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 into benzimidazole compounds, including the well-known reproductive toxicant carbendazim. However, standard toxicological tests did not indicate 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 assayed by means of two non-conventional models. Following the oral administration of 700 and 1000 mg kg(-1) body wt. for five consecutive days, short-term testicular toxicity was examined in the B6C3F1 mouse through specific parameters (sperm head count, specific enzyme activities, histopathology on days 3-35 post-dosing). In spite of the high doses administered, none of the testicular parameters examined, including histopathology, showed significant alterations as compared to controls at any 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; embryos 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 the growth of embryos and adnexa were observed. A full understanding of MT toxicology will need more quantitative data on metabolism, including plasma kinetics and dosimetry of carbendazim at the relevant targets. Nevertheless, the absence of any clear-cut effect on a number of specific endpoints may provide reassurance that no further testing of MT is needed with regard to testicular toxicity or embryotoxicity.
Laboratorio di Igiene Ambientale, Istituto Superiore di Sanità, Rome, Italy.
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Traina
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Fazzi
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Macrì
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Ricciardi
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Stazi
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Urbani
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Mantovani
D000284:Administration, Oral; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000633:toxicity; D001755:Blastocyst / Q000187:drug effects; D001835:Body Weight; D002219:Carbamates; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D005659:Fungicides, Industrial / Q000008:administration & dosage / Q000633:toxicity*; D005865:Gestational Age; D008297:Male; D051379:Mice; D011247:Pregnancy; D051381:Rats; D012098:Reproduction / Q000187:drug effects*; D013723:Teratogens / Q000633:toxicity*; D013737:Testis / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D013875:Thiophanate / Q000008:administration & dosage / Q000633:toxicity*
D001562:Benzimidazoles; D002219:Carbamates; D005659:Fungicides, Industrial; D013723:Teratogens; D013875:Thiophanate; C006698:carbendazim