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2.
Toxicol In Vitro ; 5(5-6): 457-61, 1991.
Article in English | MEDLINE | ID: mdl-20732056

ABSTRACT

Photosensitizing compounds may cause severe skin reactions after appropriate light exposure. On the cellular level this cutaneous in vivo response can be demonstrated by an in vitro model system with adequate target cells of human skin. Normal keratinocytes and fibroblasts were used to establish a predictive assay for phototoxic compounds. To develop a sensitive, specific and easy-to-handle screening system we determined different viability and proliferation parameters, like neutral red (NR) uptake, MTT-reduction, kenacid blue (KB) test, [(3)H]thymidine incorporation and a fluorometric assay in response to UVA light after treatment with different classes of compounds. These experiments resulted in the selection of a final test pattern, which we used to screen 26 substances of different phototoxic potential in vivo. We found a qualitative correlation between the phototoxic response in vitro and phototoxicity reported in different test systems in vivo.

3.
Toxicol In Vitro ; 5(5-6): 539-42, 1991.
Article in English | MEDLINE | ID: mdl-20732073

ABSTRACT

A national interlaboratory study to validate two alternative methods to the Draize rabbit's eye test, co-ordinated by ZEBET at the German Federal Health Office (BGA), is described. The aim of the study is to classify chemicals according to their irritation potential using the neutral red/kenacid blue (NR/KB) cytotoxicity assay and the hen's egg chorioallantoic membrane (HET-CAM) test. During the last two years 12 toxicology laboratories from industry, universities and other research institutions have tested 32 substances from a variety of chemical classes, characterized by a broad spectrum of locally irritating properties, using the NR/KB cytotoxicity test and the HET-CAM assay. Intra- and interlaboratory reproducibility of the two methods was investigated under standardized conditions. The so-far limited evaluation of the interlaboratory assessment phase of validation indicates that the results of the Draize rabbit's eye test correlate better with the results of the HET-CAM test than with those of the cytotoxicity test as far as false negative results are concerned. However, the intra- and interlaboratory reproducibility of the cytoxicity test is better than that of the HET-CAM test. The validation project has recently entered the stage of database development during which 150 chemicals will be tested in seven laboratories to provide information on whether and to what extent the NR/KB test and the HET-CAM test can replace the Draize rabbit's eye test for the classification and labelling of chemicals with regard to their eye irritation potential.

4.
Arzneimittelforschung ; 40(2 Pt 1): 200-6, 1990 Feb.
Article in English | MEDLINE | ID: mdl-2334462

ABSTRACT

Blood and plasma levels and renal and faecal excretion of 14C-oxaceprol (N-acetyl-4-hydroxyproline, AHP 200) were measured after p.o. and after i.m. administration to 3 male Beagle dogs each. In addition, the concentration of 14C-oxaceprol equivalents in synovia was determined at tmax and at tmax + t1/2(elim.). The pattern of metabolites was investigated for plasma, synovia, and urine samples. Peak plasma levels were obtained for the individual animals between 20 and 30 min after i.m. administration and between 2 and 2.5 h after p.o. administration, respectively. The concentrations of 14C-oxaceprol equivalents in synovia 2.5 and 3.5 h after oral administration and 1.3 h after i.m. administration were comparable to the respective plasma levels at the same time. After oral administration the amount of absorbed oxaceprol varied between 43 and 79% of the dose. Oxaceprol was exclusively eliminated via the kidneys. Excretion was complete within 72 h p.a. for both administration routes. Elimination half-lives were 44 +/- 9 min. or 68 +/- 14 min. (means +/- S.D.) after i.m. and p.o. administration, respectively. Oxaceprol was not metabolized.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Hydroxyproline/analogs & derivatives , Administration, Oral , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Dogs , Feces/analysis , Hydroxyproline/administration & dosage , Hydroxyproline/metabolism , Hydroxyproline/pharmacokinetics , Injections, Intramuscular , Male , Synovial Fluid/metabolism
5.
Arzneimittelforschung ; 37(3): 340-1, 1987 Mar.
Article in German | MEDLINE | ID: mdl-3593449

ABSTRACT

In investigations on rabbits a low-molecular polyvinylpyrrolidone-iodine complex was tested upon its facultative teratological effects after intramuscular application. The dams showed a dose dependent loss of weight increase. The average embryo- and placenta weights of test animals were lower than those of the control animals. Some malformations in kidneys were realised, but they did not show any relation to dosage. Concerning the applied doses no teratological effect was observed.


Subject(s)
Povidone-Iodine/toxicity , Povidone/analogs & derivatives , Teratogens , Animals , Embryo, Mammalian/drug effects , Female , Organ Size/drug effects , Placenta/drug effects , Pregnancy , Rabbits
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