Towards virtual histology with X-ray grating interferometry.

Breast cancer is the most common type of cancer worldwide. Diagnosing breast cancer relies on clinical examination, imaging and biopsy. A core-needle biopsy enables a morphological and biochemical characterization of the cancer and is considered the gold standard for breast cancer diagnosis. A histopathological examination uses high-resolution microscopes with outstanding contrast in the 2D plane, but the spatial resolution in the third, Z-direction, is reduced. In the present paper, we propose two high-resolution table-top systems for phase-contrast X-ray tomography of soft-tissue samples. The first system implements a classical Talbot-Lau interferometer and allows to perform ex-vivo imaging of human breast samples with a voxel size of 5.57 µm. The second system with a comparable voxel size relies on a Sigray MAAST X-ray source with structured anode. For the first time, we demonstrate the applicability of the latter to perform X-ray imaging of human breast specimens with ductal carcinoma in-situ. We assessed image quality of both setups and compared it to histology. We showed that both setups made it possible to target internal features of breast specimens with better resolution and contrast than previously achieved, demonstrating that grating-based phase-contrast X-ray CT could be a complementary tool for clinical histopathology.

Yttrium-90 DOTATOC: first clinical results.

In a pilot study, DOTA-d-Phe(1)-Tyr(3)-octreotide (DOTATOC), which can be labelled with the beta-emitting radioisotope yttrium-90, has recently been used for the treatment of patients with advanced somatostatin receptor-positive tumours who had no other treatment option. The aim of the present study was to elucidate the therapeutic potential of (90)Y-DOTATOC in a larger number of patients employing a standardized treatment protocol. Careful attention was paid to any side-effects (renal and/or haematological toxicity). Of 44 patients with advanced somatostatin receptor-positive tumours of different histology, 29 could be included in the study. The 15 patients who were excluded from the study protocol were assigned to our institution for purely compassionate reasons. The 29 patients who were included received four or more single doses of (90)Y-DOTATOC with ascending activity at intervals of approximately 6 weeks (cumulative dose 6120+/-1347 MBq/m(2)) with the aim of performing an intra-patient dose escalation study. In total, 127 single treatments were given. In eight of these 127 single treatments, total doses of > or = 3700 MBq were administered. In an effort to prevent renal toxicity, two patients received Hartmann-Hepa 8% solution during all therapy cycles, while 13 patients did so during some but not all therapy cycles; in 14 patients no solution was administered during the therapy cycles. The treatment was monitored by computed tomography and indium-111 DOTATOC scintigraphy. Blood parameters were controlled weekly, while tumour markers and liver enzymes were controlled 6-weekly. Of the 29 patients, 24 patients showed no severe renal or haematological toxicity (toxicity < or = grade 2 according to the National Cancer Institute grading criteria). These 24 patients received a cumulative dose of < or = 7400 MBq/m(2). Five patients developed renal and/or haematological toxicity. All of these five patients received a cumulative dose of >7400 MBq/m(2) and had received no Hartmann-Hepa 8% solution during the therapy cycles. Four of the five patients developed renal toxicity; two of these patients showed stable renal insufficiency and two require haemodialysis. Two of the five patients exhibited anaemia (both grade 3) and thrombopenia (grade 2 and 4, respectively). To date, 20 of the 29 patients have shown a disease stabilization, two a partial remission, four a reduction of tumour mass <50% and three a progression of tumour growth. (90)Y-DOTATOC could be a powerful and promising new therapeutic agent for anti-cancer treatment - at least in terms of an adjuvant starting point of the disease. However, problems with toxicity have to be solved. Evaluation of the effect of amino acid infusions (e.g. Hartmann-Hepa 8% solution) during (90)Y-DOTATOC treatments with the aim of reducing renal toxicity is ongoing.

Loco-regional radioimmunotherapy of high-grade malignant gliomas using specific monoclonal antibodies labeled with 90Y: a phase I study.

