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R Schwabe

Publications and source records attributed to R Schwabe.

16 recordsLinked to original sources

[Comparison of local differential luminance sensitivity (dls) between Oculus Twinfield Perimeter and Humphrey Field Analyzer 630 (HFA I) in normal volunteers of varying ages].

PURPOSE: Purpose of this study was to compare age-corrected normal values of differential luminance sensitivity (dls) of the Oculus Twinfield Perimeter with those of the Humphrey Field Analyzer 630 (HFA I). Furthermore, naso-temporal and superior-inferior asymmetries in the central visual field were analyzed. METHODS: 72 ophthalmologically normal volunteers, 12 per decade, were examined with both perimeters using a 4-2 dB bracketing strategy with two reversals for threshold estimation. A biometric model, which fits a hill of vision to the data, was developed. The age-related hills, created by the model, were compared between the instruments and analyzed for asymmetries. RESULTS: The normal dls values for the Twinfield perimeter were about 1.5 dB above those of the HFA I. The shape of the hill in regard to slope in corresponding locations did not differ substantially. The decline of local differential luminance sensitivity showed a nonlinear correlation to age: it remained almost constant up to the 4th decade, with a steeper decline beyond that age. A naso-temporal as well as a superior-inferior asymmetry was found. Along the vertical meridian, the slope of the hill was steeper in the superior part than in the inferior. At an excentricity of 20 degrees we found a superior-inferior difference of 2.1 dB for the HFA and of 1.8 dB for the Twinfield perimeter benefitting the inferior meridian. Along the horizontal meridian there was a distinct difference in regard to the shape of the hill. The sensitivity was greater in the temporal half of the visual field than in the nasal. At an excentricity of 30 degrees, the difference was about 2.75 dB for the HFA and 2.5 dB for the Twinfield perimeter. These asymmetries seem to appear in all age groups. Unfortunately, the exact influence of age on the appearing asymmetries cannot be quantified by the used model. CONCLUSION: The normal dls values benefit the Twinfield for about 1.5 dB compared to the HFA. There seems to be a critical age of about 40 - 50 years, beyond which a decline of dls becomes manifest.

Adolescent↗

Chondrotoxicity of ciprofloxacin in immature beagle dogs: immunohistochemistry, electron microscopy and drug plasma concentrations.

The systemic effects of ciprofloxacin in immature Beagles were studied. Dogs of 10-11 weeks were dosed orally for 5 days with 0 (n=3), 30 (n=5) and 200 (n=5) mg ciprofloxacin/kg body wt. Plasma concentrations were measured by high-performance liquid chromatography (HPLC) 1 h after dosing (assuming to be peak concentrations). In view of the high doses used, the plasma concentrations were rather low and declined during the study period. For example, plasma concentrations in the high dose group were 6.6 +/- 0.9 mg/l (day 1), 3.9 +/- 1.4 mg/l (day 3), and 2.6 +/- 1.6 mg/l (day 5). In control dogs and in dogs treated with the low dose of ciprofloxacin no pathological changes were seen by light microscopy. However, cleft formation and erosions were observed in joint cartilage from two of five dogs treated with 200 mg/kg. It is noteworthy that despite the high dose used cartilage lesions were not detectable in all five dogs of this group by light microscopy. Using antibodies against cell membrane receptors (e.g. the alpha(5)beta(1)-integrin) or matrix components (fibronectin, collagen II) the articular cartilage effects were studied in detail by immunohistochemistry. The most sensitive alteration was an increase in fibronectin which was detectable in the vicinity of the lesions in cartilage samples from the group of dogs administered the high dose. No clear-cut changes were seen with the use of antibodies against other matrix components. Electron microscopy revealed typical alterations in chondrocytes from dogs treated with ciprofloxacin: e.g., swollen mitochondria and enlarged rough endoplasmic reticulum. These changes were much more pronounced in dogs from the high dose group than in dogs from the low dose group. Our main conclusion is that after oral administration ciprofloxacin exhibits rather low chondrotoxicity, even in the most sensitive species known to date. This correlates with the findings in humans that ciprofloxacin seems to be less chondrotoxic than pefloxacin or other quinolones.

Animals↗

Ultrastructure of Achilles tendons of rats treated with ofloxacin and fed a normal or magnesium-deficient diet.

