Studies On The Effect Of Flumorph To Endocrine Disruptors

Endocrine disruptors are the exogenous substances that not only change the structure and function of endocrine system but also cause adverse effects at the levels of organism, its progeny, and the subpopulation of organism. It is extensively concerned about the current researches on endocrine disruptors increasingly. The major resources of endocrine disruptors are pesticides, among which flumorph is the first agricultural fungicide which has independent intellectual property rights in China, and it's known little about its function on interference function of endocrine system, thus we fully explore the possible mechanisms in vivo and in vitro.Firstly, in the repeated 28-day oral toxicity study based on the OECD draft protocols we fully investigate the interference effects on endocrine system. The results show that the flumorph has some effects on the growth of male rats that the toxicity showed up in the dose of 100mg/kg in about 27 days, while it showed up soon after taking poison in the dose of 300mg/kg, and the body gradually recovered. For female rats, the toxicity showed up in the dose of 300mg/kg soon after taking poison, and the body gradually recovered until 14 days. In general, flumorph has toxic effects on not only the female rats but also the males, the lasting time is longer for the female rats and the toxic effect is larger for the male ones.Flumorph has damage to the liver of rats which causes the liver steatosis, lobular lesions occurred mainly in the surrounding area, and liver steatosis has caused the change of globulin, blood sugar and cholesterol. The results of blood-biochemistry show that flumorph can cause anemia of male rats, mainly small cell hypo-pigment anemia; anemia caused by flumorph in female rats is less serious than that in male rats, which may be due to the reason that flumorph damage the hematopoietic function of rats, and anemia has caused the change of serum potassium simultaneously. The research results shows that flumorph probably don't have the functions of paraandrogen and anti-androgen, as well as paraestrogen and anti-estrogen under this experimental condition. Flumorph may cause a light interference function of thyroid from the results obtained from thyroid hormone. The NOAEL of flumorph was<30mg/kg/day.Secondly, our group chooses the Uterotrophic assay and the MCF-7 cell-proliferation assay to detect the para-interference function of its estrogen. In the Uterotrophic assay, the absolute and the relative weights of the uterine dry weight and wet weight increases significantly in the estrogen-group, which says the estrogen model is made successfully; While the absolute and the relative weights of the uterine dry weight and wet weight decreases significantly in the tamoxifen-group, indicating that the method in this test is suitable for the detection of paraestrogen or anti-estrogen. Flumorph probably doesn't have the effects of para-estrogenic or anti-estrogenic estrogenic under this experimental condition. In the MCF-7 cell-proliferation assay, the result of the estradiol acting on the MCF-7 cells-proliferation shows that it is credible for estradiol acts as a negative drug. And it shows that under this experimental condition, flumorph doesn't have the activity of estrogen receptors, which is the same as the previous studies about the results of the uterine weight-gain test and the improved the repeated 28-day oral toxicity study. In addition, estradiol did not show cytotoxicity in the dose of 10-5 -10-9mol/L. In summary, flumorph doesn't have estrogenic activity.Thirdly, our group used Hershberger assay to detect the interfere function of androgen, with the results of the experiment group vice gonadal testosterone propionate indicating that the testosterone propionate model was made successfully; Uniformly, the result of flutamide illustrates that this test method is suitable for the detection of para-androgenic effect and anti-androgenic effect. Under this experimental condition, it is proved that flumorph probably doesn't have para-androgenic or anti-androgenic effect, and it is the same as the result of the repeated 28-day oral toxicity study.Finally, our group used 20-day pubertal female assay and 20-day pubertal male assay to detect the interference function of thyrine, and to study its possible mechanisms. From the results of 20-day pubertal female assay we can see that flumorph has interfere function to the thyroid, causing hypothyroidism in animals, and is more toxical to adolescent rats. From the results of 20-day pubertal male assay we can see flumorph has interfere function to the thyroid, causing adolescent male rats hypothyroidism.In conclusion, flumorph probably doesn't have the effects of para-androgen and anti-androgen e as well as the effects of para-estrogen and anti-estrogen, while it has a weak interference function to thyroid.