Study On Estrogenity Of Substituted Phenols And Analysis Of The Relationship Between Structure And Activity

With the rapid development of industrialization, more and more man-made chemicals appeared in environment where man live, of which a kind of chemical with estrogenity attracted more attention because of their latent destroying to the living and reproduction of man and other animals. And with more new chemicals developed, more estrogenic chemicals will be detected. So it is urgent to find out a practical method to determine estrogenicity of chemicals. Method pertinent to Vitellogenin(VTG) of fishes is prevalent to determine estrogenicity of chemicals because of its feasibility and sensitivity. Polyclonal antibody raised against carp VTG was used as the first antibody in this paper to measure juvenile goldfish VTG The traditional method to measure VTG in serum was changed into detect VTG in liver, so that rapid sampling and measuring can be made to the small fish or juvenile fish, and then this method was used to evaluate the estrogenicity of many substituted phenols. QSAR Analysis was made to estimate the factors of molecule characteristic parameters affecting estrogenicity of chemicals so that some theories of estrogenic mechanism can be found. Some conclusions were achieved through lots of experiments:1. Polyclonal antibody raised against carp VTG can identify goldfish VTG, and there exists good sensitivity to measure VTG in liver. This method is a good surrogate for measuring VTG in serum for small fish. Chemical's concentration and exposure time had impaction on the accumulation of VTG.2. A serials of substituted phenols were tested, of which some are estrogenic such as Diethylstilbestrol(DES),Hexestrol(HES),4-nonylphenol(NP),4-tert-octylphenol(O P),4-tert-pentylphenol(PP),4-tert-butylphenol(BP),4-heptyloxyphenol(HP),4-tert-b utylcateehol(BOP),4-chloro-3-methylphenol(BClP), but others are non-estrogenic such as Pentachlorophenol(PCP) 2,3,5,6-tetrachlorophenol(TeCP) 2,3,4-trichlorophenol(TCP).3. QSAR analysis was made for 9 substituted phenols with obvious estrogenicity. Equations were founded between molecule parameters and log1/EC₅₀, and the results showed that they were the most important factors to affect estogenicity of substituted phenols. R² is 0.963, which showed that the Equation has some ability to reflect and dope out the estrogenicity. This provided a new idea to filter and evaluate the estrogenicity of chemicals.