Fluoroquinolones can cause tendinitis and tendon rupture. However, toxicological as well as clinical information on quinolone-induced tendopathy is scarce. We performed extensive electron microscopic studies with Achilles tendon specimens from ofloxacin-treated rats. The drug was given at a dose of 1,200 mg/kg (body weight) orally. Juvenile Wistar rats received one or three oral doses each of 1,200 mg of ofloxacin/kg (body weight)/day. Three days after treatment, the tenocytes of their Achilles tendons showed degenerative alterations, such as multiple vacuoles and vesicles in the cytoplasm that had developed due to swellings and dilatations of cell organelles. Other indications of cell degradation were the occurrence of cell debris and cell detachment from the extracellular matrix accompanied by a loss of cell-matrix interaction. The tenocytes of juvenile Wistar rats that had been treated at day 36 with a single oral dose of 1,200 mg of ofloxacin/kg (body weight) and sacrificed either 3 or 6 months later exhibited similar degenerative alterations. The number of degenerative alterations of tenocytes after ofloxacin treatment was considerably higher in rats that had received a magnesium-deficient diet than in rats with normal magnesium status. Of the adult rats that had been treated once, 5 times, and 10 times with ofloxacin and killed 1 day later, only those with the 10-times treatment showed a significantly increased number of degeneratively altered tenocytes. In summary, effects observed in tendons show similar pathological features as described earlier in cartilage, indicating that quinolone-induced arthropathy and quinolone-induced tendopathy probably are different clinical manifestations of the same toxic effect on cellular components of connective tissue structures.

Achilles Tendon↗

Combined prenatal toxicity of 6-mercaptopurine riboside and hydroxyurea in mice.

Hydroxyurea (HU) and 6-mercaptopurine riboside (6-MPr) are used as cytostatic chemotherapeutics. Their teratogenic potential in experimental animals has been well known for several decades. Generally, it is assumed that the toxicity of both agents is due to an interference with enzymes of DNA synthesis. In the case of 6-MPr, it was speculated that the teratogenicity in rodents might be paralleled by or even correlated to an incorporation of 6-thioguanine into the DNA of the embryos. In this study, the interaction between these two compounds with regard to teratogenicity in NMRI mice was investigated. Dose-response data of 6-MPr (s.c.-treatment) were published earlier. First, a dose-response study with HU alone (i.p.-treatment) was performed. From these data, the doses for the combination study were derived: HU 250 mg/kg (NOAEL dose) and 6-MPr 16 mg/kg (strongly teratogenic dose). In all experimental groups the substances were administered to the dams once on day 11 of gestation. Combination effects were investigated applying various dosing regimens. In group I treatment was simultaneous, in group II HU was administered 2 h before 6-MPr, in group III 2 h after 6-MPr. The differences in the overall frequency of gross structural abnormalities were moderate. However, when analysing the effects in more detail (single abnormalities), group III exhibited great differences: 1) 6-MPr co-treatment increased the frequency of HU effects (skull defects) and 2) HU co-treatment decreased the frequency of 6-MPr effects (limb defects) when compared to the findings of the dose-response studies. In addition, the influence of HU on the 6-MPr-induced DNA modification was determined by measuring the incorporation of 6-thioguanine into the DNA of day-11 embryos. As expected, the HU co-treatment corresponding to the group III dosing regimen of the teratogenicity experiment decreased the incorporation rate by ca. 40%. This was in parallel to the decrease in the frequency of 6-MPr effects in the teratogenicity III group. This finding may be considered as a further indication that in the case of 6-MPr, DNA modification is accompanying teratogenicity.

Abnormalities, Drug-Induced↗

Chondrotoxicity and toxicokinetics of sparfloxacin in juvenile rats.