A Phase I radioimmunotherapy trial was conducted in which radioconjugated monoclonal antibody (MAb) was directly infused into the tumor or postoperative tumoral bed in patients with high-grade malignant glioma. BC-4, a murine MAb that recognizes tenascin, was used in these studies. The MAb was labeled with 90Y, a pure beta emitter with maximum energy of 2.284 MeV, which can penetrate into tissue up to 0.5-0.7 cm. Stable 90Y-labeled MAb conjugates were prepared using the chelator p-isothiocyanatobenzyl derivative of diethylenetriaminepentaacetic acid (ITC-Bz-DTPA), obtaining >95% labeling efficiency and conserving the antibodies' immunoreactivity (>85%). Twenty patients, 2 with anaplastic astrocytoma and 18 with glioblastoma, were included in the study. All of the patients had been treated previously with conventional therapies (surgery, external radiotherapy, and chemotherapy) and presented with progressive disease not amenable to further treatment. A dose-escalation study was performed using doses ranging from 5-30 mCi (185-1110 MBq) of 90Y-labeled MAb BC-4. The protein dose of MAb was always 1 mg. Three patients were treated at the 5, 10, 15, and 20 mCi levels, and the 25- and 30-mCi doses were each administered to 4 patients. Systemic toxicity was completely absent in all of the patients. The maximum tolerated dose to the brain was 25 mCi (925 MBq). The average dose to the tumor was 3200 cGy/mCi. Doses to the liver, bone marrow, and kidneys were below 10 cGy/mCi in all of the cases. Biodistribution studies demonstrated that the 90Y-labeled MAb accreted exclusively in the neoplastic area without any diffusion into the normal brain or other normal organs. No clinical responses were recorded because of the very advanced stage of disease at the time of radioimmunotherapy.

Biokinetics and dosimetry in patients administered with (111)In-DOTA-Tyr(3)-octreotide: implications for internal radiotherapy with (90)Y-DOTATOC.

Recent advances in receptor-mediated tumour imaging have resulted in the development of a new somatostatin analogue, DOTA-dPhe(1)-Tyr(3)-octreotide. This new compound, named DOTATOC, has shown high affinity for somatostatin receptors, ease of labelling and stability with yttrium-90 and favourable biodistribution in animal models. The aim of this work was to evaluate the biodistribution and dosimetry of DOTATOC radiolabelled with indium-111, in anticipation of therapy trials with (90)Y-DOTATOC in patients. Eighteen patients were injected with DOTATOC (10 microg), labelled with 150-185 MBq of (111)In. Blood and urine samples were collected throughout the duration of the study (0-2 days). Planar and single-photon emission tomography images were acquired at 0.5, 3-4, 24 and 48 h and time-activity curves were obtained for organs and tumours. A compartmental model was used to determine the kinetic parameters for each organ. Dose calculations were performed according to the MIRD formalism. Specific activities of >37 GBq/ micromol were routinely achieved. Patients showed no acute or delayed adverse reactions. The residence time for (111)In-DOTATOC in blood was 0.9+/-0.4 h. The injected activity excreted in the urine in the first 24 h was 73%+/-11%. The agent localized primarily in spleen, kidneys and liver. The residence times in source organs were: 2.2+/-1.8 h in spleen, 1.7+/-1.2 h in kidneys, 2.4+/-1.9 h in liver, 1.5+/-0.3 h in urinary bladder and 9. 4+/-5.5 h in the remainder of the body; the mean residence time in tumour was 0.47 h (range: 0.03-6.50 h). Based on our findings, the predicted absorbed doses for (90)Y-DOTATOC would be 7.6+/-6.3 (spleen), 3.3+/-2.2 (kidneys), 0.7+/-0.6 (liver), 2.2+/-0.3 (bladder), 0.03+/-0.01 (red marrow) and 10.1 (range: 1.4-31.0) (tumour) mGy/MBq. These results indicate that high activities of (90)Y-DOTATOC can be administered with low risk of myelotoxicity, although with potentially high radiation doses to the spleen and kidneys. Tumour doses were high enough in most cases to make it likely that the desired therapeutic response desired would be obtained.

Locoregional regulatory peptide receptor targeting with the diffusible somatostatin analogue 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC): a pilot study in human gliomas.

