PubMed Health⌕ Search

Biomedical subjects

F Pott

Publications and source records attributed to F Pott.

At least 55 records · Page 3Linked to original sources

[Methods of risk assessment from data of experimental carcinogenesis studies].

A comparison of the carcinogenic potencies of different substances and an assessment of the risk to exposed people can contribute significantly to the management of carcinogenic hazards including adequate regulatory decisions. A mathematical estimation of the risk caused by a certain height of exposure is usually done under the assumption of a linear dose-response relationship by means of an arithmetical factor which gives the ratio of risk to dose in the low-response range and which has to be found on the basis of epidemiological or experimental data. This work deals with calculations of risk/dose ratios from the data of three carcinogenicity tests by means of statistical methods. The influence of the selection of mathematical model, background assumption and the point of the function chosen for the calculation of the ratio was tested. The results show that an additivity assumption for the background leads to linearity of the curve in the low-response range such that the ratios calculated with different models (multistage, weibull, logit, probit) or for different points of the functions do not differ significantly within the data sets tested. Even under the assumption of independence of the background risk the influence of the model selected is still small if the ratios are calculated for the lowest experimental dose or for an exposure associated risk of 1%. Risk/dose ratios calculated by one of these methods utilize the information of several experimental groups. They seem to be well suited for a direct comparison of the potency of different carcinogens and as a basis for an assessment of the carcinogenic risk to humans, which can serve as a measure of the hazard of a single exposed person or may give an idea about the tumour incidences to be expected within an exposed population.

Administration, Oral↗

Ultrastructure of mesothelial regeneration after intraperitoneal injection of asbestos fibres on rat omentum.

In order to describe the ultrastructural features of the early phases of regenerating mesothelium in rat peritoneum, 69 cases were examined after intraperitoneal injection of 0.05-15 mg crocidolite, chrysotile B and other mineral and synthetic fibers. The findings show the presence of intermediate or transition cells between proliferating submesothelial connective tissue cells bearing the ultrastructural phenotype of myofibroblasts and mature fully regenerated mesothelium. Our results and data accumulated in the literature provide strong support for the hypothesis of submesothelial cells origin for regenerating mesothelium.

Animals↗

Mesothelial proliferation due to asbestos and man-made fibres. Experimental studies on rat omentum.

The intraperitoneal test in rats has proven to be an appropriate method controlling fibrogenicity and carcinogenicity of asbestos fibres and other fibrous dusts. We analyzed the reaction patterns of mesothelial cover layer to different natural mineral fibres (crocidolite, chrysotile, actinolite, erionite, wollastonite) and man-made mineral and synthetic fibres (glass fibres 104/475, polypropylene, aramide fibres). The injection of doses between 0.01 and 100 mg dust suspended in saline solution led to a continued repairing proliferation of submesothelial connective tissue cells and focal submesothelial fibrosis. These changes were never observed after application of granular dusts as mine dust and quartz. After 15 to 28 months we often found an association of fibrosis and local reactive hyperplasia of partly atypical proliferation of rat omentum mesothelium. These changes were also demonstrated in cases without macroscopically visible tumors. In later stages the underlying fibrosis was often infiltrated and dissolved by mesotheliomas.

Animals↗

Relative significance of different hydrocarbons for the carcinogenic potency of emissions from various incomplete combustion processes.

Animal experiments have shown that the carcinogenic activity of organic extracts of exhaust condensates is caused predominantly by PAHs containing 4-6 rings. The carcinogenic potency not only of PAH-containing extracts but also of the whole exhausts has often been estimated from their benzo[a]pyrene (BP) content. However, this simplified yardstick should not be applied for comparison of the carcinogenic potency of different types of PAH-containing exhausts. Epidemiological and experimental studies indicate that, for the induction of a certain tumour incidence, inhaled cigarette smoke contains about 100 times less BP and inhaled diesel exhaust contains about 1000 times less BP than the exhausts from coke ovens or heated tar pitch which yield the same results. This means that diesel exhaust and cigarette smoke contain--apart from PAHs--highly potent carcinogenic substances and/or they induce tumorigenic reactions which are very effective.

Animals↗

[The persistence of chemically different glass fibers in rat lungs].

The half-times of glass fibre samples of different chemical composition and size was analysed in the rat lung. Up to two years after intratracheal instillation the number of fibres in the ashed lungs was determined by SEM. Half-times of fibre clearance of 40 to 240 days were calculated.

Animals↗

[Carcinogenicity of glass fibers of different stability].

A new type of fibrous glass showing a low durability in the body was injected intraperitoneally into rats. In the range of the doses applied (up to 10(9) of a thinner product and up to 0.24 x 10(9) of a thicker product) a carcinogenicity was not detected; in contrast, durable glass fibres induced tumours. It is recommended to use mineral fibres with low durability as far as possible.

