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Biomedical subjects

J Angerer

Publications and source records attributed to J Angerer.

At least 19 recordsLinked to original sources

Transplacental exposure of neonates to perfluorooctanesulfonate and perfluorooctanoate: a pilot study.

OBJECTIVES: Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) can be released of perfluorinated compounds by biotic and/or metabolic decomposition. Due to their ubiquitous occurrence, persistence and bioaccumulative properties they can be found in blood of the general population all over the world. In animal studies PFOS and PFOA provoked cancer and showed developmental toxic potential besides other adverse health effects. On the basis of the comparison of maternal and umbilical cord plasma sample pairs we wanted to examine whether infants are exposed to PFOS and PFOA via their mothers' blood. METHODS: We determined PFOS and PFOA in 11 plasma samples of mothers and the 11 corresponding cord plasma samples of neonates. An analytical method based on plasma protein precipitation followed by HPLC with MS/MS-detection was employed. As internal standards we used 1,2,3,4-(13)C(4)-PFOS and 1,2-(13)C(2)-PFOA. RESULTS: We found PFOS and PFOA in every plasma sample analysed. In maternal plasma samples PFOS concentrations were consistently higher compared to those of the related cord plasma samples (median: 13.0 microg/l vs. 7.3 microg/l). In the case of PFOA we observed only minor differences between PFOA concentrations within the analysed sample pairs (median: 2.6 microg/l vs. 3.4 microg/l for maternal and cord plasma samples, respectively). DISCUSSION: For both substances a crossing of the placental barrier could be shown. For PFOS we observed a decrease from maternal to cord plasma concentrations by a factor of 0.41-0.80. To the contrary, PFOA crosses the placental barrier obviously unhindered. These findings show that neonates are exposed to PFOS and PFOA via their mothers' blood. Given the current situation that only little is known about the consequences of PFOS and PFOA exposure in the early state of development of humans and the fact that in animal studies both substances showed developmental toxic effects further research regarding human health effects is indispensable.

Adult↗

Percutaneous absorption of aromatic amines in rubber industry workers: impact of impaired skin and skin barrier creams.

BACKGROUND: Several aromatic amines (AA) could cause bladder cancer and are an occupational hygiene problem in the workplace. However, little is known about the percutaneous absorption of chemicals via impaired skin and about the efficacy of skin protection measures to reduce internal exposure. AIMS: To determine the impact of skin status and of skin protection measures on the internal exposure to AA in workers manufacturing rubber products. METHODS: 51 workers occupationally exposed to aniline and o-toluidine were examined. The workplace conditions, risk factors for skin and the use of personal protective equipment were assessed by means of a self-administered questionnaire. The skin of hands and forearms was clinically examined. Exposure to aniline and o-toluidine was assessed by ambient air and biological monitoring (analyses of urine samples and of haemoglobin adducts). RESULTS: Haemoglobin-AA-adduct levels in workers with erythema (73%) were significantly higher (p<0.04) than in workers with healthy skin (mean values: aniline 1150.4 ng/l vs 951.7 ng/l, o-toluidine 417.9 ng/l vs 118.3 ng/l). The multiple linear regression analysis showed that wearing gloves significantly reduced the internal exposure. A frequent use of skin barrier creams leads to a higher internal exposure of AA (p<0.03). However, the use of skincare creams at the workplace was associated with a reduced internal exposure (p<0.03). From these findings we assume that internal exposure of the workers resulted primarily from the percutaneous uptake. CONCLUSIONS: The study demonstrates a significantly higher internal exposure to AA in workers with impaired skin compared with workers with healthy skin. Daily wearing of gloves efficiently reduced internal exposure. However, an increased use of skin barrier creams enhances the percutaneous uptake of AA. Skincare creams seem to support skin regeneration and lead to reduced percutaneous uptake.

Adult↗

Occurrence of perfluorinated substances in an adult German population in southern Bavaria.