Human gliomas, especially of low-grade type, have been shown to express high-affinity somatostatin receptor type 2 (J-C. Reubi et al., Am. J. Pathol, 134: 337-344, 1989). We enrolled seven low-grade and four anaplastic glioma patients in a pilot study using the diffusible peptidic vector 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) for receptor targeting. The radiopharmakon was locoregionally injected into a stereotactically inserted Port-a-cath. DOTATOC competes specifically with somatostatin binding to somatostatin receptor type 2 in the low nanomolar range as shown by a displacement curve of 125I-[Tyr3]-octreotide in tumor tissue sections. Diagnostic (111)In-labeled DOTATOC-scintigraphy following local injection displayed homogeneous to nodular intratumoral vector distribution. The cumulative activity of regionally injected peptide-bound 90Y amounted to 370-3300 MBq, which is equivalent to an effective dose range between 60 +/- 15 and 550 +/- 110 Gy. Activity was injected in one to four fractions according to tumor volumes; 1110 MBq of 90Y-labeled DOTATOC was the maximum activity per single injection. We obtained six disease stabilizations and shrinking of a cystic low-grade astrocytoma component. The only toxicity observed was secondary perifocal edema. The activity:dose ratio (MBq:Gy) represents a measure for the stability of peptide retention in receptor-positive tissue and might predict the clinical course. We conclude that SR-positive human gliomas, especially of low-grade type, can be successfully targeted by intratumoral injection of the metabolically stable small regulatory peptide DOTATOC.

Determination of selected microbial volatile organic compounds by diffusive sampling and dual-column capillary GC-FID--a new feasible approach for the detection of an exposure to indoor mould fungi?

A new, analytically valid procedure is described to assess the exposure of human beings to the so-called microbial volatile organic compounds (MVOCs) in air. The method can be used routinely for large sample numbers and is especially valuable as a basis for further research on the correlation between single MVOCs and indoor mould growth. The procedure is based on the fact that fungi produce a variety of volatile organic compounds, such as 3-methylbutan-1-ol, 3-methylbutan-2-ol, fenchone, heptan-2-one, hexan-2-one, octan-3-one, octan-3-ol, pentan-2-ol, alpha-terpineol, and thujopsene, which they emit into the indoor environment. Using diffusive samplers, these MVOCs are adsorbed onto charcoal during a sampling interval of four weeks. The described method is thus superior to existing methods which use short-term active sampling. After desorption with carbon disulfide, the MVOCs were determined by dual-column gas chromatography with flame ionization detection using the large-volume injection technique for sample introduction. The detection limits ranged between 0.15 and 0.53 microgram m-3, within-series precision was found to range between 6.5 and 19.0%, and recovery was between 77 and 118%. The procedure has been successfully applied in the context of a large field study to measure the indoor MVOC exposure in children's rooms of 132 dwellings. The objective of the study was to examine the relation between indoor mould growth, the indoor MVOC exposure and the prevalence of adverse health effects. Information about mould formation has been obtained by a questionnaire and by the determination of colony forming units of mould fungi in mattress dust. With the exception of 3-methylbutan-2-ol, fenchone, nonan-2-one, octan-2-one, and thujopsene, indoor air concentrations of all MVOCs under investigation were significantly higher inside damp and mouldy dwellings. From the primary MVOCs under investigation, 3-methylbutan-1-ol, hexan-2-one, heptan-2-one, and octan-3-ol were found to be most reliable indicators for mould formation. A correlation was also found between selected MVOCs and the occurrence of mould species in mattress dust. Aspergillus sp. correlated with heptan-2-one, hexan-2-one, octan-3-ol, octan-3-one, and alpha-terpineol, while the occurrence of Eurotium sp. was correlated with higher indoor air concentrations of 3-methylbutan-1-ol, 3-methylbutan-2-ol, heptan-2-one, hexan-2-one, octan-3-ol, and thujopsene. Children living in dwellings with elevated MVOC levels had a higher prevalence of asthma, hay fever, wheezing, and irritations of the eyes. These positive associations persisted after controlling for confounding factors such as age, sex, body-mass index, number of siblings, social status, passive smoking, type of heating, and ventilation habits. However, they were not statistically significant. This lack of significance may be a result of the small number of investigated samples.

Determination of physiological levels of volatile organic compounds in blood using static headspace capillary gas chromatography with serial triple detection.