Sparfloxacin is a fluoroquinolone with improved antibacterial activity against gram-positive pathogens. Like other quinolones, use of this drug is contraindicated in children and adolescents because of its potential chondrotoxicity in juveniles. We performed histological and immunohistochemical studies on the knee joint cartilage in 5-week-old rats after treatment with 600 or 1,800 mg of sparfloxacin/kg of body weight. Treatment with single or multiple oral doses of 600 mg of sparfloxacin/kg was not sufficient to induce joint cartilage lesions. However, five of eight rats treated with a single oral dose of 1,800 mg of sparfloxacin/kg of body weight showed typical cartilage lesions in the femoral part of the knee joint. The concentrations of the drug in plasma measured 0.25, 0.75, 1.5, 3, 6, 12, and 24 h after the administration of an oral dose of 600 mg of sparfloxacin/kg were 6.3 +/- 1.8, 9.2 +/- 1.7, 9.6 +/- 2.7, 13.0 +/- 1.8, 12.3 +/- 1.6, 3.4 +/- 0.4, and 0.30 +/- 0.20 mg/liter, respectively (mean +/- standard deviation [SD]; n = 5 to 6 per group). The concentrations in plasma measured 0.75, 1.5, 3, 6, 24, and 48 h after the administration of an oral dose of 1,800 mg of sparfloxacin/kg were 10.9 +/- 1.5, 15.9 +/- 1.6, 19.1 +/- 1.7, 14.9 +/- 3.1, 4.1 +/- 0.6, and 0.46 +/- 0.37 mg/liter, respectively (mean +/- SD; n = 3 to 4 per group). The concentrations of sparfloxacin in joint cartilage were significantly higher at all time points studied (114.8 +/- 80, 99.4 +/- 31.5, 84.9 +/- 16.8, 44.4 +/- 13.9, and 14.2 +/- 4.8 mg of sparfloxacin/kg at 1.5, 3, 6, 24, and 48 h after the administration of 1,800 mg/kg, respectively). The range of concentrations in bone were similar to the range of concentrations in cartilage (peak, 115 +/- 12 mg/kg after 3 h). Our data indicate that chondrotoxic doses of sparfloxacin in juvenile rats are approximately 300 times higher than the doses of sparfloxacin used therapeutically (1,800 versus approximately 6 mg/kg of body weight), but due to species differences in kinetics, concentrations in plasma differ by a factor of only approximately 15. More data on quinolone concentrations in cartilage from animals and humans could provide a better basis for a reasonable risk assessment.

Animals↗

[Pyrethroids in house dust of the German housing population--results of 2 nationwide cross-sectional studies].

As a part of the German Environmental Surveys performed in 1985/86 (West Germany), 1990/91 (West Germany) and 1991/92 (East Germany), dust samples were collected in the households of about 1600 randomly selected adults (25 to 69 years) and an analysis of these samples was performed in respect of their content of 8 different pyrethroids and of the synergist piperonyl butoxide (PBO). In the 1990-92 survey about 90% of the samples contained permethrin in concentrations above the limit of quantification. This showed permethrin to be the most widespread of the 8 compounds investigated. The geometric mean of the permethrin content in domestic dust was 0.22 mg/kg. Only about 8% of the samples contained one or more of the other investigated substances (cyfluthrin, lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, deltamethrin, empenthrin, d-phenothrin) in quantifiable amounts. About 76% of the samples contained quantifiable amounts of PBO. In East Germany the geometric mean of the PBO content (0.21 mg/kg) was significantly higher than in West Germany (0.07 mg/kg), but no difference for permethrin was found. Significant associations could be shown for the permethrin content and the application of biocides as well as for the PBO content and regional factors (size of community, type of dwelling area). Samples collected in 1985/86 (West Germany) showed a geometric mean for permethrin of 0.06 mg/kg and for PBO of 0.07 mg/kg. Comparing the values of 1985/86 and 1990/91, a significant increase can be observed for permethrin, whereas the PBO concentration remained constant.

Adult↗

Quinolone-induced arthropathy: exposure of magnesium-deficient aged rats or immature rats, mineral concentrations in target tissues and pharmacokinetics.