OBJECTIVES: Perfluorinated compounds (PFCs) are a large group of chemicals produced for several decades and widely used for many industrial and consumer applications. Because of their global occurrence in different environmental media, their persistence, and their potential to bioaccumulate in organisms they are of toxicological and public concern. METHODS: In the present study, the internal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in 356 human plasma samples collected from an adult population in Germany in 2005 is quantified. RESULTS: We were able to detect the target analytes in all plasma samples and observed a significant correlation between the PFOS and PFOA concentrations. In female participants, the levels of PFOS and PFOA ranged between 2.5-30.7 (median: 10.9 microg/l) and 1.5-16.2 microg/l (median: 4.8 microg/l), respectively. In males we observed concentrations from 2.1 to 55.0 microg/l (median: 13.7 microg/l) for PFOS and from 0.5 to 19.1 microg/l (median: 5.7 microg/l) for PFOA. A significant correlation between both PFOS and PFOA concentrations and gender was observed. We also found increased levels of the PFCs with increasing age of the participants, but this association reached statistical significance among females only. CONCLUSIONS: Our data agree well with results of other recent studies in Europe and suggest that the current exposure of the adult German population is lower than the exposure of the US and Canadian population. The sources of human exposure are currently not well understood. Toxicological implications are restricted to animal studies and occupational investigations not adequate for quantitative risk assessment in humans. Overall, more scientific research is necessary to characterize the body burden of PFCs (especially for relevant subsets of the population) and the main sources and routes, which are responsible for human exposure and possible health implications of these compounds.

Adolescent↗

Investigations on safety of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with Mitomycin C.

AIMS: Previous safety monitoring of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with Mitomycin C (MMC) did not demonstrate any detectable safety hazard to the personnel. Nevertheless, those results have been discussed controversially because of the methodological problems employed in the evaluation of potential exposure. We re-evaluated possible safety hazards of HIPEC by applying different monitoring strategies. METHODS: We monitored air samples in the operation room during HIPEC. In addition, we measured MMC in plasma of the surgeon with a newly developed analytical method. All samples were analysed by HPLC-UV at 360nm. The permeability of the gloves was tested using two in vitro techniques: diffusion cells and a glass cell chamber. In-use and worst-case exposure scenarios were imitated for in vitro experiments. RESULTS: The analysis of the air samples (n=3) could not detect any MMC. We found no drug above the limit of detection (1microg MMC/L) in the plasma samples of the surgeons (n=5). A breakthrough of latex glove material was detected in only one (worst-case exposure scenario) of 40 diffusion cell experiments. CONCLUSIONS: Established methods of safety monitoring could not reveal any detectable risk on in-use exposure conditions. The wearing of doubled latex gloves should prevent the surgeon from dermal exposure to MMC during HIPEC.

Air Pollutants, Occupational↗

Di(2-ethylhexyl)phthalate (DEHP): human metabolism and internal exposure-- an update and latest results.

Di(2-ethylhexyl)phthalate (DEHP) is a reproductive and developmental toxicant in animals and a suspected endocrine modulator in humans. There is widespread exposure to DEHP in the general population. Patients can be additionally exposed through DEHP-containing medical devices. Toxicokinetic and metabolic knowledge on DEHP in humans is vital not only for the toxicological evaluation of DEHP but also for exposure assessments based on human biomonitoring data. Secondary oxidized DEHP metabolites like mono-(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl)phthalate (5oxo-MEHP), mono-(2-ethyl-5-carboxypentyl)phthalate (5cx-MEPP) and mono-[2-(carboxymethyl)hexyl]phthalate (2cx-MMHP) are most valuable biomarkers of DEHP exposure. They represent the major share of DEHP metabolites excreted in urine (about 70% for these four oxidized metabolites vs. about 6% for MEHP); they are immune to external contamination and possibly the ultimate developmental toxicants. Long half-times of elimination make 5cx-MEPP and 2cx-MMHP excellent parameters to measure the time-weighted body burden to DEHP. 5OH-MEHP and 5oxo-MEHP more reflect the short-term exposure. We calculated the daily DEHP intake for the general population (n = 85) and for children (n = 254). Children were significantly higher exposed to DEHP than adults. Exposures at the 95th percentile (21 and 25 microg/kg/day, respectively) scooped out limit values like the Reference Dose (RfD, 20 microg/kg/day) and the Tolerable Daily Intake (TDI, 20-48 microg/kg/day) to a considerable degree. Up to 20-fold oversteppings for some children give cause for concern. We also detected significant DEHP exposures for voluntary platelet donors (n = 12, 38 microg/kg/apheresis, dual-needle technique). Premature neonates (n = 45) were exposed to DEHP up to 100 times above the limit values depending on the intensity of medical care (median: 42 microg/kg/day; 95th percentile: 1,780 microg/kg/day).

