Biomedical subjects

J Angerer

Publications and source records attributed to J Angerer.

At least 37 records · Page 2Linked to original sources

PubMed2002

New gas chromatographic-mass spectrometric method for the determination of urinary pyrethroid metabolites in environmental medicine.

We have developed and validated a new, reliable and very sensitive method for the determination of the urinary metabolites of the most common pyrethroids in one analytical run. After acidic hydrolysis for the cleavage of conjugates, the analytes cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cis-Cl(2)CA), trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (trans-Cl(2)CA), cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Br(2)CA), 4-fluoro-3-phenoxybenzoic acid (F-PBA) and 3-phenoxybenzoic acid (3-PBA) were extracted from the matrix with a liquid-liquid extraction procedure using n-hexane under acidic conditions. For further clean-up, NaOH was added to the organic phase and the carboxylic acids were re-extracted into the aqueous phase. After acidification and extraction into n-hexane again, the metabolites were then derivatised to volatile esters using N-tert.-butyldimethylsilyl-N-methyltrifluoroacetamid (MTBSTFA). Separation and detection were carried out using capillary gas chromatography with mass-selective detection (GC-MS). 2-Phenoxybenzoic acid (2-PBA) served as internal standard for the quantification of the pyrethroid metabolites. The limit of detection for all analytes was 0.05 microg/l urine. The RSD of the within-series imprecision was between 2.0 and 5.4% at a spiked concentration of 0.4 microg/l and the relative recovery was between 79.3 and 93.4%, depending on the analyte. This method was used for the analysis of urine samples of 46 persons from the general population without known exposure to pyrethroids. The metabolites cis-Cl(2)CA, trans-Cl(2)CA and 3-PBA could be found in 52, 72 and 70% of all samples with median values of 0.06, 0.11 and 0.16 microg/l, respectively. Br(2)CA and F-PBA could also be detected in 13 and 4% of the urine samples.

Adolescent↗

PubMed2002

Quality assurance of biological monitoring in occupational and environmental medicine.

Biological monitoring of chemical exposure in the workplace has become increasingly important in the assessment of health risk as an integral part of the overall occupational health and safety strategy. In environmental medicine biological monitoring plays also an important role in the assessment of excessive, acute or chronic exposure to chemical agents. To guarantee that the results obtained in biological monitoring are comparable with threshold limit values and results from other laboratories, the analysis must be carried out with tested and reliable analytical methods and accompanied by a quality assurance scheme. Confounding influences and interferences during the pre-analytical phase can be minimised by recommendations from experienced laboratories. For internal quality control commercially available control samples with an assigned concentration are used. External quality control programs for biological monitoring are offered by several institutions. The external quality control program of the German Society of Occupational and Environmental Medicine has been organised since 1982. In the meantime the 27th program has been carried out offering 96 analytes in urine, blood and plasma for 47 substances. This program covers most of the parameters relevant to occupational and environmental medicine. About 350 laboratories take part in these intercomparison programs. At present, ten German and 14 international laboratories are commissioned to determine the assigned values. The data evaluated from the results of the intercomparison programs give a good overview of the current quality of the determination of analytes assessed in occupational and environmental toxicological laboratories. For the analysis of inorganic substances in blood and urine the tolerable variation ranges from 7.5 to 43.5%. For organic substances in urine the tolerable variation ranges from 12 to 48%. The highest variations (36-60%) were found for the analysis of organochlorine compounds in plasma. The tolerable variations for the determination of solvents in blood by head space gas chromatography range from 26 to 57%. If the recommendations for the pre-analytical phase, the selection of reliable analytical methods by the laboratory and the carrying out of adequate quality control are observed, the pre-requisites for reliable findings during biological monitoring are fulfilled

Chromatography↗

PubMed2002

Ambient and biological monitoring of coke plant workers -- determination of exposure to polycyclic aromatic hydrocarbons.