Quinolone treatment or magnesium deficiency induce identical cartilage lesions in juvenile rats and show additive arthropathogenic effects. It has been shown previously that neither condition is arthropathogenic in 8-week-old rats. Joint cartilage from aged individuals is rather prone to pathological alterations but information on prolonged quinolone treatment and/or dietarily induced magnesium deficiency in aged animals is not available. We treated magnesium-deficient (n = 9) aged Wistar rats (age 15 months) and age-matched controls with daily doses of 600 mg ofloxacin/kg body wt. by gastric intubation for 28 days. Further groups of magnesium-deficient and control rats (n = 9 and n = 10, respectively) received the vehicle only. Peak plasma concentrations of ofloxacin in adult rats were 20.5 +/- 5.6 mg/l (mean +/- SD) following treatment with a single dose of 600 mg/kg body wt. At the end of the experiment the degree of magnesium deficiency was most pronounced in plasma (Mg2+-def., 0.33 +/- 0.12 mmol/l; control, 0.97 +/- 0.08 mmol/l) and less pronounced in sternal cartilage (Mg2+-def., 10.8 +/- 3.6 mmol/kg dry wt; control, 13.3 +/- 2.8 mmol/kg dry wt), whereas the magnesium concentration in femoral bone remained unchanged (Mg2+-def., 201 +/- 13 mmol/kg dry wt; control, 204 +/- 11 mmol/kg dry wt). Histological investigation of the knee joints revealed no cartilage lesions following ofloxacin treatment, magnesium deficiency or a combination of both conditions. By contrast, cartilage lesions such as scars and erosions of the joint surface, chondrocyte clusters within acellular areas of the cartilage matrix and persisting clefts were detectable in knee joints from 7 of 10 adult rats (age 9 months) which had been treated with 4 x 600 mg fleroxacin/kg body wt. at 5 weeks of age. Mean plasma concentration of fleroxacin in juvenile rats was approx. 50 mg/l between 1.5 and 6 h after dosing and the drug was still detectable in plasma 48 h after dosing (0.4 +/- 0.1 mg/l). Our data indicate that joint cartilage in aged rats is not altered by a 4-week quinolone treatment, even during magnesium deficiency. Cartilage lesions in adult rats were only detectable if the animals had been treated during the sensitive phase at 5 weeks postnatally.

Age Factors↗

Safety profile of grepafloxacin compared with other fluoroquinolones.

Preclinical investigations with grepafloxacin showed that its toxicological profile is similar to that of other fluoroquinolones. The photosensitizing effect of grepafloxacin was relatively weak and similar to that of ciprofloxacin. Grepafloxacin did not cause convulsions in mice when administered in conjunction with the non-steroidal anti-inflammatory drug fenbufen. Intravenous injection of grepafloxacin caused transient dysrhythmias in rabbits at a dosage of 10 mg/kg and ventricular tachycardia at 30 mg/kg iv. Joint cartilage lesions were found in juvenile dogs after iv treatment with 100 mg/kg daily. Plasma concentrations (19-24 mg/L) under these conditions were approximately ten times above a therapeutic level. Data derived from patients who had been treated with grepafloxacin in phase II and phase III multiple-dose studies (400 mg, n = 1069; 600 mg, n = 925) were available for an analysis of the patients' tolerance of the drug. The most common adverse events observed for the 400 mg and 600 mg treatments during these studies were gastrointestinal reactions, such as nausea (11% and 15%, respectively), vomiting (1% and 6%) and diarrhoea (3% and 4%). In both groups a considerable number of patients (9% and 17%) reported an unpleasant taste; this was less common in the pooled controls (1%) after treatment with drugs such as doxycycline, ciprofloxacin, amoxycillin or cefixime. Headache occurred in 4% (400 mg) and 5% (600 mg) and insomnia in 1% (400 mg) or 2% (600 mg) of the patients. Similar incidences were found for photosensitivity (1% and 2%, respectively) and for rash (1% and 2%) in the 400 mg and 600 mg groups. So far, tolerance of the new compound seems to be similar to that of other fluoroquinolones. However, incidences of nausea, vomiting and unpleasant taste were rather high during the first clinical trials, particularly after treatment with 600 mg daily. Further data are necessary for a sound evaluation of the tolerance of grepafloxacin.

Animals↗

CD40 function in nonhematopoietic cells. Nuclear factor kappa B mobilization and induction of IL-6 production.

CD40 is a member of the TNF receptor family that was first characterized as an important T-B cell interaction molecule. This receptor is also expressed on many other cell types, including normal basal epithelium, carcinomas, and transformed cell lines. The functions of CD40 in non-B cells are largely unknown. Our studies demonstrate that CD40 mediates nuclear factor kappa B (NF-kappa B) mobilization and IL-6 production in nonhematopoietic cells. Stimulation of the transformed fibroblast cell line SV80 with CD40 ligand (CD40L) or anti-CD40 Ab resulted in the production of IL-6; this could be increased by IFN-gamma pretreatment, which is known to up-regulate CD40 expression. Studies with transfectants overexpressing CD40 demonstrated that activation of CD40 alone is sufficient to induce IL-6 production. The transcription factor NF-kappa B appears to play a central role in CD40-mediated activation of the IL-6 gene; NF-kappa B mobilization directly preceded CD40-mediated IL-6 production, and suppression of NF-kappa B mobilization with the metabolic inhibitor D609 also suppressed the IL-6 response. A striking similarity to the requirements for TNF-induced IL-6 production, which is mediated by the p55TNF receptor in SV80 cells, was observed. In view of the intracellular homologies between CD40 and the p55TNF receptor, it should be considered that the two receptors share common components in their signaling pathways that lead to IL-6 production.

