The bioaccumulation and biotransformation of synthetic estrogen quinestrol in crucian carp.

The occurrence and fate of endocrine disrupting chemicals (EDCs) in aquatic species have attracted close attention during the last decades. In this study, the bioaccumulation and biotransformation of synthetic estrogen quinestrol, one of the typical EDCs, in the plasma and liver of crucian carp, were investigated by a newly developed and validated reversed-phase high performance liquid chromatography with fluorescent detection method. Crucian carp were exposed to quinestrol in concentration of 2, 10, 50, 100 µg/L (5.49, 27.43, 137.17, 274.34 nmol/L) for 60 days. After 60 days' exposure, the concentrations of quinestrol found in liver and plasma were in the range of 0.25-0.69 mg/kg and 0.19-0.30 mg/L respectively, positively correlated with the exposure concentrations ranged 2-100 µg/L (5.49-274.34 nmol/L). There was a negative correlation between the bio-accumulation ratios and the exposure concentrations of quinestrol. 17α-Ethinylestradiol was also found in liver and plasma, and the concentrations were 0.02-0.19 mg/kg and 0.37-0.96 mg/L, respectively. The results indicated that quinestrol can be accumulated and transformed to 17α-ethinylestradiol in crucian carp. Moreover, exposure to quinestrol caused oxidative damages to crucian carp and the content of malondialdehyde increased in all treatment concentrations.

Synthesis and estrogenic properties of 17-epi-ethynylestradiol and its ether derivatives epimestranol and epiquinestrol.

The synthesis of 17-epi-ethynylestradiol (10), the 17 beta-ethynyl-17 alpha-ol epimer of the well-known orally active estrogen, ethynylestradiol (1), was achieved by LiA1H4 reduction of epoxide 9, as well as by demethylating epimestranol (11) with CH3MgI. Compound 11 was obtained by the unusual 17 beta-ethynylation of estrone 3-methyl ether 22 under equilibrating conditions. The in vitro estrogen receptor-binding affinity and the oral estrogenicity in the rat for the 17-epi compounds 10, 11 and 20 (epiquinestrol) was evaluated. Despite moderate estrogen receptor-binding affinity, compound 10 was devoid of measurable estrogenicity at 10 mg/kg or antiestrogenicity at 3 mg/kg.

[Comparative studies on biological activity and the kinetics of fat accumulation of estrogens]. / Vergleichende Untersuchungen über die biologische Aktivität und die Kinetik der Fettspeicherung von Ostrogenen

PIP: The biological activity of quinestrol and J 96, a recently developed estrogen, were compared in castrated female rats. Uterine weight was somewhat greater 4-15 days after a single administration of quinestrol than after similar dose of J 96. The quantity of secretion in the uterine lumen was over 2000 mg 6 days after administration of quinestrol, more than twice that seen after J 96 Elimination of Quinestrol from all fat tissues was slower than that of J 96. Differences in elimination times were seen for subcutaneous, perirenal, and mesenteric fat.^ieng

[Contraceptive effect and tolerance of monthly oral doses of quinestrol (author's transl)].

PIP: 86 fertile women aged 18 to 37 were given 3.5 mg of Quinestrol monthly for a total of 457 cycles and were studied for the effectiveness and tolerance of this contraceptive. In order to induce periodic hemorrhage, 6 mg of the synthetic progestogen ethynodiol diacetate was added to the Quinestrol. Patients were advised to use an additional contraceptive during the first cycle. Only 1 pregnancy took place throughout the study and this occurred in the first month in a patient who had neglected to use another contraceptive during this time. Side effects, which included nausea and vomiting, were reported most often during the 1st month of treatment and became less troublesome as therapy continued. Exceptions were hypermenorrhea and spotting, which occurred more frequently during later treatment cycles. Ovulation was found to occur in 28% to 39% of the cycles, suggesting that the antifertility property of Quinestrol is not due solely to its inhibitory effect on ovulation.^ieng