OBJECTIVES: The aims of this study were to determine external and internal polycyclic aromatic hydrocarbon (PAH) exposure in a coke plant and to contribute to the evaluation of biological limit values. METHODS: Personal air sampling was carried out on a study population of 24 coke plant workers. In detail, 16 PAHs were determined, among them phenanthrene, pyrene and benzo[ a]pyrene. For the determination of internal exposure, post-shift urine samples from the workers were examined for hydroxylated metabolites of pyrene (1-hydroxypyrene, 1-OHP) and phenanthrene (1-, 2+9-, 3-, 4-hydroxyphenanthrene, 1-, 2+9-, 3-, 4-OHPhe). In both cases, approved HPLC methods were used. RESULTS: The workers were classified into three groups. The group most exposed was that on the top side of the coke oven, with a mean value of 491.2 microg/m(3) for the sum of all sixteen PAHs. The mean value at the bench side was 26.61 microg/m(3), while it was 76.18 microg/m(3) in the group of workers with no dedicated location (=complete area). Both the excretion of 1-OHP and the sum of hydroxyphenanthrenes had the highest mean levels in the top side group of workers (mean: 19.70 microg/g creatinine (crea.) and 39.18 microg/g crea.), followed by the bench-side workers (mean: 7.01 microg/g crea. and 12.95 microg/g crea.) and the whole-area workers (mean: 3.57 microg/g crea. and 8.70 micorg/g crea.). The concentrations of all urinary metabolites correlated significantly with benzo[ a]pyrene (BaP) in the air. CONCLUSIONS: According to these correlations, urinary concentrations of 8 and 11 microg 1-OHP/g crea., respectively 16 and 23 microg/g crea. for the sum of hydroxyphenanthrenes, correspond to BaP concentrations in air of 2 and 5 micorg/m(3), the German technical guiding concentration (TRK value). Our results are in line with others reported in the literature. That means that it should be possible today to define a standard of occupational hygiene and medicine in coke plants using the elimination of hydroxyphenanthrenes and hydroxypyrene in urine as markers for internal PAH exposure.

Adult↗

PubMed2002

Analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine and DNA strand breaks in white blood cells of occupationally exposed workers: comparison with ambient monitoring, urinary metabolites and enzyme polymorphisms.

The relationship between biomarkers of effect (8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo, HPLC system) and tail extent moment (comet assay)), markers of external and internal exposure, and biomarkers of susceptibility was evaluated for coke-oven and graphite-electrode-producing plant workers exposed to polycyclic aromatic hydrocarbons (PAHs). Mean 8-oxodGuo levels in white blood cells (WBC) of exposed workers were between 1.38 times (coke-oven, n = 20; P < 0.01) and 2.15 times (graphite-electrode-producing plant, n = 30; P < 0.01) higher than levels found in control samples (mean +/- SD 0.52 +/- 0.16 8-oxodGuo/10(5) dGuo, n = 47). The mean tail extent moment in lymphocytes was 1.38 times higher for coke-oven workers (n = 19; P = 0.09) and 3.13 times higher for graphite-electrode-producing plant workers (n = 29; P < 0.01) when compared with controls (mean plus minus SD 2.54 +/- 0.68, n = 32). Elevated tail extent moments (>3.73) were found in the majority (84%) of PAH-exposed workers showing increased DNA adduct levels (>0.78 8-oxodGuo/10(5) dGuo). However, no association (P > 0.05) was found between DNA damage (8-oxodGuo/10(5) dGuo or tail extent moment) in WBC of all PAH-exposed workers and either benzo[a]pyrene levels or the sum of 16 PAH levels in the air at work place. Furthermore, no relation (P > 0.05) could be established between DNA damage in WBC and biomarkers of internal exposure (1-hydroxypyrene (1-OHP) and sum of five hydroxyphenanthrenes (OHPHs)). Higher exposure to airborne pyrene and phenanthrene led to increasing concentrations of the metabolites 1-OHP (P < 0.01) and the sum of five OHPHs (P < 0.01) in the urine of PAH-exposed workers. The polymorphisms of genes CYP1A1, GSTM1, GSTT1 and GSTP1 (biomarkers of susceptibility) showed no association with biomarkers of effect. In conclusion, both biomarkers of effect may be appropriate for further surveillance studies of workers under PAH exposure.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2001

Determination of palladium in human urine by high-performance liquid chromatography and ultraviolet detection after ultraviolet photolysis and selective solid-phase extraction.