Base Sequence↗

Toxicity of beta-blockers in a rat whole embryo culture: concentration-response relationships and tissue concentrations.

Beta-adrenoceptor blockers are widely used drugs for the treatment of cardiovascular diseases. Since beta-blockers cross the placenta, it is essential to consider possible adverse effects on the embryo. Six beta-adrenoceptor blockers were tested at various concentrations (10-5000 microM) in a rat whole embryo culture. Although inducing a very similar pattern of dysmorphogenetic effects (incomplete flexure, disturbed development of the neural tube, the head, the heart and the tail bud), the compounds exhibited a wide range of embryotoxic potency. Estimation of the EC50 (median-concentration producing dysmorphogenesis in 50% of the embryos) for the six compounds revealed differences of more than two orders of magnitude: propranolol 25 microM, alprenolol 30 microM, metoprolol 100 microM, pindolol 150 microM, acebutolol 500 microM, atenolol 4000 microM. Measurements of the concentrations of the various drugs in the cultured embryos at corresponding EC50 levels showed differing values: metoprolol 4.5 microM, propranolol 5.2 microM, alprenolol 8.4 microM, pindolol 9.0 microM, acebutolol 12.5 microM and atenolol 77.0 microM. With regard to the EC50 and the degree of substance transfer to the embryo it can be stated that propranolol and metoprolol show a much higher intrinsic potency to interfere with normal in vitro embryonic development than, e.g. atenolol.

Acebutolol↗

DNA modification induced by 6-mercaptopurine riboside in murine embryos.

The cytostatic drug 6-mercaptopurine riboside (6-MPr) was investigated in mice in order to test the hypothesis that the teratogenicity of this antimetabolite is paralleled by an incorporation into the DNA of the embryos during organogenesis. DNA modification in the embryos was analysed 4 h following s.c. administration of [35S]-labelled 6-MPr to the dams on day 11 of pregnancy. The DNA of the embryos was isolated and hydrolysed to the bases by formic acid. Following separation by cation-exchange HPLC 6-thioguanine was found in the hydrolysate. Quantitation was performed by liquid scintillation counting. Evaluations of 6 doses in the range of 8-25 mg/kg were performed. An incorporation rate of 6-thioguanine from 32-56 pmol per mumol guanine was found in the DNA of the embryos. These findings suggest that, similar to the previously studied alkylating agents, the teratogenicity of 6-MPr may be, at least in part, induced via DNA modification of the embryos.

Animals↗

Effects of a single haloperidol application to neonatal and early postnatal rats on the neurotransmitter content in the corpus striatum.

We investigated the influence of the dopamine antagonist haloperidol on the neurotransmitter content in the developing rat brain. Dopamine (DA), serotonin (5-HT) and the corresponding metabolites dopac, HVA and HIAA were determined in the corpus striatum of the rat between day 1 and day 21 pn by HPLC with electro-chemical detection. A consistent increase in the content of dopamine was found during postnatal development. The concentrations (ng/g wet tissue; mean +/- standard deviation) increased from 793 +/- 237 on day 1 pn to 4584 +/- 581 on day 21 pn, but remained still lower than in adult animals (9763 +/- 494). Similar results were found for the metabolites dopac and HVA. The content of dopac increased from 59 +/- 22 (day 1 pn) to 551 +/- 59 (day 21 pn) and the content of HVA from 53 +/- 18 (day 1 pn) to 419 +/- 41 (day 21 pn). Both metabolites were also about two times lower than in adult animals (dopac 1090 +/- 282, HVA 744 +/- 206). In contrast to dopamine and its metabolites we found no age-dependent changes in the content of 5-HT from day 1 pn (99 +/- 11) to day 14 pn (121 +/- 21). A remarkable increase in the content of 5-HT was seen from day 14 pn to day 21 pn (438 +/- 56), reaching almost adult levels (570 +/- 92). The metabolite HIAA was nearly three times higher on day 21 pn (610 +/- 123) than on day 14 pn (223 +/- 28) and two times higher than in adults (321 +/- 58).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Device for monitoring locomotor activity of 120 animals: motility of offspring of dams exposed to haloperidol.