Biomarkers↗

Dermal and bronchial symptoms in children: are they caused by PAH containing parquet glue or by passive smoking?

OBJECTIVE: In 1997 a new source of potential polycyclic aromatic hydrocarbon (PAH) exposure was discovered: very high levels of (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 a standard building practice in Germany. Children were considered to be at special risk for exposure to PAHs when playing on the floor via mouthing. Therefore, the children's symptoms and complaints were analysed for association with PAH contamination in parquet glue and household dust as well as with internal exposure to PAHs via determination of 1-hydroxypyrene in urine samples. PARTICIPANTS AND METHODS: Two hundred and eighty seven children <6 years of age living more than 12 months in the former US-housing estates are enrolled in this analysis, representing 22.3% of the children <6 years of age living there. Their spot urine samples were analysed for 1-hydroxypyrene. The level of BaP in parquet glue and in household dust was available in the homes of 215 and 212 children, respectively. There were no hints for differences in PAH contamination in parquet glue or in household dust of the participants' flats compared to the flats of the non responders. In 246 cases data on environmental tobacco smoke exposure at home was known as well. Data on symptoms and complaints observed by their parents during the preceding 12 months (1-year prevalence) were obtained using the ISAAC questionnaire (modified). RESULTS: The following 1-year prevalences were reported: 15% itching eczema in elbows, 10% itching and urticaria, 6% itching in the palate and throat, 20% sneezing and running nose or stuffed nose, 15% nosebleed; 25% wheezing, 42% dry cough, and 60% frequent infectious disease. No consistent associations between symptoms and BaP in parquet glue or in household dust or urinary levels of 1-hydroxypyrene in the children could be found. However, associations between symptoms and exposure to environmental tobacco smoke at home were to be seen, significant for dermal and bronchial symptoms. CONCLUSION: Informed about PAHs in parquet glue and household dust many parents demanded for total redevelopment of their flats. According to statistical evaluation of the children's symptoms, observed by their parents, no hints for an association with exposure via BaP in parquet glue or household dust were found. However, significant associations between symptoms and the exposure to environmental tobacco smoke were observed, especially bronchial and dermal symptoms. Therefore instead of redevelopment of flats with parquet glue containing coal tar, intensified information on the harmful effects of passive smoking in childhood seems to be mandatory.

Adhesives↗

Genotoxic risk assessment in white blood cells of occupationally exposed workers before and after alteration of the polycyclic aromatic hydrocarbon (PAH) profile in the production material: comparison with PAH air and urinary metabolite levels.

