biological tolerance (BAT) value 200 micrograms/l[ at the time of diagnosis. Chest X-ray showed unspecific changes. HRCT findings were characterised by small, centrilobular, nodular opacities and slightly thickened interlobular septae. Exposure to other fibrotic agents could be excluded. CONCLUSIONS: HRCT was more sensitive than chest X-rays for detecting this early stage of Al-dust-induced lung disease. The suitability of HRCT in the surveillance of workers highly exposed to aluminium powder should be evaluated in further studies. Biological monitoring can be used to define workers at high risk.

Adult↗

Analytical validity of the determination of mercury in whole blood and urine--results of the German external assurance programme for toxicological analysis in biological materials.

The determination of mercury concentrations in blood and urine is currently the best way of monitoring individual uptake of organic and inorganic mercury. In Germany these determinations must be carried out under the conditions of an external quality assurance programme. The German performance evaluation, based on reference values established by reference laboratories yields success rates in percent for the participants in the intercomparison programme of about 60%. A Canadian evaluation system based on two evaluations scores, yields success rates of 25-50% for "good performance" and of 65-80% for "acceptable performance". The determination of mercury in blood and urine is at present not carried out with the necessary reliability.

Germany↗

Biological monitoring of workers exposed to N,N-dimethylformamide in the synthetic fibre industry.

OBJECTIVES: Monitoring of workplace air and biological monitoring of 23 workers exposed to N,N-dimethylformamide (DMF) in the polyacrylic fibre industry was carried out on 4 consecutive days. The main focus of the investigation was to study the relationship between external and internal exposure, the suitability of the metabolites of DMF for biological monitoring and their toxicokinetic behaviour in humans. METHODS: Air samples were collected using personal air samplers. The limit of detection (LOD) for DMF using an analytical method recommended by the Deutsche Forschungsgemeinschaft (DFG) was 0.1 ppm. The urinary metabolites, N-hydroxymethyl-N-methylformamide (HMMF), N-methylformamide (NMF), and N-acetyl-S-(N-methylcarbamoyl)-cysteine (AMCC), were determined in one analytical run by gas chromatography with thermionic sensitive detection (GC/TSD). The total sum of HMMF and NMF was determined in the form of NMF. The LOD was 1.0 mg/l for NMF and 0.5 mg/l for AMCC. RESULTS AND CONCLUSIONS: The external exposure to DMF vapour varied greatly depending on the workplace (median 1.74 ppm, range < 0.1-159.77 ppm). Urinary NMF concentrations were highest in post-shift samples. They also covered a wide range (< 1.0-108.7 mg/l). This variation was probably the result of different concentrations of DMF in the air at different workplaces, dermal absorption and differences in the protective measures implemented by each individual (gloves, gas masks etc.). The urinary NMF concentrations had decreased almost to zero by the beginning of the next shift. The median half-time for NMF was determined to be 5.1 h. The concentrations of AMCC in urine were determined to be in the range from < 0.5 to 204.9 mg/l. Unlike the concentrations of NMF, the AMCC concentrations did not decrease during the intervals between the shifts. For the exposure situation investigated in our study, a steady state was found between the external exposure to DMF and the levels of AMCC excreted in urine about 2 days after the beginning of exposure. AMCC is therefore excreted more slowly than NMF. The half-time for AMCC is more than 16 h. Linear regression analysis for external exposure and urinary excretion of metabolites was carried out for a sub-group of 12 workers. External exposure to 10 ppm DMF in air (the current German MAK value) corresponds to an average NMF concentration of about 27.9 mg/l in post-shift urine from the same day and an average AMCC concentration of 69.2 mg/l in pre-shift urine from the following day. NMF in urine samples therefore represents an index of daily exposure to DMF, while AMCC represents an index of the average exposure over the preceding working days. AMCC is considered to be better suited for biomonitoring purposes because (1) it has a longer half-time than NMF and (2) its formation in humans is more closely related to DMF toxicity.

