Dill seed essential oil (DSEO) is a candidate for pharmaceutical and nutraceutical applications but the safety data is not available. In this study we aim to evaluate the acute and repeated dose toxicity of DSEO in female mice via histopathological and immunohistochemical evaluations with focus on reproductive organs. After providing DSEO and characterizing its chemical composition through gas chromatography-mass spectrometry (GC-MS), toxicity tests were performed in accordance with OECD 425 and OECD 407 guidelines, followed by additional immunohistochemistry tests on sex hormone receptors in reproductive organs of female mice. Acute tests did not show any mortality or signs of toxicity within the first 24 h and follow-up period. No-observed-adverse-effect-level (NOAEL) was determined as 25 mg/kg after daily administrations of 25, 250, 500, and 1000 mg/kg doses of DSEO in a 28-day regimen. Although the low dose (25 mg/kg) didn’t show any organ toxicity, this regimen caused significant decrease in serum estradiol levels [16.21(0.02) vs. 60.8(0.1) pg/ml, p < 0.001], significant uteri weight gain (0.075 g vs. 0.004 g, p = 0.004), and mild edema in endometrial tissues compared to control. Endometrial overexpression of estrogen receptor alpha (ERα) was further detected in DSEO treated animals. Primary anti-estrogenic effects of DSEO at low doses (25 mg/kg) suggest it as a future herbal supplement for preventive and therapeutic applications in clinical setting.
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