A static capillary gas chromatographic method using three different detectors [photoionization detector (PID), electron capture detector (ECD) and flame ionization detector (FID)] switched in series is presented for the determination of volatile organic compounds (VOCs) in sub microgram l-1 levels. The method was applied for the analysis of selected environmentally and occupationally relevant non-halogenated and chlorinated aromatic hydrocarbons (e.g., benzene, toluene, xylenes, dichlorobenzenes) as well as chlorinated aliphatic hydrocarbons (e.g., trichloroethene, tetrachloroethene) in blood samples. Detailed investigations, in respect to the figures of merit were carried out. For most of the selected VOCs detection limits (calculated as the three-fold standard deviation of low level calibration standards) in the range from 26 (benzene) to 67 ng l-1 (m/p-xylene) were achieved which are comparable with those reported for dynamic headspace techniques in combination with mass spectrometric detection. For the individual VOCs the within-series precision varied from 4 to 19% and the day-to-day precision from 11 to 28%. Regarding PID as well as FID the calibration graphs for all substances were linear up to at least 10 micrograms l-1 while the ECD response was linear up to concentrations of about 0.6 microgram l-1 for the halogenated compounds. Our method is applicable for the quantitative determination of VOCs in blood in the occupationally as well as in the physiologically relevant (normal) concentration range.

Determination of benzene, toluene, ethylbenzene and xylenes in indoor air at environmental levels using diffusive samplers in combination with headspace solid-phase microextraction and high-resolution gas chromatography-flame ionization detection.

An improved analytical method for passive air sampling is presented based on a combination of commercially available diffusive samplers with headspace solid-phase microextraction and high-resolution gas chromatography with flame ionization detection (HRGC-FID). This procedure is targeted for short-term BTEX (benzene, toluene, ethylbenzene and o-, m- and p-xylenes) determinations at environmental concentrations and can be applied for sampling intervals between 30 min and 24 h. The analytes are adsorbed onto the charcoal pad of a passive sampler and then extracted with carbon disulphide-methanol. After removal of the carbon disulphide by xanthation, the BTEXs are enriched on a Carboxen SPME fiber, thermally desorbed and analysed by HRGC-FID. Detection limits for a sampling interval of 2 h are between 0.4 and 2 micrograms/m3, within-series precision ranges between 6.6 and 12.8%, day-to-day precision is between 11.1 and 15.2%. The results obtained with this procedure are validated by comparison with active sampling. Detection limits and a further reduction of the sampling time are limited by blanks of the chemicals and the diffusive samplers. Procedures to eliminate these blanks are described in detail. Applications such as the determination of BTEXs in indoor air inside buildings, inside a train and a car are presented, indicating the usefulness of the described procedure for short-term measurements of environmental BTEX concentrations. An advantage of passive samplers is the storage stability for at least six months, which is essential for its use in large epidemiological studies.

DOTATOC: a powerful new tool for receptor-mediated radionuclide therapy.

This study presents the first successful use of a peptidic vector, DOTATOC, labelled with the beta-emitting radioisotope yttrium-90, for the treatment of a patient with somatostatin receptor-positive abdominal metastases of a neuroendocrine carcinoma of unknown localization. Tumour response and symptomatic relief were achieved. In addition, the new substance DOTATOC was labelled with the diagnostic chemical analogue indium-111 and studied in three patients with histopathologically verified neuroendocrine abdominal tumours for its diagnostic sensitivity and compared with the commercially available OctreoScan. In all patients the kidney-to-tumour uptake ratio (in counts per pixel) was on average 1. 9-fold lower with 111In-DOTATOC than with OctreoScan. DOTATOC could be a potential new diagnostic and therapeutic agent in the management of neuroendocrine tumours.

Biodistribution of 111In-labelled SCN-bz-DTPA-BC-2 MAb following loco-regional injection into glioblastomas.

We analyzed the biodistribution of the 111In-labelled murine anti-tenascin-C MAb BC-2 after intralesional injection in 15 glioblastoma patients. The activated ligand DTPA was conjugated via the isothiocyanato-benzyl group onto BC-2. Conjugates were labelled with 111In, displaying immunoreactivity greater than 90% and labelling efficiency of 99 +/- 1%. In contrast to i.v. injections, excellent tumor uptake was obtained by direct intralesional injection of conjugates that showed only slow systemic release. In serum, conjugates were found to be intact; in urine, only low-molecular-weight decay products were detected. In 8 patients, outflow from the site of injection into systemic circulation was low; daily activity in the serum and urine was found to be below 2% of the total injected radioactivity; most of the injected activity was retained within the tumor, resulting in effective half-lives of 58 +/- 5 hr. In contrast, higher outflow up to 10% of regionally injected 111In-DTPA-BC-2 MAb into systemic circulation resulted in considerable shortening of the effective half-lives to 20 to 40 hr in 7 patients. This outflow was found to correlate with tumor size and blood/brain barrier disruption. In one patient, HPLC analysis of tumor cyst fluid 3 and 6 days after intralesional injection revealed conjugates to be intact and allowed the estimate of about 70% of the total injected 111In-DTPA-BC-2 to be confined to tumor tissue. We conclude that different outflow patterns can be observed following locoregional injection of 111In-DTPA-BC-2, leading to considerable variations in the effective half-lives of isotopes within the tumor, requiring adjustment of the radiation dose in therapeutic trials.