Acetylcysteine↗

Occupational exposure to polycyclic aromatic hydrocarbons in a fireproof stone producing plant: biological monitoring of 1-hydroxypyrene, 1-, 2-, 3- and 4-hydroxyphenanthrene, 3-hydroxybenz(a)anthracene and 3-hydroxybenzo(a)pyrene.

OBJECTIVES: Assessment of external and internal exposure to polycyclic aromatic hydrocarbons (PAH) in a fireproof stone producing plant. METHODS: Five personal and four stationary air measurements were performed to determine the concentrations of benz(a)anthracene, benzo(a)pyrene, benzo(b)fluoranthene, chrysene, dibenz(a,h)anthracene, fluoranthene, phenanthrene and pyrene, in air. To estimate internal exposure, we determined the urinary excretion of 1-hydroxypyrene, 1-, 2-, 3-, and 4-hydroxyphenanthrene, 3-hydroxybenz(a)anthracene and 3-hydroxybenzo(a)pyrene in 19 workers, using a sensitive and reliable high-performance liquid chromatographic method with fluorescence detection. RESULTS: During the production of fireproof stones, the German technical exposure limit (TRK) for benzo(a)pyrene of 2 microg/m3 was exceeded in two cases. The mean values of the sum of eight PAHs were 12.6 microg/m3 (stationary air measurement) and 22.2 microg/m3 (personal air measurement). Urinary 1-hydroxypyrene excretion predominated, with a median of 11.1 microg/g creatinine (creat.), followed by 3-hydroxyphenanthrene (median 2.2 microg/g creat.), 1-hydroxyphenanthrene (median 1.9 microg/g creat.) and 2-hydroxyphenanthrene (median 1.6 microg/g creat.). 4-Hydroxyphenanthrene (median 0.3 microg/g creat.) and 3-hydroxybenz(a)anthracene (median 0.17 microg/g creat.) were found in far lower concentrations, while 3-hydroxybenzo(a)pyrene was found only in very low concentrations (median 0.014 microg/g creat.). No correlations could be detected for a relationship between external and internal exposure. A significant correlation between urinary metabolite concentrations could be calculated only for 3-hydroxybenz(a)anthracene and 1-hydroxypyrene. CONCLUSIONS: In comparison with other industries, the internal PAH exposure at workplaces in a fireproof stone producing plant is high. This is probably caused by dermal PAH-absorption. Therefore, biological monitoring must be performed in the health surveillance of fireproof stone producing workers. The urinary PAH metabolites should be determined: 3-hydroxybenz(a)anthracene could probably be used as a biomarker representing the group of carcinogenic PAH.

Adult↗

PCP in the blood plasma: current exposure of the population in Germany, based on data obtained in 1998.

The fungicidal substance pentachlorophenol (PCP) had been used commonly for wood protection and leather impregnation in Germany until 1989, when this substance was prohibited by law. Hence, the body burden in the general population in Germany has been steadily declining. The reference values (95th percentiles) in blood plasma decreased from 20 micrograms PCP/l in 1991 to 12 micrograms/l in 1996. In 1998 the current exposure in a large residential population was investigated. 623 persons with an average age of 34.6 years (0-62 years) were investigated. For all of them there was neither evidence of occupational contact with PCP nor of the presence of PCP in the residential indoor environment. The mean PCP concentration in the plasma samples was 2.4 +/- 3.9 micrograms/l, the median 1.7 micrograms/l, and the 95th percentile 6.1 micrograms/l, the maximum value was 59.3 micrograms/l. In children and adolescents higher median and 95th percentiles were obtained than in adults (median 2.5 vs. 1.5 micrograms/l and 95th percentile 7.7 vs. 5.9 micrograms/l). All values above 20 micrograms/l were checked again individually: relationships with the level of PCP in household dust could not be detected. In one family leather clothing containing PCP, however, was found to be the cause of unusually high PCP values in the blood. Our investigations confirm a trend observed in recent years: exposure to PCP in the population in Germany decreases steadily and leads to an actualized reference value of 6.1 micrograms PCP/l plasma. In individual cases, however, greatly increased PCP levels in blood can still occur today, for example due to leather clothing treated with PCP.