OBJECTIVE: Workers in various industries can be exposed to polycyclic aromatic hydrocarbons (PAHs). The relationship between biomarkers of genotoxic risk, PAH compounds in air (ambient monitoring) and PAH metabolites in urine (internal exposure) were studied in 17 workers exposed to PAHs in a fireproof-material producing plant before and 3 months after the PAH profile was altered in the binding pitch. METHODS: Two biomarkers of exposure, specific DNA adducts of (+/-)-r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) and non-specific DNA adduct of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) were determined in white blood cells (WBCs). In addition, DNA strand breaks were analysed in lymphocytes by single-cell gel electrophoresis in a genotoxic risk assessment. Sixteen PAH compounds in air were determined by personal air sampling, and hydroxylated metabolites of phenanthrene, pyrene and naphthalene were determined in urine. RESULTS: After substitution of the binding pitch the concentrations of benzo[a]pyrene in air decreased (P<0.01). No changes could be observed for pyrene, while levels of phenanthrene (P=0.0013) and naphthalene (P=0.0346) in air increased. Consequently, median DNA adduct rates of anti-BPDE decreased after alteration of the production material (from 0.9 to <0.5 adducts/10(8) nucleotides). No changes in the excretion of 1-hydroxypyrene in urine could be determined, whereas increased levels of 1-, 2+9-, 3- and 4-hydroxyphenanthrene (P<0.0001) and 1-naphthol and 2-naphthol (P=0.0072) were found in urine. In addition, a statistically significant increase in DNA strand break frequencies (P<0.01) and elevated 8-oxodGuo adduct levels (P=0.7819, not statistically significant) were found in the WBCs of exposed workers 3 months after the PAH profile in the binding pitch had been altered. CONCLUSION: The results presented here show that the increased concentration of naphthalene and/or phenanthrene in the air at the work place could induce the formation of DNA strand breaks and alkali-labile sites in WBCs of exposed workers.

Adult↗

[Lactational transfer of presumed carcinogenic and teratogenic organochlorine compounds within the first six months of life].

BACKGROUND: Despite a decline of 70 to 90 % during the past 20 years, many presumed carcinogenic and teratogenic organochlorine compounds (OC) are still present in our biosphere and accumulate in our food-chain. They are prenatally transmitted from mother to fetus, and mother's milk due to its high lipid content is an elimination pathway of special importance in all mammals. It was the aim of the present study to investigate whether breast-feeding increases the body pollution of human infants with OC during the first six months of life. METHODS: The study was approved by the committee on Biomedical Research of the Heinrich Heine University Düsseldorf, Germany. With written informed consent of the parents, blood samples were taken from 10 breast-fed and bottle-fed infants at the age of six weeks and six months, respectively. Three higher chlorinated PCB (polychlorinated biphenyls) congeners (IUPAC nos. 138, 153, and 180), HCB, and DDE, the main metabolite of DDT in mammals, were analyzed with capillary gas chromatography with electron capture detection. Reliability was tested with gas chromatography-mass spectrometry. Furthermore, the sum of the three higher chlorinated biphenyls (SigmaPCB) was calculated. RESULTS: There were no differences between the study groups of breast-fed and bottle-fed infants with regard to sex distribution, gestational age, birth weight, age of the mothers, and smoking behavior of the parents. However, serum concentrations of all OC were significantly higher (p < 0.0001) in breast-fed than in bottle-fed infants as early as at six weeks of age, and their concentrations nearly doubled until the age of six months (median [microg/L]; A = six weeks; B = six months): PCB 138, A: 0.40 vs. 0.09; B: 0.72 vs. 0.07; PCB 153, A: 0.57 vs. 0.11; B: 0.99 vs. 0.09; PCB 180, A: 0.33 vs. 0.04; B: 0.58 vs. 0.02; Sigma PCB, A: 1.19 vs. 0.29; B: 2.28 vs. 0.18; HCB, A: 0.13 vs. 0.04; B: 0.43 vs. 0.07; DDE, A: 1.05 vs. 0.18 ; B: 1.90 vs. 0.19. DISCUSSION: Breast-feeding significantly increases the serum concentration of our infants with different OC within the first six months of life, which leads to a body burden with OC, in this amount last measured in the mid-1980 s in Germany. In face of these results, common recommendations for breast-feeding should be reconsidered, taken into account the availability of infants formula (industrial vs. Third World countries).

Breast Feeding↗

The use of biomarkers of exposure of N,N-dimethylformamide in health risk assessment and occupational hygiene in the polyacrylic fibre industry.

