IN-VIVO STUDIES ON POSSIBLE ADVERSE-EFFECTS ON REPRODUCTION OF THE FUNGICIDE METHYL THIOPHANATE

The fungicide methyl thiophanate (MT), widely used to control some of the most common fungal diseases in crops, is metabolized in animals in to benzimidazole compounds, including the well-known reproductive toxi cant carbendazim, However, standard toxicological tests did not indica te that MT may cause testicular toxicity and/or embryotoxicity, which are typical effects of many benzimidazoles. In the present study some aspects of the MT potential for reproductive toxicity have been assaye d by means of two non-conventional models. Following the oral administ ration of 700 and 1000 mg kg(-1) body wt. for five consecutive days, s hort-term testicular toxicity was examined in the B6C3F1 mouse through specific parameters (sperm head count, specific enzyme activities, hi stopathology on days 3-35 post-dosing). In spite of the high doses adm inistered, none of the testicular parameters examined, including histo pathology, showed significant alterations as compared to controls at a ny time post-dosing, Pregnant CD rat dams were administered orally the limit dose of 650 mg kg(-1) body wt. day(-1) during preimplantation ( gestational day or GD 2-5) or peri-implantation (GD 6-9) phases; embry os and adnexa were evaluated morphologically on GD 12 as a window for the early observation of embryotoxicity, Evident maternal toxicity was present in both treated groups, whereas only marginal reductions of t he growth of embryos and adnexa were observed. A full understanding of MT toxicology will need more quantitative data on metabolism, includi ng plasma kinetics and dosimetry of carbendazim at the relevant target s. Nevertheless, the absence of any clear-cut effect on a number of sp ecific endpoints may provide reassurance that no further testing of MT is needed with regard to testicular toxicity or embryotoxicity, (C) 1 998 John Wiley & Sons, Ltd.