A device using four infra-red light photocells per cage which monitor simultaneously the motility of 120 individual rodents, was developed at our institute. The measuring interval can be chosen freely, the starting time may be set freely and the test may last several weeks. The motility of the offspring (day 35-39) of dams exposed to the neuroleptic haloperidol during lactation was investigated, because of the important stage of the brain development in the neonatal age and of the relatively high concentration of haloperidol in the milk. Mice dams were treated sc. with a single dose (1.5 mg/kg) of haloperidol postnatally on day 3 to 6. Compared to the controls the body weight gain of treated (via milk) pups was reduced (controls = 72%, haloperidol = 30%) and the mortality was higher (controls = 10%, haloperidol = 77%) during the treatment period. The quantitative and qualitative analysis of the locomotor activity from day 35 to day 39 shows a distinct shift in the kind of motility: the locomotor activity of haloperidol offspring is significantly reduced while the number of activity phases is increased. It appears that there is a persistent alteration in the central nervous system that leads to a higher frequency but a lower efficacy of activity.

Animals↗

[Changeable bridge-work prosthesis. Proposal for solution].

A newly developed solution is introduced, which makes it possible to design artificial bridges conditionally variable. Thus the frame is fixed on tangential bridges--departing from common techniques--by means of lateral assembled barriers.

Denture Design↗

Enzyme cytochemistry combined with electron microscopy, pharmacokinetics, and clinical chemistry for the evaluation of the effects of steady-state valproic acid concentrations on the mouse.

A number of organs from adult female mice were investigated after continuous application of the anticonvulsant drug valproic acid (VPA) by enzyme cytochemistry, light and electron microscopy, pharmacokinetics and clinical chemistry. VPA plasma levels were maintained between 55 micrograms/ml and 67 micrograms/ml for three days following subcutaneous implantation of drug reservoirs. Effects detectable by enzyme cytochemical or electron microscopical means were mainly observed in liver, kidney, thymus and spleen. A strict concentration-dependency of drug effects could not be found. In the liver, the activities of some surface-membrane hydrolases were increased at the biliary pole; the activities of other hydrolases were decreased or unchanged. Electron microscopically, number and length of microvilli of hepatocytes were increased and many of them showed fat inclusions, mitochondrial swellings and autophagic vacuoles. In some of the proximal convoluted tubules of the kidney, the reaction product originating from microvillous and lysosomal hydrolases was diffusely distributed and its amount lowered. This was paralleled by tubular cells with an increased number of fat droplets and swollen mitochondria or destroyed tubular cells, as demonstrated by electron microscopy. Additionally, peritubular endothelial cells were arranged in a garland-like pattern. Alkaline phosphatase was activated in the straight portion of the proximal tubules. Increased glucose, creatinine and total protein concentrations and increased gamma-glutamyl transpeptidase and alkaline phosphatase activities in the urine reflected well the damage of the proximal renal tubules. Cortical and medullary morphology varied considerably in the thymus. In extreme cases, the cortical zone was either reduced in size or the medulla showed a cortex-like structure or vice versa (inverted type of thymus). The thymic cortical reticular cells showed increased aminopeptidase A activity accompanied by a generalized aminopeptidase M and alkaline phosphatase reaction. Our data indicate that--in addition to the liver--also the kidney, thymus and spleen are target organs of VPA-induced toxicity in the mouse.

Alkaline Phosphatase↗

Nitrate in drinking water in the West German wine-growing areas of Baden and Württemberg.

Nitrate is regarded as a substance whose presence in drinking water is not considered as desirable. If reduced to nitrite it may cause methomoglobinemia in infants. Onward reaction with amines capable of coupling will result in the formatin of nitrosamins. Excessive use of fertilizers in agriculture is the most frequent cause of elevated nitrate contents of drinking water. To quantify this problem, drinking water was sampled at taps at 200 sites arranged on a grid covering the wine-growing areas of Baden and Württember. These samples were examined for their content of nitrate, chloride, and sulphate by means of ion chromatography. Clearly elevated nitrate contents were revealed by the resuls of measurements: 13% of samples showed values above the maximal concentration admissible under the EC Drinking Water Directive of 50 mg NO-3/l and 42% above the EC guide level. The excessive levels were mostly found in the regions of Kaiserstuhl-Tuniberg-Markgräflerland and Württembergisch Unterland. Many samples with an elevated nitrateacontent exhibited also elevated sulphate contents. The high nitrate levels are attributed to the use of nitrogen fertilizers in the vineyards.

Germany, West↗