BACKGROUND: N,N-dimethylformamide (DMF) was recently prioritised for field studies by the National Toxicology Program based on the potency of its reproductive toxic effects. AIMS: To measure accurately exposure to DMF in occupational settings. METHODS: In 35 healthy workers employed in the polyacrylic fibre industry, N-methylformamide (NMF) and N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) in urine, and N-methylcarbamoylated haemoglobin (NMHb) in blood were measured. Workplace documentation and questionnaire information were used to categorise workers in groups exposed to low, medium, and high concentrations of DMF. RESULTS: All three biomarkers can be used to identify occupational exposure to DMF. However, only the analysis of NMHb could accurately distinguish between workers exposed to different concentrations of DMF. The median concentrations were determined to be 55.1, 122.8, and 152.6 nmol/g globin in workers exposed to low, medium, and high concentrations of DMF, respectively. It was possible by the use of NMHb to identify all working tasks with increased exposure to DMF. While fibre crimpers were found to be least exposed to DMF, persons washing, dyeing, or towing the fibres were found to be highly exposed to DMF. In addition, NMHb measurements were capable of uncovering working tasks, which previously were not associated with increased exposure to DMF; for example, the person preparing the fibre forming solution. CONCLUSIONS: Measurement of NMHb in blood is recommended rather than measurement of NMF and AMCC in urine to accurately assess exposure to DMF in health risk assessment. However, NMF and AMCC are useful biomarkers for occupational hygiene intervention. Further investigations regarding toxicity of DMF should focus on highly exposed persons in the polyacrylic fibre industry. Additional measurements in occupational settings other than the polyacrylic fibre industry are also recommended, since the population at risk and the production volume of DMF are high.

Acetylcysteine↗

Organochlorine compounds in breast-fed vs. bottle-fed infants: preliminary results at six weeks of age.

BACKGROUND: Polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) are ubiquitous compounds with carcinogenic and teratogenic properties. They are chemically very stable and lipophilic and, therefore, accumulate in our food-chain. They are prenatally transmitted from mother to foetus, and mother's milk due to its high lipid content is an elimination pathway of special importance. Therefore, breast-feeding has been held responsible for elevated concentrations of these organochlorine compounds as well as for harmful effects in children later in life. METHODS: Blood samples (2.5 ml) were taken from each 10 breast-fed and bottle-fed infants at 6 weeks of age. Blood specimens were immediately centrifuged, and serum was stored in glass tubes at -20 degrees C until analysis. Three higher chlorinated PCB congeners (IUPAC nos. 138, 153 and 180), HCB, and the organic metabolite of DDT, p,p << -DDE, were analysed with capillary gas chromatography with electron capture detection. Reliability was tested with gas chromatography-mass spectrometry. RESULTS: There were no differences between the study groups of breast-fed and bottle-fed infants with regard to sex distribution, gestational age, birth-weight, age of the mothers, and smoking behaviour of the parents. In contrast, serum concentrations of all organochlorine compounds were significantly higher (P < 0.0001) in breast-fed than in bottle-fed infants (mean): PCB 138, 0.38 vs. 0.10 microg/l; PCB 153, 0.49 vs. 0.1 microg/l; PCB 180, 0.31 vs. 0.04 microg/l; SigmaPCB, 1.19 vs. 0.29 microg/l; HCB, 0.13 vs. 0.04 microg/l; p,p << -DDE, 1.05 vs. 0.18 microg/l. CONCLUSIONS: Breast-feeding significantly increases the pollution of our infants with different organochlorine compounds as early as at 6 weeks of age. The progress of the present study will show whether this pollution will further increase with longer duration of breast-feeding, and whether breast-feeding bears any health risks for our offspring.

Adipose Tissue↗

Analysis of metabolites of N,N-dimethylformamide in urine samples.