Adolescent↗

Parental smoking and neonatal serum levels of polychlorinated biphenyls and hexachlorobenzene.

Polychlorinated biphenyls (PCB) and hexachlorobenzene (HCB) are ubiquitous compounds that have tumor-promoting properties if applied together with tobacco-specific carcinogens. It was the purpose of the present study to investigate whether parental smoking by itself will increase the prenatal uptake of such organochloric compounds. With the informed consent of the parents, blood samples were taken from 80 full-term neonates before the first oral feeding. Six PCB congeners (PCB 28, 52, 101, 138, 153, and 180) and HCB were analyzed with capillary gas chromatography. Information about parental smoking behavior, the geographic origin of the parents, and their actual and previous working places was recorded. We composed three study groups for statistical analyses: active smoking mothers (n = 12), passive smoking mothers (n = 33), and nonsmoking families (n = 35). Neonates born to active smoking mothers had the highest PCB and HCB concentrations compared with children of passive or nonsmoking mothers. These differences were statistically significant (p < 0.01) in the cases of PCB 138, total PCB, and HCB. Newborns of passive smoking mothers had higher PCB and HCB concentrations than children of nonsmoking families but lower values than those of active smoking mothers. These differences were statistically significant for all compounds with the exception of PCB 180. It is concluded that active and passive maternal smoking increases the neonatal burden with PCB and HCB.

Environmental Monitoring↗

Simultaneous determination of two human urinary metabolites of N,N-dimethylformamide using gas chromatography-thermionic sensitive detection with mass spectrometric confirmation.

Two human urinary metabolites of the industrial solvent N,N-dimethylformamide (DMF), N-hydroxymethyl-N-methylformamide (HMMF) and N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC), were assayed using a new analytical method (gas chromatography and thermionic sensitive detection). Clean-up of urine samples includes a liquid-liquid extraction step followed by a solid-phase extraction step to separate HMMF and AMCC from other urine components. During clean-up, AMCC is converted into ethyl-N-methylcarbamate (EMC), and during gas chromatography, HMMF is degraded in the injector to N-methylformamide (NMF). All the validation data necessary for a quantitative procedure are given. The method was applied to urine samples from workers exposed to DMF and from the general population. The results were confirmed by mass spectrometric determination. For this purpose a further liquid-liquid extraction step was introduced in the clean-up procedure. Background levels of AMCC in the general population were identified.

Acetylcysteine↗

Determination of metabolites of pirimicarb in human urine by gas chromatography-mass spectrometry.

The analytical method described permits the determination of 2-dimethylamino-5,6-dimethyl-4-hydroxypyrimidine (DDHP), 2-methylamino-5,6-dimethyl-4-hydroxypyrimidine (MDHP) and 2-amino-5,6-dimethyl-4-hydroxypyrimidine (ADHP) in human urine. These hydroxypyrimidines are metabolites of pirimicarb (2-dimethylamino-5,6-dimethylpyrimidin-4-yldimethylcarbamate ) which is applied as insecticide. The analytes are extracted into a mixture of diethyl ether and acetonitrile. Pentafluorobenzyl bromide serves as derivatising reagent. The derivatives are analysed using capillary gas chromatography with mass selective detection. 2-Amino-4-hydroxy-6-methylpyrimidine and 4-hydroxy-6-trifluoromethylpyrimidine are used as internal standards. The detection limits are 0.5 microg/l (DDHP), 1 microg/l (MDHP) and 4 microg/l (ADHP), respectively. The method was used for analysing seven urine samples collected from workers who had applied pirimicarb. The three metabolites were found in every sample in concentrations up to 60 microg/l.

Carbamates↗

Biological monitoring of exposure to pirimicarb: hydroxypyrimidines in human urine.

