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Comparison of toxicity studies based on the draft protocol for the 'Enhanced OECD Test Guideline no. 407' and the research protocol of 'Pubertal Development and Thyroid Function in Immature Male Rats' with 6-n-propyl-2-thiouracil

Comparison of toxicity studies based on the draft protocol for the 'Enhanced OECD Test Guideline no. 407' and the research protocol of 'Pubertal Devel

Comparison of toxicity studies based on the draft protocol for the 'Enhanced OECD Test Guideline no. 407' and the research protocol of 'Pubertal Development and Thyroid Function in Immature Male Rats' with 6-n-propyl-2-thiouracil   (Citations: 18)
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Two repeated-dose studies of 6-n-propyl-2-thiouracil (PTU) in male rats based on the research protocol 'Pubertal Development and Thyroid Function in Immature Male Rats' (pubertal assay) proposed by the Endocrine Disrupter Screening and Testing Advisory Committee (EDSTAC) and the draft protocol of the 'Enhanced OECD Test Guideline 407' (enhanced TG 407) were performed to investigate the suitability of both assays as screening methods for the detection of endocrine-mediated effects and to compare their sensitivity for the endocrine-mediated effects. In the pubertal assay, PTU at doses of 0, 0.01, or 1 mg/kg per day was orally administered to male Sprague-Dawley rats for 30 days, starting at 23 days of age. In the enhanced TG 407 the same doses of PTU were orally administered to male Sprague-Dawley rats for 28 days, starting at 7 weeks of age. In the pubertal assay, decreased serum thyroxine (T4) and triiodothyronine (T3), increased thyroid and pituitary weights, hypertrophy of follicular epithelial cells in the thyroid, and increased basophilic cells in the pituitary were detected as endocrine-mediated effects of PTU in the 1 mg/kg group. In the enhanced TG 407, decreased T4 and T3 were detected in both the 0.01 and 1 mg/kg groups, together with increased thyroid-stimulating hormone in the 1 mg/kg group, increased thyroid and pituitary weights in the 1 mg/kg group, and hypertrophy of follicular epithelial cells in the thyroid and increased basophilic cells in the pituitary of the 1 mg/kg group. Thus, among the parameters tested, the thyroid hormone levels, organ weight changes, and the histopathological assessment allowed detection of the endocrine-related effects of PTU in both the pubertal assay and the enhanced TG 407, but the sensitivity of the hormone analysis was higher in the latter.
Journal: Archives of Toxicology - ARCH TOXICOL , vol. 76, no. 9, pp. 495-501, 2002
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    • ...Some studies of various chemicals have been conducted based on the enhanced TG 407 assay, and the usefulness of this assay has been assessed (Toyoda et al. 2000; Andrews et al. 2001; Okazaki et al. 2001, 2002a, b; Yamasaki et al. 2002a, b; Kennel et al. 2003; Mellert et al. 2003; Wason et al. 2003; Kunimatsu et al. 2004; Miyata et al. 2006; Shin et al. 2006a, b; Shiraishi et al. 2006; Gelbke et al. 2007; Woo et al. 2007)...
    • ...The enhanced TG 407 assay is considered a suitable screening assay for detecting eVects of chemicals on the thyroid (Yamasaki et al. 2002a; Mellert et al. 2003; OECD 2006, 2007)...

    Kanji Yamasakiet al. Uterotrophic assay, Hershberger assay, and subacute oral toxicity stud...

    • ...Mammalian studies have provided evidence that EDC-induced alterations of thyroid homeostasis can result from inhibition of thyroidal iodide uptake (Siglin et al., 2000), suppression of thyroid peroxidase activity (Yamasaki et al., 2002), displacement of TH from plasma transport proteins (Meerts et al., 2000), and upregulation of hepatic TH transformation/elimination (Hood et al., 2003)...
    • ...In mammalian studies, measurements of plasma concentrations of T4, T3, and thyroid-stimulating hormone (TSH), combined with histopathological and morphometric analyses of the thyroid gland, represent a common approach to detect anti-thyroidal effects of EDC (O’Connoret al., 1999; Yamasaki et al., 2002)...
    • ...The development of sensitive and diagnostic bioassays for detection of thyroid system-disrupting chemicals has been recognized as an important research need (Colborn, 2002; Yamasaki et al., 2002; Zoeller, 2003)...

    Robert Opitzet al. Evaluation of Histological and Molecular Endpoints for Enhanced Detect...

    • ...Several results with various chemicals based on the draft of the OECD protocol have been published and the usefulness of this assay as an in vivo screening test to detect endocrine properties has been confirmed (Toyoda et al. 2000; Andrews et al. 2001, 2002; Okazaki et al. 2001, 2002a, 2002b; Yamasaki et al. 2002a, 2002b; Cho et al. 2003; Kennel et al. 2003; Mellert et al. 2003; Wason et al. 2003; Kunimatsu et al. 2004; Miyata et al. 2005; ...
    • ...Recently the usefulness of the Enhanced TG407 was confirmed as an in vivo screening test for endocrinemediated effects and an international validation study of the Enhanced TG407 was coordinated by the OECD and conducted based on the OECD protocols (Toyoda et al. 2000; Andrews et al. 2001, 2002; Okazaki et al. 2001, 2002a, 2002b; Yamasaki et al. 2002a, 2002b; Cho et al. 2003; Kennel et al. 2003; Mellert et al. 2003; Wason et al. 2003; ...

    Jae-Ho Shinet al. Repeated 28-day oral toxicity study of vinclozolin in rats based on th...

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