AIM: To assess the suitability of different methods for biological monitoring of internal dose to N,N-dimethylformamide (DMF) in occupational settings. METHODS: The determination of urinary metabolites of DMF, N-hydroxymethyl- N-methylformamide (HMMF), N-methylformamide (NMF) and N-acetyl- S-(N-methylcarbamoyl) cysteine (AMCC) was carried out by four selected analytical procedures. Two methods solely measured total NMF (HMMF and NMF). The other two methods measured both total NMF and AMCC in one analytical run. All four methods were tested on 34 urine samples from workers exposed to DMF. RESULTS: Comparison of the four methods for determination of total NMF in urine showed that results were similar for three methods, while the remaining one provided NMF levels significantly lower (by 22%) than the other methods. Thus, all but one of the tested methods for the determination of total NMF can be considered to be suitable for biological monitoring of internal dose to DMF. The two tested methods for the determination of AMCC afforded results that showed high correlation but differed significantly (by 10%). CONCLUSION: The choice of the biomonitoring method depends mainly on the purpose for which the measurement is conducted. For evaluation of acute exposures or to assess safety measures in the working area, an updated version of the traditional method of Kimmerle and Eben (1975a, b) for the determination of total NMF in urine is sufficient. For risk assessment after exposure to DMF, the determination of AMCC should be carried out, since AMCC, but not total NMF, is supposed to be related to the toxicity of DMF. However, there is still a need to develop an easier, more sensitive and more selective method for the determination of AMCC in urine until AMCC can be considered for regulatory purposes in occupational settings.

Acetylcysteine↗

Trans-placental exposure of neonates to acrylamide--a pilot study.

OBJECTIVES: Acrylamide (AA) (CAS No 79-06-1) has most recently been identified as a food-borne toxicant generated during the heating process of starch-containing foods. It was the aim of the present study to investigate the trans-placental exposure of newborn infants to this possible human carcinogen by analysis of the specific haemoglobin adduct of AA ( N-2-carbamoylethylvaline, AAV) in the blood of mothers and the corresponding umbilical cord blood of neonates as a parameter of biochemical effects. METHODS: We investigated the blood of 11 women advanced in pregnancy (one smoker, ten non-smokers) and the corresponding umbilical cord blood of neonates for the N-terminal haemoglobin adducts of AA (AAV) and the smoking-specific adduct of acrylonitrile (CAS No 107-13-1) ( N-cyanoethylvaline, CEV). The limit of detection (LOD) was 5 pmol/g globin for AAV and 4 pmol/g globin for CEV. RESULTS: AAV could be determined in all blood samples of the mothers (median 21 pmol/g globin, range 18-104 pmol/g globin) as well as in the umbilical cord blood of neonates (median 10 pmol/g globin, range 6-43 pmol/g globin). The highest values were detected in the blood of the smoking mother and her child. CEV was detected only in the blood of the smoking mother (185 pmol/g globin) and the corresponding umbilical cord blood (69 pmol/g globin). DISCUSSION: AAV adduct levels in non-smoking mothers and neonates showed a good correlation (r=0.859). The concentration of AA adducts in the blood of neonates is approximately 50% of the adduct level found in the blood of the mother. In view of the shorter life span of neonatal erythrocytes and the lower body weight of newborn infants, the relative internal dose of AA in neonates (in microgrammes per kilogramme body weight) must be assumed to be at least equal to that of the mother. Because of the high cell-replication rates during foetal development, trans-placental exposure of neonates to AA might raise concerns. Neonates of smoking mothers take up much higher doses of AA than those of non-smoking mothers.

Acrylamide↗

[PCB in interiors - a relevant health risk?].