The high-performance liquid chromatographic method with UV detection described below permits the selective determination of traces of palladium in human urine. After UV photolysis, during which the complete organic matrix was destroyed, the palladium was selectively enriched by solid-phase extraction (SPE). The reversed-phase C18 SPE column material was loaded with the ligand N,N-diethyl-N'-benzoylthiourea (DEBT) which shows an excellent complexing capacity for palladium in acidic solutions and at room temperature. The Pd(DEBT)2 complex was eluted with ethanol. After isocratic separation on the analytical column (MeOH/H2O 98:2 (v/v)), the complex was detected at 274 nm. The detection limit was 10 ng Pd/l. The relative standard deviations (RSD) of the within-series imprecision were in the range between 11% (75 ng Pd/l) and 7% (180 ng Pd/l). The between-day imprecision was 11% (75 ng Pd/l) and 5% (180 ng Pd/l). The recovery rates ranged between 94 and 96%. Using this method, urine samples of 44 persons from the general population were analysed. Only in one urine sample could palladium be detected. For comparison, 10 persons with occupational palladium exposure were examined. The urinary concentrations ranged from <10 to 2,538 ng/l.

Calibration↗

PubMed2001

Analysis of 3,5,6-trichloro-2-pyridinol in urine samples from the general population using gas chromatography-mass spectrometry after steam distillation and solid-phase extraction.

We have developed a new method for the quantitative trace determination of 3,5,6-trichloro-2-pyridinol (TCPyr). TCPyr is a urinary metabolite specific to the organophosphorus pesticides chlorpyrifos and chlorpyrifos-methyl. After hydrolysis and separation of TCPyr from the urinary matrix using semi-automated steam distillation and solid-phase extraction on a new polystyrol-divinylbenzene copolymer (Isolute 101) the analyte was converted into its tert-butyldimethylsilyl derivative by N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA). Separation and quantitative analysis were carried out by capillary gas chromatography and mass selective detection in selected ion monitoring mode. 2,6-Dibromophenol (DBP) was used as the internal standard. The detection limit was 0.05 microg/l; the limit of quantification was 0.1 microg/l urine. The relative standard deviation of the within-series imprecision was 4.2% at a concentration of 3.5 microg/l. The relative recovery was 104%. The new method was used to analyse the urine samples of 12 persons from the general population without known exposure to the above-mentioned pesticides. TCPyr concentrations between 0.27 and 6.6 microg/l urine were detected in all urine samples. This indicates that there is a baseline excretion of TCPyr in the general population. Four urine samples collected from workers who had applied chlorpyrifos were also analysed. In these samples TCPyr was found in concentrations from 4.7 to 7.9 microg/l.

Calibration↗

PubMed2001

Chromosome painting for cytogenetic monitoring of occupationally exposed and non-exposed groups of human individuals.

The suitability of a three-color fluorescence in situ suppression hybridization technique was examined for monitoring five different groups of individuals: 30 occupied in radiology, 26 occupied in nuclear medicine or radiation physics, 32 patients with breast cancer, 26 occupied with military waste disposal, all presumably exposed to low doses of radiation or chemical mutagens and a non-exposed control group (N=29). The average frequency of breaks constituting the various aberrations did not significantly differ between the groups of medical radiation appliers and the control group. However, breast tumor patients and military waste disposers, as groups, showed a higher aberration rate than did healthy controls. Stable rearrangements mainly characterized the groups of controls, tumor patients, and radiation appliers, while a higher proportion of unstable aberrations was found in the chemically exposed individuals. Individuals with an increased frequency of aberrations could be detected within each examined group, which clearly determined the average values of the whole group. With respect to interchromosomal distribution of the breakpoints constituting the found aberrations and the involvement of the labeled chromosomes in rearrangements, the observed values were very close to the expected ones in the controls. A rather similar trend of deviations from expectation was observed in all other groups. Chromosome 4 was slightly over-affected, while chromosome 2 was slightly underrepresented in all analyzed groups (except tumor patients). Rearrangements of the labeled chromosomes with the unlabeled ones exceeded expectation. In conclusion, chromosome painting if included in further attempts of human population monitoring will broaden the basis of argumentation with respect to health risks introduced by mutagen exposure.

