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T Platzek

Publications and source records attributed to T Platzek.

22 records · Page 2Linked to original sources

Embryotoxicity induced by alkylating agents. Teratogenicity of acetoxymethyl-methylnitrosamine: dose-response relationship, application route dependency and phase specificity.

Acetoxymethyl-methylnitrosamine, the acetate ester of the presumed reactive metabolite of dimethylnitrosamine, is an effective teratogen in NMRI mice. An unusual phenomenon of application route specificity and a pronounced phase specificity of the teratogenic effects induced are demonstrated. Dose-response relationships are established. Some further arguments are given to support the basic hypothesis that the teratogenicity of alkylating agents is closely correlated to the DNA alkylation rate of embryonic cells.

Alkylating Agents↗

Development of N-demethylase activity measured with the 13C-aminopyrine breath test.

The 13C-aminopyrine (AP) breath test was used to measure the normal development of N-demethylase activity in 25 children, aged 2 days to 14 years, with normal liver function. Five mg of 13C-AP per kg body weight were administered orally. After AP-demethylation by the hepatic mixed function oxidase system 13CO2 excess was analysed in expired breath by mass spectrometry. In the first days of life no 13C excretion could be detected in unstimulated newborns. N-demethylase activity then slowly increased and reached adult levels by two years of life. Though the range of normal values showed considerable scattering, patients with liver disease or with enzyme induction following anticonvulsant therapy could be well discriminated. This study of the 13C-aminopyrine breath test in children provides evidence for the assumption that hepatocellular function and development of specific enzymatic activities can be measured by such non-invasive methods. It may be expected that breath tests making use of a broader spectrum of 13C-labeled substrates will prove applicable to study prenatal inducibility and other aspects of developing hepatocellular and intestinal function of children in health and disease.

Adolescent↗

Harmonisation of rat fetal skeletal terminology and classification. Report of the Third Workshop on the Terminology in Developmental Toxicology. Berlin, 14-16 September 2000.

The initial efforts of the Federal Institute for Health Protection of Consumers and Veterinary Medicine (BgVV) and the Free University of Berlin to standardise terminology in the field of developmental toxicology began in 1995. Procedures were undertaken to harmonise the terminology used by the International Federation of Teratology Societies (IFTS) and the International Programme on Chemical Safety (IPCS). This article reflects these activities and is a report on the Third Workshop on the Terminology in Developmental Toxicology held in September 2000. This Workshop served as a forum to discuss the results of a survey on the classification of skeletal anomalies that had been previously sent to scientists active in the field. Although high agreement was reached among the evaluators for several terms, the use of a number of terms was rather variable. Therefore, the discussions at the workshop among the experts from research institutions, regulatory agencies, and industry were mainly focussed on those terms for which there was disagreement and/or uncertainties and the possible reasons. Pictures provided by the participants for the illustration of "grey zone" anomalies constituted the basis for detailed discussions. In many of the cases with lower agreement, decisions were facilitated by the provision of the corresponding picture. The main reasons for lower agreement were imprecise terms, insufficient knowledge on postnatal consequences, theoretical terms that are unlikely to occur in isolation, and the possibility of observing a range of severity that might be decisive for the classification of either a malformation or variation. The attendees concluded that "grey-zone" anomalies will never disappear completely and that for the assessment, the grade of severity and/or the frequency of the observation can be decisive for the terminology chosen. A Joint IPCS/IFTS Project was proposed to further consensus of terminology and classification and to link these anomalies to pictures at different skeletal sites. In order to support the harmonisation of regulatory decisions, it was proposed to establish a "Clearinghouse" System under the umbrella of the IPCS. The Clearinghouse could be contacted either by the regulatory authorities or by any company to clarify their queries, particularly with regard to registration or authorisation processes. Finally, it was recommended to also carry out a similar survey on "soft tissue anomalies" and "external findings." The results of this survey will be discussed at a Joint IPCS/IFTS Workshop in Berlin in 2002.

Abnormalities, Drug-Induced↗