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Biomedical subjects

R Preussmann

Publications and source records attributed to R Preussmann.

At least 55 records · Page 3Linked to original sources

New sulfenamide accelerators derived from 'safe' amines for the rubber and tyre industry.

A reduction of the high exposures to N-nitrosamines in the rubber and tyre industry is possible using the concept of 'safe' amines, in which vulcanization accelerators contain amine moieties that are both difficult to nitrosate and, on nitrosation, yield noncarcinogenic N-nitroso compounds. The toxicological and technological properties of more than 50 benzothiazole sulfenamides derived from 'safe' amines have been evaluated. Some of the new compounds show excellent vulcanization properties and seem suitable as replacements for traditional accelerators in this class of compounds.

Benzothiazoles↗

N-nitroso compounds and their precursors in Brassica oleracea.

In the present study, Brassica a dried green vegetable from Kashmir, which is a major constituent of the local diet, was analysed for nitrosatable aliphatic amines, N-nitrosamines prior to and after nitrosation) and alkylating activity due to N-nitrosamides following nitrosation. The cooked vegetable contained 11 micrograms/kg nitrosodimethylamine and 21 micrograms/kg nitrosopyrrolidine. Nitrosation under chemical conditions yielded 1200 micrograms/kg N-methylnitrosourea.

Brassica↗

Assay of suntan lotions for the carcinogenic, non-volatile N-nitrosamine N-nitrosodiethanolamine.

N-nitrosodiethanolamine (NDELA) is a carcinogenic, non-volatile nitrosamine that has been shown to pass readily through the skin of animals and humans. It has often been found as a contaminant in cosmetics. Twenty different suntan lotions, available in Israel, both liquids and creams, were analyzed for NDELA content. Most products contained undetectable or trace levels, but 3 were found to be contaminated with as much as 27 ppb of the nitrosamine. Continual use of such products, especially by small children and infants, may significantly increase their exposure to NDELA.

Carcinogens↗

Tobacco-specific nitrosamines in Canadian cigarettes.

Twenty-five brands of Canadian commercial cigarettes were analyzed for tobacco-specific nitrosamines (TSNA) in tobacco and in mainstream smoke as well as for nitrate in tobacco. Preformed N'-nitrosonor-nicotine (NNN) in the tobacco ranged from 265 ng to 979 ng/cigarette, preformed 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) ranged from 465 ng to 878 ng/cigarette. The mainstream smoke concentration for NNN was between 5 ng and 39 ng/cigarette and for NNK between 5 ng and 97 Ng/cigarette. The nitrate levels were between 0.3 mg and 3.4 mg/cigarette. The NNK levels in tobacco and in mainstream smoke were higher than the NNN levels, which is typical for Virginia-type cigarettes. Based upon the average mainstream smoke concentration of the three most popular Canadian cigarette brands, an average TSNA delivery for 20 cigarettes of 0.7 micrograms NNN and 1.7 micrograms NNK can be calculated, which is less than the average for West German cigarettes. The results of this investigation demonstrate that there seems to be a good correlation between the TSNA and tar deliveries in mainstream smoke. However, no correlation between the level of preformed TSNA in tobacco and the tar delivery in mainstream smoke could be observed. It is demonstrated that the good correlation between the tar and TSNA deliveries in mainstream smoke can only be attributed to the unusual good correlation between the tar delivery and the ventilation ratio. For the cigarettes investigated, which seemed to be Virginia-type cigarettes, with few exceptions, the ventilation ratio had a much higher influence on the mainstream smoke concentration than the level of preformed TSNA in tobacco.

Canada↗

Inhalation carcinogenesis of N-nitrosomorpholine (NMOR) in rats and hamsters.