Animals↗

Urinary and faecal excretion of pyrene and hydroxypyrene by rats after oral, intraperitoneal, intratracheal or intrapulmonary application.

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.

Animals↗

Risk modelling: which models to choose?

Using as examples excess lung cancer mortality in coke oven workers and lung tumor induction in rats by inhalation of diesel engine emissions or cadmium chloride aerosol, the maximum likelihood estimate and the upper limit of risk were determined using a set of conventional risk models. The additional safety offered by going to the upper limit of the 95% confidence interval when deriving a unit risk value was found to be less than a factor of 5 in all but one case, and usually much less than 2. It is concluded that the selection of an adequate model is the most critical step in risk assessment, and that an additional safety factor may be required to allow for a better protection of the public in case models other than the most conservative ones come into use.

Animals↗

Carcinogenicity studies on natural and man-made fibres with the intraperitoneal test in rats.

Female Wistar rats were injected intraperitoneally (i.p.) with a suspension of 11 fibrous and 3 granular dusts. A dose of 0.25 mg actinolite or UICC chrysotile induced tumours of the peritoneum in more than 50% of the animals. Even 0.05 and 0.01 mg proved to be carcinogenic, although no adhesions of the abdominal organs could be observed. The findings are in conflict with the hypothesis that a scar is always the morphological precondition for the development of an asbestos-induced tumour. Actinolite injected i.p. in a solution of polyvinylpyridine-N-oxide gave a lower tumour incidence than when suspended only in saline, possibly due to inactivation of the fibre surface. Persistent glass fibres were less effective than actinolite having a similar fibre size distribution. On the other hand, relatively thick basalt fibres and ceramic fibres gave higher tumour incidences than expected. Wollastonite fibres were not carcinogenic, probably because of their low durability. Large amounts of polyvinylchloride, alpha-ferric oxide hydrate and wood dust also led only to adhesions of the abdominal organs and fibrosis; a definite carcinogenic effect was not detected.

Animals↗

Urinary and faecal excretion of chrysene and chrysene metabolites by rats after oral, intraperitoneal, intratracheal or intrapulmonary application.

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.

Administration, Inhalation↗

Extrapolation from rat studies with environmental tobacco smoke (ETS) to humans: comparison of particle mass deposition and of clearance behavior of ETS compounds.

The relative deposition of inhaled heterodisperse particles of the size of environmental tobacco smoke (ETS, mass median aerodynamic diameter 0.2 micron, geometric standard deviation 1.5) is about the same in the tracheobronchial tree and is lower in the pulmonary region of the rat than in the same regions of humans. However, model calculations show that per cm2 of surface area the deposition rate of ETS particle mass shows a doubling in rats as compared to humans in the transitional zone of the lung, i.e., airway generations 16-20. Within the human airways, mainstream smoke particles are deposited to a higher degree in generations 2-5 than in the transitional zone, whereas the opposite applies to ETS particles. Significantly higher pulmonary retention in man than in rats of inhaled ETS particles and their constituents (e.g. cadmium) leads to additional differences in the dose accumulating in the lung over time. Such differences in deposition and retention characteristics of inhaled ETS have to be considered when extrapolating results from rat studies to humans.

Aerosols↗

Carcinogenicity studies on fibres, metal compounds, and some other dusts in rats.

About 50 dusts were examined on their carcinogenicity in rats mainly after intraperitoneal injection and some after intratracheal instillation. In the i.p. test, very low doses between 0.05 and 0.5 mg asbestos led to tumour incidences of about 20 to 80%. Polyvinyl-pyridine-N-oxide prolonged the tumour latency after injection of actinolite. 60 mg attapulgite from three sources with short fibre lengths were not shown to be carcinogenic but an attapulgite sample with longer fibres had a moderate effect. Relatively thick rock and ceramic fibres (median greater than 1 micron) induced tumours, but slag and wollastonite fibres did not, probably because of their better solubility. Intratracheal instillations of glass microfibres (20 X 0.5 mg) led to lung tumours in 5 of 34 rats (0 in control). The carcinogenic potency of an inorganic fibre depends on its size and persistency, and possibly also on other properties, especially on the surface. Nickel powder, nickel oxide, nickel subsulfide and cadmium sulfide were all found to be carcinogenic in the two tests. Cadmium chloride and cadmium oxide could only be administered in very low doses because of their high acute toxicity. A high amount of magnetite (15 X 15 mg i.tr.) led to an unexpected lung tumour incidence of 69%. The i.p. test in rats proved to be very sensitive for detecting the carcinogenic potency of non-acute toxic natural and man-made mineral dusts as well as metal compounds. This means that, if a high dose of one of these dusts does not induce tumours in this test, no suspicion of carcinogenic potency can be substantiated.

Animals↗