Yttrium-90 and indium-111 labelling, receptor binding and biodistribution of [DOTA0,d-Phe1,Tyr3]octreotide, a promising somatostatin analogue for radionuclide therapy.

In vitro octreotide receptor binding of [111In-DOTA0,d-Phe1, Tyr3]octreotide (111In-DOTATOC) and the in vivo metabolism of 90Y- or 111In-labelled DOTATOC were investigated in rats in comparison with [111In-DTPA0]octreotide [111In-DTPAOC). 111In-DOTATOC was found to have an affinity similar to octreotide itself for the octreotide receptor in rat cerebral cortex microsomes. Twenty-four hours after injection of 90Y- or 111In-labelled DOTATOC, uptake of radioactivity in the octreotide receptor-expressing tissues pancreas, pituitary, adrenals and tumour was a factor of 2-6 that after injection of 111In-DTPAOC. Uptake of labelled DOTATOC in pituitary, pancreas, adrenals and tumour was almost completely blocked by pretreatment with 0.5 mg unlabelled octreotide, indicating specific binding to the octreotide receptors. These findings strongly indicate that 90Y-DOTATOC is a promising radiopharmaceutical for radiotherapy and that 111In-DOTATOC is of potential value for diagnosis of patients with octreotide receptor-positive lesions, such as most neuroendocrine tumours.

Internal and external tetrachloroethene exposure of persons living in differently polluted areas of Northrhine-Westphalia (Germany).

An epidemiological study was performed to measure the internal and external tetrachloroethene exposure of persons living in two differently polluted areas of Northrhine-Westphalia (Germany). Tetrachloroethene concentrations were determined in venous blood samples of 5- to 7-year-old children (n = 81) and 55-year-old women (n = 91) living in Essen, an industrial city located in the Ruhr area. 103 children und 131 women of the same age living in Borken, a small town north of the Ruhr area, served as reference group. Outdoor air samples were collected on passive samplers (sampling period: 4 weeks) from 70 measurement points per study area (about 2 km2, mean distance 100 m). In the course of a year these measurements were repeated three times to cover seasonal variations. Parallel to the outdoor measurement periods, indoor air concentrations were determined in the homes of those women from Essen and Borken, who donored a blood sample. Tetrachloroethene levels in blood were generally low with a geometric mean of 0.05 microgram/L in women and 0.021 microgram/L in children. Nevertheless, children and women living in the industrial area were found to have significantly higher tetrachloroethene levels in blood than those of the reference group. In both study areas blood levels of women exceeded those of children by a factor of 2. Participants living in the neighbourhood of a dry-cleaning shop had distinctly elevated blood levels. The same applied to persons who stored dry-cleaned clothes at home. Like the internal exposure, external exposure was also higher in Essen than in Borken. In both areas tetrachloroethene concentrations indoors exceeded those outdoors. Outdoor tetrachloroethence concentrations were significantly increased during the cold season, while the opposite was true for indoor levels. The correlation between indoor and outdoor exposure was found to be significant, while those between blood levels and outdoor exposure became only significant when people living next to a dry-cleaning shop were excluded. No significant relationship was observed between blood and indoor tetrachlorethene levels. It is concluded that the higher tetrachloroethene blood levels of the urban population result from the higher atmospheric concentrations in industrial areas with tetrachloroethene emitting sources like metal and textile industry. The fact that indoor air tetrachloroethene levels exceeded those outdoors can only be explained by the presence of additional indoor sources. Provided that women spend on average more time indoors than children the higher indoor air concentrations may be the reason for the higher blood tetrachloroethene levels found in women. Persons living near a dry-cleaning shop or storing dry-cleaned clothes at home showed a higher internal and external exposure to tetrachloroethene than other persons. In individual cases it can by far exceed the average exposure of the general population, so that health impairments can not be generally excluded.

Neurobehavioral and neurophysiological outcome of chronic low-level tetrachloroethene exposure measured in neighborhoods of dry cleaning shops.