N-Nitrosomorpholine (NMOR) is a potent liver carcinogen in rats when administered orally. NMOR was found in the atmosphere at working places in the rubber industry in concentrations up to several hundred micrograms/m3. It can be assumed that NMOR inhalation may play a role in human carcinogenesis. Therefore an inhalation study was carried out to evaluate the carcinogenic potency of NMOR vapors in rats and hamsters. The concentration of volatile NMOR in the inhalation chamber was continuously determined with a Thermal Energy Analyzer. The rats received 29 administrations (4th/day, 5 days/week; mean inhaled daily dose: 130 micrograms/animal; total dose: 15 mg/kg bodyweight). The hamsters inhaled a total of 38 mg/kg of NMOR (21 applications, daily dose 260 micrograms/animal). In rats 4 carcinomas and 5 neoplastic nodules of the liver, 1 neuroblastoma and 1 mucoepidermoidal carcinoma of the nose, and 1 carcinoma of the thyroid gland were induced. In treated hamsters 4 carcinomas of the liver, 2 neurogenic sarcomas of the nasal region, and 5 papillomas of the trachea were found. None of these tumors were observed in control rats and control hamsters.

Administration, Inhalation↗

Investigations on the origin of tobacco-specific nitrosamines in mainstream smoke of cigarettes.

The origin of tobacco-specific nitrosamines (TSNA) in mainstream smoke and the possible contribution of synthesis during the smoking procedure was investigated. Addition of the nitrosamine precursors nitrate and nicotine to the tobacco prior to smoking did not change the mainstream smoke concentrations of N'-nitrosonornicotine (NNN) and 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), whereas the mainstream smoke concentration of N'-nitrosoanabasine (NAB) and N'-nitrosoanatabine (NAT) increased after spiking the cigarettes with nitrate. Data for TSNA in tobacco and in mainstream smoke and for nitrate in tobacco of commercial cigarettes of the West German market, taken from previous investigations, were used to calculate the mainstream smoke/tobacco ratios for NNN and NNK. These ratios were corrected for ventilation and cigarette length. It is shown that the ratios are constant and neither depend on the nicotine level nor on the nitrate level of the tobacco except for NNK in the nitrate rich dark tobacco type cigarettes. For nonfilter cigarettes the transfer rates of NNN and NNK which had been corrected for ventilation and cigarette length amounted to 23 or 34% respectively. For filter cigarettes a transfer rate of 13% for NNN and 23% for NNK was calculated. Furthermore it is shown that the mainstream smoke/tobacco ratios for NNN and NNK are constant over the whole length of the cigarettes except for NNK in dark tobacco type cigarettes. The results of this investigation indicate that pyrosynthesis of NNN does not occur and that it is very unlikely for NNK at least for lower nitrate levels. Thus with few exceptions the TSNA burden of smokers is predominantly influenced by the amount of preformed NNN and NNK in tobacco.

Carcinogens↗

Tobacco-specific nitrosamines in European and USA cigarettes.

More than 170 types of commercial cigarettes from several European countries and the USA were analyzed for tobacco-specific nitrosamines (TSNA) in tobacco and mainstream smoke as well as for nitrate in tobacco. The cigarettes included filter and nonfilter cigarettes with different tar and nicotine yields. The observed range for N'-nitrosonornicotine (NNN) was from 4 to 1353 ng/cigarette in mainstream smoke and from 45 to 12454 ng/cigarette in tobacco. For 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) the values were between not detected (less than 4 ng/cigarette) and 1749 ng/cigarette in mainstream smoke and between not detected (less than 50 ng/cigarette) and 10745 ng/cigarette in tobacco. Nitrate levels ranged from 0.6 to 19.4 mg/cigarette. The TSNA levels for the cigarettes from the different countries investigated were in a similar range with the exception of few individual brands. The results demonstrated that there is no correlation between TSNA and tar deliveries in mainstream smoke. The TSNA deliveries in mainstream smoke depend on the amount or preformed TSNA in the actual tobacco composition, which is influenced by the nitrate level of the tobacco and the tobacco type. According to these results the tar delivery, although crucial, is not a sufficient index for the biological activity and the carcinogenic potential of cigarette smoke. Reduction of TSNA exposure can be achieved by selecting tobaccos with low levels of preformed TSNA in tobacco, which means a low nitrate content and reduction of the amount of Burley tobaccos and stems in blended cigarettes.