Polychlorinated biphenyls (PCB) were manufactured between 1929 and 1989. Due to their great chemical persistence, these substances have been used for many different purposes. These chemical properties, however, caused PCB to accumulate in the food chain and resulted in background exposure of the general population. PCB has also been used as plasticizer for sealants in prefabricated buildings, thus causing problems to the present date. At the end of the 90-ties in a school in Nuremberg, Germany, elevated PCB concentrations were measured in indoor air. Some of these results were higher than 3,000 ng/m(3) which means decontamination according to the German "PCB directive". Press coverage made these results a matter of public debate, so that teachers, school children and parents were highly worried because of possible health effects. The Bavarian Minister for Health, Nutrition and Consumer Protection asked us to examine school children and teachers with regard to their internal PCB exposure and health complaints. A group of school children from a non-contaminated school served as controls. For the determination of PCB levels the plasma samples were blinded before analysis. Lower chlorinated PCB (PCB 28, 52, 101) were detected more often and in higher concentrations in plasma samples of school children of the contaminated school compared to the controls. The plasma levels of the higher chlorinated PCBs (PCB 138, 153, 180) did not show similar differences between exposed and non-exposed school children. The relative PCB doses additionally taken up in the contaminated school were less then 5 % of the background exposure of the children. That is why it could finally be concluded that no appreciable additional health risk may result from inhalation of PCB contaminated indoor air in this school. Due to the design, performance and interpretation of this study, including representatives of parents and teachers, these results were widely accepted by most of the parents who initially had been very concerned about possible health effects.

Air Pollution, Indoor↗

Dimethyl sulphate; a hidden problem in occupational medicine.

BACKGROUND: In a chemical plant, alkylating agents (mainly ethylene oxide and propylene oxide, but also dimethyl sulphate) are utilised for the production of special surfactants. AIMS: To determine possible uptakes of dimethyl sulphate by workers using N-methylvaline. METHODS: Sixty two workers in a chemical plant (38 smokers, 24 non-smokers) with potential exposure to dimethyl sulphate were monitored with respect to their blood levels of N-methylvaline. Ten laboratory workers without exposure to methylating agents were controls. Blood samples of eight workers from a specific working area were analysed for N-methylvaline in a follow up investigation four months later. RESULTS: The 95th centile for N-methylvaline was 80.7 microg/l blood in the exposed workers compared to 12.4 microg/l blood in controls. In a hot spot area, 10 workers exceeded the German exposure equivalent value for dimethyl sulphate (40 microg/l blood) up to fourfold. In contrast, dimethyl sulphate has not been detectable in workplace air in this area. In a follow up investigation of eight of these 10 workers, N-methylvaline levels were significantly lower, but still increased. CONCLUSIONS: The present study is to our knowledge the first to report increased N-methylvaline levels after occupational exposure to dimethyl sulphate. As ambient monitoring values in the plant could not explain this exposure, skin contact was considered to be the main route of uptake for this substance. Dimethyl sulphate may therefore represent an occupational problem that has been generally underestimated in the past.

Adult↗

Current internal exposure to pesticides in children and adolescents in Germany: blood plasma levels of pentachlorophenol (PCP), lindane (gamma-HCH), and dichloro(diphenyl)ethylene (DDE), a biostable metabolite of dichloro(diphenyl)trichloroethane (DDT).

Pesticides are widely used throughout the world in agriculture to protect crops, and in public health to control diseases transmitted by animal vectors or intermediate hosts. After the prohibition of organochlorines such as DDT internal exposure of the general population to the organochlorines has been reduced markedly. Herein, current internal exposure of children and adolescents in an urban area in Germany to PCP, lindane, and DDT/E is reported. One hundred and thirty children and adolescents took part in this voluntary investigation. All of them stated they had never used pesticides in their homes or for medical reasons. Blood plasma was analysed for pentachlorophenol (PCP), lindane (gamma-HCH), and dichloro(diphenyl)ethylene (DDE), a biostable metabolite of dichloro(diphenyl)trichloroethane (DDT), using gas chromatography/electron capture detection according to well established methods approved by the Deutsche Forschungsgemeinschaft. Median (and 95th percentiles) in the age groups < 6, 6- < 12, and 12- < 18 years of age were (microgram/l): DDE: 0.75 (4.45), 0.95 (5.04), 0.89 (8.77); DDT: < 0.1 (0.22), < 0.1 (0.25), < 0.1 (0.30); PCP: 2.48 (17.32), 2.69 (5.85), 2.08 (8.04); lindane: < 0.1 (0.12, < 0.1 (0.08), < 0.1 (0.09). High levels of internal exposure to DDT in two girls were probably obtained during a holiday stay in India; high PCP-levels in two other girls were caused by a leather jacket impregnated with PCP, and a holiday abroad, respectively. Current background levels of internal exposure to organochlorine insecticides in children and adolescents in Germany are quantified. Exposure to these substances in the general population is thought to occur mainly via residues in food, which are low in general, today. In special cases, however, individual exposures may be dominated by other sources, i.e. impregnated leather clothes.