The effects of chronic low-level tetrachloroethene (TCE) exposure on functions of the central nervous system (CNS) were measured in subjects living in the neighborhood of dry cleaning shops with a mean residential time of 10.6 years. Neurobehavioral tests were performed using a German version of the NES battery. Additionally, a pattern reversal visual-evoked potentials (VEPs) were recorded. the mean blood TCE concentration in the subjects was 17.8 micrograms/liter and the median indoor TCE air concentration measured in the residences was 1.36 mg/m3. The outcome of the NES subtests for vigilance, simple reaction time, as well as visual memory differed statistically significantly between the exposed subjects and the controls, whereas for VEP latencies the differences were statistically not significant. It is concluded that despite the low exposure levels, CNS functions might be affected by TCE in subjects living close to a dry cleaning facility if the exposure lasts for several years.

[Exposure to mercury in the population. I. Mercury concentrations in the urine of normal subjects]. / Untersuchungen zur Quecksilberbelastung der Bevölkerung. I. Quecksilberkonzentrationen im Urin bei Normalpersonen.

The levels of mercury were determined in 24 h urine samples collected from 703 subjects (age 1-79 years) living in the Eastern part of the Ruhr area (West-Germany). The mean HgU level was 0.75 micrograms/l (range less than 0.1-19.3 micrograms/l) and the mean HgU level standardized for creatinine was 0.64 micrograms/g creatinine (range: less than 0.1-27.4 micrograms/g creatinine). The mean mercury excretion per 24 h was 0.48 micrograms in subjects less than 18 years and 0.99 micrograms in subjects greater than 18 years. Females were found to have, on average, higher HgU levels and also a higher excretion of mercury per 24 h than males. Subjects greater than 18 years had significantly higher HgU levels than subjects less than 18 years of age. The effect of age was found to be substantially more pronounced in females than in males. Smoking did not affect the urinary mercury excretion.

[Exposure to mercury in the population. II. Mercury release from amalgam fillings]. / Untersuchungen zur Quecksilberbelastung der Bevölkerung. II. Quecksilberfreisetzung aus Amalgamfüllungen.

Urinary levels of mercury (HgU) were measured in 93 males and females aged 18-63 years. Subjects with amalgam fillings (n = 72) had, on average, significantly higher levels of mercury in urine (mean = 0.57 microgram Hg/l and 0.79 microgram Hg/g creatinine, respectively) than subjects without amalgam fillings (n = 21; mean = 0.18 micrograms Hg/l and 0.24 microgram Hg/g creatinine, respectively). Urinary mercury excretion was significantly correlated with the number of amalgam surfaces (log HgU (microgram/l) vs. number of amalgam fillings: r = 0.435, P less than 0.001; log HgU (microgram/g creatinine) vs. number of amalgam fillings: r = 0.575, p less than 0.001). The results indicate that internal mercury exposure from amalgam fillings is, on average, higher than internal exposure to mercury from food and other sources.

[Blood lead and blood cadmium concentrations in 55-66-year-old women fron different areas of Nordrhein-Westfalen--chronological trends during 1982-1988]. / Blutblei- und Blutcadmiumkonzentrationen bei 55-66jährigen Frauen aus verschiedenen Gebieten Nordrhein-Westfalens--Entwicklungstrends 1982-1988.

Blood lead levels were determined in 3098 55-66 year-old women living in different areas of Northrhine-Westphalia (F.R.G.). Blood cadmium levels were determined in a subgroup of 2538 women. The studies were performed between 1982 and 1988. The results show that there has been a further fall of blood lead levels in the general population of West-Germany since the CEC blood lead surveys of 1979 and 1981. A comparable reduction of blood cadmium was not noted. Residents of large urban agglomerations had, on average, slightly higher blood lead levels than residents of small cities located in rural areas (+0.2-0.5 microgram/dl). With regard to blood cadmium, no differences were seen. Smokers were found to have, on average, 3-4 times higher blood cadmium levels than non-smokers. Blood lead was also elevated in smokers when compared to non-smokers. The highest blood lead levels recorded were in the range of 15-30 micrograms/dl. The data further suggest that lead mobilization during conditions of bone demineralization, e.g. in cases of osteoporosis, does not result in toxic blood lead levels in postmenopausal women.

