@article{KlaunigDekantPlotzkeetal.2016, author = {Klaunig, James E. and Dekant, Wolfgang and Plotzke, Kathy and Scialli, Anthony R.}, title = {Biological relevance of decamethylcyclopentasiloxane (D5) induced rat uterine endometrial adenocarcinoma tumorigenesis: Mode of action and relevance to humans}, series = {Regulatory Toxicology and Pharmacology}, volume = {74}, journal = {Regulatory Toxicology and Pharmacology}, number = {Supplement}, doi = {10.1016/j.yrtph.2015.06.021}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-190952}, pages = {S44-S56}, year = {2016}, abstract = {Decamethylcyclopentasiloxane (D5) is a cyclic siloxane used in the production and formulation of consumer products with potential exposure to manufacturing workers, consumer, and the general public. Following a combined 2-year inhalation chronic bioassay performed in Fischer 344 (F344) rats, an increase in uterine endometrial adenocarcinomas was noted at the highest concentration to which animals were exposed. No other neoplasms were detected. In this study, a dose of 160 ppm produced an incidence of 8\% endometrial adenocarcinomas. Based on a number of experimental studies with D5, the current manuscript examines the biological relevance and possible modes of action for the uterine endometrial adenocarcinomas observed in the rat following chronic exposure to D5. Variable rates of spontaneous uterine endometrial adenocarcinomas have been reported for untreated F344 CrIBr rats. As such, we concluded that the slight increase in uterine endometrial adenocarcinomas observed in the D5 chronic bioassay might not be the result of D5 exposure but may be related to variability of the spontaneous tumor incidence in this strain of rat. However, if the uterine endometrial adenocarcinomas are related to D5-exposure, alteration in the estrous cycle in the aging F344 rat is the most likely mode of action. D5 is not genotoxic or estrogenic. The alteration in the estrous cycle is caused by a decrease in progesterone with an increase in the estrogen:progesterone ratio most likely induced by a decrease in prolactin concentration. Available data support that exposure to D5 influences prolactin concentration. Although the effects on prolactin concentrations in a number of experiments were not always consistent, the available data support the conclusion that D5 is acting via a dopamine receptor agonist-like mechanism to alter the pituitary control of the estrous cycle. In further support of this mode of action, studies in F344 aged animals showed that the effects of D5 on estrous cyclicity produced a response consistent with a dopamine-like effect and further suggest that D5 is accelerating the aging of the reproductive endocrine system in the F344 rat utilized in this study. This mode of action for uterine endometrial adenocarcinoma tumorigenesis is not relevant for humans.}, language = {en} } @article{RaslanAlbertWeissenbergerWestermaieretal.2012, author = {Raslan, Furat and Albert-Weißenberger, Christiane and Westermaier, Thomas and Saker, Saker and Kleinschmitz, Christoph and Lee, Jin-Yul}, title = {A modified double injection model of cisterna magna for the study of delayed cerebral vasospasm following subarachnoid hemorrhage in rats}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76038}, year = {2012}, abstract = {Delayed cerebral vasospasm following subarachnoid hemorrhage (SAH) is a serious medical complication, characterized by constriction of cerebral arteries leading to varying degrees of cerebral ischemia. Numerous clinical and experimental studies have been performed in the last decades; however, the pathophysiologic mechanism of cerebral vasospasm after SAH still remains unclear. Among a variety of experimental SAH models, the double hemorrhage rat model involving direct injection of autologous arterial blood into the cisterna magna has been used most frequently for the study of delayed cerebral vasospasm following SAH in last years. Despite the simplicity of the technique, the second blood injection into the cisterna magna may result in brainstem injury leading to high mortality. Therefore, a modified double hemorrhage model of cisterna magna has been developed in rat recently. We describe here step by step the surgical technique to induce double SAH and compare the degree of vasospasm with other cisterna magna rat models using histological assessment of the diameter and cross-sectional area of the basilar artery}, subject = {Medizin}, language = {en} } @article{WeyersJankeMachtetal.1993, author = {Weyers, P. and Janke, W. and Macht, Michael and Weijers, H.-G.