Testing of endocrine active substances using an enhanced OECD test guideline 407: Experiences from studies on flutamide and ethinylestradiol
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| 024 | 7 | 0 | |a 10.1351/pac200375112483 |2 doi |
| 035 | |a (NATIONALLICENCE)gruyter-10.1351/pac200375112483 | ||
| 245 | 0 | 0 | |a Testing of endocrine active substances using an enhanced OECD test guideline 407: Experiences from studies on flutamide and ethinylestradiol |h [Elektronische Daten] |c [A. Freyberger, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, U. Schmidt, M. Temerowski, Andree Folkerts, Michael Becka, B. Stahl, Martin Kayser] |
| 520 | 3 | |a Groups of five male and five female Wistar rats were treated by gavage with 0, 1, 10, and 100 mg/kg body weight (b.w.) flutamide (FLU) or 0.01, 0.05, and 0.2 mg/kg b.w. of ethinylestradiol (EE2) for at least 28 days according to an enhanced Organization for Economic Cooperation and Development (OECD) test guideline (TG) 407 to investigate which of the current and/or additional parameters would detect effects on the endocrine system and to provide data on intralaboratory variability. Two identical studies were performed in parallel on each compound. Common enhancements were determination of thyroid hormones (T3, T4) and thyroid stimulating hormone (TSH), of the stage of the estric cycle to ensure necropsy of females in diestrus, of the number and morphology of epididymal sperm, and of additional organ weights (e.g., male accessory sex organs, MASO) and histopathology of additional organs (e.g., pituitary, vagina). Endocrine-mediated findings consistently observed in these studies were decreased relative weights of MASO at 100 mg/kg FLU and at 0.2 mg/kg EE2, histological changes in pituitary and testes at > or = 10 mg/kg and in MASO, epididymis and adrenals at 100 mg/kg in FLU-treated males, histological changes in the mammary gland at > or = 0.05 mg/kg and in testes, MASO and adrenals at 0.2 mg/kg in EE2-treated males, estrogenization of uterus and vagina (despite necropsy in diestrus) at > or = 0.01 mg/kg EE2, and changes in the ovary at 0.2 mg/kg EE2. Spermatology was insensitive (EE2) or revealed changes only at the maximum tolerated dose (MTD). Determination of T3, T4, and TSH did not contribute to the detection of the endocrine effects (FLU) or provided equivocal results. Doubling the group size to 10 animals by combining the studies run in parallel did not increase the sensitivity of detection of endocrine-mediated effects above the level obtained by histopathological examination of groups of five animals. Only some of the proposed enhancements evaluated were helpful in detecting the endocrine-mediated effects of FLU and EE2. Evaluation of studies according to an enhanced TG 407 on 10 compounds with different endocrine activities will identify the most appropriate enhancements. | |
| 540 | |a © 2013 Walter de Gruyter GmbH, Berlin/Boston | ||
| 700 | 1 | |a Freyberger |D A. |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | |
| 700 | 1 | |a Andrews |D Peter |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | |
| 700 | 1 | |a Hartmann |D Elke |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | |
| 700 | 1 | |a Eiben |D Rolf |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | |
| 700 | 1 | |a Loof |D Ingo |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | |
| 700 | 1 | |a Schmidt |D U. |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | |
| 700 | 1 | |a Temerowski |D M. |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | |
| 700 | 1 | |a Folkerts |D Andree |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | |
| 700 | 1 | |a Becka |D Michael |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | |
| 700 | 1 | |a Stahl |D B. |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | |
| 700 | 1 | |a Kayser |D Martin |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | |
| 773 | 0 | |t Pure and Applied Chemistry |d De Gruyter |g 75/11-12(2003-01-01), 2483-2489 |x 0033-4545 |q 75:11-12<2483 |1 2003 |2 75 |o pac | |
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| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Freyberger |D A. |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Andrews |D Peter |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Hartmann |D Elke |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Eiben |D Rolf |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Loof |D Ingo |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Schmidt |D U. |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Temerowski |D M. |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Folkerts |D Andree |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Becka |D Michael |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Stahl |D B. |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Kayser |D Martin |u Alexius Freyberger ‡, Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, Ulrich Schmidt, Michael Temerowski, Andree Folkerts, Michael Becka, Bernhard Stahl, and Martin Kayser |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Pure and Applied Chemistry |d De Gruyter |g 75/11-12(2003-01-01), 2483-2489 |x 0033-4545 |q 75:11-12<2483 |1 2003 |2 75 |o pac | ||
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