Study Of The Association Between The Phthalate Acid Esters Exposure And Gynecological Diseases

[Objective]①To investigate the status about the understandings and daily exposure of PAEs plasticizer of 244 female population;②To develop methods to determine the PAEs in serum,pathological tissue and the PAEs metabolites in urine;③to analyze the correlation between the serum PAEs level and factors such as types of gynecological diseases, serum sex hormone levels and daily exposure to plasticizers.④To analyze the correlation between the pathological tissue PAEs level and factors such as types of gynecological diseases and daily exposure to plasticizers.⑤To analyze the correlation between the urine PAEs metabolites level and factors such as types of gynecological diseases and daily life exposure to plasticizers.⑥To develop a rapid and accurate method to determine the PAEs level of 49 plastic bottled drinks.[Methods]①design a questionnaire, get the basic information such as age, gender, height and weight, and investigate the status about the understandings and daily exposure of PAEs plasticizer of 244 female subjects;②With the pre-processor techniques of liquid phase extraction, solid phase extraction and neutral alumina column pre-purification, We developped methods to determine the PAEs in serum, pathological tissue and the PAEs metabolites in urine by gas chromatograph(GC) and High Performance Liquid Chromatography(HPLC);③Statistically analyze the correlation between PAEs level of 244 female population and related factors by SPSS 16.0;④Determine the PAEs levels of 49 plastic bottled drinks by Gas Chromatography (GC)[Results]①244 female subjects were composed of 164 gynecological cases and 80 healthy control; Case group included 80 cases of uterine fibroids,67 cases of ovarian cysts and 17 cases of primary infertility patients.220 out of 244 subjects completed the questionnaire,176 out of 220 respondents know little about phthalate plasticizers; 178 subjects do not know the plastics containing plasticizers; as the aspect of the plasticizer can integrate into the food and then cause harm to our health,46.8% and 50.9% of the respondents think that will not happen; the survey shows that people can get extensive PAEs exposure in daily life;②In serum of 244 female subjects,positive ratios of DEP, DBP and DEHP are 26.2%,95.5% and 92.2%, respectively; the geometric means are 0.071,0.270and 0.193mg/L,respectively; the level of serum DBP in case group were negatively correlated with follicle stimulating hormone(FSH) and prolactin(PRL) (-0.201, P=0.034;-0.187, P=0.050); levels of serum DBP in case group are significantly higher than those in the control (0.342 vs 0.165, P<0.01), levels of serum DBP are positively correlated with age; significant association are not found between the levels of serum PAEs and the exposure factors;③In pathological tissue of uterine fibroids and ovarian cysts, the positive ratios of DEP, DBP and DEHP are 0,74.8% and 99.3% respectively; the levels of DBP and DEHP in ovarian cysts tissue are significantly higher than those of uterine fibroids (0.457 vs 0.202μg/g, P<0.001; 4.123 vs 2.317μg/g, P<0.001); levels of PAEs in pathological tissue and serum are not significantly correlated; Spearman correlation analysis shows that levels of DBP and DEHP in pathological are negatively correlated with age (P=0.05 and P<0.01), but after the correction of generalized linear models, the impact of the age factor on the levels of PAEs disappears; significant association are not found between the levels of pathological tissue PAEs and the exposure factors;④Concentrations of Phthalate monoesters in urine is quite low, HPLC detection sensitivity can not meet the requirements, we failed to get the proper data about the levels of PAEs metabolites in urine by HPLC;⑤In 49 plastic bottled drinks, the positive ratios of DEP, DBP and DEHP are 0, 98.0% and 100.0%, respectively; the levels of DBP in fruit juice and dairy drinks were significantly higher than those tea drinks (p=0.018 and p=0.041); levels of DEHP in fruit juice are higher than those in tea and dairy drinks (p=0.009 and p= 0.054); Spearman correlation analysis do not show that levels of DBP, DEHP in plastic bottled drinks are significantly asociated with soaking time; levels of DEHP are negatively correlation with PH value (-0.434, P=0.002).[Conclusion]①The female population know little or even do not know about the PAEs platicizer, lack of understandings about these substances will further increase the levels of daily exposure to PAEs;②Positive ratios of DBP and DEHP in serum are fairly high; levels of serum DBP in case group are significantly higher than those of the control; and the serum DBP levels are positively correlated with age; significant association are not found between the levels of serum PAEs and the exposure factors;③we successfully established the method to detect the pathological tissue PAEs. With the help of neutral alumina chromatography purification, smaller noise of instruments and higher column Efficiency are achieved;④Positive ratios of DBP and DEHP in pathological tissue are fairly high; levels of PAEs in ovarian cyst tissue are significantly higher than uterine fibroids;⑤Positive ratios of DBP and DEHP in plastic bottled drinks are fairly high, and levels of DEHP are higher than DBP. Fruit juices contain higher PAEs than ohers. Levels of PAEs are negatively associated with PH value of drinks; no significant association are found between the PAEs levesl and the soaking time.