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R Preussmann

Publications and source records attributed to R Preussmann.

At least 127 records · Page 7Linked to original sources
PubMed1982

Carcinogenicity of N-nitrosodiethanolamine in rats at five different dose levels.

N-nitrosodiethanolamine, an N-nitroso compound of environmental significance, has been tested for carcinogenicity in male Sprague-Dawley rats at five different dose levels. Administration p.o. in the drinking water of 1.5, 6, 25, 100, or 400 mg N-nitrosodiethanolamine per kg per day was tolerated well. Median total doses administered were between 0.86 g/kg body weight at the highest and 100.3 g/kg body weight at the lowest dose level. Treatment-related tumors were observed in the liver and the nasal cavity. The induction of hepatocellular carcinomas was clearly dose related, low doses also inducing benign lesions. Other liver tumors were of mesenchymal and ductal origin and nasal cavity neoplasms were diagnosed as squamous-cell carcinomas and neuroepitheliomas of the olfactory epithelium. Statistical evaluation of the 1.5-mg/kg dose regimen clearly indicates that even such low doses are carcinogenic. This potent carcinogenic activity is surprising since a high percentage (60 to 90%) of an administered dose of N-nitrosodiethanolamine is excreted unchanged in the urine. Thus, we propose that an as yet unidentified metabolite may possess high carcinogenic potential.

Adenocarcinoma↗
PubMed1982

Nitrosamines and rubber.

Occupational exposure to N-nitrosamines in the rubber industry was first reported by Fajen et al. (1979). In order to study the origin and formation of nitrosamines in this industry, chemicals and industrial products, as well as the air in various working areas, were analysed (Spiegelhalder et al., 1980). All chemicals used for rubber compounding contain nitrosamines if they are derivatives of secondary amines; e.g., tetramethylthiurame, zinc-diethyldithiocarbamate or N-oxydiethylene benzothiazolylsulfenamide. All rubber products containing these dialkyl amine derivatives exhibited considerable levels of the corresponding nitrosamines. Accordingly, variable concentrations of airborne nitrosamines could be detected at places where rubber products are manufactured or stored. The nitrosamines found correspond to the compounded chemicals. The original nitrosamine level in rubber chemicals is not high enough to explain the amounts found in rubber products and in air, so that additional nitrosation must occur. The responsible nitrosating agents are described. Preliminary results show that, in most cases, the elimination of nitrosating agents or the use of different rubber chemicals can drastically reduce nitrosamine levels in rubber products and in working areas.

Air Pollutants↗
PubMed1982

Urinary excretion of N-nitrosamines in rats and humans.

Various sources may contribute to the total human exposure to nitrosamines (foods, drugs, cosmetics, polluted air and endogenous formation of N-nitroso compounds). The average intake of nitrosamines can be calculated using analytical data. The more relevant method of biological monitoring can be used, however, to estimate individual exposure, in which case possible in vivo formation may also be detected. Since blood measurements can be carried out only under great difficulty and reflect only the momentary situation, the urinary excretion of nitrosamines was studied in animal experiments. The urinary excretion of nitrosodimethylamine (NDMA), nitrosomorpholine (NMOR) and nitrosodiethanolamine (NDELA) in SD-rats was measured within 24 h after epicutaneous, intratracheal, oral and intravenous application. The dose range covered was 5, 50 and 500 micrograms/animal for NDMA, 4, 44 and 440 micrograms/animal for NMOR and 0.03-300 mg/animal for NDELA. Under the influence of diethylether, a 7- to 20-fold increase of excretion was observed. Biological monitoring in humans at low doses (10-100 micrograms NDMA) is possible only if the excretion rate is increased by administration of ethanol. By reducing the activity of metabolizing enzymes with ethanol or other suitable compounds, possible in vivo formation of nitrosamines might also be more easily detectable. Excretion rates do not seem to be dose-dependent in the ranges investigated.

Animals↗
PubMed1982

In-vitro metabolism of fluorinated diakylnitrosamines.

To elucidate differences in metabolism caused by fluorination of NDEA and NDBA, these compounds and their fluorinated analogs (NDEA-F3, NDEA-F6, NDBA-F3, NDBA-F6 and NDBA-F1 4) were incubated with rat liver microsomal fractions. Aldehydes, nitrite and unchanged nitrosamines were determined. Additionally, the mutagenicity was investigated with a Salmonella/mammalian microsome assay. NDEA-F6 and NDBA-F1 4 were not appreciably metabolized and were not mutagenic. NDEA, NDEA-F3, NDBA, NDBA-F3 and NDBA-F6 were dealkylated and, to a lesser extent, denitrosated. Dealkylation at the fluorinated alkyl group was inhibited, especially in the case of NDEA-F3. Whereas NDEA, NDBA, NDBA-F3 and NDBA-F6 were clearly mutagenic, mutagenicity of NDEA-F3 was only marginal.

Animals↗
PubMed1981

Fluoro-substituted N-nitrosamines. 1. Inactivity of N-nitrosobis(2,2,2-trifluoroethyl)amine in carcinogenicity and mutagenicity tests.

N-Nitroso-bis(2,2,2-trifluoroethyl)amine (hexafluorodiethylnitrosamine, 6-F-DEN) was synthesized as a derivative of diethylnitrosamine (DEN) with blocked terminal C-atoms to avoid metabolic oxidation at this site. Chronic oral administration of 6-F-DEN in drinking water did not induce tumours in Sprague-Dawley and in Fischer 344 rats. On the other hand, equimolar doses of DEN or even much lower ones are clearly carcinogenic. Mutagenicity tests using Salmonella typhimurium strains TA 1535 and TA 100 and metabolic activation by rat liver S-9 fraction were equally negative with 6-F-DEn. The substitution of fluorine in the beta-position of DEn apparently inhibits the alpha-oxidation considered necessary for carcinogenesis and mutagenesis of dialkylnitrosamines.