Pirimicarb (2-dimethylamino-5,6-dimethylpyrimidin-4-yldimethylcarbamate ) is used as insecticide in agriculture and fruit growing. During its metabolism in mammals the carbamate moiety is hydrolysed and subsequent demethylation at the dimethylaminogroup which is attached to the heterocyclic moiety results in the following major metabolites which are excreted in urine: 2-dimethylamino-5,6-dimethyl-4-hydroxypyrimidine (DDHP), 2-methylamino-5,6-dimethyl-4-hydroxypyrimidine (MDHP), and 2-amino-5,6-dimethyl-4-hydroxypyrimidine (ADHP). These metabolites were detected in every urine sample of seven workers who had applied pirimicarb. Concentrations of the MDHP and ADHP were much higher than that of DDHP indicating a considerable demethylation capacity in humans. No metabolites were found in urine specimens of controls. The investigated pyrimidines represent sensitive and specific parameters for biological monitoring of exposure to pirimicarb.

Carbamates↗

Determination of urinary 2-thiazolidinethione-4-carboxylic acid after exposure to alkylene bisdithiocarbamates using gas chromatography-mass spectrometry.

This is a newly developed method which permits the quantitative determination of 2-thiazolidinethione-4-carboxylic acid (TTCA, an established biomarker of exposure to CS2) as a metabolite of alkylene bisdithiocarbamates (ABDCs) in human urine. After separation of TTCA from the urinary matrix using liquid-liquid extraction the analyte was converted into its diethyl derivative. Separation and quantitative analysis was carried out by capillary gas chromatography and mass selective detection in single ion monitoring mode. 4-(4-Chloro-2-methylphenoxy)butanoic acid (MCPBA) served as internal standard. The detection limit was 0.7 microg/l in urine. The relative standard deviation of the within-series imprecision was 4.3% at a concentration of 13 microg/l. The relative recovery was within the range of 86 to 98%. In order to determine the suitability of TTCA for biological monitoring after exposure to ABDCs, we analysed 87 24-h urine samples from occupationally exposed workers. The results were compared with the levels of TTCA excreted in urine by 50 control persons without known exposure to dithiocarbamates or CS2. This collective of unexposed persons also provided TTCA reference values for the general population. The urinary TTCA concentrations of the exposed persons were in the range from 0.8 microg/g creatinine to 515 microg/g creatinine. Unexposed persons excreted TTCA in concentrations from below the detection limit to 182 microg/g creatinine. The median concentration found in exposed persons (27 microg/g) was nearly 2.5 times higher than in non-exposed persons (11 microg/g). The difference between the exposed and unexposed collective was highly significant. Assessment of an individual's exposure by determining the level of TTCA in urine nevertheless was not possible. This was due to the relatively wide range of concentrations and because the ranges of both collectives overlapped.

Calibration↗

Gas chromatographic method with mass-selective detection for the determination of 2-isopropoxyphenol in human urine.

Human metabolism of the insecticide propoxur yields 2-isopropoxyphenol (IPP) which is excreted conjugated in urine. In this publication a sensitive and selective analytical method is described which permits the determination of IPP as a suitable parameter for biomonitoring. The clean-up of the hydrolysed urine samples consisted of steam distillation and solid-phase extraction using a reversed-phase column. IPP and the internal standard 2-ethoxyphenol were converted to their pentafluorobenzyl ethers. Excess of the derivatisation reagent was removed using deactivated silica gel. Separation and quantitative analysis was carried out by capillary gas chromatography and mass selective detection. Coefficients of variation were below 5% for concentrations from 6 to 300 microg/l. The detection limit was 0.5 microg/l. The method was checked by analysing six urine samples from pest controllers after indoor application of propoxur. The IPP concentrations ranged from 45 to 306 microg/g creatinine. IPP was not detected in urine specimens from 10 non-exposed persons. The sensitivity of the developed method permits the detection of latent exposure to propoxur.

Gas Chromatography-Mass Spectrometry↗

Occupational chronic exposure to organic solvents XVII. Ambient and biological monitoring of workers exposed to xylenes.