}, title = {Social and nonsocial open field behaviour of rats under light and noise stimulation}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61246}, year = {1993}, abstract = {ln two experiments, male rats were observed in pairs under different environmental stimulations in an open field. ln Experiment 1, white noise of 85 dB(A) reduced social activities and increased defecation compared to 75 dB(A) and 65 dß(A). ln Experiment 2, the illumination of the open field was varied in addition to a variation of the noise intensity. Again, 85 dB(A) as compared to 50 dB(A) reduced social activities and increased defecation, but also led to changes in non-social behaviours such as sniffing, grooming, and rearing. ln contrast, 400 lx did not differ substantially in its effects from 40 lx in any of the observed behavioural categories. Altogether, the behaviour pattern under 85 dß(A) white noise cannot satisfactorily be explained only by increased anxiety or fear. Alternative explanations are discussed.}, subject = {Psychologie}, language = {en} } @article{BaertschLutzSchlatter1991, author = {Baertsch, A. and Lutz, Werner K. and Schlatter, C.}, title = {Effect of inhalation exposure regimen on DNA binding potency of 1,2-dichloroethane in the rat}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-60743}, year = {1991}, abstract = {1 ,2-Dichloroethane (DCE) was reported to be carcinogenic in rats in a long-tenn bioassay using gavage in com oil (24 and 48 mg/kg/day), but not by inhalation (up to 150-250 ppm, 7 h/day, 5 days/week). The daily dose metabolized was similar in the two experiments. In order to address this discrepancy, the genotoxicity of DCE was investigated in vivo under different exposure conditions. Fernale F-344 rats (183-188 g) were exposed to [1,2-14C]DCE in a closed inhalation chamber to either a low, constant concentration (0.3 mg/l = 80 ppm for 4 h) or to a peak concentration (up to 18 mg/1 = 4400 ppm) for a few minutes. After 12 h in the chamber, the dose metabolized under the two conditions was 34 mg/kg and 140 mg/k:g. DNA was isolated from liver and lung and was purified to constant specific radioactivity. DNA was enzymaticaBy hydrolyzed to the 3' -nucleotides which were separated by reverse phase HPLC. Most radioactivity eluted without detectable or with little optical density' indicating that the major part of the DNA radioactivity was due to covalent binding of the test compound. The Ievel of DNA adducts was expressed in the dose-nonnalized units ofthe Covalent Binding Index, CBI = f.Lmol adduct per mol DNA nucleotide/ mmol DCE per kg body wt. In liver DNA, the different exposure regimens resulted in markedly different CBI values of 1.8 and 69, for "constant-low" and ''peak" DCE exposure Ievels. In the Jung, the respective values were 0.9 and 31. It is concluded that the DNA darnage by DCE depends upon the concentration-time profile and that the carcinogenic potency determined in the gavage study should not be used for low-Ievel inhalation exposure.}, subject = {Toxikologie}, language = {en} } @article{RettenmayrRodriguesdeMirandaRijntjesetal.1990, author = {Rettenmayr, N. M. and Rodrigues de Miranda, J. F. and Rijntjes, N. V. M. and Russel, F. G. M. and van Ginneken, C. A. M. and Strohmann, C. and Tacke, Reinhold and Lambrecht, G. and Mutschler, E.}, title = {Pharmacokinetic properties of the antimuscarinic drug [\(^3\)H]-hexahydro-sila-difenidol in the rat}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64022}, year = {1990}, abstract = {The pharmacokinetics of tritiated hexahydrosila- difenidol ([\(^3\)H]-HHSiD) were examined in rats. Furthermore, the distribution of radioactivity was studied by means of whole body autoradiography. After i. v. administration of 2.9 mg/kg HHSiD plus [\(^3\)H]-HHSiD to anaesthetized rats bearing a catheter implanted in the ductus choledochus and receiving a mannitol infusion, HHSiD was rapidly distributed and metabolized. Only 5\% ofthe radioactivity was recovered in blood after 23 s and 0.4\% after 2.5 h. 64\% of the plasma radioactivity could be extracted with hexane from the samples taken 23 s after administration. 52\% of the radioactivity was eliminated within 2.5 h, 13\% by urinary and 39\% by biliary excretion. Following oral administration of 8.6 mg/kg HHSiD plus [\(^3\)H]-HHSiD there was an absorption of approximately one fourth of the administered radioactivity within 4 h. By means of whole body autoradiography (i. v. injection) as well as by tissue distribution measurement the highest Ievels of radioactivity were found in bile, urine, lung, kidney, adrenals, liver and .pancreas. Thus, after i. v. administration to rats HHSiD is rather quickly distributed, metabolized and excreted. This explains its low antimuscarinic potency in vivo.}, subject = {Anorganische Chemie}, language = {en} }