[Exposure of children to benzene and other motor vehicle emissions]. / Belastung von Kindern durch Benzol und andere verkehrsbedingte Immissionen.

The concentrations of benzene, toluene, and lead and the percentage of carboxyhemoglobin (COHb) were measured in the venous blood of 48 children living in a central urban area with high traffic density (Cologne, FRG). The same parameters were also evaluated in a reference group of children (n = 72) living in a small city located in a rural area of West-Germany (Borken, Münsterland). The above named parameters could be quantitated in all blood samples. The children living in the central urban area had, on average, significantly higher concentrations of benzene, toluene, lead, and COHb in blood than the children of the reference group. The blood benzene concentrations were, on average, 71% and the toluene concentrations 56% higher in the urban children when compared to the reference group. The median values of the urban group/reference group were: benzene, 115/70 ng/l; toluene, 545/370 ng/l; lead, 5.2/4.7 micrograms/dl; COHb, 0.9/0.6%. It is concluded that the higher levels of benzene, toluene, lead, and COHb found in the blood of the urban children result from the higher atmospheric concentrations of these pollutants generally found in central urban areas with high traffic density.

Exposure to lead and cadmium of children living in different areas of north-west Germany: results of biological monitoring studies 1982-1986.

Between 1982 and 1986 several surveys were carried out to determine the levels of lead and cadmium in blood, urine, and shed deciduous teeth (incisors only) of children living in rural, suburban, urban, and industrial areas of North-West Germany. Blood lead (PbB) and blood cadmium (CdB) were measured in about 4000 children. In rural, suburban and urban areas the median PbB levels vary between 5.5 and 7 micrograms/dl, with 98th percentiles varying between 10 and 13 micrograms/dl. The median CdB levels are between 0.1 and 0.2 microgram/dl, with 95th percentiles between 0.3 and 0.4 microgram/l. Children from urban areas have significantly higher PbB levels than children from rural and suburban areas. Regarding CdB no differences could be detected. Children living in areas around lead and zinc smelters, particularly those living very close to the smelters, have substantially increased PbB and CdB levels. Children from lead worker families also have substantially increased PbB and CdB levels. The lead levels in shed milk teeth (PbT) were determined in about 3000 children. In rural, suburban and urban areas the median PbT levels are between 2 and 3 micrograms/g, with 95th percentiles between 4 and 7 micrograms/g. Children from urban areas have significantly higher PbT levels than children from rural and suburban areas. The highest PbT levels (on a group basis) are in children from nonferrous smelter areas. The median levels of lead in urine (PbU) are between 6 and 10 micrograms/g creatinine, with 95th percentiles between 20 and 30 micrograms/g creatinine. Children from polluted areas have higher PbU levels than children from less polluted areas. The median levels of cadmium in urine (CdU) are in the order of 0.1 microgram/g creatinine, with 95th percentiles being in the range of 0.5 and 1.0 microgram/g creatinine. Girls have higher CdU levels than boys. There are no differences between groups of children from different areas. Children from lead worker families have higher PbU and CdU levels than otherwise comparable children. The results of the present studies indicate a further decrease of PbB in children from North-West Germany since the CEC blood lead campaigns carried out in 1979 and 1981. The decrease of lead exposure also seems to be reflected by a decrease of tooth lead levels.

Cadmium in kidney cortex of inhabitants of North-West Germany: its relationship to age, sex, smoking and environmental pollution by cadmium.

The cadmium concentration in kidney cortex (CdKc) was determined in 388 deceased persons, who at the time of death had lived in the cities of Düsseldorf and Duisburg, Federal Republic of Germany (FRG), and surrounding areas. The average CdKc concentration was found to be 17.1 micrograms/g wet weight. Individual values range from less than 0.4 to 94.3 micrograms/g wet weight. The CdKc levels rapidly increase during the first decades of life. At the age of about 40 years, a plateau phase is reached. At high ages (greater than 70 years), the CdKc levels tend to decrease. Cigarette smokers have significantly higher CdKc concentrations than non-smokers. The increase of CdKc depends on the number of cigarettes smoked. Cigar and pipe smokers have slightly increased CdKc levels compared to non-smokers. Non-smokers who had spent the major part of their life in the area of Duisburg, a cadmium-polluted area, have, on the average, significantly higher CdKc levels than non-smokers from the less-polluted surrounding areas. In smokers the residential factor is masked by the effect of cigarette smoking.