Adult↗

PubMed2001

Metabolites of organophosphorous insecticides in urine specimens from inhabitants of a residential area.

The most frequently used pesticide in U.S. homes, as well as in schools and day care centers, is chlorpyrifos. In 1998, this insecticide was detected in household dust from the former U.S. Forces housing estates in Frankfurt am Main, Germany, resulting from its earlier use up to 1993, i.e., at least 4 years ago. This led to great concern in the new inhabitants. To investigate their internal exposure to the substance, they were offered the opportunity of taking part in biomonitoring examinations. Children playing on the floor were assumed to be especially at risk due to increased exposure to chlorpyrifos via oral or dermal intake. A total of 1146 inhabitants took part in this voluntary investigation. All of them stated that they had never used chlorpyrifos in their homes. Spot urine samples of the study participants were analyzed for six metabolites of organophosphorous insecticides [dimethylphosphate (DMP), diethylphosphate (DEP), dimethylthiophosphate (DMTP), diethylthiophosphate (DETP), dimethyldithiophosphate (DMDTP), and diethyldithiophosphate (DEDTP)] using a very sensitive gas chromatographic method with mass-selective detection and a limit of detection of 1 microg/L. No evidence was found of increased internal exposure due to former chlorpyrifos application in these homes (>4 years ago), either in children or in adults. The median values and 95th percentiles of the urinary metabolite concentrations in 484 adults were (microg/g creatinine): DMP, 15.5 and 102.5; DMTP, 13.5 and 125.8; DMDTP, <1 and 13.1; DEP, 2.1 and 11.6; DETP, <1 and 6.4; DEDTP, both <1. The urinary metabolite concentrations in children <6 years of age were higher; this was caused mainly by lower creatinine concentrations. To conclude, no increase in internal exposure due to former indoor application of chlorpyrifos could be found, and the reference values published for internal organophosphate exposure in adults in Germany were confirmed. However, as shown in other environmental studies, the urinary excretion of organophosphorous metabolites exceeds dietary intake several fold; this has been estimated from the data in various duplicate dietary studies. This observation calls for further investigation.

Adolescent↗

PubMed2001

Biological monitoring of phenmedipham: determination of m-toluidine in urine.

Phenmedipham [methyl-3-(3-methylphenylcarbamoyloxy)carbamate] is used as a herbicide, especially in the growing of sugar beet and strawberries. During metabolism of the substance in rats, the two carbamate moieties of phenmedipham are cleaved and the metabolites methyl-N-(3-hydroxyphenyl)-carbamate, m-aminophenol and hydroxyacetanilide are formed. These compounds and their conjugates are excreted in urine. Additionally, it has been suggested that m-toluidine is formed during metabolism. For the first time it has been possible to detect this metabolite in the urine of workers after agricultural use of phenmedipham. The concentrations of m-toluidine in urine were significantly higher in persons occupationally exposed than in controls. The median values for each group were 0.36 microg/l and 0.16 microg/l, respectively. This means that persons not exposed to phenmedipham also excrete m-toluidine, possibly as a result of the uptake of pesticides like phenmedipham from the diet.

Adult↗

PubMed2001

Internal exposure to polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/PCDFs) of Bavarian chimney sweeps.