OBJECTIVE: Ambient-air and biological monitoring of occupational xylene exposure were carried out on 2 groups of workers (13 and 10 men, respectively) exposed to a mixture of xylenes during the production of paints or during spraying. METHODS: Personal ambient-air monitoring was performed for one complete work shift. Blood and urine samples were collected directly at the end of the shift. Biological monitoring was based on the determination of the concentration of xylenes in blood and on the quantification of the sum of the three methylhippuric acids in urine. RESULTS: Average xylene ambient-air concentrations were 29 ppm (production) and 8 ppm (spraying), ranging from 5 to 58 ppm and from 3 to 21 ppm, respectively. The concentrations of xylenes in blood ranged from 63 to 715 microg/l and from 49 to 308 microg/l, with average values being 380 and 130 microg/l, respectively. Accordingly, the workers engaged in paint production also excreted more methylhippuric acids in their urine (average 1221 mg/l, range 194 2333 mg/l) than did the sprayers (average 485 mg/l, range 65-1633 mg/l). DISCUSSION: Our results as well as a literature review indicate that occupational xylene exposure on average barely exceeds the threshold limit value of 100 ppm as proposed by both American and German institutions. Biological monitoring based on the determination of xylenes in blood and of methylhippuric acids in urine provides sufficient sensitivity and specificity for occupational health surveillance. The results also confirm the current limit values (BAT values) proposed by the Deutsche Forschungsgemeinschaft for xylenes in blood (1500 microg/l) and methylhippuric acids in urine (2000 mg/l).

Adult↗

Determination of N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) in the general population using gas chromatography-mass spectrometry.

Carbamoylation of glutathione, peptides and DNA is thought to be one of the most important reactions occurring in an organism after exposure to nitrosoureas, methylformamides or isocyanates. The carcinogenic effects of carbamoylation are not yet fully clarified. Although carbamoylation is known to occur after occupational exposure, it has never been reported in the general population. To clarify the situation, we investigated the levels of N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) in urine samples from persons without occupational exposure using a sensitive and specific method (gas chromatography-mass spectrometry, GC-MS). AMCC is the degradation product of N-methylcarbamoylated glutathione. The clean-up procedure of urine samples includes two liquid-liquid extraction steps and solid phase extraction using a cation-exchange resin to separate AMCC from other urinary components. N,N-Dimethylpropionic acid amide (DMPA) is used as internal standard. During the preparation of the samples, AMCC is converted to ethyl-N-methylcarbamate (EMC) in the presence of anhydrous potassium carbonate (K2CO3) and ethanol. The reliability and accuracy of this method have been proven in detail. The relative standard deviation for the within-series imprecision for three different concentrations was determined to be between 10.9% and 14.3%, while the relative standard deviation for the between-day imprecision was between 11.3% and 14.8%. The mean recovery for AMCC was determined to be between 79.2% and 85.6%. The limit of detection for the simultaneous measurement of two fragment masses was 30 micrograms L-1. Using this GC-MS method, we analysed urine samples from 42 individuals of the general population in order to determine their urinary excretion of AMCC. It was identified in 40 samples. The mean concentration was 40 micrograms L-1. AMCC can be formed in two ways. The first possibility is the dietary intake of isothiocyanates, especially methyl isothiocyanate, which is a component of wine and cruciferous vegetables (such as cabbage, turnips and cress). During the metabolism of isothiocyanates in humans, the sulfur is partly exchanged for oxygen resulting in the formation of the corresponding isocyanate derivatives. The other possibility is the physiological formation of AMCC. In humans, this may occur via a two step process: carbamoylation and methylation, or vice versa. However, as AMCC was identified in about 95% of urine samples, and the standard deviation for the level of AMCC excreted was low, physiological formation seems to be the more probable pathway.

Acetylcysteine↗

Lead induced anaemia due to traditional Indian medicine: a case report.

Lead intoxication in adults without occupational exposure is a rare and unexpected event. The case of a western European is reported who had severe anaemia after ingestion of several ayurvedic drugs, obtained during a trip to India. Laboratory findings showed high blood lead concentrations, an increased urinary lead concentration, and an increased urinary excretion of delta-aminolaevulinic acid. Also, slightly increased urinary concentrations of arsenic and silver were found. Physicians should be aware that with growing international travel and rising self medication with drugs from uncontrolled sources the risk of drug induced poisoning could increase in the future.

Adult↗