Roughening and fragmentation of strained Ag islands on Pt(111).
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Biomedical subjects
Publications and source records attributed to H Brune.
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The carcinogenic potential of 4 highly purified polycyclic aromatic compounds (PAC) was studied in the respiratory tract of rats. Using a beeswax/trioctanoin mixture as vehicle, 10, 3 and 1 mg phenanthrene (PHE), 3 and 1 mg chrysene (CHR), 0.1 mg dibenz(a,h)anthracene (DBahA) and 6, 3 and 1 mg benzo(b)naphto(2,1-d)thiophene (BNT) were injected into the lungs of 35 female Osborne-Mendel rats per group. Benzo(a)pyrene (BaP, 0.3, 0.1 and 0.03 mg) was used as the reference substance. Whereas only one squamous cell carcinoma developed at the highest PHE dose, a dose-dependent tumor incidence was found for CHR. BNT showed a carcinogenic effect similar to CHR, but an increasing incidence of neoplasms was not seen between the median and high dose. DBahA induced carcinomas in even more than half of the animals at the dose level of 0.1 mg and, therefore, has to be classified as the most potent PAC under investigation. BaP resulted in a clear dose-response relationship. According to probit analysis of the results, the carcinogenic potencies of the PAC relative to BaP (1.00) rank as follows: DBahA, 1.91; CHR, 0.03; BNT, 0.02; and PHE, 0.001. The estimated ED10- values were 0.031 mg for BaP, 0.016 mg for DBahA, 1.02 mg for CHR, 1.65 mg for BNT and 22.84 mg for PHE.
The urinary and faecal excretion of pyrene and 1-hydroxypyrene after oral (53.4%), intraperitoneal (3.1%), intratracheal (30-37%) and intrapulmonary application (0.003%) to rats has been determined by means of gas chromatography/mass spectrometry and the excretion rates were found to depend on the mode of application. With regard to the low urinary excretion rates, 1-hydroxypyrene seems not to be very suitable as a biological marker for PAH exposure to man.
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A carcinogenicity bioassay of 2-ethylhexyl acrylate (2-EHA) was conducted by applying 25 microliters 86.5%, 21%, or 2.5% 2-EHA in acetone three times a week to the clipped dorsal skin of male C3H/HeJ mice (80 per group) over their lifetime. Another group was treated with a 43% 2-EHA solution for 24 weeks and thereafter observed for lifetime (stop-test). An untreated group and a group that received only the diluent acetone served as controls. Treatment-related changes in the skin indicative of irritation (scaling, scabbing, hyperkeratosis, hyperplasia) were found in all 2-EHA-treated groups. These lesions were reversible in the 43% group immediately after treatment was stopped, and in the 2.5% group after the 11th week of treatment. Only in the 86.5% and 21% test groups showing chronic irritative skin damage was there a high incidence of nepolastic skin lesions (papillomas, carcinomas, and melanomas) with no dose dependency. In contrast, no skin tumors were found in the control groups, in the group treated with 2.5% 2-EHA for lifetime or in the group treated with 43% 2-EHA for about 6 months and observed for lifetime.
A 90-day feasibility study was performed in which rats and hamsters were exposed to the sidestream smoke of cigarettes. The only histopathological changes observed were hyperplasia and metaplasia of the epithelium covering the dorsal nasal turbinate bones in rats. These effects were reversible within 90 days.
Particles and semivolatiles from sidestream smoke of cigarettes smoked on a smoking machine were collected by a filter combination consisting of a glass fibre filter and silanized polystyrene beads. The extract of the glass fibre filter was separated by a Sephadex LH-20 column chromatography into a fraction containing non-aromatic material plus polycyclic aromatic compounds (PAC) with 2 and 3 rings and a fraction consisting of PAC with 4 and more rings. To evaluate the carcinogenicity, both fractions as well as the semivolatiles were implanted into the lungs of Osborne-Mendel rats at a dose level of one cigarette per animal and compared with three dose levels of benzo[a]pyrene (BaP). The most pronounced carcinogenic effect of the sidestream smoke (100 ng BaP per cigarette) was caused by the fraction containing polycyclic aromatic hydrocarbons (PAH) with 4 and more rings (5 carcinomas of the lungs/35 rats). This fraction represents only 3.5% by weight of the total sidestream smoke condensate. By contrast, the semivolatile material did not provoke any tumors. Only a small contribution to the total carcinogenicity (1 carcinoma of the lungs/35 rats) was observed for the fraction containing non-aromatic material and 2- and 3-ring PAHs.
The urinary and faecal excretion of chrysene and its phenolic metabolites after oral, intraperitoneal, intratracheal, and intrapulmonary administration to rats have been studied by means of gas chromatography/mass spectrometry. The metabolite profile was found to depend on the mode of excretion and on the route of administration. In all cases the oxidation of chrysene in the 1,2- or 3,4-position predominates, whereas oxidation in the 5,6-position (K-region) seems be a minor pathway.