This study was carried out to evaluate the internal exposure to polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/PCDFs) of chimney sweeps in Bavaria compared to a control group without occupational exposure. The PCDD/PCDF concentrations in the blood fat of 227 chimney sweeps were compared with the concentrations in samples from 60 controls. Using an internal standard containing 17 (13)C(12)-labeled PCDD/F congeners, the samples were cleaned up after fat elution using standard methods. The statistical analysis was adjusted to account for demographic differences, dietary habits, smoking status, and both occupational and nonoccupational contact with chlorinated hydrocarbons. Detailed information on the type of heating in the households swept, the length of time the chimney sweeps had carried out the profession (min 34, med 195, max 466 months) and the protective measures employed, were used to examine the influence of the working conditions specific to chimney sweeps on the internal PCDD/PCDF exposure. The correlation between blood-fat PCB concentrations as well as urinary chlorophenol concentrations and the exposure to PCDDs/PCDFs was evaluated. The sum of PCDD/PCDF components in chimney sweeps, expressed by International Toxic Equivalents (I-TEQ), was significantly increased compared to the control group (median: 26.36 versus 20.75 pg I-TEQ/g blood fat). For 37 chimney sweeps (16.3%) the sum of PCDDs/PCDFs exceeded the 95th percentile of the control group, i.e., 38.23 pg I-TEQ/g blood fat. Multiple regression analysis revealed that in addition to occupation, the variables age, district, and proximity to a waste incineration plant seem to have an effect on the internal PCDD/PCDF exposure. An additional influence on the internal exposure could not be determined for any of the special aspects of the work. We identified no high correlations between the concentrations of PCBs and chlorophenols and PCDDs/PCDFs. This study revealed significantly higher internal exposure to PCDDs/PCDFs in chimney sweeps than in the control group. The differences are small and within the range of the internal exposure to PCDDs/PCDFs in blood found in the general population in Germany since 1989. Further investigations in to PCDD/PCDF-related diseases in these study groups were not carried out.

Adult↗

PubMed2001

Internal exposure to PAHs of children and adults living in homes with parquet flooring containing high levels of PAHs in the parquet glue.

UNLABELLED: PAHs form during the incomplete combustion of organic substances and hence they are distributed ubiquitously in the environment. PAHs in the diet are the main source of exposure in man. In 1997 a new source of potential PAH exposure was discovered: very high levels of polycyclic aromatic hydrocarbons (PAHs) and benzo-a-pyrene (BaP) were detected in household dust from former American Forces housing in Frankfurt am Main, Germany, built in 1955/1956. This contamination was caused by a parquet glue containing coal tar, the use of which was formerly standard building practice in Germany. Because the inhabitants of these flats were very concerned about the effects on their health, they were offered the opportunity to take part in biomonitoring examinations to assess individual internal PAH exposure. PARTICIPANTS AND METHODS: 1213 inhabitants from 511 flats/houses took part in the investigation; this corresponds to 12.7% of the total inhabitants of the former US housing estates in Frankfurt am Main. Spot urine samples were collected and frozen until analysis for 1-, 2-, 3- and 4-hydroxyphenanthrene and 1-hydroxypyrene, which was carried out using a very sensitive and practical high performance liquid chromatographic method with fluorescence detection, approved by the Deutsche Forschungsgemeinschaft. RESULTS: The level of internal exposure to PAHs in study participants living in homes where parquet glue containing PAHs had been used did not differ from the levels found in participants in whose homes PAH-containing parquet glue was not used. This was true for the whole group as well as subgroups divided according to age and smoking behaviour. Internal exposure was not influenced by different levels of external exposure (BaP in parquet glue and in household dust). Spearman rank correlations between the level of BaP in parquet glue and in household dust were low and insignificant. CONCLUSION: An increase in internal PAH exposure due to high levels of PAHs in parquet glue and household dust could not be detected. This confirms earlier results with small collectives, where only low and insignificant trends were found towards higher internal PAH exposure caused by contaminated homes. Therefore, the ad-hoc working group of the Commission for Indoor Air Quality of the German Federal Environmental Agency stated that a definitive threshold limit value cannot be defined for PAH contamination in parquet glue and household dust. For reasons of disease prevention, however, BaP contamination in household dust exceeding 10 mg/kg should be minimised.

Adhesives↗

PubMed2001

Urinary monohydroxylated phenanthrenes and hydroxypyrene--the effects of smoking habits and changes induced by smoking on monooxygenase-mediated metabolism.