Adolescent↗

Exposure to nitroaromatic explosives and health effects during disposal of military waste.

AIMS: To investigate the exposure to dinitrotoluene (DNT) and trinitrotoluene (TNT) and the resulting effects in workers which occur during the disposal of military waste. METHODS: Eighty two employees from a mechanical plant in Germany were studied, of whom 51 were regularly exposed to ammunition containing TNT and DNT, 19 occasionally, and 12 not at all. RESULTS: Air analyses yielded maximum concentrations of 20 micro g/m(3) for 2,4-DNT and 3250 micro g/m(3) for 2,4,6-TNT, respectively. The maximum concentrations in the urine of workers regularly exposed amounted to 5.0 micro g/l of 2,4,6-TNT, 1464.0 micro g/l of 2-amino-4,6-dinitrotoluene, 6693.0 of micro g/l 4-amino-2,6-dinitrotoluene, 2.1 micro g/l of 2,4-DNT, 95.0 micro g/l of 2,4-dinitrobenzoic acid, and 3.6 micro g/l of 2,6-DNT. There was a highly significant linear correlation between the urinary concentrations of the two main metabolites of TNT, 2-amino-4,6-dinitrotoluene and 4-amino-2,6-dinitrotoluene. In 63 persons TNT or DNT or metabolite concentrations above the analytical detection limit were found in urine. These persons reported more frequently symptoms like bitter taste, burning eyes, and discoloration of the skin and hair than persons (n = 19) without detectable TNT and/or DNT exposure. CONCLUSION: During the disposal of military waste containing relevant TNT and DNT, exposure can occur of occupational-medical relevance. Biological monitoring is suitable for the early detection of possible adverse effects at workplaces exposed to TNT. Protective measures should be improved, together with adequate occupational-medical surveillance of persons exposed to nitroaromatic explosives. Further studies are necessary to exclude possible long term effects.

Adult↗

Arsenic species excretion after dimercaptopropanesulfonic acid (DMPS) treatment of an acute arsenic trioxide poisoning.

We studied the urinary excretion of the different arsenic species in urine samples from a young man who tried to commit suicide by ingesting about 0.6 g arsenic trioxide. He received immediate therapy with dimercaptopropanesulfonic acid (DMPS) after his delivery into the hospital. We assessed urinary arsenite (inorganic trivalent arsenic), arsenate (inorganic pentavalent arsenic), pentavalent dimethylarsinic acid (DMA) and pentavalent monomethylarsonic acid (MMA) in urine with ion-exchange chromatography and on-line hydride-technique atomic absorption spectrometry. The predominant amount of the excreted arsenic was unchanged trivalent inorganic arsenic (37.4%), followed by pentavalent inorganic arsenic (2.6%), MMA (2.1%), DMA (0.2%) and one unidentified arsenic species (0.7%, if calculated as DMA). In the first urine voiding in the clinic, the total arsenic concentration was 215 mg/l, which fell 1000-fold after 8 days of DMPS therapy. A most striking finding was the almost complete inhibition of the second methylation step in arsenic metabolism. As mechanisms for the reduced methylation efficiency, the saturation of the enzymatic process of arsenic methylation, the high dosage of antidote DMPS, which might inhibit the activity of the methyl transferases, and analytical reasons are discussed. The high dosage of DMPS is the most likely explanation. The patient left the hospital after a 12-day treatment with antidote.

Adult↗