Reproductive and Growth Responses of the Fathead Minnow (Pimephales Promelas) and Japanese Medaka (Oryzias Latipes) to the Synthetic Progestin, Norethindrone

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A commonly prescribed contraceptive, the synthetic progestin norethindrone (NET) inhibits ovulation in humans. However, ecotoxicological data are lacking. Preliminary tests produced an LC50 for NET of > 1.0 mg/L (96-hour, fathead minnow (FHM) and medaka) and a NOEC of 242.0 µg/L, a LOEC of 485.0 µg/L (7-day, growth for FHM and medaka). Reproductive testing revealed a LOEC for fecundity of 24.1 ng/L (21 days, medaka). Further testing confirmed the LOEC of 24.1 ng/L while defining a NOEC of 4.7 ng/L (28 days, medaka). Effect of NET in medaka life-cycle exposure at concentrations exceeding 4.7 ng/L was evident. Few females were ... continued below

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Paulos, Peter M. May 2011.

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A commonly prescribed contraceptive, the synthetic progestin norethindrone (NET) inhibits ovulation in humans. However, ecotoxicological data are lacking. Preliminary tests produced an LC50 for NET of > 1.0 mg/L (96-hour, fathead minnow (FHM) and medaka) and a NOEC of 242.0 µg/L, a LOEC of 485.0 µg/L (7-day, growth for FHM and medaka). Reproductive testing revealed a LOEC for fecundity of 24.1 ng/L (21 days, medaka). Further testing confirmed the LOEC of 24.1 ng/L while defining a NOEC of 4.7 ng/L (28 days, medaka). Effect of NET in medaka life-cycle exposure at concentrations exceeding 4.7 ng/L was evident. Few females were present in the 24.7 ng/L exposure concentration, with none in the 104.6 ng/L. Egg production was significantly reduced at concentrations exceeding 4.7 ng/L. Additionally, weight, condition factor and somatic indices were significantly different in males exposed to concentrations exceeding 4.7 ng/L. For fecundity and sexual differentiation; the NOEC was 4.7 ng/L, the LOEC 24.6 ng/L; growth and somatic indices, the NOEC was more appropriately 0.9 ng/L, with effect evident at 4.7 ng/L. Sexual differentiation of the F1 population was similar to the F0. A defining result of this test was development of exceptionally large ovaries in NET- exposed female medaka, perhaps indicative of a threshold limit for exposure in these fish. Results of FHM life-cycle testing were similar, establishing a NOEC for fecundity of 0.9 ng/L, a LOEC of 4.8 ng/L. NET's inhibitory effect on gonadal development was obvious; GSI NOEC for males, 4.8 ng/L, and histological examination confirmed the presence of intersex development at elevated concentrations. Normal physical development and growth were impaired, generally at concentrations exceeding 24.1 ng/L. At exposure concentrations exceeding 4.8 ng/L, external sexual confirmation of fish was difficult; LOEC for finspot development in females, 4.8 ng/L. Sexual determination of the 97.1 ng/L exposure group was impossible; externally, all fish appeared male and internal examination revealed no gonadal development.

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  • May 2011

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  • Jan. 9, 2012, 9:53 p.m.

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  • Jan. 21, 2014, 3:48 p.m.

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Paulos, Peter M. Reproductive and Growth Responses of the Fathead Minnow (Pimephales Promelas) and Japanese Medaka (Oryzias Latipes) to the Synthetic Progestin, Norethindrone, dissertation, May 2011; Denton, Texas. (digital.library.unt.edu/ark:/67531/metadc68029/: accessed July 27, 2017), University of North Texas Libraries, Digital Library, digital.library.unt.edu; .