OBJECTIVES: Internal polycyclic aromatic hydrocarbon (PAH) exposure is usually studied by determining 1-hydroxypyrene in urine. In many studies, increased urinary levels of 1-hydroxypyrene have been found in smokers compared with non-smokers. The disadvantage of this procedure, however, is that it is based on only one substance. Therefore, in our study, urine specimens from smokers and non-smokers were tested for four monohydroxylated phenanthrenes in addition to 1-hydroxypyrene. SUBJECTS AND METHODS: Spot urine samples from 288 non-smokers and 100 smokers were analysed for 1-, 2-, 3- and 4-hydroxyphenanthrene and 1-hydroxypyrene by a very sensitive high performance liquid chromatography (HPLC) method with fluorescence detection. The detection limit of the method is 5 ng metabolite/l urine. The data were calculated on a creatinine basis (ng/g creatinine). RESULTS: Highly significant differences and dose-response relationships with regard to cigarettes smoked per day were found for 2-, 3- and 4-hydroxyphenanthrene and 1-hydroxypyrene, but not for 1-hydroxyphenanthrene. When the ratio of the sum of hydroxyphenanthrenes to 1-hydroxypyrene, and the ratio of 1- and 2-/3- and 4-hydroxyphenanthrene were taken into consideration, significant negative dose-response relationships to the numbers of cigarettes smoked per day, were found. CONCLUSION: 1-Hydroxypyrene as well as 2-, 3- and 4-monohydroxylated phenanthrenes in urine may be used as parameters to detect PAH exposure from cigarette smoking. Moreover, 3,4-oxidation of phenanthrenes was found to be enhanced in smokers, with a significant dose-response relationship. This phenomenon is thought to be caused by an induction of the CYP 1A2 (or CYP 3A4) monooxygenase system in smokers. Therefore, it may be recommended that monohydroxylated phenanthrenes be analysed in order to assess the balance between the PAH-metabolising cytochrome isoforms, and the activity or induction of cytochrome P450 isoforms, respectively.

Adult↗

PubMed2001

Trends in the musk xylene concentrations in plasma samples from the general population from 1992/1993 to 1998 and the relevance of dermal uptake.

OBJECTIVES: Musk xylene (MX), an environmentally important nitromusk compound, is used in different fragrances and soaps as substitute for natural musk. MX is known to occur in breast milk and plasma samples from the general population. Biological monitoring was carried out to study the change in MX concentrations in plasma from the general population over a period of about 6 years. METHODS: Forty-one human plasma samples from the general population were collected and analyzed in 1998. The MX concentrations in plasma were compared with those in samples collected from the general population in 1992/1993. In order to study possible routes of exposure, we also analyzed perfumes (n = 8), various body-care products (n = 17), and detergents (n = 5) in the households from the persons who were exposed in 1998. The body-care products or the detergents were used every day or at least 3 -4 times per week. RESULTS AND DISCUSSION: A remarkable decrease in MX levels was found on comparing the values from 1992,1993 and 1998. In 1998 12% (five out of 41) of the samples analyzed yielded positive results for MX (median: <0.1 microg/l, range: <0.1-0.29 microg/l), while in 1993 MX was found in 92% (66 out of 72) of the samples (median: 0.24 microg/l, range: <0.1- 1.12 microg/l). The observed decrease is explained by the discontinued use of MX in detergents in Germany since 1993. As a consequence, no MX could be found in the investigated detergents in the present study. However, MX could be analyzed in at least one perfume and/or perfumed bodycare product of the exposed individuals. The concentrations were in the range between 8.8 and 28.8 mg/kg in the investigated products. Because other confounding factors, e.g. diet and occupational exposure, could be excluded, the results point to the possibility that MX can be taken up through the skin. However, the small number of investigated persons limits this assumption.

Adult↗

PubMed2001

N-methylcarbamoylated valine of hemoglobin in humans after exposure to N,N-dimethylformamide: evidence for the formation of methyl isocyanate?