Chromatography, Gas↗

Causes of cancer--an alternative view to Doll and Peto (1981).

This paper presents an alternative view to a commonly held misconception. The extent to which the causes of human cancer can be known is less than generally believed on the basis of the formal summation of estimates on the causal role of certain carcinogenic factors that have been tabulated by Doll and Peto (1981). Here it is stressed that the factors with known causal relation in the etiology have not as yet been ascertained for up to 97% of human cancers. Currently only one-third of the cancer deaths registered in the Federal Republic of Germany can be assigned etiologically to known exogenous carcinogenic agents or lifestyle. Accordingly, the causes of less than 50% of all malignant neoplasms are known and amenable to direct causal primary prevention. This, however, does not preclude a concept of "indirect primary prevention" which, based on the probable summation of subcarcinogenic effects of single carcinogens, enables removal from the environment of compounds that show carcinogenicity in animals, even if these compounds lack epidemiological evidence of carcinogenic activity.

Cocarcinogenesis↗

Trapping of reactive intermediates from the nitrosation of primary amines by a new type of scavenger reagent.

N-Methyl-N-nitrosoethanolamine has been used as a scavenger reagent for the in vitro detection of unstable alkylating intermediates. The nucleophilic hydroxy group of the scavenger reagent binds with electrophiles to yield chemically stable ethers, which are analysed using gas-liquid chromatography with the highly sensitive and specific chemiluminescence detector, the thermal energy analyser. In contrast to other test systems for the in vitro detection of alkylating species, non-physiological reaction conditions are avoided and direct conclusions on the structure of the reaction products can be drawn. This test system is shown to be effective for investigating the alkylating capacity of primary amines on nitrosation. From methylamine to butylamine the yield of alkylated scavenger is low, decreasing with elongation of the carbon chain. In contrast, nitrosation of aniline, benzylamine or phenylethylamine leads to much greater yields of alkylated scavenger. These compounds should therefore be included in risk assessment of endogenous nitrosation of primary amine precursors.

Alkylation↗

A sensitive analytical procedure for the detection of N-nitrosamides via their alkylating activity.

Based on a method for trapping direct-alkylating intermediates with scavenger reagents possessing a nucleophilic side-chain and an N-nitroso group as a marker, a sensitive test system for the detection of N-nitrosamides and related compounds has been developed. N-Nitroso-N-tert-butylglycine is an effective scavenger reagent for this purpose. It reacts readily with diazoalkanes released from N-nitrosamides on treatment with alkali to form the corresponding esters which are analysed by gas-liquid chromatography using a thermal energy analyser. The method is easy to perform and specific for N-nitroso compounds that decompose to non-polar diazoalkanes on treatment with alkali. A determination limit of 2 ng solids/sample was established for methylated NTBG formed from N-methyl-N-nitro-sourea following treatment with alkali.

Alkylation↗

The occurrence of N-nitroso compounds in kiwam tobacco.

The concentrations of tobacco-specific nitrosamines (TSNA), volatile and non-volatile N-nitroso compounds in kiwam, a fermented Indian tobacco product are presented. Total identified N-nitroso compound concentrations in kiwam ranged from 6.19 to 25.4 mg/kg fresh weight tobacco, the concentration range of TSNA was 5.43-22.2 mg/kg tobacco which accounted for 67-87% of the total identified N-nitroso compound burden. The high concentrations of TSNA found in kiwam tobacco may present a considerable exposure source to carcinogenic N-nitroso compounds for people using this type of tobacco.

India↗

Tobacco-specific nitrosamines in mainstream smoke of West German cigarettes--tar alone is not a sufficient index for the carcinogenic potential of cigarette smoke.

