Font Size: a A A

Male Reproductive & Developmental Toxicity And Health-based Risk Assessment Of Phthalates

Posted on:2005-01-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y H ZhangFull Text:PDF
GTID:1104360125467296Subject:Occupational and Environmental Health
Abstract/Summary:PDF Full Text Request
Phthalate is a class of chemical compounds widely used in industrial activities. Theyare mainly used as plasticizers for polyvinyl chloride (PVC) resins, adhesives, andcellulose film coating. Phthalates can be easily released into the environment throughvolatilization and leaching from plastics during the process of production of plastics andplastic materials or their disposal. Organisms can bioaccumulate phthalate compounds andthe subsequent adverse effects could be biomagnified for hundreds of times. In this study, environmental samples were collected from surface water, soil, sedimentand aquatic organisms in the Yangtze Delta. Human biological samples (serum, semen andfat tissues) were collected from Shanghai residents. Concentrations of three commonlyused phthalates (DEP DBP and DEHP) in these samples were measured by reversed-phaseHPLC. The result showed that the three phthalates were detected in most of the samples,suggesting that people residing in the Yangtze Delta were exposed to phthalates(particularly to DBP and DEHP) though the level was still relatively mild. The associations between phthalate levels and female serum hormone levels or malesemen quality parameters were analyzed using multiple stepwise regression method. It wasfound that there were positive associations between DEP and FSH in female serum, semenDBP level and semen liquefied time, and negative associations between DBP level andsemen volume or density, DEHP level and sperm malformation ratio. Di-n-butyl phthalate is one of the commonly used plasticizers in China. DBP can enterenvironment and organisms through various routes and then affect the reproductive anddevelopmental process of the organism and its descendants (mainly affect male offspring).The most sensitive window period of DBP exposure in animals is in utero and duringlactation. Accordingly, pregnant rats were treated with different dose of DBP (0, 50, 250and 500mg per kg per day) by gavage from GD1 to PND21 in this study. The adverseeffects of DBP on the development of F1 rats have been observed until sexual maturalperiod (PND70). The results showed that DBP had no obvious effect on pregnant rats but couldsignificantly decline pups` born weight, live pups per litter, body weight gain and malepups` anogenital distance. On sexual matural period (PND70), slight adverse effects on rat 3testis could be recuperated, but severe damages on the reproductive system of F1 male rats(testicular atrophy, underdeveloped epididymis, obvious decline of epididymal spermparameters, etc.) could still be observed in the groups of 250 and 500 mg per kg per day.These results showed that male reproductive system was the target organ of DBP. Thisstudy also showed that the damages on pups were partly reversible. According to these results, the NOAEL of DBP, which was not available in the currentdatabase, was established based on the outcomes of this study, i.e., 50mg per kg bw per day.Taking 100 as the uncertainty factor, the RfD for human exposure to DBP through oralintake was recommended as 500 g per kg bw per day. In recent years, the reproductive toxicity of phthalate was considered to be related toendocrine disrupting activity. In this study, the mechanism of reproductive toxicity ofphthalate was explored. The results showed that phthalate could destroy the tight junctionbetween Sertoli cells and germ cells and then induce the detachment of germ cells fromgerm epithelium by activating the Fas/FasL system. This might be one of the reseaons oftestis atropy, which was observerd in phthalate-treated rats. The result of uterotrophicbioassay in immature rats excluded estrogenic activity of DBP, DEHP and their metablitesMBP and MEHP. The results from serum hormone levels measurement of rats andRT-PCR assays showed that DBP could decrease the expression of testosterone bindingABP, but not MIS, suggesting that antiadrogenic activity might be one of the rea...
Keywords/Search Tags:phthalates, male reproductive toxicity, health-based risk assessment
PDF Full Text Request
Related items