Animals↗
PubMed1981

[Carcinogenicity in BD-IX rats of 7 homologues of N-nitroso-N-n-alkylureas in different stages of postnatal development (author's transl)].

Carcinogenic activity of seven N-Nitroso-N-n-alkylureas was investigated in 679 BD-IX rates in different stages of postnatal development after administration of a single s.c. dose of the test compound. The results are compared with a former investigation using N-nitroso-N-ethylurea. The nitrosoureas in a series from the methyl- to the n-octyl derivative showed a pronounced neurotropic carcinogenic effect on treatment during the first ten days after birth. Malignant neurinomas of the heart, subcutaneous sarcomas at the site of injection and malignant tumors in other organs varied distinctly, depending mainly on the time of treatment. All observed effects were similar in all 7 alkylnitrosoureas investigated.

Animals↗
PubMed1980

Volatile nitrosamines in food.

The results of the systematic survey of food from the German market in regard to the occurrence of volatile nitrosamines are presented. The average daily intake for male persons amount to 1.1 microgram for N-nitrosodimethylamine (NDMA) and 0.1-0.15 microgram for N-nitroso-pyrrolidine (NPYR). About 64% of this total daily intake for NDMA is found in beer, 10% result from cured meat products. The surprising contamination of beer is formed during the drying (kilning) of malt and can be eliminated.

Beer↗
PubMed1980

Nitrate and nitrite in saliva.

A survey is given on the occurrence of nitrate and nitrite in human saliva and the influence of the dietary nitrate intake. Nitrate, after its absorption in the upper gastrointestinal tract, reaches the salivary glands via the blood circulation where it is secreted into the oral cavity and partially reduced to nitrite by the oral microflora. There is a linear relationship between the amounts of nitrate ingested and amounts of nitrate and nitrite found in saliva. The ability of the oral microflora to reduce nitrate to nitrite depends on he individual ages. Mean salivary nitrite was found to increase from well below 1 ppm in infants of up to 6 months to about 7 ppm in adults. a remarkably different situation has been found in areas of high esophageal cancer incidence in Iran: although dietary intake of nitrate and nitrite is very low, nitrite levels in saliva, especially in children of this area tend to be much higher than those in children of western European countries.

Adolescent↗
PubMed1980

Dose-response studies and 'no-effect-levels' of N-nitroso compounds: some general aspects.

One major problem in the evaluation of potential carcinogenic food additives and contaminants is that of thresholds or, better, of 'no-adverse-effect-levels'. Arguments in favor of the postulated 'irreversibility' of carcinogenic effects are based on dose-response studies, single dose and multigeneration experiments as well as on the concept of somatic mutation as the first step in carcinogenesis with subsequent transmittance of induced defects during cell replication. The problem of extrapolation of results of animal experiments using high doses to low exposure and low incidences in man is not yet solved satisfactorily. Possible practical consequences include zero tolerance, acceptable thresholds at low risk and safety factors. Acceptable intakes should never be considered constants but should be changeable as soon as new facts in regard to the safety evaluation are available.

Animals↗
PubMed1980

Formation of N-nitroso compounds of the pesticides atrazine, simazine and carbaryl with nitrogen oxides.

The nitrosation of atrazine, simazine and carbaryl by nitrogen oxides was investigated in model experiments. Pure pesticides and their corresponding formulations were exposed, as dry powders and as aqueous suspensions, to defined concentrations of NOx (1000, 100, 10 and 1 ppm) in a reaction chamber. Nitrosated pesticides were determined by HPLC-TEA. Generally, the amount of nitrosation increased with the reaction time. At high NOx concentrations (1000 and 100 ppm), nitrosation approached saturation. For atrazine and simazine, further reaction with nitrogen oxides might occur. Nitrosation rates of dry powdered pesticides were inversely proportional to grain size and to air moisture content. Nitrosation of aqueous pesticide suspensions by nitrogen oxides was strongly inhibited at pH values higher than 5.

Atrazine↗
PubMed1980

Occurrence of volatile nitrosamines in food: a survey of the West German market.

More than 3000 food samples from the West German market have been analysed for volatile nitrosamines. N-nitrosopyrrolidine (NPYR) and N-nitrosopiperidine (NPIP) in concentrations above 0.5 micrograms/kg were found in only 3 and 2% of the samples, respectively. N-Nitrosodimethylamine (NDMA) was detectable in 30% of the samples and 6% of them were found to contain more than 5 micrograms/kg. Consumption data given in the "Nutritional Report, 1976" allow calculation of the average daily intake of volatile nitrosamines from food. Intakes for West German males are 1.1 micrograms/day for NDMA and 0.1 micrograms/day for NPYR. With regard to NDMA, the relative contributions are 64% for beer, 10% for meat and meat products and 25% for all other foods (150 types). NDMA in beer originates in the malt, where it is formed during kilning (drying). Technological improvements to eliminate NDMA contamination of beer are reported.

Beer↗
PubMed1979

Lung carcinoma induction in BD rats after a single intratracheal instillation of an arsenic-containing pesticide mixture formerly used in vineyards.

A single intratracheal 0.1-ml instillation of a calcium-arsenate containing vineyard pesticide induced multi-focal bronchogenic adenocarcinomas and bronchiolar-alveolar-cell carcinomas in nine out of 15 treated BD rats. This seems to be the first experimental confirmation of carcinogenicity of arsenic-containing pesticides used formerly in vineyards.

Adenocarcinoma↗