Diesel exhaust condensate was separated by a liquid-liquid distribution into a hydrophilic (I; about 25% by weight of the total condensate) and a hydrophobic part (II; about 75%-wt.). To evaluate the carcinogenicity, the proportionately dosed fractions have been implanted into the lungs of Osborne Mendel rats and compared with several doses of benzo[a]pyrene and the vehicle, a mixture of trioctanoin plus beeswax. Only the hydrophobic part which contained polycyclic aromatic compounds (PAC) resulted in 5 malignant tumors in a group of 35 animals. In addition, the hydrophobic part was separated by column chromatography on Sephadex LH 20 and subsequently on silica gel into several fractions, such as non-aromatic compounds plus PAC with 2 and 3 rings (IIa; 72%-wt of the total condensate), polycyclic aromatic compounds (PAH) with 4 and more rings (IIb; 0.8%-wt), polar PAC (IIc; 1.1%-wt) and nitro-PAH (IId; 0.7%-wt). PAH consisting of 4 and more rings (IIb) were found to be the most potent subfraction and provoked when proportionately dosed 6 carcinomas in a group of 35 rats. Only a low contribution to the carcinogenicity was observed by the subfraction of nitro-PAH (IId) which produced 1 carcinoma/35 rats. The polar PAC (IIc) and the fraction of non-aromatics plus PAC with 2 and 3 rings (IIa), although the main subfraction (72%-wt of the total condensate) did not provoke any tumors. The reconstitution of all hydrophobic subfractions (IIa-d) resulted in the same carcinogenic potency as the unfractionated hydrophobics (II), provoking 7 carcinoma in 35 rats. It may be concluded from these findings that most of the carcinogenicity of diesel exhaust originates from the PAH consisting of 4 or more rings.
For identification of the substances chiefly responsible for the carcinogenic action of the emission condensate from coal-fired residential furnaces, the implantation method was used as a carcinogen-specific bioassay for comparison of the carcinogenic effect of various fractions with that of a total sample of flue gas condensate tested in 2 or 3 different doses. After implantation into the lungs of Osborne-Mendel rats, the condensate from coal-fired residential furnaces, a fraction containing polycyclic aromatic hydrocarbons (PAHs) and thiaarenes [sulfur-containing polycyclic aromatic compounds (S-PACs)] with 4-7 rings, as well as fraction containing more polar polycyclic aromatic compounds (PACs) and PAHs with higher molecular weight, induced lung carcinomas and sarcomas. According to probit analysis, the fraction containing PAHs plus S-PACs with 4-7 rings accounted for about 68.2% of the total carcinogenicity of flue gas condensate, whereas the fraction containing more polar PACs and higher PAHs accounted for about 54.6%. All other fractions, such as nonaromatic compounds and PACs with 2 and 3 rings, constituting about 70% of the weight of the total condensate, seemed not to be carcinogenic. Only 1.4% of the total carcinogenicity of the flue gas condensate was found to be attributable to the amount of benzo[a]pyrene (CAS: 50-32-8) present in the condensate (1.14 mg/g condensate). The contribution of more than 100% of both active fractions to the total carcinogenicity (68.2 and 54.6%) may suggest an interrelation of the fractions.
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Flue gas condensate from briquet-fired residential furnaces was separated into a polycyclic aromatic compound (PAC)-free and a PAC-containing part, followed by a subfractionation of the PAC-containing fraction into 3 parts: PAC consisting predominantly of (a) 2 and 3 rings, (b) 4 and 5 rings and (c) 6 and more rings. To evaluate the carcinogenic potency of the condensate and its fractions, local application onto skin of mice in 2 or 3 doses was used. Since it was known from an earlier investigation that both the PAC-free fraction and the fraction containing PAC with 2 and 3 rings were almost ineffective, only PAC-fractions containing more than 3 rings were tested. The probit and Weibull analysis of the results showed that the condensate and the fractions containing PAC with 4 and 5 rings as well as 6 and more rings provoke local tumors after repeated application to the dorsal skin of mice. The tumor incidence exhibited a clear cut dose-response relationship. Fractions (b) and (c) were almost equally active, each contributing by about 50% to the total carcinogenicity. The content of benzo[a]pyrene (0.72 mg/g condensate) contributed by 10-11% to the total carcinogenicity of the emission.
Using the epicutaneous test as an experimental model for detecting carcinogenicity, 3 doses each of nitrosomethylurea (NMU), nitrosonornicotine (NNN) and nitrosocarbaryl (NC) were administered to the skin of 65 female CFLP mice/group. To compare the carcinogenic potency of the nitroso compounds, benzo[a]pyrene (BaP) was taken as reference substance. Dose-response relationships were obtained for NMU and NC as well as for BaP. NNN exhibited only a weak carcinogenic effect in the dose range from 12.5 micrograms to 200 micrograms tested in the skin painting model. It showed, however, no dose dependent activity. After probit analysis of the results, the carcinogenic potencies of the nitroso compounds investigated in this system rank as follows: NC, 0.18; NMU, 0.04; NNN, 0.008 (BaP, 1.00).