Abstracts / Toxicology Letters 164S (2006) S1–S324 S303 but a positive response does not necessarily mean that tumours will be induced by that chemical in that organ. TMA are useful tools for mechanistic studies and may be suitable for proving a non-genotoxic mode of action of a carcinogen. doi:10.1016/j.toxlet.2006.07.287 P26 Others P26-01 Challenges associated with toxicity testing of tradi- tional medicines in South Africa using nonhuman primate models J¨ urgen Seier 1 , Mongezi Mdhluli 1 , Motlalepula Matsabisa 2 1 Primate Unit, Medical Research Council of South Africa; 2 Indigenous Knowledge Systems, MRC, Cape Town, Western Cape, South Africa Traditional medicines are used by about 80% of the South African population and substitute for conventional pharmaceuticals in many cases. Apart from strong cul- tural reasons, many people have limited access to other medication due to economic circumstances. In response, African institutions are increasingly striving to provide scientific evidence for the efficacy and safety of tra- ditional medicines. According to some local opinion, safeguarding against toxic effects is the least that should be done, even in the absence of scientifically proven effi- cacy. The Primate Unit of the MRC is being increasingly approached by local commercial and non-commercial organisations to conduct toxicity tests on traditional medicines. These usually consist of a blend of dried and milled plant materials, which are administered orally. Having to work with such materials during testing on animals provides challenges, that are quite distinct from administering pure compounds, and makes adherence to internationally standards on toxicity testing at times impossible. The main reasons are that usually no in vitro and pharmacokinetic data can be established, poor palatability, the materials can not be gavaged, high thera- peutic doses frequently limit the quantity that can admin- istered, and often no actual toxic doses can be predicted. Additionally, there is invariably limited funding avail- able. Our presentation illustrates how the Primate Unit approaches toxicity testing of whole plant materials in a vervet monkey model, and how we deal with the chal- lenges of above mentioned limitations. Our approach includes a special diet that serves as an excellent vehi- cle for even higher concentrations, improving palata- bility, a 90-day subchronic repeat-dose testing regimen, and monitoring consumption by determining daily food intake. With our methods, we have been able to demonstrate toxicity at moderate and high doses, in two out of six traditional medicines tested by us so far. doi:10.1016/j.toxlet.2006.07.288 P26-02 Pyrazinamide and disulfiram effects on male rat’s reproductive function V.M. Kovalenko , L.B. Bondarenko, T.F. Byshovetz, G.M. Shayakhmetova,A.K. Voronina, O.S. Voloshina, N.A. Saprykina Institute of Pharmacology and Toxicology, Academy of Medical Sciences of Ukraine, Kyiv, Ukraine In spite of broad utilization of pyrazinamide in tuberculo- sis and AIDS treatment schemes, its effects on reproduc- tive function and posterity remains insufficiently inves- tigated and present results are discrepant. Effects of pyrazinamide (500, 1000 and 2000 mg/kg b.w.) and disulfiram (30mg/kg) on liver and testis bio- chemical parameters and reproductive toxicity indices have been studied in experiments on Wistar rats. It was shown that pyrazinamide caused dose depen- dent increasing of p-nitrophenol hydroxylase activity (from 1.4 to 2.3 times), cytochrome P-450 (CYP P450) contents (from 1.3 to 1.8 times) and NADPH-dependent lipid peroxidation (to 86%) in liver microsomal frac- tion with simultaneous decrease of DNA (to 30%), RNA (to 34%), total histones (to 49%), phospholipids (to 31%), esterified cholesterol contents (to 47%) in testis. Ratio DNA/histones was increased from 1.2 to 1.4 times. Use of CYP 450 2E1 inhibitor disulfiram prevented p- nitrophenol hydroxylase activation, the increase of total CYP 450 2E1 and the rate of NADPH-dependent for- mation of TBA-products. Administration of disulfiram caused normalization of DNA, RNA, histones contents and ratio DNA/histones. On phospholipids and ester- ified cholesterol contents in testis, effects of pyrazi- namide and disulfiram had opposite directions. Pyraz- inamide administration produced spermatozoid num- ber decreasing in epididimys in dependence of dose. Decrease of spermatogonia number and compensatory increase of 12th meiosis stages with synchronous dys- trophic changes of spermatogenic epithelia also were registered at these conditions. Disulfiram introduction with pyrazinamide produced three times decreased mei-