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Biomedical subjects

B Spiegelhalder

Publications and source records attributed to B Spiegelhalder.

At least 109 records · Page 6Linked to original sources

Biological monitoring in the metal working industry.

N-Nitrosodiethanolamine (NDELA) is a strong carcinogen in animal experiments. Its occurrence in cutting and grinding fluids represents a major risk for workers who come into contact with those compounds. But until now it was not possible to describe the extent of N-nitrosodiethanolamine exposure at the workplace. Since 60-90% of N-nitrosodiethanolamine given by oral, intravenous, epicutaneous or intratracheal application in rat experiments is excreted unchanged in the urine, N-nitrosodiethanolamine should be found in the urine of workers in the metal working industry. Analyses of grinding fluids containing di- and triethanolamine in combination with up to 30% nitrite showed concentrations of up to 593 mg/kg N-nitrosodiethanolamine in the original, concentrated fluid and up to 90 mg/kg in ready-to-use emulsions. In preliminary investigations, it was also found in the urines of metal grinders: of 264 urines analysed, 166 showed positive results (greater than 0.5 micrograms/kg) with levels up to 103 micrograms/kg N-nitrosodiethanolamine. These results indicate that workers' exposure to NDELA can be monitored by urine analysis.

Air Pollutants, Occupational↗

Nitrosamine metabolism in kwashiorkor rats.

The in vitro metabolism of nitrosodimethylamine (NDMA) was studied in liver tissue obtained from male weanling kwashiorkor wistar rats. The elimination of this compound and that of nitrosomorpholine (NMOR) from the blood, after a single intravenous dose, was also investigated. N-demethylase activity in liver microsomes of the test animals was not significantly different from that of the controls although the activity of this enzyme per gram wet liver tissue was considerably reduced in the model animals. On the other hand, the glutathione (GSH) content in liver cytosol of the kwashiorkor animals was much higher than that of the controls. The elimination of NDMA and NMOR from the blood of the experimental animals over 8 hr following i.v. administration of the carcinogens, showed that the clearance rate of each nitrosamine was significantly lower in the kwashiorkor rats.

Animals↗

Occupational nitrosamine exposure. 1. Rubber and tyre industry.

To determine the role of N-nitrosamines in the known increased cancer risk of rubber workers, air concentrations of such carcinogens were measured by area sampling or personal monitoring in 19 factories. N-Nitrosodimethylamine (NDMA) and N-nitrosomorpholine (NMOR) were found regularly, the air concentrations varying between 0.1 and 380 micrograms/m3 personal monitoring. The mean concentration was usually in the range of 1-10 micrograms/m3. Several other nitrosamines could be detected in certain production branches. In retail shops and storage rooms of tyres NDMA and NMOR were found. Most rubber chemicals based on amines are contaminated with N-nitrosamines, but this contamination cannot explain the air concentrations of nitrosamines found. The occurrence of nitrosamines mainly depends upon their formation during production of rubber and rubber products from used vulcanisation accelerators based on amines and the presence of nitrosating agents, such as diphenylnitrosamine (retarder A) and of nitrous gases, in products or production areas. Elimination of one or both precursors for nitrosamine formation resulted in significant reduction of airial contamination of nitrosamines. The results are discussed in regard to the mechanisms of nitrosamine formation during rubber production, as basis for future epidemiological studies and their potential for exposure prevention.

Air Pollutants↗

Carcinogens in the workroom air in the rubber industry.

Only a few data are available on the occurrence of carcinogenic compounds in the air at workplaces in the rubber industry, with the exception of data on total particulates and solvents. The available information allows the indication of some specific workplaces with elevated exposure levels. Recent investigations of nitrosamines in the rubber industry indicate the widespread occurrence of considerable levels of nitrosodimethylamine and nitrosomorpholine. In an effort to elucidate the origin and formation of nitrosamines in this industry, chemicals as well as the air in various areas were analyzed. All chemicals used for rubber compounding contain nitrosamines if they are derivatives of secondary amines, eg, tetramethylthiuram, zinc diethyldithiocarbamate or N-oxydiethylene benzothiazolylsulfenamide. 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. Therefore additional nitrosation had to be considered. The responsible nitrosating agents are described. Preliminary results show that, in most cases, either by elimination of the nitrosating agent or by the exchange of rubber chemicals nitrosamine levels in the work area can be drastically reduced.

Air Pollutants, Occupational↗

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↗

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↗

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↗