Fifty-five types of commercial cigarettes on the West German market were analyzed for tobacco-specific nitrosamines (TSNA) in mainstream smoke. The cigarettes included filter and nonfilter cigarettes with very high, high, medium, low and ultra-low tar and nicotine yields. The observed range for N'-nitrosonornicotine was from 5 to 625 ng/cigarette and for 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone from not detected (less than 4 ng/cigarette) to 432 ng/cigarette. The highest TSNA values were obtained for nonfilter cigarettes made of dark tobaccos and the lowest values for nonfilter Oriental-type cigarettes. Relatively high TSNA yields were also observed in filter cigarettes with moderate and lower tar deliveries. The results demonstrated that there is no correlation between TSNA and tar deliveries in mainstrain smoke. The TSNA deliveries in mainstream smoke depended on the actual tobacco composition. According to these results the tar delivery, although crucial, is not a sufficient index for the biological activity and the carcinogenic potential of cigarette smoke.

Filtration↗

Increased urinary nitrosamine excretion in patients with urinary diversions.

Tumor development at the site of ureterointestinal anastomosis is a recognized complication in patients with continent urinary diversions. Aerobic cultures of rectal urine samples from 30 patients with urinary diversions (26 ureterosigmoidostomies, two colon conduits, one ileal conduit and a Gersuny bladder) showed a complex bacterial flora containing nitrate-reducing organisms (Escherichia coli, Proteus and Klebsiella spp.). In comparison to normal bladder urine samples from control volunteers (n = 20), rectal urine samples from ureterosigmoidostomy patients (n = 26) showed a significant decrease (P less than 0.0001) in urinary nitrate (0.93 +/- 0.39 versus 0.27 +/- 0.23 mmol/l), a significant increase (P less than 0.0001) in urinary nitrite (not detected versus 29.24 +/- 39.93 mumol/l) as well as a significant increase (P = 0.013) in urinary N-nitroso compound excretion (57.33 +/- 33.87 versus 93.96 +/- 65.76 nmol/l). Significant increases were also found for the urinary excretion of individual volatile and non-volatile N-nitroso compounds, clearly demonstrating a bacterially mediated in vivo formation of N-nitroso compounds in the 'colon' bladders of patients with urointestinal diversions that may be an important etiological risk factor for colon carcinogenesis in this patient group.

Bacteria↗

Urinary excretion of nitrate, nitrite and N-nitroso compounds in Schistosomiasis and bilharzia bladder cancer patients.

Saliva and 24-h urine samples were collected from male Schistosomiasis (bilharzia) patients with S. haematobium infection and possible concurrent S. mansoni infection without diagnosed bladder cancer (n = 27), bilharzia patients with diagnosed bladder cancer (n = 23) as well as a comparative control group (n = 27) of healthy Egyptian volunteers with no current bilharzia infection and/or bacterial urinary tract infections from the Nile Delta area of Egypt. Saliva samples were analysed for the presence of nitrate and nitrite; urine samples were analysed for the presence of nitrate, nitrite, volatile and non-volatile N-nitroso compounds. Bilharzia patients prior to, and after, diagnosed bladder cancer regularly excreted free nitrite as well as volatile nitrosamines (N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosopiperidine and N-nitrosopyrrolidine) in addition to which elevated concentrations of non-volatile N-nitrosamino acids (N-nitrosoproline, N-nitrososarcosine, N-nitrosothiazolidine-4-carboxylic acid and its 2-methyl derivative) were also present. Total urinary excretion of volatile N-nitroso compounds (0.32 +/- 0.64 micrograms/day; mean +/- SD) and non-volatile N-nitroso compounds (31.20 +/- 22.07 micrograms/day) was observed in the Egyptian control group. Significantly higher concentrations were found in bilharzia patients: 3.47 +/- 6.42 (P less than 0.05) and 62.91 +/- 21.96 (P less than 0.05); as well as in bilharzia patients with diagnosed bladder cancer: 1.71 +/- 1.96 (P less than 0.02) and 44.94 +/- 7.31 respectively. Free nitrite was found in the urine of two volunteers in the Egyptian control group (1.7 and 3.0 micrograms/day), urinary nitrite was significantly increased in bilharzia patients (5.18 +/- 9.11 micrograms/day, P less than 0.02) and in bladder cancer patients (1.75 +/- 2.81 micrograms/day, P less than 0.05). Nitrate concentrations were elevated from 139.3 +/- 82.2 in the control group to 143.6 +/- 136.3 and 175 +/- 190 in the bilharzia and bladder cancer groups respectively. These results indicate that significant in vivo formation of nitrite and volatile N-nitroso compounds occurs in the urinary bladder of bilharzia patients and this may be an oetiological factor in the induction of bilharzial bladder cancer associated with S. haematobium infection.