N,N-Dimethylformamide (DMF) is reported to cause testicular germ-cell tumors in exposed workers. The reports, however, are not in line with results obtained in animal and in vitro experiments, where DMF was shown not to be mutagenic and also not to be carcinogenic. Considerable interest raised on the formation of a reactive intermediate, presumably methyl isocyanate (MIC), during metabolism of DMF in humans over the last years. We report the formation of N-methylcarbamoylated valine of hemoglobin (Hb) in blood samples from workers exposed to DMF in the polyacrylic fiber industry. N-Methylcarbamoylated Hb was formed by the reaction of MIC with Hb. For this purpose, Hb adducts were monitored by means of a modified Edman degradation involving the release of the N-terminal valine adduct in form of 3-methyl-5-isopropylhydantoin (MIH). For internal standardization of the method, 3-ethyl-5-isopropylhydantoin (EIH) was used. Separation and analysis of MIH and EIH were carried out by gas chromatography and mass spectrometry with electron impact ionization (GC/EI-MS). Hb adducts in form of MIH were quantified in blood samples from exposed persons in concentrations between 26.1 and 412.0 nmol of MIH/g of globin. The observed adducts were proven to be identical to those derived from the in situ reaction between Hb and MIC. Taken together with the fact that only N-methylcarbamoylated Hb can undergo ring closure to the corresponding hydantoin, the reaction is indirect evidence for the occurrence of MIC in vivo. The formation of MIC directly in the cell and its possible distribution through the human body may lead to critical effects after exposure to DMF. Adducts were determined not to be totally specific for exposure to DMF since an identical adduct was also found in blood samples from the general population. However, concentrations were lower by a factor of about 100. The sources for background adducts are currently unknown.

Antisickling Agents↗

PubMed2001

Biological monitoring of exposure of the general population to the organophosphorus pesticides chlorpyrifos and chlorpyrifos-methyl by determination of their specific metabolite 3,5,6-trichloro-2-pyridinol.

In this study we determined the concentrations of 3,5,6-trichloro-2-pyridinol (TCPyr) in urine samples from the general population. TCPyr is a specific metabolite of the organophosphorus pesticides chlorpyrifos and chlorpyrifos-methyl. By the introduction of a new sensitive analytical method a limit of quantification (LOQ) of 0.1 microgram per litre urine could be achieved, a tenfold improvement of recent methods. Extraction of TCPyr from the urine and the clean up process were carried out by automatic steam distillation. Separation and quantitative analysis were performed using capillary gas chromatography and mass selective detection in selected ion monitoring mode. The excretion of TCPyr was studied by analysing spontaneous urine samples from 5 women and 45 men between the ages of 22 and 57 (median: 40 years) living in Mecklenburg-Vorpommern (Germany) who were not occupationally exposed to organophosporus pesticides. TCPyr was detected in all specimens and the concentrations were quantified. The median excretion was 1.4 micrograms/l (range: 0.12 to 124.8 micrograms/l), the 95th percentile 11.3 micrograms/l. Under the worst case assumption that all TCPyr measured in urine originated from the intake of intact pesticides and not (less toxic) breakdown products, a TCPyr concentration of 1.4 micrograms/l urine corresponds to a daily intake of approximately 2.5 micrograms chlorpyrifos/chlorpyrifos-methyl. The intake at the 95th percentile would be about 23 micrograms chlorpyrifos/chlorpyrifos-methyl per day. According to FAO/WHO the acceptable daily intake (ADI) is 10 micrograms per kg bodyweight and day for both chlorpyrifos and chlorpyrifos-methyl.

Adult↗

PubMed2001

Exposure assessment in the hard metal manufacturing industry with special regard to tungsten and its compounds.

OBJECTIVES: To assess the exposure to tungsten, cobalt, and nickel in a plant producing hard metals. The main components of hard metals are tungsten carbide and cobalt metal. According to recent studies, these two components may be responsible for both fibrogenic and carcinogenic effects. METHODS: 87 workers were investigated (86 male, one female) with a median age of 42 (range 22-58) and a mean duration of exposure of 13 years (range 1-27 years). Stationary and personal air sampling, and biological monitoring were carried out. RESULTS: Ambient monitoring yielded maximum tungsten concentrations of 417 microg/m3 in the production of heavy alloys. A maximum cobalt concentration of 343 microg/m3 and a maximum nickel concentration of 30 microg/m3 were found at the sintering workshop. The highest urinary cobalt concentrations were found in the powder processing department. The mean concentration was 28.5 microg/g creatinine and the maximum value was 228 microg/g creatinine. The maximum nickel concentration in urine of 6.3 microg/g creatinine was detected in the department producing heavy alloys. The highest tungsten concentrations excreted in urine were found in grinders and had a mean value of 94.4 microg/g creatinine and a maximum of 169 microg/g creatinine. Due to the different solubility and bioavailability of the substance, there was no correlation between the tungsten concentrations in air and urine on a group basis. CONCLUSIONS: Despite its low solubility, tungsten carbide is bioavailable. The different bioavailability of tungsten metal and tungsten compounds has to be considered in the interpretation of ambient and biological monitoring data in the hard metal producing industry. The bioavailability increases in the order: tungsten metal, tungsten carbide, tungstenate. Only if both monitoring strategies are considered in combination can a valid and effective definition of high risk groups be derived.

Adult↗

PubMed2001

Metabolites of pyrethroid insecticides in urine specimens: current exposure in an urban population in Germany.

Pyrethroids are important insecticides used in agriculture, forestry, horticulture, and in the home. In humans, they are rapidly metabolized and renally eliminated. In numerous studies, pyrethroid metabolites have been detected in urine after occupational exposure to insecticides. In this study, we used a new, reliable, easy, and sensitive analytical method to assess the internal pyrethroid exposure of an urban population without exposure to pyrethoids at home or at work (children and adults). A total of 1,177 persons took part in this investigation, including 331 children under 6 years of age and 247 children between 6 and 12 years of age. None of them reported exposure to pyrethroids at home or at work. Accordingly, the levels of permethrin found in household dust from their homes were lower than expected (median < limit of detection; 95th percentile, 4.8 mg/kg; maximum value, 19 mg/kg). Urine specimens were analyzed for cis-3-(2,2-dibromo-vinyl)-2,2-dimethylcyclo-propanecarboxylic acid (Br(2)CA), cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-carboxylic acid (cis-Cl(2)CA and trans-Cl(2)CA), and 4-fluoro-3-phenoxybenzoic acid (F-PBA) using a gas chromatographic method with mass-selective detection. The limit of detection for pyrethroid metabolites was between 0.1 and 0.2 microg/L. trans-Cl(2)CA was detected in 65% of the urine specimens tested, cis-Cl(2)CA was detected in 30%, and Br(2)CA and F-PBA were found in 19% and 16%, respectively, of the urine specimens. The urinary metabolite levels in children did not differ from those in adults, and there was no correlation between the levels of metabolites and indoor exposure to permethrin in household dust. Moreover, no seasonal correlations could be found. The 95th percentile levels in urine specimens were as follows: Br(2)CA, 0.30 microg/L; cis-Cl(2)CA, 0.51 microg/L; trans-Cl(2)CA, 1.43 microg/L; F-PBA, 0.27 microg/L. Background exposure to pyrethroids was found in the general population; it seems to be caused by the uptake of pyrethroids with the diet. This hypothesis needs to be tested in duplicate diet studies combined with biomonitoring. As long as representative data are lacking, however, the rounded 95th percentile values obtained in our study may be used as reference values for pyrethroid metabolites in urine samples from the population in Germany; 95th percentile values for children and adults are as follows: Br(2)CA, 0.3 microg/L; cis-Cl(2)CA, 0.5 microg/L; trans-Cl(2)CA, 1.5 microg/L; and F-PBA, 0.3 microg/L.

Adolescent↗

PubMed2000

Longitudinal study of neurotoxicity with occupational exposure to aluminum dust.

Two cross-sectional studies were conducted at a German aluminum (Al) powder plant to evaluate possible nervous system effects from occupational Al exposure. The investigation included biological monitoring, a neuropsychological test battery, and event-related P300 potentials. Neurophysiologic findings in workers chronically exposed to Al dust did not differ from non-Al-exposed controls from the same plant. The authors suggest that chronic exposure to Al dust, at the levels documented in this study, does not induce measurable cognitive decline.

Adult↗