Adult↗

Influence of smoking parameters on the delivery of tobacco-specific nitrosamines in cigarette smoke--a contribution to relative risk evaluation.

The influence of the smoking parameters (puff profile, puff duration, puff volume, puff frequency) on the delivery of tobacco-specific nitrosamines (TSNAs) in mainstream smoke was investigated for six different cigarette brands, including filter cigarettes with very low to medium smoke yields and non-filter cigarettes with high and very high smoke yields. The puff profile did not influence the TSNA yields. The puff duration also had no remarkable influence on the TSNA delivery with the exception of a non-filter cigarette made of dark tobaccos. The puff volume and the puff frequency significantly influenced the TSNA yields. Increasing puff volume and frequency resulted in increasing TSNA values. The total volume drawn through a cigarette was calculated. The dependency of the TSNA delivery on the total volume was almost linear at least up to a total volume of approximately 500 ml/cigarette. The TSNA yield was the same for the same total volume no matter whether the total volume was due to a changing puff volume or a changing puff frequency. The total volume drawn through a cigarette is the main responsible factor for the TSNA delivery in mainstream smoke. Total volume data from smokers of low- and medium-tar cigarettes are used to calculate TSNA intake. The different smoking behaviour observed for smokers of low-tar and low-nicotine cigarettes as compared to standard smoking conditions is discussed with respect to the TSNA dependency on smoke parameters.

Humans↗

Preformed tobacco-specific nitrosamines in tobacco--role of nitrate and influence of tobacco type.

Fifty-five types of commercial cigarettes on the open market in the FRG and several samples of pure tobacco types were analyzed for preformed tobacco-specific nitrosamines (TSNA) and nitrate in the tobacco. For the cigarette tobaccos the observed range for N'-nitrosonornicotine (NNN) was 50-5316 ng/cigarette and for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) from not detected (less than 50 ng/cigarette) to 1120 ng/cigarette. Nitrate levels ranged from 0.6 to 14.4 mg/cigarette. The highest TSNA values were obtained for cigarettes made of dark tobaccos and the lowest for Oriental type cigarettes. The results demonstrated that there is a correlation between TSNA and nitrate levels. The tobacco type is another important influencing factor, especially for NNK. In Virginia tobaccos unexpectedly high NNK values were observed. For the samples of the pure tobacco types, NNN levels ranged from 20 to 8850 p.p.b. and NNK levels from not detected (less than 50 p.p.b.) to 1400 p.p.b. The observed range for nitrate was from traces (less than 0.005%) to 4.1%. Pure Oriental tobaccos which are low in nitrate showed the lowest TSNA concentrations. In the high nitrate Burley tobaccos the highest TSNA concentrations could be determined. Virginia tobaccos which show a low nitrate content are low in NNN but rather high NNK concentrations were found. The results from these pure tobacco types demonstrate that the nitrate content of the tobacco has a great influence on the TSNA level. However, Virginia tobaccos show higher NNK concentrations than expected according to their low nitrate content.

Chromatography, Gas↗